Functional network integrity presages cognitive decline in preclinical Alzheimer disease.

PubMed

Buckley, Rachel F; Schultz, Aaron P; Hedden, Trey; Papp, Kathryn V; Hanseeuw, Bernard J; Marshall, Gad; Sepulcre, Jorge; Smith, Emily E; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Chhatwal, Jasmeer P

2017-07-04

To examine the utility of resting-state functional connectivity MRI (rs-fcMRI) measurements of network integrity as a predictor of future cognitive decline in preclinical Alzheimer disease (AD). A total of 237 clinically normal older adults (aged 63-90 years, Clinical Dementia Rating 0) underwent baseline β-amyloid (Aβ) imaging with Pittsburgh compound B PET and structural and rs-fcMRI. We identified 7 networks for analysis, including 4 cognitive networks (default, salience, dorsal attention, and frontoparietal control) and 3 noncognitive networks (primary visual, extrastriate visual, motor). Using linear and curvilinear mixed models, we used baseline connectivity in these networks to predict longitudinal changes in preclinical Alzheimer cognitive composite (PACC) performance, both alone and interacting with Aβ burden. Median neuropsychological follow-up was 3 years. Baseline connectivity in the default, salience, and control networks predicted longitudinal PACC decline, unlike connectivity in the dorsal attention and all noncognitive networks. Default, salience, and control network connectivity was also synergistic with Aβ burden in predicting decline, with combined higher Aβ and lower connectivity predicting the steepest curvilinear decline in PACC performance. In clinically normal older adults, lower functional connectivity predicted more rapid decline in PACC scores over time, particularly when coupled with increased Aβ burden. Among examined networks, default, salience, and control networks were the strongest predictors of rate of change in PACC scores, with the inflection point of greatest decline beyond the fourth year of follow-up. These results suggest that rs-fcMRI may be a useful predictor of early, AD-related cognitive decline in clinical research settings. © 2017 American Academy of Neurology.

Contrasting olfaction, vision, and audition as predictors of cognitive change and impairment in non-demented older adults.

PubMed

MacDonald, Stuart W S; Keller, Connor J C; Brewster, Paul W H; Dixon, Roger A

2018-05-01

This study examines the relative utility of a particular class of noninvasive functional biomarkers-sensory functions-for detecting those at risk of cognitive decline and impairment. Three central research objectives were examined including whether (a) olfactory function, vision, and audition exhibited significant longitudinal declines in nondemented older adults; (b) multiwave change for these sensory function indicators predicted risk of mild cognitive impairment (MCI); and (c) change within persons for each sensory measure shared dynamic time-varying associations with within-person change in cognitive functioning. A longitudinal sample (n = 408) from the Victoria Longitudinal Study was assembled. Three cognitive status subgroups were identified: not impaired cognitively, single-assessment MCI, and multiple-assessment MCI. We tested independent predictive associations, contrasting change in sensory function as predictors of cognitive decline and impairment, utilizing both linear mixed models and logistic regression analysis. Olfaction and, to a lesser extent, vision were identified as the most robust predictors of cognitive status and decline; audition showed little predictive influence. These findings underscore the potential utility of deficits in olfactory function, in particular, as an early marker of age- and pathology-related cognitive decline. Functional biomarkers may represent potential candidates for use in the early stages of a multistep screening approach for detecting those at risk of cognitive impairment, as well as for targeted intervention. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Contrasting Olfaction, Vision, and Audition as Predictors of Cognitive Change and Impairment in Non-Demented Older Adults

PubMed Central

MacDonald, Stuart W.S.; Keller, Connor J.C.; Brewster, Paul W.H.; Dixon, Roger A.

2017-01-01

Objective This study examines the relative utility of a particular class of non-invasive functional biomarkers -- sensory functions -- for detecting those at risk of cognitive decline and impairment. Three central research objectives were examined including whether: (1) olfactory function, vision, and audition exhibited significant longitudinal declines in non-demented older adults, (2) multi-wave change for these sensory function indicators predicted risk of mild cognitive impairment, and (3) change within persons for each sensory measure shared dynamic time-varying associations with within-person change in cognitive functioning. Method A longitudinal sample (n=408) from the Victoria Longitudinal Study was assembled. Three cognitive status subgroups were identified: not impaired cognitively (NIC), single assessment mild cognitive impairment (SA-MCI), and multiple assessment mild cognitive impairment (MA-MCI). Results We tested independent predictive associations, contrasting change in sensory function as predictors of cognitive decline and impairment, utilizing both linear mixed models and logistic regression analysis. Olfaction and, to a lesser extent, vision were identified as the most robust predictors of cognitive status and decline; audition showed little predictive influence. Conclusions These findings underscore the potential utility of deficits in olfactory function, in particular, as an early marker of age- and pathology-related cognitive decline. Functional biomarkers may represent potential candidates for use in the early stages of a multi-step screening approach for detecting those at risk of cognitive impairment, as well as for targeted intervention. PMID:29809033

Association of Source of Memory Complaints and Increased Risk of Cognitive Impairment and Cognitive Decline: A Community-Based Study.

PubMed

Qi, Xue-Mei; Gu, Lin; Tang, Hui-Dong; Chen, Sheng-Di; Ma, Jian-Fang

2018-04-20

Memory complaint is common in the elderly. Recently, it was shown that self-report memory complaint was predictive of cognitive decline. This study aimed to investigate the predictive value of the source of memory complaints on the risk of cognitive impairment and cognitive decline in a community-based cohort. Data on memory complaints and cognitive function were collected among 1840 Chinese participants (aged ≥55 years old) in an urban community at baseline interview and 5-year follow-up. Incident cognitive impairment was identified based on education-adjusted Mini-Mental State Examination score. Logistic regression model was used to estimate the association between the source of memory complaints and risk of cognitive impairment conversion and cognitive decline, after adjusting for covariates. A total of 1840 participants were included into this study including 1713 normal participants and 127 cognitive impairment participants in 2009. Among 1713 normal participants in 2009, 130 participants were converted to cognitive impairment after 5 years of follow-up. In 2014, 606 participants were identified as cognitive decline. Both self- and informant-reported memory complaints were associated with an increased risk of cognitive impairment (odds ratio [OR] = 1.60, 95% confidence interval [CI]: 1.04-2.48) and cognitive decline (OR = 1.30, 95% CI: 1.01-1.68). Furthermore, this association was more significant in males (OR = 2.10, 95% CI: 1.04-4.24 for cognitive impairment and OR = 1.87, 95% CI: 1.20-2.99 for cognitive decline) and in higher education level (OR = 1.79, 95% CI: 1.02-3.15 for cognitive impairment and OR = 1.40, 95% CI: 1.02-1.91 for cognitive decline). Both self- and informant-reported memory complaints were associated with an increased risk of cognitive impairment conversion and cognitive decline, especially in persons with male gender and high educational background.

Preexisting depressive symptoms are associated with long-term cognitive decline in patients after cardiac surgery.

PubMed

Patron, Elisabetta; Messerotti Benvenuti, Simone; Zanatta, Paolo; Polesel, Elvio; Palomba, Daniela

2013-01-01

To examine whether preoperative psychological dysfunctions rather than intraoperative factors may differentially predict short- and long-term postoperative cognitive decline (POCD) in patients after cardiac surgery. Forty-two patients completed a psychological evaluation, including the Trail Making Test Part A and B (TMT-A/B), the memory with 10/30-s interference, the phonemic verbal fluency and the Center for Epidemiological Studies of Depression (CES-D) scale for cognitive functions and depressive symptoms, respectively, before surgery, at discharge and at 18-month follow-up. Ten (24%) and 11 (26%) patients showed POCD at discharge and at 18-month follow-up, respectively. The duration of cardiopulmonary bypass significantly predicted short-term POCD [odds ratio (OR)=1.04, P<.05], whereas preoperative psychological factors were unrelated to cognitive decline at discharge. Conversely, long-term cognitive decline after cardiac surgery was significantly predicted by preoperative scores in the CES-D (OR=1.26, P<.03) but not by intraoperative variables (all Ps >.23). Our findings showed that preexisting depressive symptoms rather than perioperative risk factors are associated with cognitive decline 18 months after cardiac surgery. This study suggests that a preoperative psychological evaluation of depressive symptoms is essential to anticipate which patients are likely to show long-term cognitive decline after cardiac surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

Roles of Arterial Stiffness and Blood Pressure in Hypertension-Associated Cognitive Decline in Healthy Adults.

PubMed

Hajjar, Ihab; Goldstein, Felicia C; Martin, Greg S; Quyyumi, Arshed A

2016-01-01

Although there is strong evidence that hypertension leads to cognitive decline, especially in the executive domain, the relationship between blood pressure and cognition has been conflicted. Hypertension is characterized by blood pressure elevation and increased arterial stiffness. We aimed at investigating whether arterial stiffness would be superior to blood pressure in predicting cognitive decline and explaining the hypertension-executive decline association. A randomly selected asymptomatic population (n=591, age=49.2 years, 70% women, 27% black, and education=18 years) underwent annual vascular and cognitive assessments. Cognition was assessed using computerized versions commonly used cognitive tests, and principal component analysis was used for deriving cognitive scores for executive function, memory, and working memory. Arterial stiffness was measured by carotid-femoral pulse wave velocity (PWV). Higher PWV, but not blood pressure, was associated with a steeper decline in executive (P=0.0002), memory (P=0.05), and working memory (P=0.02) scores after adjusting for demographics, education, and baseline cognitive performance. This remained true after adjusting for hypertension. Hypertension was associated with greater decline in executive score (P=0.0029) and those with combined hypertension and elevated PWV (>7 m/s) had the greatest decline in executive score (P value hypertension×PWV=0.02). PWV explained the association between hypertension and executive function (P value for hypertension=0.0029 versus 0.24 when adjusting for PWV). In healthy adults, increased arterial stiffness is superior to blood pressure in predicting cognitive decline in all domains and in explaining the hypertension-executive function association. Arterial stiffness, especially in hypertension, may be a target in the prevention of cognitive decline. © 2015 American Heart Association, Inc.

The MMSE orientation for time domain is a strong predictor of subsequent cognitive decline in the elderly.

PubMed

Guerrero-Berroa, Elizabeth; Luo, Xiaodong; Schmeidler, James; Rapp, Michael A; Dahlman, Karen; Grossman, Hillel T; Haroutunian, Vahram; Beeri, Michal Schnaider

2009-12-01

The mini-mental state exam (MMSE) has been used to address questions such as determination of appropriate cutoff scores for differentiation of individuals with intact cognitive function from patients with dementia and rate of cognitive decline. However, little is known about the relationship of performance in specific cognitive domains to subsequent overall decline. To examine the specific and/or combined contribution of four MMSE domains (orientation for time, orientation for place, delayed recall, and attention) to prediction of overall cognitive decline on the MMSE. Linear mixed models were applied to 505 elderly nursing home residents (mean age = 85, > 12 years education = 27%; 79% F, mean follow-up = 3.20 years) to examine the relationship between baseline scores of these domains and total MMSE scores over time. Orientation for time was the only domain significantly associated with MMSE decline over time. Combination of poor delayed recall with either attention or orientation for place was associated with significantly increased decline on the MMSE. The MMSE orientation for time predicts overall decline on MMSE scores over time. A good functioning domain added to good functioning delayed recall was associated with slower rate of decline. Copyright (c) 2009 John Wiley & Sons, Ltd.

Corpus callosum atrophy as a marker of clinically meaningful cognitive decline in secondary progressive multiple sclerosis. Impact on employment status.

PubMed

Papathanasiou, Athanasios; Messinis, Lambros; Zampakis, Petros; Papathanasopoulos, Panagiotis

2017-09-01

Cognitive impairment in Multiple Sclerosis (MS) is more frequent and pronounced in secondary progressive MS (SPMS). Cognitive decline is an important predictor of employment status in patients with MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. The aim of the study was to designate the MRI marker that predicts cognitive decline in SPMS and explore its effect on employment status. 30 SPMS patients and 30 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Employment status was obtained as a quality of life measure. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, thalamic and corpus callosum atrophy. The frequency of cognitive decline for our SPMS patients was 80%. SPMS patients differed significantly from controls in all neuropsychological measures. Corpus callosum area was correlated with cognitive flexibility, processing speed, composite memory, executive functions, psychomotor speed, reaction time and phonological verbal fluency task. Processing speed and composite memory were the most sensitive markers for predicting employment status. Corpus callosum area was the most sensitive MRI marker for memory and processing speed. Corpus callosum atrophy predicts a clinically meaningful cognitive decline, affecting employment status in our SPMS patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vivo cholinergic basal forebrain atrophy predicts cognitive decline in de novo Parkinson's disease.

PubMed

Ray, Nicola J; Bradburn, Steven; Murgatroyd, Christopher; Toseeb, Umar; Mir, Pablo; Kountouriotis, George K; Teipel, Stefan J; Grothe, Michel J

2018-01-01

See Gratwicke and Foltynie (doi:10.1093/brain/awx333) for a scientific commentary on this article.Cognitive impairments are a prevalent and disabling non-motor complication of Parkinson's disease, but with variable expression and progression. The onset of serious cognitive decline occurs alongside substantial cholinergic denervation, but imprecision of previously available techniques for in vivo measurement of cholinergic degeneration limit their use as predictive cognitive biomarkers. However, recent developments in stereotactic mapping of the cholinergic basal forebrain have been found useful for predicting cognitive decline in prodromal stages of Alzheimer's disease. These methods have not yet been applied to longitudinal Parkinson's disease data. In a large sample of people with de novo Parkinson's disease (n = 168), retrieved from the Parkinson's Progressive Markers Initiative database, we measured cholinergic basal forebrain volumes, using morphometric analysis of T1-weighted images in combination with a detailed stereotactic atlas of the cholinergic basal forebrain nuclei. Using a binary classification procedure, we defined patients with reduced basal forebrain volumes (relative to age) at baseline, based on volumes measured in a normative sample (n = 76). Additionally, relationships between the basal forebrain volumes at baseline, risk of later cognitive decline, and scores on up to 5 years of annual cognitive assessments were assessed with regression, survival analysis and linear mixed modelling. In patients, smaller volumes in a region corresponding to the nucleus basalis of Meynert were associated with greater change in global cognitive, but not motor scores after 2 years. Using the binary classification procedure, patients classified as having smaller than expected volumes of the nucleus basalis of Meynert had ∼3.5-fold greater risk of being categorized as mildly cognitively impaired over a period of up to 5 years of follow-up (hazard ratio = 3.51). Finally, linear mixed modelling analysis of domain-specific cognitive scores revealed that patients classified as having smaller than expected nucleus basalis volumes showed more severe and rapid decline over up to 5 years on tests of memory and semantic fluency, but not on tests of executive function. Thus, we provide the first evidence that volumetric measurement of the nucleus basalis of Meynert can predict early cognitive decline. Our methods therefore provide the opportunity for multiple-modality biomarker models to include a cholinergic biomarker, which is currently lacking for the prediction of cognitive deterioration in Parkinson's disease. Additionally, finding dissociated relationships between nucleus basalis status and domain-specific cognitive decline has implications for understanding the neural basis of heterogeneity of Parkinson's disease-related cognitive decline. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Longitudinal decline in structural networks predicts dementia in cerebral small vessel disease

PubMed Central

Lawrence, Andrew J.; Zeestraten, Eva A.; Benjamin, Philip; Lambert, Christian P.; Morris, Robin G.; Barrick, Thomas R.

2018-01-01

Objective To determine whether longitudinal change in white matter structural network integrity predicts dementia and future cognitive decline in cerebral small vessel disease (SVD). To investigate whether network disruption has a causal role in cognitive decline and mediates the association between conventional MRI markers of SVD with both cognitive decline and dementia. Methods In the prospective longitudinal SCANS (St George's Cognition and Neuroimaging in Stroke) Study, 97 dementia-free individuals with symptomatic lacunar stroke were followed with annual MRI for 3 years and annual cognitive assessment for 5 years. Conversion to dementia was recorded. Structural networks were constructed from diffusion tractography using a longitudinal registration pipeline, and network global efficiency was calculated. Linear mixed-effects regression was used to assess change over time. Results Seventeen individuals (17.5%) converted to dementia, and significant decline in global cognition occurred (p = 0.0016). Structural network measures declined over the 3-year MRI follow-up, but the degree of change varied markedly between individuals. The degree of reductions in network global efficiency was associated with conversion to dementia (B = −2.35, odds ratio = 0.095, p = 0.00056). Change in network global efficiency mediated much of the association of conventional MRI markers of SVD with cognitive decline and progression to dementia. Conclusions Network disruption has a central role in the pathogenesis of cognitive decline and dementia in SVD. It may be a useful disease marker to identify that subgroup of patients with SVD who progress to dementia. PMID:29695593

Longitudinal associations between physical and cognitive performance among community-dwelling older adults.

PubMed

Tolea, Magdalena I; Morris, John C; Galvin, James E

2015-01-01

To assess the directionality of the association between physical and cognitive decline in later life, we compared patterns of decline in performance across groups defined by baseline presence of cognitive and/or physical impairment [none (n = 217); physical only (n = 169); cognitive only (n = 158), or both (n = 220)] in a large sample of participants in a cognitive aging study at the Knight Alzheimer's Disease Research Center at Washington University in St. Louis who were followed for up to 8 years (3,079 observations). Rates of decline reached 20% for physical performance and varied across cognitive tests (global, memory, speed, executive function, and visuospatial skills). We found that physical decline was better predicted by baseline cognitive impairment (slope = -1.22, p<0.001), with baseline physical impairment not contributing to further decline in physical performance (slope = -0.25, p = 0.294). In turn, baseline physical impairment was only marginally associated with rate of cognitive decline across various cognitive domains. The cognitive-functional association is likely to operate in the direction of cognitive impairment to physical decline although physical impairment may also play a role in cognitive decline/dementia. Interventions to prevent further functional decline and development of disability and complete dependence may benefit if targeted to individuals with cognitive impairment who are at increased risk.

Predicting cognitive function from clinical measures of physical function and health status in older adults.

PubMed

Bolandzadeh, Niousha; Kording, Konrad; Salowitz, Nicole; Davis, Jennifer C; Hsu, Liang; Chan, Alison; Sharma, Devika; Blohm, Gunnar; Liu-Ambrose, Teresa

2015-01-01

Current research suggests that the neuropathology of dementia-including brain changes leading to memory impairment and cognitive decline-is evident years before the onset of this disease. Older adults with cognitive decline have reduced functional independence and quality of life, and are at greater risk for developing dementia. Therefore, identifying biomarkers that can be easily assessed within the clinical setting and predict cognitive decline is important. Early recognition of cognitive decline could promote timely implementation of preventive strategies. We included 89 community-dwelling adults aged 70 years and older in our study, and collected 32 measures of physical function, health status and cognitive function at baseline. We utilized an L1-L2 regularized regression model (elastic net) to identify which of the 32 baseline measures were strongly predictive of cognitive function after one year. We built three linear regression models: 1) based on baseline cognitive function, 2) based on variables consistently selected in every cross-validation loop, and 3) a full model based on all the 32 variables. Each of these models was carefully tested with nested cross-validation. Our model with the six variables consistently selected in every cross-validation loop had a mean squared prediction error of 7.47. This number was smaller than that of the full model (115.33) and the model with baseline cognitive function (7.98). Our model explained 47% of the variance in cognitive function after one year. We built a parsimonious model based on a selected set of six physical function and health status measures strongly predictive of cognitive function after one year. In addition to reducing the complexity of the model without changing the model significantly, our model with the top variables improved the mean prediction error and R-squared. These six physical function and health status measures can be easily implemented in a clinical setting.

Memory complaints and APOE-epsilon4 accelerate cognitive decline in cognitively normal elderly.

PubMed

Dik, M G; Jonker, C; Comijs, H C; Bouter, L M; Twisk, J W; van Kamp, G J; Deeg, D J

2001-12-26

To investigate to what extent subjective memory complaints and APOE-epsilon4 allele carriage predict future cognitive decline in cognitively intact elderly persons, by evaluating both their separate and combined effects. We selected 1,168 subjects from the population-based Longitudinal Aging Study Amsterdam who were 62 to 85 years of age and had no obvious cognitive impairment at baseline (Mini-Mental State Examination [MMSE] score, > or =27). Memory complaints and APOE phenotypes were assessed at baseline. MMSE, the Auditory Verbal Learning Test (memory: immediate recall and delayed recall), and the Alphabet Coding Task-15 (information processing speed) were used to study cognitive decline. Follow-up data were collected after 3 and 6 years. Data were analyzed with generalized estimating equations, adjusted for age, sex, education, and depression. Baseline memory complaints were reported by 25.5% of the cognitively intact elderly persons. Overall, 25.3% of the subjects were carriers of at least one APOE-epsilon4 allele. Memory complaints were associated with a greater rate of decline in all cognitive measures, except immediate recall. In addition, APOE-epsilon4 allele carriers had a greater rate of cognitive decline shown by MMSE scores and slower information processing speeds after 6 years. The effects of both memory complaints and APOE-epsilon4 allele carriage were additive: subjects with both factors had a two times higher cognitive decline than did subjects without both factors. Both memory complaints and APOE-epsilon4 allele carriage predict cognitive decline at an early stage. This finding highlights the importance of subjective memory complaints, which are important even at an early stage when objective tests are still unable to detect cognitive deficits and are especially important for elderly carriers of the APOE-epsilon4 allele because they have an additional risk.

Impaired Sleep Predicts Cognitive Decline in Old People: Findings from the Prospective KORA Age Study.

PubMed

Johar, Hamimatunnisa; Kawan, Rasmila; Emeny, Rebecca Thwing; Ladwig, Karl-Heinz

2016-01-01

To investigate the association between sleep-related characteristics and cognitive change over 3 years of follow up in an aged population. Sleep characteristics and covariates were assessed at baseline in a standardized interview and clinical examination of the population-based KORA Age Study (n = 740, mean age = 75 years). Cognitive score (determined by telephone interview for cognitive status, TICS-m) was recorded at baseline and 3 years later. At baseline, 82.83% (n = 613) of participants had normal cognitive status, 13.51% (n = 100) were classified with mild cognitive impairment (MCI), and 3.64% (n = 27) with probable dementia. The effect of three distinct patterns of poor sleep (difficulties initiating [DIS] or maintaining sleep [DMS], daytime sleepiness [DS] or sleep duration) were considered on a change in cognitive score with adjustments for potential confounders in generalized linear regression models. Cognitive decline was more pronounced in individuals with DMS compared to those with no DMS (β = 1.33, 95% CI = 0.41-2.24, P < 0.001). However, the predictive power of DMS was only significant in individuals with normal cognition and not impaired subjects at baseline. Prolonged sleep duration increased the risk for cognitive decline in cognitively impaired elderly (β = 1.86, 95% CI = 0.15-3.57, P = 0.03). Other sleep characteristics (DIS and DS) were not significantly associated with cognitive decline. DMS and long sleep duration were associated with cognitive decline in normal and cognitively impaired elderly, respectively. The identification of impaired sleep quality may offer intervention strategies to deter cognitive decline in the elderly with normal cognitive function. © 2016 Associated Professional Sleep Societies, LLC.

Cognitive Decline Is Associated with Risk Aversion and Temporal Discounting in Older Adults without Dementia

PubMed Central

James, Bryan D.; Boyle, Patricia A.; Yu, Lei; Han, S. Duke; Bennett, David A.

2015-01-01

Risk aversion and temporal discounting are preferences that are strongly linked to sub-optimal financial and health decision making ability. Prior studies have shown they differ by age and cognitive ability, but it remains unclear whether differences are due to age-related cognitive decline or lower cognitive abilities over the life span. We tested the hypothesis that cognitive decline is associated with higher risk aversion and temporal discounting in 455 older persons without dementia from the Memory and Aging Project, a longitudinal cohort study of aging in Chicago. All underwent repeated annual cognitive evaluations using a detailed battery including 19 tests. Risk aversion was measured using standard behavioral economics questions: participants were asked to choose between a certain monetary payment versus a gamble in which they could gain more or nothing; potential gamble gains varied across questions. Temporal discounting: participants were asked to choose between an immediate, smaller payment and a delayed, larger one; two sets of questions addressed small and large stakes based on payment amount. Regression analyses were used to examine whether prior rate of cognitive decline predicted level of risk aversion and temporal discounting, controlling for age, sex, and education. Over an average of 5.5 (SD=2.9) years, cognition declined at an average of 0.016 units per year (SD=0.03). More rapid cognitive decline predicted higher levels of risk aversion (p=0.002) and temporal discounting (small stakes: p=0.01, high stakes: p=0.006). Further, associations between cognitive decline and risk aversion (p=0.015) and large stakes temporal discounting (p=0.026) persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or mild cognitive impairment); the association of cognitive decline and small stakes temporal discounting was no longer statistically significant (p=0.078). These findings are consistent with the hypothesis that subtle age-related changes in cognition can detrimentally affect individual preferences that are critical for maintaining health and well being. PMID:25838074

Cognitive decline is associated with risk aversion and temporal discounting in older adults without dementia.

PubMed

James, Bryan D; Boyle, Patricia A; Yu, Lei; Han, S Duke; Bennett, David A

2015-01-01

Risk aversion and temporal discounting are preferences that are strongly linked to sub-optimal financial and health decision making ability. Prior studies have shown they differ by age and cognitive ability, but it remains unclear whether differences are due to age-related cognitive decline or lower cognitive abilities over the life span. We tested the hypothesis that cognitive decline is associated with higher risk aversion and temporal discounting in 455 older persons without dementia from the Memory and Aging Project, a longitudinal cohort study of aging in Chicago. All underwent repeated annual cognitive evaluations using a detailed battery including 19 tests. Risk aversion was measured using standard behavioral economics questions: participants were asked to choose between a certain monetary payment versus a gamble in which they could gain more or nothing; potential gamble gains varied across questions. Temporal discounting: participants were asked to choose between an immediate, smaller payment and a delayed, larger one; two sets of questions addressed small and large stakes based on payment amount. Regression analyses were used to examine whether prior rate of cognitive decline predicted level of risk aversion and temporal discounting, controlling for age, sex, and education. Over an average of 5.5 (SD=2.9) years, cognition declined at an average of 0.016 units per year (SD=0.03). More rapid cognitive decline predicted higher levels of risk aversion (p=0.002) and temporal discounting (small stakes: p=0.01, high stakes: p=0.006). Further, associations between cognitive decline and risk aversion (p=0.015) and large stakes temporal discounting (p=0.026) persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or mild cognitive impairment); the association of cognitive decline and small stakes temporal discounting was no longer statistically significant (p=0.078). These findings are consistent with the hypothesis that subtle age-related changes in cognition can detrimentally affect individual preferences that are critical for maintaining health and well being.

Poor Decision Making Is a Consequence of Cognitive Decline among Older Persons without Alzheimer’s Disease or Mild Cognitive Impairment

PubMed Central

Boyle, Patricia A.; Yu, Lei; Wilson, Robert S.; Gamble, Keith; Buchman, Aron S.; Bennett, David A.

2012-01-01

Objective Decision making is an important determinant of health and well-being across the lifespan but is critical in aging, when many influential decisions are made just as cognitive function declines. Increasing evidence suggests that older adults, even those without dementia, often make poor decisions and are selectively vulnerable to scams. To date, however, the factors associated with poor decision making in old age are unknown. The objective of this study was to test the hypothesis that poor decision making is a consequence of cognitive decline among older persons without Alzheimer’s disease or mild cognitive impairment. Methods Participants were 420 non-demented persons from the Memory and Aging Project, a longitudinal, clinical-pathologic cohort study of aging in the Chicago metropolitan area. All underwent repeated cognitive evaluations and subsequently completed assessments of decision making and susceptibility to scams. Decision making was measured using 12 items from a previously established performance-based measure and a self-report measure of susceptibility to scams. Results Cognitive function data were collected over an average of 5.5 years prior to the decision making assessment. Regression analyses were used to examine whether the prior rate of cognitive decline predicted the level of decision making and susceptibility to scams; analyses controlled for age, sex, education, and starting level of cognition. Among 420 persons without dementia, more rapid cognitive decline predicted poorer decision making and increased susceptibility to scams (p’s<0.001). Further, the relations between cognitive decline, decision making and scams persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or even mild cognitive impairment). Conclusions Poor decision making is a consequence of cognitive decline among older persons without Alzheimer’s disease or mild cognitive impairment, those widely considered “cognitively healthy.” These findings suggest that even very subtle age-related changes in cognition have detrimental effects on judgment. PMID:22916287

Crowdsourced estimation of cognitive decline and resilience in Alzheimer’s disease

PubMed Central

Allen, Genevera I; Amoroso, Nicola; Anghel, Catalina; Balagurusamy, Venkat; Bare, Christopher J; Beaton, Derek; Bellotti, Roberto; Bennett, David A; Boehme, Kevin; Boutros, Paul C; Caberlotto, Laura; Caloian, Cristian; Campbell, Frederick; Neto, Elias Chaibub; Chang, Yu-Chuan; Chen, Beibei; Chen, Chien-Yu; Chien, Ting-Ying; Clark, Tim; Das, Sudeshna; Davatzikos, Christos; Deng, Jieyao; Dillenberger, Donna; Dobson, Richard JB; Dong, Qilin; Doshi, Jimit; Duma, Denise; Errico, Rosangela; Erus, Guray; Everett, Evan; Fardo, David W; Friend, Stephen H; Fröhlich, Holger; Gan, Jessica; St George-Hyslop, Peter; Ghosh, Satrajit S; Glaab, Enrico; Green, Robert C; Guan, Yuanfang; Hong, Ming-Yi; Huang, Chao; Hwang, Jinseub; Ibrahim, Joseph; Inglese, Paolo; Jiang, Qijia; Katsumata, Yuriko; Kong, Dehan; Krause, Roland; Lalonde, Emilie; Lauria, Mario; Lee, Eunjee; Lin, Xihui; Liu, Zhandong; Livingstone, Julie; Logsdon, Benjamin A; Lovestone, Simon; Lyappan, Anandhi; Ma, Michelle; Malhotra, Ashutosh; Maxwell, Taylor J; Merrill, Emily; Nagorski, John; Namasivayam, Aishwarya; Narayan, Manjari; Naz, Mufassra; Newhouse, Stephen J; Norman, Thea C; Nurtdinov, Ramil N; Oyang, Yen-Jen; Pawitan, Yudi; Peng, Shengwen; Piccolo, Stephen R; Praveen, Paurush; Priami, Corrado; Sabelnykova, Veronica Y; Senger, Philipp; Shen, Xia; Simmons, Andrew; Sotiras, Aristeidis; Stolovitzky, Gustavo; Tangaro, Sabina; Tateo, Andrea; Tung, Yi-An; Tustison, Nicholas J; Varol, Erdem; Vradenburg, George; Weiner, Michael W; Xiao, Guanghua; Xie, Lei; Xie, Yang; Xu, Jia; Yang, Hojin; Zhan, Xiaowei; Zhou, Yunyun; Zhu, Fan; Zhu, Hongtu; Zhu, Shanfeng

2017-01-01

Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer’s Disease. The Alzheimer’s Disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer’s Disease based on high-dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for to prediction of cognitive performance. PMID:27079753

Framingham risk score can predict cognitive decline progression in Alzheimer's disease.

PubMed

Viticchi, Giovanna; Falsetti, Lorenzo; Buratti, Laura; Boria, Cristiano; Luzzi, Simona; Bartolini, Marco; Provinciali, Leandro; Silvestrini, Mauro

2015-11-01

The role of vascular factors in influencing cognitive decline has been extensively investigated, and some difficulties in defining their weight in dementia pathogenesis have emerged. The aim of the study was to investigate the relevance of the Framingham cardiovascular risk profile (FCRP) in influencing cognitive deterioration in a population of Alzheimer's disease (AD) patients. Two hundred eighty-four consecutive AD patients were enrolled. For each patient, FCRP score was calculated. We did a 1-year follow-up to quantify the cognitive decline by recording changes in the Clinical Dementia Rating score. The FCRP score predicted cognitive deterioration with an area under the curve of 0.63 (95% confidence interval: 0.57-0.69; p < 0.0001). In the subpopulation of patients with a genetic increased predisposition to develop cognitive deterioration and with an advanced vascular impairment, the FCRP predictive value significantly increased with an area under the curve of 0.77 (95% confidence interval: 0.52-0.93; p < 0.05). Our findings show that FCRP can predict the progression of deterioration in AD patients. This was particularly evident in patients with major genetic and atherosclerotic risk factors. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS

PubMed Central

Rocca, Maria A.; Leavitt, Victoria M.; Dackovic, Jelena; Mesaros, Sarlota; Drulovic, Jelena; DeLuca, John; Filippi, Massimo

2014-01-01

Objective: Based on the theories of brain reserve and cognitive reserve, we investigated whether larger maximal lifetime brain growth (MLBG) and/or greater lifetime intellectual enrichment protect against cognitive decline over time. Methods: Forty patients with multiple sclerosis (MS) underwent baseline and 4.5-year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test, Paced Auditory Serial Addition Task) and memory (Selective Reminding Test, Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression: percentage brain volume change (cerebral atrophy), percentage change in T2 lesion volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual enrichment (cognitive reserve) was estimated with vocabulary. We performed repeated-measures analyses of covariance to investigate whether larger MLBG and/or greater intellectual enrichment moderate/attenuate cognitive decline over time, controlling for disease progression. Results: Patients with MS declined in cognitive efficiency and memory (p < 0.001). MLBG moderated decline in cognitive efficiency (p = 0.031, ηp2 = 0.122), with larger MLBG protecting against decline. MLBG did not moderate memory decline (p = 0.234, ηp2 = 0.039). Intellectual enrichment moderated decline in cognitive efficiency (p = 0.031, ηp2 = 0.126) and memory (p = 0.037, ηp2 = 0.115), with greater intellectual enrichment protecting against decline. MS disease progression was more negatively associated with change in cognitive efficiency and memory among patients with lower vs higher MLBG and intellectual enrichment. Conclusion: We provide longitudinal support for theories of brain reserve and cognitive reserve in MS. Larger MLBG protects against decline in cognitive efficiency, and greater intellectual enrichment protects against decline in cognitive efficiency and memory. Consideration of these protective factors should improve prediction of future cognitive decline in patients with MS. PMID:24748670

Sleep Disturbance and the Risk of Cognitive Decline or Clinical Conversion in the ADNI Cohort.

PubMed

Mecca, Adam P; Michalak, Hannah R; McDonald, Julia W; Kemp, Emily C; Pugh, Erika A; Becker, Melinda L; Mecca, Marcia C; van Dyck, Christopher H

2018-06-08

We investigated the relationship between sleep disturbance and cognitive decline or clinical conversion in individuals with normal cognition (CN), as well as those with mild cognitive impairment (MCI) and dementia due to Alzheimer disease (AD-dementia). Secondary analysis of 1,629 adults between 48 and 91 years of age with up to 24 months of follow-up from the ADNI (Alzheimer's Disease Neuroimaging Initiative), a longitudinal cohort study. Sleep disturbance was not associated with decline in memory, executive function, or global cognition. The presence of sleep disturbance did not significantly increase the risk of diagnostic conversion in CN, early MCI, or late MCI participants. This study investigated the effect of sleep disturbance on cognitive decline using several outcomes and does not support the hypothesis that sleep disturbance predicts subsequent cognitive decline. © 2018 S. Karger AG, Basel.

Cognitive mediators of treatment for social anxiety disorder: comparing acceptance and commitment therapy and cognitive-behavioral therapy.

PubMed

Niles, Andrea N; Burklund, Lisa J; Arch, Joanna J; Lieberman, Matthew D; Saxbe, Darby; Craske, Michelle G

2014-09-01

To assess the relationship between session-by-session mediators and treatment outcomes in traditional cognitive-behavioral therapy (CBT) and acceptance and commitment therapy (ACT) for social anxiety disorder. Session-by-session changes in negative cognitions (a theorized mediator of CBT) and experiential avoidance (a theorized mediator of ACT) were assessed in 50 adult outpatients randomized to CBT (n=25) or ACT (n=25) for DSM-IV social anxiety disorder. Multilevel modeling analyses revealed significant nonlinear decreases in the proposed mediators in both treatments, with ACT showing steeper decline than CBT at the beginning of treatment and CBT showing steeper decline than ACT at the end of treatment. Curvature (or the nonlinear effect) of experiential avoidance during treatment significantly mediated posttreatment social anxiety symptoms and anhedonic depression in ACT, but not in CBT, with steeper decline of the Acceptance and Action Questionnaire at the beginning of treatment predicting fewer symptoms in ACT only. Curvature of negative cognitions during both treatments predicted outcome, with steeper decline of negative cognitions at the beginning of treatment predicting lower posttreatment social anxiety and depressive symptoms. Rate of change in negative cognitions at the beginning of treatment is an important predictor of change across both ACT and CBT, whereas rate of change in experiential avoidance at the beginning of treatment is a mechanism specific to ACT. Copyright © 2014. Published by Elsevier Ltd.

Cognitive Mediators of Treatment for Social Anxiety Disorder: Comparing Acceptance and Commitment Therapy and Cognitive-Behavioral Therapy

PubMed Central

Niles, Andrea N.; Burklund, Lisa J.; Arch, Joanna J.; Lieberman, Matthew D.; Saxbe, Darby; Craske, Michelle G.

2016-01-01

Objective To assess the relationship between session-by-session mediators and treatment outcomes in traditional cognitive-behavioral therapy (CBT) and acceptance and commitment therapy (ACT) for social anxiety disorder. Method Session-by-session changes in negative cognitions (a theorized mediator of CBT) and experiential avoidance (a theorized mediator of ACT) were assessed in 50 adult outpatients randomized to CBT (n = 25) or ACT (n = 25) for DSM-IV social anxiety disorder. Results Multilevel modeling analyses revealed significant nonlinear decreases in the proposed mediators in both treatments, with ACT showing steeper decline than CBT at the beginning of treatment and CBT showing steeper decline than ACT at the end of treatment. Curvature (or the nonlinear effect) of experiential avoidance during treatment significantly mediated posttreatment social anxiety symptoms and anhedonic depression in ACT, but not in CBT, with steeper decline of the Acceptance and Action Questionnaire at the beginning of treatment predicting fewer symptoms in ACT only. Curvature of negative cognitions during both treatments predicted outcome, with steeper decline of negative cognitions at the beginning of treatment predicting lower posttreatment social anxiety and depressive symptoms. Conclusions Rate of change in negative cognitions at the beginning of treatment is an important predictor of change across both ACT and CBT, whereas rate of change in experiential avoidance at the beginning of treatment is a mechanism specific to ACT. PMID:25022777

Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease.

PubMed

Allen, Genevera I; Amoroso, Nicola; Anghel, Catalina; Balagurusamy, Venkat; Bare, Christopher J; Beaton, Derek; Bellotti, Roberto; Bennett, David A; Boehme, Kevin L; Boutros, Paul C; Caberlotto, Laura; Caloian, Cristian; Campbell, Frederick; Chaibub Neto, Elias; Chang, Yu-Chuan; Chen, Beibei; Chen, Chien-Yu; Chien, Ting-Ying; Clark, Tim; Das, Sudeshna; Davatzikos, Christos; Deng, Jieyao; Dillenberger, Donna; Dobson, Richard J B; Dong, Qilin; Doshi, Jimit; Duma, Denise; Errico, Rosangela; Erus, Guray; Everett, Evan; Fardo, David W; Friend, Stephen H; Fröhlich, Holger; Gan, Jessica; St George-Hyslop, Peter; Ghosh, Satrajit S; Glaab, Enrico; Green, Robert C; Guan, Yuanfang; Hong, Ming-Yi; Huang, Chao; Hwang, Jinseub; Ibrahim, Joseph; Inglese, Paolo; Iyappan, Anandhi; Jiang, Qijia; Katsumata, Yuriko; Kauwe, John S K; Klein, Arno; Kong, Dehan; Krause, Roland; Lalonde, Emilie; Lauria, Mario; Lee, Eunjee; Lin, Xihui; Liu, Zhandong; Livingstone, Julie; Logsdon, Benjamin A; Lovestone, Simon; Ma, Tsung-Wei; Malhotra, Ashutosh; Mangravite, Lara M; Maxwell, Taylor J; Merrill, Emily; Nagorski, John; Namasivayam, Aishwarya; Narayan, Manjari; Naz, Mufassra; Newhouse, Stephen J; Norman, Thea C; Nurtdinov, Ramil N; Oyang, Yen-Jen; Pawitan, Yudi; Peng, Shengwen; Peters, Mette A; Piccolo, Stephen R; Praveen, Paurush; Priami, Corrado; Sabelnykova, Veronica Y; Senger, Philipp; Shen, Xia; Simmons, Andrew; Sotiras, Aristeidis; Stolovitzky, Gustavo; Tangaro, Sabina; Tateo, Andrea; Tung, Yi-An; Tustison, Nicholas J; Varol, Erdem; Vradenburg, George; Weiner, Michael W; Xiao, Guanghua; Xie, Lei; Xie, Yang; Xu, Jia; Yang, Hojin; Zhan, Xiaowei; Zhou, Yunyun; Zhu, Fan; Zhu, Hongtu; Zhu, Shanfeng

2016-06-01

Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for prediction of cognitive performance. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Speech prosody impairment predicts cognitive decline in Parkinson's disease.

PubMed

Rektorova, Irena; Mekyska, Jiri; Janousova, Eva; Kostalova, Milena; Eliasova, Ilona; Mrackova, Martina; Berankova, Dagmar; Necasova, Tereza; Smekal, Zdenek; Marecek, Radek

2016-08-01

Impairment of speech prosody is characteristic for Parkinson's disease (PD) and does not respond well to dopaminergic treatment. We assessed whether baseline acoustic parameters, alone or in combination with other predominantly non-dopaminergic symptoms may predict global cognitive decline as measured by the Addenbrooke's cognitive examination (ACE-R) and/or worsening of cognitive status as assessed by a detailed neuropsychological examination. Forty-four consecutive non-depressed PD patients underwent clinical and cognitive testing, and acoustic voice analysis at baseline and at the two-year follow-up. Influence of speech and other clinical parameters on worsening of the ACE-R and of the cognitive status was analyzed using linear and logistic regression. The cognitive status (classified as normal cognition, mild cognitive impairment and dementia) deteriorated in 25% of patients during the follow-up. The multivariate linear regression model consisted of the variation in range of the fundamental voice frequency (F0VR) and the REM Sleep Behavioral Disorder Screening Questionnaire (RBDSQ). These parameters explained 37.2% of the variability of the change in ACE-R. The most significant predictors in the univariate logistic regression were the speech index of rhythmicity (SPIR; p = 0.012), disease duration (p = 0.019), and the RBDSQ (p = 0.032). The multivariate regression analysis revealed that SPIR alone led to 73.2% accuracy in predicting a change in cognitive status. Combining SPIR with RBDSQ improved the prediction accuracy of SPIR alone by 7.3%. Impairment of speech prosody together with symptoms of RBD predicted rapid cognitive decline and worsening of PD cognitive status during a two-year period. Copyright © 2016 Elsevier Ltd. All rights reserved.

Job strain and cognitive decline: a prospective study of the framingham offspring cohort.

PubMed

Agbenyikey, W; Karasek, R; Cifuentes, M; Wolf, P A; Seshadri, S; Taylor, J A; Beiser, A S; Au, R

2015-04-01

Workplace stress is known to be related with many behavioral and disease outcomes. However, little is known about its prospective relationship with measures of cognitive decline. To investigate the association of job strain, psychological demands and job control on cognitive decline. Participants from Framingham Offspring cohort (n=1429), were assessed on job strain, and received neuropsychological assessment approximately 15 years and 21 years afterwards. High job strain and low control were associated with decline in verbal learning and memory. Job strain was associated with decline in word recognition skills. Active job and passive job predicted decline in verbal learning and memory relative to low strain jobs in the younger subgroup. Active job and demands were positively associated with abstract reasoning skills. Job strain and job control may influence decline in cognitive performance.

Cognitive function trajectories and their determinants in older people: 8 years of follow-up in the English Longitudinal Study of Ageing.

PubMed

Zaninotto, Paola; Batty, G David; Allerhand, Michael; Deary, Ian J

2018-04-24

Maintaining cognitive function is an important aspect of healthy ageing. In this study, we examined age trajectories of cognitive decline in a large nationally representative sample of older people in England. We explored the factors that influence such decline and whether these differed by gender. Latent growth curve modelling was used to explore age-specific changes, and influences on them, in an 8-year period in memory, executive function, processing speed and global cognitive function among 10 626 participants in the English Longitudinal Study of Ageing. We run gender-specific models with the following exposures: age, education, wealth, childhood socioeconomic status, cardiovascular disease, diabetes, physical function, body mass index, physical activity, alcohol, smoking, depression and dementia. After adjustment, women had significantly less decline than men in memory (0.011, SE 0.006), executive function (0.012, SE 0.006) and global cognitive function (0.016, SE 0.004). Increasing age and dementia predicted faster rates of decline in all cognitive function domains. Depression and alcohol consumption predicted decline in some cognitive function domains in men only. Poor physical function, physical inactivity and smoking were associated with faster rates of decline in specific cognitive domains in both men and women. For example, relative to study members who were physically active, the sedentary experienced greater declines in memory (women -0.018, SE 0.009) and global cognitive function (men -0.015, SE 0.007 and women -0.016, SE 0.007). The potential determinants of cognitive decline identified in this study, in particular modifiable risk factors, should be tested in the context of randomised controlled trials. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The role of pre-morbid intelligence and cognitive reserve in predicting cognitive efficiency in a sample of Italian elderly.

PubMed

Caffò, Alessandro O; Lopez, Antonella; Spano, Giuseppina; Saracino, Giuseppe; Stasolla, Fabrizio; Ciriello, Giuseppe; Grattagliano, Ignazio; Lancioni, Giulio E; Bosco, Andrea

2016-12-01

Models of cognitive reserve in aging suggest that individual's life experience (education, working activity, and leisure) can exert a neuroprotective effect against cognitive decline and may represent an important contribution to successful aging. The objective of the present study is to investigate the role of cognitive reserve, pre-morbid intelligence, age, and education level, in predicting cognitive efficiency in a sample of healthy aged individuals and with probable mild cognitive impairment. Two hundred and eight aging participants recruited from the provincial region of Bari (Apulia, Italy) took part in the study. A battery of standardized tests was administered to them to measure cognitive reserve, pre-morbid intelligence, and cognitive efficiency. Protocols for 10 participants were excluded since they did not meet inclusion criteria, and statistical analyses were conducted on data from the remaining 198 participants. A path analysis was used to test the following model: age, education level, and intelligence directly influence cognitive reserve and cognitive efficiency; cognitive reserve mediates the influence of age, education level, and intelligence on cognitive efficiency. Cognitive reserve fully mediates the relationship between pre-morbid intelligence and education level and cognitive efficiency, while age maintains a direct effect on cognitive efficiency. Cognitive reserve appears to exert a protective effect regarding cognitive decline in normal and pathological populations, thus masking, at least in the early phases of neurodegeneration, the decline of memory, orientation, attention, language, and reasoning skills. The assessment of cognitive reserve may represent a useful evaluation supplement in neuropsychological screening protocols of cognitive decline.

Operationalizing the Diagnostic Criteria for Mild Cognitive Impairment: The Salience of Objective Measures in Predicting Incident Dementia.

PubMed

Brodaty, Henry; Aerts, Liesbeth; Crawford, John D; Heffernan, Megan; Kochan, Nicole A; Reppermund, Simone; Kang, Kristan; Maston, Kate; Draper, Brian; Trollor, Julian N; Sachdev, Perminder S

2017-05-01

Mild cognitive impairment (MCI) is considered an intermediate stage between normal aging and dementia. It is diagnosed in the presence of subjective cognitive decline and objective cognitive impairment without significant functional impairment, although there are no standard operationalizations for each of these criteria. The objective of this study is to determine which operationalization of the MCI criteria is most accurate at predicting dementia. Six-year longitudinal study, part of the Sydney Memory and Ageing Study. Community-based. 873 community-dwelling dementia-free adults between 70 and 90 years of age. Persons from a non-English speaking background were excluded. Seven different operationalizations for subjective cognitive decline and eight measures of objective cognitive impairment (resulting in 56 different MCI operational algorithms) were applied. The accuracy of each algorithm to predict progression to dementia over 6 years was examined for 618 individuals. Baseline MCI prevalence varied between 0.4% and 30.2% and dementia conversion between 15.9% and 61.9% across different algorithms. The predictive accuracy for progression to dementia was poor. The highest accuracy was achieved based on objective cognitive impairment alone. Inclusion of subjective cognitive decline or mild functional impairment did not improve dementia prediction accuracy. Not MCI, but objective cognitive impairment alone, is the best predictor for progression to dementia in a community sample. Nevertheless, clinical assessment procedures need to be refined to improve the identification of pre-dementia individuals. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Predicting Cognitive, Functional, and Diagnostic Change over 4 Years Using Baseline Subjective Cognitive Complaints in the Sydney Memory and Ageing Study.

PubMed

Slavin, Melissa J; Sachdev, Perminder S; Kochan, Nicole A; Woolf, Claudia; Crawford, John D; Giskes, Katrina; Reppermund, Simone; Trollor, Julian N; Draper, Brian; Delbaere, Kim; Brodaty, Henry

2015-09-01

There is limited understanding of the usefulness of subjective cognitive complaint(s) (SCC) in predicting longitudinal outcome because most studies focus solely on memory (as opposed to nonmemory cognitive) complaints, do not collect data from both participants and informants, do not control for relevant covariates, and have limited outcome measures. Therefore the authors investigate the usefulness of participant and informant SCCs in predicting change in cognition, functional abilities, and diagnostic classification of mild cognitive impairment or dementia in a community-dwelling sample over 4 years. Nondemented participants (N = 620) in the Sydney Memory and Ageing Study aged between 70 and 90 years completed 15 memory and 9 nonmemory SCC questions. An informant completed a baseline questionnaire that included 15 memory and 4 nonmemory SCC questions relating to the participant. Neuropsychological, functional, and diagnostic assessments were carried out at baseline and again at 4-year follow-up. Cross-sectional and longitudinal analyses were carried out to determine the association between SCC indices and neuropsychological, functional, and diagnostic data while controlling for psychological measures. Once participant characteristics were controlled for, participant complaints were generally not predictive of cognitive or functional decline, although participant memory-specific complaints were predictive of diagnostic conversion. Informant-related memory questions were associated with global cognitive and functional decline and with diagnostic conversion over 4 years. Informant memory complaint questions were better than participant complaints in predicting cognitive and functional decline as well as diagnoses over 4 years. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Education and the cognitive decline associated with MRI-defined brain infarct.

PubMed

Elkins, J S; Longstreth, W T; Manolio, T A; Newman, A B; Bhadelia, R A; Johnston, S C

2006-08-08

To assess whether educational attainment, a correlate of cognitive reserve, predicts the amount of cognitive decline associated with a new brain infarct. The Cardiovascular Health Study is a population-based, longitudinal study of people aged 65 years and older. Cognitive function was measured annually using the Modified Mini-Mental State Examination (3MS) and the Digit-Symbol Substitution Test (DSST). The authors tested whether education level modified 1) the cross-sectional association between cognitive performance and MRI-defined infarct and 2) the change in cognitive function associated with an incident infarct at a follow-up MRI. In cross-sectional analysis (n = 3,660), MRI-defined infarct was associated with a greater impact on 3MS performance in the lowest education quartile when compared with others (p for heterogeneity = 0.012). Among those with a follow-up MRI who had no infarct on initial MRI (n = 1,433), education level was not associated with the incidence, size, or location of new brain infarct. However, a new MRI-defined infarct predicted substantially greater decline in 3MS scores in the lowest education group compared with the others (6.3, 95% CI 4.4- to 8.2-point decline vs 1.7, 95% CI 0.7- to 2.7-point decline; p for heterogeneity < 0.001). Higher education was not associated with smaller declines in DSST performance in the setting of MRI-defined infarct. Education seems to modify an individual's decline on a test of general cognitive function when there is incident brain infarct. These findings are consistent with the hypothesis that cognitive reserve influences the impact of vascular injury in the brain.

Predicting the Rate of Cognitive Decline in Alzheimer Disease: Data From the ICTUS Study.

PubMed

Canevelli, Marco; Kelaiditi, Eirini; Del Campo, Natalia; Bruno, Giuseppe; Vellas, Bruno; Cesari, Matteo

2016-01-01

Different rates of cognitive progression have been observed among Alzheimer disease (AD) patients. The present study aimed at evaluating whether the rate of cognitive worsening in AD may be predicted by widely available and easy-to-assess factors. Mild to moderate AD patients were recruited in the ICTUS study. Multinomial logistic regression analysis was performed to measure the association between several sociodemographic and clinical variables and 3 different rates of cognitive decline defined by modifications (after 1 year of follow-up) of the Mini Mental State Examination (MMSE) score: (1) "slow" progression, as indicated by a decrease in the MMSE score ≤1 point; (2) "intermediate" progression, decrease in the MMSE score between 2 and 5 points; and (3) "rapid" progression, decrease in the MMSE score ≥6 points. A total of 1005 patients were considered for the present analyses. Overall, most of the study participants (52%) exhibited a slow cognitive course. Higher ADAS-Cog scores at baseline were significantly associated with both "intermediate" and "rapid" decline. Conversely, increasing age was negatively associated with "rapid" cognitive worsening. A slow progression of cognitive decline is common among AD patients. The influence of age and baseline cognitive impairment should always be carefully considered when designing AD trials and defining study populations.

Brain Regional Blood Flow and Working Memory Performance Predict Change in Blood Pressure Over 2 Years.

PubMed

Jennings, J Richard; Heim, Alicia F; Sheu, Lei K; Muldoon, Matthew F; Ryan, Christopher; Gach, H Michael; Schirda, Claudiu; Gianaros, Peter J

2017-12-01

Hypertension is a presumptive risk factor for premature cognitive decline. However, lowering blood pressure (BP) does not uniformly reverse cognitive decline, suggesting that high BP per se may not cause cognitive decline. We hypothesized that essential hypertension has initial effects on the brain that, over time, manifest as cognitive dysfunction in conjunction with both brain vascular abnormalities and systemic BP elevation. Accordingly, we tested whether neuropsychological function and brain blood flow responses to cognitive challenges among prehypertensive individuals would predict subsequent progression of BP. Midlife adults (n=154; mean age, 49; 45% men) with prehypertensive BP underwent neuropsychological testing and assessment of regional cerebral blood flow (rCBF) response to cognitive challenges. Neuropsychological performance measures were derived for verbal and logical memory (memory), executive function, working memory, mental efficiency, and attention. A pseudo-continuous arterial spin labeling magnetic resonance imaging sequence compared rCBF responses with control and active phases of cognitive challenges. Brain areas previously associated with BP were grouped into composites for frontoparietal, frontostriatal, and insular-subcortical rCBF areas. Multiple regression models tested whether BP after 2 years was predicted by initial BP, initial neuropsychological scores, and initial rCBF responses to cognitive challenge. The neuropsychological composite of working memory (standardized beta, -0.276; se=0.116; P =0.02) and the frontostriatal rCBF response to cognitive challenge (standardized beta, 0.234; se=0.108; P =0.03) significantly predicted follow-up BP. Initial BP failed to significantly predict subsequent cognitive performance or rCBF. Changes in brain function may precede or co-occur with progression of BP toward hypertensive levels in midlife. © 2017 American Heart Association, Inc.

Job Strain and Cognitive Decline: A Prospective Study of the Framingham Offspring Cohort

PubMed Central

Agbenyikey, W; Karasek, R; Cifuentes, M; Wolf, PA; Seshadri, S; Taylor, JA; Beiser, AS; Au, R

2017-01-01

Background Workplace stress is known to be related with many behavioral and disease outcomes. However, little is known about its prospective relationship with measures of cognitive decline. Objective To investigate the association of job strain, psychological demands and job control on cognitive decline. Methods Participants from Framingham Offspring cohort (n=1429), were assessed on job strain, and received neuropsychological assessment approximately 15 years and 21 years afterwards. Results High job strain and low control were associated with decline in verbal learning and memory. Job strain was associated with decline in word recognition skills. Active job and passive job predicted decline in verbal learning and memory relative to low strain jobs in the younger subgroup. Active job and demands were positively associated with abstract reasoning skills. Conclusions Job strain and job control may infuence decline in cognitive performance. PMID:25890602

Biomarker progressions explain higher variability in stage-specific cognitive decline than baseline values in Alzheimer disease.

PubMed

Dodge, Hiroko H; Zhu, Jian; Harvey, Danielle; Saito, Naomi; Silbert, Lisa C; Kaye, Jeffrey A; Koeppe, Robert A; Albin, Roger L

2014-11-01

It is unknown which commonly used Alzheimer disease (AD) biomarker values-baseline or progression-best predict longitudinal cognitive decline. 526 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). ADNI composite memory and executive scores were the primary outcomes. Individual-specific slope of the longitudinal trajectory of each biomarker was first estimated. These estimates and observed baseline biomarker values were used as predictors of cognitive declines. Variability in cognitive declines explained by baseline biomarker values was compared with variability explained by biomarker progression values. About 40% of variability in memory and executive function declines was explained by ventricular volume progression among mild cognitive impairment patients. A total of 84% of memory and 65% of executive function declines were explained by fluorodeoxyglucose positron emission tomography (FDG-PET) score progression and ventricular volume progression, respectively, among AD patients. For most biomarkers, biomarker progressions explained higher variability in cognitive decline than biomarker baseline values. This has important implications for clinical trials targeted to modify AD biomarkers. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Gray matter network measures are associated with cognitive decline in mild cognitive impairment.

PubMed

Dicks, Ellen; Tijms, Betty M; Ten Kate, Mara; Gouw, Alida A; Benedictus, Marije R; Teunissen, Charlotte E; Barkhof, Frederik; Scheltens, Philip; van der Flier, Wiesje M

2018-01-01

Gray matter networks are disrupted in Alzheimer's disease and related to cognitive impairment. However, it is still unclear whether these disruptions are associated with cognitive decline over time. Here, we studied this question in a large sample of patients with mild cognitive impairment with extensive longitudinal neuropsychological assessments. Gray matter networks were extracted from baseline structural magnetic resonance imaging, and we tested associations of network measures and cognitive decline in Mini-Mental State Examination and 5 cognitive domains (i.e., memory, attention, executive function, visuospatial, and language). Disrupted network properties were cross-sectionally related to worse cognitive impairment. Longitudinally, lower small-world coefficient values were associated with a steeper decline in almost all domains. Lower betweenness centrality values correlated with a faster decline in Mini-Mental State Examination and memory, and at a regional level, these associations were specific for the precuneus, medial frontal, and temporal cortex. Furthermore, network measures showed additive value over established biomarkers in predicting cognitive decline. Our results suggest that gray matter network measures might have use in identifying patients who will show fast disease progression. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurogranin as a predictor of memory and executive function decline in MCI patients.

PubMed

Headley, Alison; De Leon-Benedetti, Andres; Dong, Chuanhui; Levin, Bonnie; Loewenstein, David; Camargo, Christian; Rundek, Tatjana; Zetterberg, Henrik; Blennow, Kaj; Wright, Clinton B; Sun, Xiaoyan

2018-03-06

To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD). Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included. High levels of CSF Ng were associated with poor baseline memory scores (β = -0.21, p < 0.0001). CSF Ng predicted both memory and executive function decline over time (β = -0.0313, p = 0.0068 and β = -0.0346, p = 0.0169, respectively) independently of age, sex, education, and APOE ε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ 42 ) were controlled for in these analyses. High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ 42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD. © 2018 American Academy of Neurology.

Utility of combinations of biomarkers, cognitive markers, and risk factors to predict conversion from mild cognitive impairment to Alzheimer disease in patients in the Alzheimer's disease neuroimaging initiative.

PubMed

Gomar, Jesus J; Bobes-Bascaran, Maria T; Conejero-Goldberg, Concepcion; Davies, Peter; Goldberg, Terry E

2011-09-01

Biomarkers have become increasingly important in understanding neurodegenerative processes associated with Alzheimer disease. Markers include regional brain volumes, cerebrospinal fluid measures of pathological Aβ1-42 and total tau, cognitive measures, and individual risk factors. To determine the discriminative utility of different classes of biomarkers and cognitive markers by examining their ability to predict a change in diagnostic status from mild cognitive impairment to Alzheimer disease. Longitudinal study. We analyzed the Alzheimer's Disease Neuroimaging Initiative database to study patients with mild cognitive impairment who converted to Alzheimer disease (n = 116) and those who did not convert (n = 204) within a 2-year period. We determined the predictive utility of 25 variables from all classes of markers, biomarkers, and risk factors in a series of logistic regression models and effect size analyses. The Alzheimer's Disease Neuroimaging Initiative public database. Primary outcome measures were odds ratios, pseudo- R(2)s, and effect sizes. In comprehensive stepwise logistic regression models that thus included variables from all classes of markers, the following baseline variables predicted conversion within a 2-year period: 2 measures of delayed verbal memory and middle temporal lobe cortical thickness. In an effect size analysis that examined rates of decline, change scores for biomarkers were modest for 2 years, but a change in an everyday functional activities measure (Functional Assessment Questionnaire) was considerably larger. Decline in scores on the Functional Assessment Questionnaire and Trail Making Test, part B, accounted for approximately 50% of the predictive variance in conversion from mild cognitive impairment to Alzheimer disease. Cognitive markers at baseline were more robust predictors of conversion than most biomarkers. Longitudinal analyses suggested that conversion appeared to be driven less by changes in the neurobiologic trajectory of the disease than by a sharp decline in functional ability and, to a lesser extent, by declines in executive function.

Fuzzy-Trace Theory and Lifespan Cognitive Development

PubMed Central

Brainerd, C J.; Reyna, Valerie F.

2015-01-01

Fuzzy-trace theory (FTT) emphasizes the use of core theoretical principles, such as the verbatim-gist distinction, to predict new findings about cognitive development that are counterintuitive from the perspective of other theories or of common-sense. To the extent that such predictions are confirmed, the range of phenomena that are explained expands without increasing the complexity of the theory's assumptions. We examine research on recent examples of such predictions during four epochs of cognitive development: childhood, adolescence, young adulthood, and late adulthood. During the first two, the featured predictions are surprising developmental reversals in false memory (childhood) and in risky decision making (adolescence). During young adulthood, FTT predicts that a retrieval operation that figures centrally in dual-process theories of memory, recollection, is bivariate rather than univariate. During the late adulthood, FTT identifies a retrieval operation, reconstruction, that has been omitted from current theories of normal memory declines in aging and pathological declines in dementia. The theory predicts that reconstruction is a major factor in such declines and that it is able to forecast future dementia. PMID:26644632

Fuzzy-Trace Theory and Lifespan Cognitive Development.

PubMed

Brainerd, C J; Reyna, Valerie F

2015-12-01

Fuzzy-trace theory (FTT) emphasizes the use of core theoretical principles, such as the verbatim-gist distinction, to predict new findings about cognitive development that are counterintuitive from the perspective of other theories or of common-sense. To the extent that such predictions are confirmed, the range of phenomena that are explained expands without increasing the complexity of the theory's assumptions. We examine research on recent examples of such predictions during four epochs of cognitive development: childhood, adolescence, young adulthood, and late adulthood. During the first two, the featured predictions are surprising developmental reversals in false memory (childhood) and in risky decision making (adolescence). During young adulthood, FTT predicts that a retrieval operation that figures centrally in dual-process theories of memory, recollection, is bivariate rather than univariate. During the late adulthood, FTT identifies a retrieval operation, reconstruction, that has been omitted from current theories of normal memory declines in aging and pathological declines in dementia. The theory predicts that reconstruction is a major factor in such declines and that it is able to forecast future dementia.

Asymptomatic Alzheimer disease: Defining resilience.

PubMed

Hohman, Timothy J; McLaren, Donald G; Mormino, Elizabeth C; Gifford, Katherine A; Libon, David J; Jefferson, Angela L

2016-12-06

To define robust resilience metrics by leveraging CSF biomarkers of Alzheimer disease (AD) pathology within a latent variable framework and to demonstrate the ability of such metrics to predict slower rates of cognitive decline and protection against diagnostic conversion. Participants with normal cognition (n = 297) and mild cognitive impairment (n = 432) were drawn from the Alzheimer's Disease Neuroimaging Initiative. Resilience metrics were defined at baseline by examining the residuals when regressing brain aging outcomes (hippocampal volume and cognition) on CSF biomarkers. A positive residual reflected better outcomes than expected for a given level of pathology (high resilience). Residuals were integrated into a latent variable model of resilience and validated by testing their ability to independently predict diagnostic conversion, cognitive decline, and the rate of ventricular dilation. Latent variables of resilience predicted a decreased risk of conversion (hazard ratio < 0.54, p < 0.0001), slower cognitive decline (β > 0.02, p < 0.001), and slower rates of ventricular dilation (β < -4.7, p < 2 × 10 -15 ). These results were significant even when analyses were restricted to clinically normal individuals. Furthermore, resilience metrics interacted with biomarker status such that biomarker-positive individuals with low resilience showed the greatest risk of subsequent decline. Robust phenotypes of resilience calculated by leveraging AD biomarkers and baseline brain aging outcomes provide insight into which individuals are at greatest risk of short-term decline. Such comprehensive definitions of resilience are needed to further our understanding of the mechanisms that protect individuals from the clinical manifestation of AD dementia, especially among biomarker-positive individuals. © 2016 American Academy of Neurology.

Comparing predictors of conversion and decline in mild cognitive impairment(Podcast)(e–Pub ahead of print)

PubMed Central

Landau, S.M.; Harvey, D.; Madison, C.M.; Reiman, E.M.; Foster, N.L.; Aisen, P.S.; Petersen, R.C.; Shaw, L.M.; Trojanowski, J.Q.; Jack, C.R.; Weiner, M.W.; Jagust, W.J.

2010-01-01

Objective: A variety of measurements have been individually linked to decline in mild cognitive impairment (MCI), but the identification of optimal markers for predicting disease progression remains unresolved. The goal of this study was to evaluate the prognostic ability of genetic, CSF, neuroimaging, and cognitive measurements obtained in the same participants. Methods: APOE ε4 allele frequency, CSF proteins (Aβ1-42, total tau, hyperphosphorylated tau [p-tau181p]), glucose metabolism (FDG-PET), hippocampal volume, and episodic memory performance were evaluated at baseline in patients with amnestic MCI (n = 85), using data from a large multisite study (Alzheimer's Disease Neuroimaging Initiative). Patients were classified as normal or abnormal on each predictor variable based on externally derived cutoffs, and then variables were evaluated as predictors of subsequent conversion to Alzheimer disease (AD) and cognitive decline (Alzheimer's Disease Assessment Scale–Cognitive Subscale) during a variable follow-up period (1.9 ± 0.4 years). Results: Patients with MCI converted to AD at an annual rate of 17.2%. Subjects with MCI who had abnormal results on both FDG-PET and episodic memory were 11.7 times more likely to convert to AD than subjects who had normal results on both measures (p ≤ 0.02). In addition, the CSF ratio p-tau181p/Aβ1-42 (β = 1.10 ± 0.53; p = 0.04) and, marginally, FDG-PET predicted cognitive decline. Conclusions: Baseline FDG-PET and episodic memory predict conversion to AD, whereas p-tau181p/Aβ1-42 and, marginally, FDG-PET predict longitudinal cognitive decline. Complementary information provided by these biomarkers may aid in future selection of patients for clinical trials or identification of patients likely to benefit from a therapeutic intervention. GLOSSARY AD = Alzheimer disease; ADAS-Cog = Alzheimer's Disease Assessment Scale–Cognitive Subscale; ADNI = Alzheimer's Disease Neuroimaging Initiative; AVLT = Auditory Verbal Learning Test; CDR = Clinical Dementia Rating; CI = confidence interval; FDG = [18F]fluorodeoxyglucose; MCI = mild cognitive impairment; MNI = Montreal Neurological Institute; p-tau181p = hyperphosphorylated tau; ROC = receiver operating characteristic; t-tau = total tau. PMID:20592257

Recognition of Famous Names Predicts Episodic Memory Decline in Cognitively Intact Elders

PubMed Central

Seidenberg, Michael; Kay, Christina; Woodard, John L.; Nielson, Kristy A.; Smith, J. Carson; Kandah, Cassandra; Guidotti Breting, Leslie M.; Novitski, Julia; Lancaster, Melissa; Matthews, Monica; Hantke, Nathan; Butts, Alissa; Rao, Stephen M.

2013-01-01

Objective: Semantic memory impairment is common in both Mild Cognitive Impairment (MCI) and early Alzheimer’s disease (AD), and the ability to recognize familiar people is particularly vulnerable. A time-limited temporal gradient (TG) in which well known people from decades earlier are better recalled than those learned recently is also reported in both AD and MCI. In this study, we hypothesized that the TG pattern on a famous name recognition task (FNRT) administered to cognitively intact elders would predict future episodic memory decline, and would also show a significant correlation with hippocampal volume. Methods: 78 healthy elders (ages 65-90) with normal cognition and episodic memory at baseline were administered a FNRT. Follow-up episodic memory testing 18 months later produced two groups: Declining (≥ 1 SD reduction in episodic memory) and Stable (< 1 SD). Results: The Declining group (N=27) recognized fewer recent famous names than the Stable group (N=51), while recognition for remote names was comparable. Baseline MRI volumes for both the left and right hippocampus was significantly smaller in the Declining group than the Stable group. Smaller baseline hippocampal volume was also significantly correlated with poorer performance for recent, but not remote famous names. Logistic regression analyses indicated that baseline TG performance was a significant predictor of group status (Declining versus Stable) independent of chronological age and APOE ε4 inheritance. Conclusions: Famous name recognition may serve as an early pre-clinical cognitive marker of episodic memory decline in older individuals. PMID:23688215

The Nordic Prudent Diet Reduces Risk of Cognitive Decline in the Swedish Older Adults: A Population-Based Cohort Study.

PubMed

Shakersain, Behnaz; Rizzuto, Debora; Larsson, Susanna C; Faxén-Irving, Gerd; Fratiglioni, Laura; Xu, Wei-Li

2018-02-17

Appropriate dietary pattern for preserving cognitive function in northern Europe remains unknown. We aimed to identify a Nordic dietary pattern index associated with slower cognitive decline compared to the Mediterranean-DASH Intervention for Neurodegenerative Delay, Mediterranean Diet, Dietary Approaches to Stop Hypertension, and Baltic Sea Diet indices. A total of 2223 dementia-free adults aged ≥60 were followed for 6 years. Mini-Mental State Examination was administrated at baseline and follow-ups. Dietary intake was assessed by 98-item food frequency questionnaire, and the Nordic Prudent Dietary Pattern (NPDP) was identified. Data were analysed using mixed-effects and parametric survival models and receiver operating characteristic curves with adjustment for potential confounders. Moderate (β = 0.139, 95% CI 0.077-0.201) and high adherence (β = 0.238, 95% CI 0.175-0.300) to NPDP were associated with less cognitive decline compared to other four indices. High adherence to NPDP was also associated with the lowest risk of MMSE decline to ≤24 (HR = 0.176, 95% CI 0.080-0.386) and had the greatest ability to predict such decline (area under the curve = 0.70). Moderate-to-high adherence to the NPDP may predict a better-preserved cognitive function among older adults in Nordic countries. Regional dietary habits should be considered in developing dietary guidelines for the prevention of cognitive impairment and dementia.

Lead exposure and rate of change in cognitive function in older women

PubMed Central

Power, Melinda C; Korrick, Susan; Tchetgen Tchetgen, Eric J; Nie, Linda H; Grodstein, Francine; Hu, Howard; Weuve, Jennifer; Schwartz, Joel; Weisskopf, Marc G

2014-01-01

Background Higher long-term cumulative lead exposure predicts faster cognitive decline in older men, but evidence of an association in women is lacking. Objective To determine if there is an association between lead exposure and cognitive decline in women. Methods This study considers a sample of 584 women from the Nurses’ Health Study who live in or near Boston, Massachusetts. We quantified lead exposure using biomarkers of lead exposure assessed in 1993–2004 and evaluated cognitive decline by repeated performance on a telephone battery of cognitive tests primarily assessing learning, memory, executive function, and attention completed in 1995–2008. All cognitive test scores were z-transformed for use in analyses. We used linear mixed models with random effects to quantify the association between each lead biomarker and change in cognition overall and on each individual test. Results Consideration of individual tests showed greater cognitive decline with increased tibia lead concentrations, a measure of long-term cumulative exposure, for story memory and category fluency. The estimated excess annual decline in overall cognitive test z-score per SD increase in tibia bone lead concentration was suggestive, although the confidence intervals included the null (0.024 standard units, 95% confidence interval: −0.053 , 0.004 – an additional decline in function equivalent to being 0.33 years older). We found little support for associations between cognitive decline and patella or blood lead, which provide integrated measures of exposure over shorter timeframes. Conclusions Long-term cumulative lead exposure may be weakly associated with faster cognitive decline in community-dwelling women, at least in some cognitive domains. PMID:24529005

Fronto-Parietal Subnetworks Flexibility Compensates For Cognitive Decline Due To Mental Fatigue.

PubMed

Taya, Fumihiko; Dimitriadis, Stavros I; Dragomir, Andrei; Lim, Julian; Sun, Yu; Wong, Kian Foong; Thakor, Nitish V; Bezerianos, Anastasios

2018-04-24

Fronto-parietal subnetworks were revealed to compensate for cognitive decline due to mental fatigue by community structure analysis. Here, we investigate changes in topology of subnetworks of resting-state fMRI networks due to mental fatigue induced by prolonged performance of a cognitively demanding task, and their associations with cognitive decline. As it is well established that brain networks have modular organization, community structure analyses can provide valuable information about mesoscale network organization and serve as a bridge between standard fMRI approaches and brain connectomics that quantify the topology of whole brain networks. We developed inter- and intramodule network metrics to quantify topological characteristics of subnetworks, based on our hypothesis that mental fatigue would impact on functional relationships of subnetworks. Functional networks were constructed with wavelet correlation and a data-driven thresholding scheme based on orthogonal minimum spanning trees, which allowed detection of communities with weak connections. A change from pre- to posttask runs was found for the intermodule density between the frontal and the temporal subnetworks. Seven inter- or intramodule network metrics, mostly at the frontal or the parietal subnetworks, showed significant predictive power of individual cognitive decline, while the network metrics for the whole network were less effective in the predictions. Our results suggest that the control-type fronto-parietal networks have a flexible topological architecture to compensate for declining cognitive ability due to mental fatigue. This community structure analysis provides valuable insight into connectivity dynamics under different cognitive states including mental fatigue. © 2018 Wiley Periodicals, Inc.

The relative temporal sequence of decline in mobility and cognition among initially unimpaired older adults: Results from the Baltimore Longitudinal Study of Aging.

PubMed

Tian, Qu; An, Yang; Resnick, Susan M; Studenski, Stephanie

2017-05-01

most older individuals who experience mobility decline, also show cognitive decline, but whether cognitive decline precedes or follows mobility limitation is not well understood. examine the temporal sequence of mobility and cognition among initially unimpaired older adults. mobility and cognition were assessed every 2 years for 6 years in 412 participants aged ≥60 with initially unimpaired cognition and gait speed. Using autoregressive models, accounting for the dependent variable from the prior assessment, baseline age, sex, body mass index and education, we examine the temporal sequence of change in mobility (6 m usual gait speed, 400 m fast walk time) and executive function (visuoperceptual speed: Digit Symbol Substitution Test (DSST); cognitive flexibility: Trail Making Test part B (TMT-B)) or memory (California Verbal Learning Test (CVLT) immediate, short-delay, long-delay). there was a bidirectional relationship over time between slower usual gait speed and both poorer DSST and TMT-B scores (Bonferroni-corrected P < 0.005). In contrast, slower 400 m fast walk time predicted subsequent poorer DSST, TMT-B, CVLT immediate recall and CVLT short-delay scores (P < 0.005), while these measures did not predict subsequent 400 m fast walk time (P > 0.005). among initially unimpaired older adults, the temporal relationship between usual gait speed and executive function is bidirectional, with each predicting change in the other, while poor fast walking performance predicts future executive function and memory changes but not vice versa. Challenging tasks like the 400 m walk appear superior to usual gait speed for predicting executive function and memory change in unimpaired older adults. Published by Oxford University Press on behalf of the British Geriatrics Society 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Using Telephone and Informant Assessments to Estimate Missing Modified Mini-Mental State Exam Scores and Rates of Cognitive Decline

PubMed Central

Arnold, Alice M.; Newman, Anne B.; Dermond, Norma; Haan, Mary; Fitzpatrick, Annette

2009-01-01

Aim To estimate an equivalent to the Modified Mini-Mental State Exam (3MSE), and to compare changes in the 3MSE with and without the estimated scores. Methods Comparability study on a subset of 405 participants, aged ≥70 years, from the Cardiovascular Health Study (CHS), a longitudinal study in 4 United States communities. The 3MSE, the Telephone Interview for Cognitive Status (TICS) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were administered within 30 days of one another. Regression models were developed to predict the 3MSE score from the TICS and/or IQCODE, and the predicted values were used to estimate missing 3MSE scores in longitudinal follow-up of 4,274 CHS participants. Results The TICS explained 67% of the variability in 3MSE scores, with a correlation of 0.82 between predicted and observed scores. The IQCODE alone was not a good estimate of 3MSE score, but improved the model fit when added to the TICS model. Using estimated 3MSE scores classified more participants with low cognition, and rates of decline were greater than when only the observed 3MSE scores were considered. Conclusions 3MSE scores can be reliably estimated from the TICS, with or without the IQCODE. Incorporating these estimates captured more cognitive decline in older adults. PMID:19407461

Medical Complications Predict Cognitive Decline in Nondemented Hip Fracture Patients-Results of a Prospective Observational Study.

PubMed

Hack, Juliana; Eschbach, Daphne; Aigner, Rene; Oberkircher, Ludwig; Ruchholtz, Steffen; Bliemel, Christopher; Buecking, Benjamin

2018-03-01

The aim of this study was to identify factors that are associated with cognitive decline in the long-term follow-up after hip fractures in previously nondemented patients. A consecutive series of 402 patients with hip fractures admitted to our university hospital were analyzed. After exclusion of all patients with preexisting dementia, 266 patients were included, of which 188 could be examined 6 months after surgery. Additional to several demographic data, cognitive ability was assessed using the Mini-Mental State Examination (MMSE). Patients with 19 or less points on the MMSE were considered demented. Furthermore, geriatric scores were recorded, as well as perioperative medical complications. Mini-Mental State Examination was performed again 6 months after surgery. Of 188 previously nondemented patients, 12 (6.4%) patients showed a cognitive decline during the 6 months of follow-up. Multivariate regression analysis showed that age ( P = .040) and medical complications ( P = .048) were the only significant independent influencing factors for cognitive decline. In our patient population, the incidence of dementia exceeded the average age-appropriate cognitive decline. Significant independent influencing factors for cognitive decline were age and medical complications.

Dynamic hub load predicts cognitive decline after resective neurosurgery.

PubMed

Carbo, Ellen W S; Hillebrand, Arjan; van Dellen, Edwin; Tewarie, Prejaas; de Witt Hamer, Philip C; Baayen, Johannes C; Klein, Martin; Geurts, Jeroen J G; Reijneveld, Jaap C; Stam, Cornelis J; Douw, Linda

2017-02-07

Resective neurosurgery carries the risk of postoperative cognitive deterioration. The concept of 'hub (over)load', caused by (over)use of the most important brain regions, has been theoretically postulated in relation to symptomatology and neurological disease course, but lacks experimental confirmation. We investigated functional hub load and postsurgical cognitive deterioration in patients undergoing lesion resection. Patients (n = 28) underwent resting-state magnetoencephalography and neuropsychological assessments preoperatively and 1-year after lesion resection. We calculated stationary hub load score (SHub) indicating to what extent brain regions linked different subsystems; high SHub indicates larger processing pressure on hub regions. Dynamic hub load score (DHub) assessed its variability over time; low values, particularly in combination with high SHub values, indicate increased load, because of consistently high usage of hub regions. Hypothetically, increased SHub and decreased DHub relate to hub overload and thus poorer/deteriorating cognition. Between time points, deteriorating verbal memory performance correlated with decreasing upper alpha DHub. Moreover, preoperatively low DHub values accurately predicted declining verbal memory performance. In summary, dynamic hub load relates to cognitive functioning in patients undergoing lesion resection: postoperative cognitive decline can be tracked and even predicted using dynamic hub load, suggesting it may be used as a prognostic marker for tailored treatment planning.

Education and trajectories of cognitive decline over 9 years in very old people: methods and risk analysis.

PubMed

Muniz-Terrera, Graciela; Matthews, Fiona; Dening, Tom; Huppert, Felicia A; Brayne, Carol

2009-05-01

the investigation of cognitive decline in the older population has been hampered by analytical considerations. Most studies of older people over prolonged periods suffer from loss to follow-up, yet this has seldom been investigated fully to date. Such considerations limit our understanding of how basic variables such as education can affect cognitive trajectories. we examined cognitive trajectories in a population-based cohort study in Cambridge, UK, of people aged 75 and over in whom multiple interviews were conducted over time. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Socio-demographic variables were measured, including educational level and social class. An age-based quadratic latent growth model was fitted to cognitive scores. The effect of socio-demographic variables was examined on all latent variables and the probability of death and dropout. at baseline, age, education, social class and mobility were associated with cognitive performance. Education and social class were not related to decline or its rate of change. In contrast, poor mobility was associated with lower cognitive performance, increased cognitive decline and increased rate of change of cognitive decline. Gender, age, mobility and cognitive ability predicted death and dropout contrary to much of the current literature, education was not related to rate of cognitive decline or change in this rate as measured by MMSE. Higher levels of education do not appear to protect against cognitive decline, though if the MMSE is used in the diagnostic process, individuals with less education may be diagnosed as having dementia somewhat earlier.

Increase of EEG Spectral Theta Power Indicates Higher Risk of the Development of Severe Cognitive Decline in Parkinson’s Disease after 3 Years

PubMed Central

Cozac, Vitalii V.; Chaturvedi, Menorca; Hatz, Florian; Meyer, Antonia; Fuhr, Peter; Gschwandtner, Ute

2016-01-01

Objective: We investigated quantitative electroencephalography (qEEG) and clinical parameters as potential risk factors of severe cognitive decline in Parkinson’s disease. Methods: We prospectively investigated 37 patients with Parkinson’s disease at baseline and follow-up (after 3 years). Patients had no severe cognitive impairment at baseline. We used a summary score of cognitive tests as the outcome at follow-up. At baseline we assessed motor, cognitive, and psychiatric factors; qEEG variables [global relative median power (GRMP) spectra] were obtained by a fully automated processing of high-resolution EEG (256-channels). We used linear regression models with calculation of the explained variance to evaluate the relation of baseline parameters with cognitive deterioration. Results: The following baseline parameters significantly predicted severe cognitive decline: GRMP theta (4–8 Hz), cognitive task performance in executive functions and working memory. Conclusions: Combination of neurocognitive tests and qEEG improves identification of patients with higher risk of cognitive decline in PD. PMID:27965571

Deviation from expected cognitive ability across psychotic disorders.

PubMed

Hochberger, W C; Combs, T; Reilly, J L; Bishop, J R; Keefe, R S E; Clementz, B A; Keshavan, M S; Pearlson, G D; Tamminga, C A; Hill, S K; Sweeney, J A

2018-02-01

Patients with schizophrenia show a deficit in cognitive ability compared to estimated premorbid and familial intellectual abilities. However, the degree to which this pattern holds across psychotic disorders and is familial is unclear. The present study examined deviation from expected cognitive level in schizophrenia, schizoaffective disorder, and psychotic bipolar disorder probands and their first-degree relatives. Using a norm-based regression approach, parental education and WRAT-IV Reading scores (both significant predictors of cognitive level in the healthy control group) were used to predict global neuropsychological function as measured by the composite score from the Brief Assessment of Cognition in Schizophrenia (BACS) test in probands and relatives. When compared to healthy control group, psychotic probands showed a significant gap between observed and predicted BACS composite scores and a greater likelihood of robust cognitive decline. This effect was not seen in unaffected relatives. While BACS and WRAT-IV Reading scores were themselves highly familial, the decline in cognitive function from expectation had lower estimates of familiality. Thus, illness-related factors such as epigenetic, treatment, or pathophysiological factors may be important causes of illness related decline in cognitive abilities across psychotic disorders. This is consistent with the markedly greater level of cognitive impairment seen in affected individuals compared to their unaffected family members. Copyright © 2017 Elsevier B.V. All rights reserved.

Metabolic Syndrome and Cognitive Decline in Early Alzheimer’s Disease and Healthy Older Adults

PubMed Central

Watts, Amber S.; Loskutova, Natalia; Burns, Jeffrey M.; Johnson, David K.

2013-01-01

Metabolic syndrome (MetS) is a cluster of risk factors (i.e., abdominal obesity, hypertension, dyslipidemia, glucose and insulin dysregulation) that is associated with cardiovascular disease, diabetes, and dementia. Recent studies addressing the association of MetS with cognitive performance and risk for dementia report mixed results. An important step in clarifying these conflicting results is determining whether cognition is influenced by the effects of individual MetS components versus the additive effects of multiple components. We assessed the effect of MetS on cognitive performance and decline over two years in 75 cases of early Alzheimer’s disease (AD) and 73 healthy older adult controls in the Brain Aging Project. Using factor analytic techniques, we compared the effect of a combined MetS factor to the effect of individual MetS components on change in attention, verbal memory, and mental status. In healthy controls, a combined MetS factor did not significantly predict cognitive performance, though higher insulin predicted poorer cognitive performance outcomes. In the AD group, higher scores on a combined MetS factor predicted better cognitive outcomes. Our findings suggest that MetS does not have the same association with cognitive decline in healthy older adults and those with early AD. We suggest that individual MetS components should not be evaluated in isolation and that careful methodological approaches are needed to understand the timing and non-linear relationships among these components over time. PMID:23388170

Apolipoprotein E genotype does not moderate the associations of depressive symptoms, neuroticism and allostatic load with cognitive ability and cognitive aging in the Lothian Birth Cohort 1936.

PubMed

Crook, Zander; Booth, Tom; Cox, Simon R; Corley, Janie; Dykiert, Dominika; Redmond, Paul; Pattie, Alison; Taylor, Adele M; Harris, Sarah E; Starr, John M; Deary, Ian J

2018-01-01

In this replication-and-extension study, we tested whether depressive symptoms, neuroticism, and allostatic load (multisystem physiological dysregulation) were related to lower baseline cognitive ability and greater subsequent cognitive decline in older adults, and whether these relationships were moderated by the E4 allele of the apolipoprotein E (APOE) gene. We also tested whether allostatic load mediated the relationships between neuroticism and cognitive outcomes. We used data from the Lothian Birth Cohort 1936 (n at Waves 1-3: 1,028 [M age = 69.5 y]; 820 [M duration since Wave 1 = 2.98 y]; 659 [M duration since Wave 1 = 6.74 y]). We fitted latent growth curve models of general cognitive ability (modeled using five cognitive tests) with groups of APOE E4 non-carriers and carriers. In separate models, depressive symptoms, neuroticism, and allostatic load predicted baseline cognitive ability and subsequent cognitive decline. In addition, models tested whether allostatic load mediated relationships between neuroticism and cognitive outcomes. Baseline cognitive ability had small-to-moderate negative associations with depressive symptoms (β range = -0.20 to -0.17), neuroticism (β range = -0.27 to -0.23), and allostatic load (β range = -0.11 to 0.09). Greater cognitive decline was linked to baseline allostatic load (β range = -0.98 to -0.83) and depressive symptoms (β range = -1.00 to -0.88). However, APOE E4 allele possession did not moderate the relationships of depressive symptoms, neuroticism and allostatic load with cognitive ability and cognitive decline. Additionally, the associations of neuroticism with cognitive ability and cognitive decline were not mediated through allostatic load. Our results suggest that APOE E4 status does not moderate the relationships of depressive symptoms, neuroticism, and allostatic load with cognitive ability and cognitive decline in healthy older adults. The most notable positive finding in the current research was the strong association between allostatic load and cognitive decline.

Metabolic Syndrome and Cognitive Decline Among the Oldest Old in Okinawa: In Search of a Mechanism. The KOCOA Project

PubMed Central

Todoriki, Hidemi; Higashiuesato, Yasushi; Yasura, Shotoku; Willcox, D. Craig; Ohya, Yusuke; Willcox, Bradley J.; Dodge, Hiroko H.

2012-01-01

The study aim was to test whether the metabolic syndrome or its components predicted cognitive decline among persons aged 80 years and older (mean 85.0 years). Participants were members of the “Keys to Optimal Cognitive Aging Project,” a prospective cohort study in Okinawa, Japan. Metabolic syndrome was assessed at baseline. Cognitive functions were assessed annually for up to 3 years. One hundred and forty-eight participants completed at least one follow-up with 101 participating in all three assessments and 47 participating in two of the three assessments. The mean and median duration of follow-up were 1.8 and 2 years, respectively. Metabolic syndrome and four components were not associated with decline in global and executive cognitive functions. However, high glycosylated hemoglobin was associated with decline in memory function at the second follow-up. Our study supports accumulating evidence that the positive association between metabolic syndrome and cognitive function might not hold for the oldest old. PMID:22016359

Retrospective lifetime dietary patterns predict cognitive performance in community-dwelling older Australians.

PubMed

Hosking, Diane E; Nettelbeck, Ted; Wilson, Carlene; Danthiir, Vanessa

2014-07-28

Dietary intake is a modifiable exposure that may have an impact on cognitive outcomes in older age. The long-term aetiology of cognitive decline and dementia, however, suggests that the relevance of dietary intake extends across the lifetime. In the present study, we tested whether retrospective dietary patterns from the life periods of childhood, early adulthood, adulthood and middle age predicted cognitive performance in a cognitively healthy sample of 352 older Australian adults >65 years. Participants completed the Lifetime Diet Questionnaire and a battery of cognitive tests designed to comprehensively assess multiple cognitive domains. In separate regression models, lifetime dietary patterns were the predictors of cognitive factor scores representing ten constructs derived by confirmatory factor analysis of the cognitive test battery. All regression models were progressively adjusted for the potential confounders of current diet, age, sex, years of education, English as native language, smoking history, income level, apoE ɛ4 status, physical activity, other past dietary patterns and health-related variables. In the adjusted models, lifetime dietary patterns predicted cognitive performance in this sample of older adults. In models additionally adjusted for intake from the other life periods and mechanistic health-related variables, dietary patterns from the childhood period alone reached significance. Higher consumption of the 'coffee and high-sugar, high-fat extras' pattern predicted poorer performance on simple/choice reaction time, working memory, retrieval fluency, short-term memory and reasoning. The 'vegetable and non-processed' pattern negatively predicted simple/choice reaction time, and the 'traditional Australian' pattern positively predicted perceptual speed and retrieval fluency. Identifying early-life dietary antecedents of older-age cognitive performance contributes to formulating strategies for delaying or preventing cognitive decline.

Single neuropsychological test scores associated with rate of cognitive decline in early Alzheimer disease.

PubMed

Parikh, Mili; Hynan, Linda S; Weiner, Myron F; Lacritz, Laura; Ringe, Wendy; Cullum, C Munro

2014-01-01

Alzheimer disease (AD) characteristically begins with episodic memory impairment followed by other cognitive deficits; however, the course of illness varies, with substantial differences in the rate of cognitive decline. For research and clinical purposes it would be useful to distinguish between persons who will progress slowly from persons who will progress at an average or faster rate. Our objective was to use neurocognitive performance features and disease-specific and health information to determine a predictive model for the rate of cognitive decline in participants with mild AD. We reviewed the records of a series of 96 consecutive participants with mild AD from 1995 to 2011 who had been administered selected neurocognitive tests and clinical measures. Based on Clinical Dementia Rating (CDR) of functional and cognitive decline over 2 years, participants were classified as Faster (n = 45) or Slower (n = 51) Progressors. Stepwise logistic regression analyses using neurocognitive performance features, disease-specific, health, and demographic variables were performed. Neuropsychological scores that distinguished Faster from Slower Progressors included Trail Making Test - A, Digit Symbol, and California Verbal Learning Test (CVLT) Total Learned and Primacy Recall. No disease-specific, health, or demographic variable predicted rate of progression; however, history of heart disease showed a trend. Among the neuropsychological variables, Trail Making Test - A best distinguished Faster from Slower Progressors, with an overall accuracy of 68%. In an omnibus model including neuropsychological, disease-specific, health, and demographic variables, only Trail Making Test - A distinguished between groups. Several neuropsychological performance features were associated with the rate of cognitive decline in mild AD, with baseline Trail Making Test - A performance best separating those who declined at an average or faster rate from those who showed slower progression.

A lower ratio of omega-6 to omega-3 fatty acids predicts better hippocampus-dependent spatial memory and cognitive status in older adults.

PubMed

Andruchow, Nadia D; Konishi, Kyoko; Shatenstein, Bryna; Bohbot, Véronique D

2017-10-01

Evidence from several cross-sectional studies indicates that an increase in omega-6 to omega-3 fatty acids (FAs) may negatively affect cognition in old age. The hippocampus is among the first neural structures affected by age and atrophy in this brain region is associated with cognitive decline. Therefore, we hypothesized that a lower omega-6:3 FA ratio would predict better hippocampus-dependent spatial memory, and a higher general cognitive status. Fifty-two healthy older adults completed a Food Frequency Questionnaire, the Montreal Cognitive Assessment test (MoCA; a test of global cognition) and virtual navigation tasks that assess navigational strategies and spatial memory. In this cross-sectional study, a lower ratio of omega-6 to omega-3 FA intake strongly predicted more accurate hippocampus-dependent spatial memory and faster learning on our virtual navigation tasks, as well as higher cognitive status overall. These results may help elucidate why certain dietary patterns with a lower omega-6:3 FA ratio, like the Mediterranean diet, are associated with reduced risk of cognitive decline. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The recency ratio as predictor of early MCI.

PubMed

Bruno, Davide; Koscik, Rebecca L; Woodard, John L; Pomara, Nunzio; Johnson, Sterling C

2018-04-18

ABSTRACTObjectives:Individuals with Alzheimer's disease (AD) present poor immediate primacy recall accompanied by intact or exaggerated recency, which then tends to decline after a delay. Bruno et al. (Journal of Clinical and Experimental Neuropsychology, Vol. 38, 2016, pp. 967-973) have shown that higher ratio scores between immediate and delayed recency (i.e. the recency ratio; Rr) are associated with cognitive decline in high-functioning older individuals. We tested whether Rr predicted conversion to early mild cognitive impairment (early MCI) from a cognitively healthy baseline. Data were analyzed longitudinally with binomial regression. Baseline scores were used to predict conversion to early MCI after approximately nine years. Data were collected at the Wisconsin Registry of Alzheimer's Prevention, in Madison, Wisconsin. For the study, 427 individuals were included in the analysis; all participants were 50 years of age or older and cognitively intact at baseline, and were native English speakers. Memory data were collected using the Rey's Auditory Verbal Learning Test, and the early MCI diagnosis was obtained via consensus conference. Our results showed that higher Rr scores are correlated with greater risk of later early MCI diagnosis, and this association is independent of total recall performance. Rr is an emerging cognitive marker of cognitive decline.

Progression and effect of cognitive-behavioral changes in patients with amyotrophic lateral sclerosis.

PubMed

Bock, Meredith; Duong, Y-Nhy; Kim, Anthony; Allen, Isabel; Murphy, Jennifer; Lomen-Hoerth, Catherine

2017-12-01

To prospectively evaluate the progression of cognitive-behavioral function in amyotrophic lateral sclerosis (ALS) and examine the association of cognitive-behavioral deficits with disease progression, patient quality of life (QOL), and caregiver burden. We evaluated cognitive-behavioral function using the Amyotrophic Lateral Sclerosis Cognitive Behavioral Screen at enrollment and after 7 months in a cohort of patients with ALS. Paired t tests were used to evaluate the change in the 2 assessments. Linear regression and Kruskal-Wallis tests were applied to investigate how initial cognitive or behavioral status related to outcomes. The mean test-retest interval was 6.8 months (SD 1.6). Cognitive status of the study population (n = 49) overall did not change over the study period ( p = 0.06) despite progression of motor weakness ( p < 0.001), though small subsets of the sample demonstrate cognitive change. Patients initially classified as behaviorally normal showed increased behavioral problems over time ( t = -2.8, p = 0.009). Decline in cognitive (β = -1.3, p = 0.03) and behavioral (β = -0.76, p = 0.002) status predicted increasing caregiver burden. Behavioral abnormalities predicted decline in forced vital capacity and ALS Functional Rating Scale-Revised score ( p = 0.008, 0.012) in the study population and patient QOL in the most severely affected group ( t = 4.3, p = 0.003). Cognitive-behavioral change is a key aspect of disease heterogeneity in ALS. Executive function in ALS overall remains stable over 7 months as detected by an administered screening tool. However, patients may develop caregiver-reported behavioral symptoms in that time period. Screening for caregiver-reported symptoms has a particular utility in predicting future clinical decline, increased caregiver burden, and worsening patient QOL.

APOE epsilon 4 allele predicts faster cognitive decline in mild Alzheimer disease.

PubMed

Cosentino, S; Scarmeas, N; Helzner, E; Glymour, M M; Brandt, J; Albert, M; Blacker, D; Stern, Y

2008-05-06

To determine whether APOE epsilon 4 predicts rate of cognitive change in incident and prevalent Alzheimer disease (AD). Individuals were recruited from two longitudinal cohort studies-the Washington Heights and Inwood Columbia Aging Project (WHICAP; population-based) and the Predictors Study (clinic-based)--and were followed for an average of 4 years. Three samples of participants diagnosed with AD, with diverse demographic characteristics and baseline cognitive functioning, were studied: 1) 199 (48%) of the incident WHICAP cases; 2) 215 (54%) of the prevalent WHICAP cases; and 3) 156 (71%) of the individuals diagnosed with AD in the Predictors Study. Generalized estimating equations were used to test whether rate of cognitive change, measured using a composite cognitive score in WHICAP and the Mini-Mental State Examination in Predictors, varied as a function of epsilon 4 status in each sample. The presence of at least one epsilon 4 allele was associated with faster cognitive decline in the incident population-based AD group (p = 0.01). Parallel results were produced for the two prevalent dementia samples only when adjusting for disease severity or excluding the most impaired participants from the analyses. APOE epsilon 4 may influence rate of cognitive decline most significantly in the earliest stages of Alzheimer disease.

Brain volumetric changes and cognitive ageing during the eighth decade of life

PubMed Central

Dickie, David Alexander; Cox, Simon R.; Valdes Hernandez, Maria del C.; Corley, Janie; Royle, Natalie A.; Pattie, Alison; Aribisala, Benjamin S.; Redmond, Paul; Muñoz Maniega, Susana; Taylor, Adele M.; Sibbett, Ruth; Gow, Alan J.; Starr, John M.; Bastin, Mark E.; Wardlaw, Joanna M.; Deary, Ian J.

2015-01-01

Abstract Later‐life changes in brain tissue volumes—decreases in the volume of healthy grey and white matter and increases in the volume of white matter hyperintensities (WMH)—are strong candidates to explain some of the variation in ageing‐related cognitive decline. We assessed fluid intelligence, memory, processing speed, and brain volumes (from structural MRI) at mean age 73 years, and at mean age 76 in a narrow‐age sample of older individuals (n = 657 with brain volumetric data at the initial wave, n = 465 at follow‐up). We used latent variable modeling to extract error‐free cognitive levels and slopes. Initial levels of cognitive ability were predictive of subsequent brain tissue volume changes. Initial brain volumes were not predictive of subsequent cognitive changes. Brain volume changes, especially increases in WMH, were associated with declines in each of the cognitive abilities. All statistically significant results were modest in size (absolute r‐values ranged from 0.114 to 0.334). These results build a comprehensive picture of macrostructural brain volume changes and declines in important cognitive faculties during the eighth decade of life. Hum Brain Mapp 36:4910–4925, 2015. © 2015 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc PMID:26769551

CSF tau and tau/Aβ42 predict cognitive decline in Parkinson's disease.

PubMed

Liu, Changqin; Cholerton, Brenna; Shi, Min; Ginghina, Carmen; Cain, Kevin C; Auinger, Peggy; Zhang, Jing

2015-03-01

A substantial proportion of patients with Parkinson's disease (PD) have concomitant cognitive dysfunction. Identification of biomarker profiles that predict which PD patients have a greater likelihood for progression of cognitive symptoms is pressingly needed for future treatment and prevention approaches. Subjects were drawn from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, a large clinical trial that enrolled initially untreated PD patients. For the current study, Phase One encompassed trial baseline until just prior to levodopa administration (n = 403), and Phase Two spanned the initiation of levodopa treatment until the end of cognitive follow-up (n = 305). Correlations and linear mixed models were performed to determine cross-sectional and longitudinal associations between baseline amyloid β1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) and measures of memory and executive function. Analyses also considered APOE genotype and tremor- vs. rigidity-dominant phenotype. No association was found between baseline CSF biomarkers and cognitive test performance during Phase One. However, once levodopa treatment was initiated, higher p-tau and p-tau/Aβ42 predicted subsequent decline on cognitive tasks involving both memory and executive functions. The interactions between biomarkers and cognition decline did not appear to be influenced by levodopa dosage, APOE genotype or motor phenotype. The current study has, for the first time, demonstrated the possible involvement of tau species, whose gene (MAPT) has been consistently linked to the risk of PD by genome-wide association studies, in the progression of cognitive symptoms in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

A decade of changes in brain volume and cognition.

PubMed

Aljondi, Rowa; Szoeke, Cassandra; Steward, Chris; Yates, Paul; Desmond, Patricia

2018-05-09

Brain atrophy can occur several decades prior to onset of cognitive impairments. However, few longitudinal studies have examined the relationship between brain volume changes and cognition over a long follow-up period in healthy elderly women. In the present study we investigate the relationship between whole brain and hippocampal atrophy rates and longitudinal changes in cognition, including verbal episodic memory and executive function, in older women. We also examine whether baseline brain volume predicts subsequent changes in cognitive performance over a 10-year period. A total of 60 individuals from the population-based Women's Healthy Ageing Project with a mean age at baseline of 59 years underwent 3T MRI. Of these, 40 women completed follow-up cognitive assessments, 23 of whom had follow-up MRI scans. Linear regression analysis was used to examine the relationship between brain atrophy and changes in verbal episodic memory and executive function over a 10-year period. The results show that baseline measurements of frontal and temporal grey matter volumes predict changes in verbal episodic memory performance, whereas hippocampal volume at baseline is associated with changes in executive function performance over a 10-year period of follow-ups. In addition, higher whole brain and hippocampal atrophy rates are correlated with a decline in verbal episodic memory. These findings indicate that in addition to atrophy rate, smaller regional grey matter volumes even 10 years prior is associated with increased rates of cognitive decline. This study suggests useful neuroimaging biomarkers for the prediction of cognitive decline in healthy elderly women.

The Relationship between Functional Status and Judgment/Problem Solving Among Individuals with Dementia

PubMed Central

Mayo, Ann M.; Wallhagen, Margaret; Cooper, Bruce A.; Mehta, Kala; Ross, Leslie; Miller, Bruce

2012-01-01

Objective To determine the relationship between functional status (independent activities of daily living) and judgment/problem solving and the extent to which select demographic characteristics such as dementia subtype and cognitive measures may moderate that relationship in older adult individuals with dementia. Methods The National Alzheimer’s Coordinating Center Universal Data Set was accessed for a study sample of 3,855 individuals diagnosed with dementia. Primary variables included functional status, judgment/problem solving, and cognition. Results Functional status was related to judgment/problem solving (r= 0.66; p< .0005). Functional status and cognition jointly predicted 56% of the variance in judgment/problem solving (R-squared = .56, p <.0005). As cognition decreases, the prediction of poorer judgment/problem solving by functional status became stronger. Conclusions Among individuals with a diagnosis of dementia, declining functional status as well as declining cognition should raise concerns about judgment/problem solving. PMID:22786576

Cognitive decline in Parkinson disease

PubMed Central

Aarsland, Dag; Creese, Byron; Politis, Marios; Chaudhuri, K. Ray; ffytche, Dominic H.; Weintraub, Daniel; Ballard, Clive

2017-01-01

Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition — or even reversal to normal cognition — is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β42, a marker of comorbid Alzheimer disease (AD), predict future cognitive decline and dementia in PD. Emerging genetic evidence indicates that in addition to the APOE*ε4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms. Cognitive enhancing medications have some effect in PD dementia, but no convincing evidence that progression from MCI to dementia can be delayed or prevented is available, although cognitive training has shown promising results. PMID:28257128

Do Arterial Hemodynamic Parameters Predict Cognitive Decline Over a Period of 2 Years in Individuals Older Than 80 Years Living in Nursing Homes? The PARTAGE Study.

PubMed

Watfa, Ghassan; Benetos, Athanase; Kearney-Schwartz, Anna; Labat, Carlos; Gautier, Sylvie; Hanon, Olivier; Salvi, Paolo; Joly, Laure

2015-07-01

Several studies have highlighted a link between vascular alterations and cognitive decline. The PARTAGE study showed that arterial stiffness as evaluated by carotid-femoral pulse wave velocity (cfPWV) was associated with a more pronounced cognitive decline over a 1-year period in very old frail institutionalized individuals. The aim of the present analysis was to assess the role of hemodynamic parameters, such as blood pressure (BP), heart rate (HR), cfPWV, and central/peripheral pulse pressure amplification (PPA) on cognitive decline over 2 years in very old frail individuals. A total of 682 individuals from the PARTAGE study cohort, aged older than 80 years (mean age at inclusion: 87.5 ± 5.0 years) and living in French and Italian nursing homes, were analyzed. Mini-Mental State Examination (MMSE) score was assessed at baseline (BL) and at the end of the first and second year of follow-up (2y-FU). Those with a decrease in MMSE of 3 or more points between BL and 2y-FU were considered as "decliners." The cfPWV and PPA at baseline were assessed with an arterial tonometer. After adjustment for baseline MMSE, HR, body mass index, age, education level, and activities of daily living (ADLs), cfPWV was higher and PPA lower in "decliners" compared with "nondecliners," whereas BP did not differ between the 2 groups. Logistic multivariate analysis also revealed that high cfPWV, low PPA, high HR, and low ADLs were all determinants of MMSE decline. This 2-year longitudinal study in very old institutionalized individuals shows that arterial stiffness and high HR enabled us to identify subjects at higher risk of cognitive decline, whereas BP alone did not appear to have a significant predictive value. These findings highlight the contribution of vascular determinants in cognitive decline even in this very old population. Copyright © 2015 AMDA - The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Incident Subjective Cognitive Decline Does Not Predict Mortality in the Elderly--Results from the Longitudinal German Study on Ageing, Cognition, and Dementia (AgeCoDe).

PubMed

Roehr, Susanne; Luck, Tobias; Heser, Kathrin; Fuchs, Angela; Ernst, Annette; Wiese, Birgitt; Werle, Jochen; Bickel, Horst; Brettschneider, Christian; Koppara, Alexander; Pentzek, Michael; Lange, Carolin; Prokein, Jana; Weyerer, Siegfried; Mösch, Edelgard; König, Hans-Helmut; Maier, Wolfgang; Scherer, Martin; Jessen, Frank; Riedel-Heller, Steffi G

2016-01-01

Subjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer's disease (AD), which is associated with increased mortality. Only few studies, however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality. Data were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD. Among 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8-1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7-1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years (SD = 0.1) after onset. Incident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases.

Apolipoprotein E genotype does not moderate the associations of depressive symptoms, neuroticism and allostatic load with cognitive ability and cognitive aging in the Lothian Birth Cohort 1936

PubMed Central

Booth, Tom; Cox, Simon R.; Corley, Janie; Dykiert, Dominika; Redmond, Paul; Pattie, Alison; Taylor, Adele M.; Harris, Sarah E.; Starr, John M.; Deary, Ian J.

2018-01-01

Objectives In this replication-and-extension study, we tested whether depressive symptoms, neuroticism, and allostatic load (multisystem physiological dysregulation) were related to lower baseline cognitive ability and greater subsequent cognitive decline in older adults, and whether these relationships were moderated by the E4 allele of the apolipoprotein E (APOE) gene. We also tested whether allostatic load mediated the relationships between neuroticism and cognitive outcomes. Methods We used data from the Lothian Birth Cohort 1936 (n at Waves 1–3: 1,028 [M age = 69.5 y]; 820 [M duration since Wave 1 = 2.98 y]; 659 [M duration since Wave 1 = 6.74 y]). We fitted latent growth curve models of general cognitive ability (modeled using five cognitive tests) with groups of APOE E4 non-carriers and carriers. In separate models, depressive symptoms, neuroticism, and allostatic load predicted baseline cognitive ability and subsequent cognitive decline. In addition, models tested whether allostatic load mediated relationships between neuroticism and cognitive outcomes. Results Baseline cognitive ability had small-to-moderate negative associations with depressive symptoms (β range = -0.20 to -0.17), neuroticism (β range = -0.27 to -0.23), and allostatic load (β range = -0.11 to 0.09). Greater cognitive decline was linked to baseline allostatic load (β range = -0.98 to -0.83) and depressive symptoms (β range = -1.00 to -0.88). However, APOE E4 allele possession did not moderate the relationships of depressive symptoms, neuroticism and allostatic load with cognitive ability and cognitive decline. Additionally, the associations of neuroticism with cognitive ability and cognitive decline were not mediated through allostatic load. Conclusions Our results suggest that APOE E4 status does not moderate the relationships of depressive symptoms, neuroticism, and allostatic load with cognitive ability and cognitive decline in healthy older adults. The most notable positive finding in the current research was the strong association between allostatic load and cognitive decline. PMID:29451880

Ten-year change in plasma amyloid beta levels and late-life cognitive decline.

PubMed

Okereke, Olivia I; Xia, Weiming; Selkoe, Dennis J; Grodstein, Francine

2009-10-01

Plasma levels of amyloid beta peptide (Abeta) are potential biomarkers of early cognitive impairment and decline and of Alzheimer disease risk. To relate midlife plasma Abeta measures and 10-year change in plasma Abeta measures since midlife to late-life cognitive decline. Prospective study of a population-based sample. Academic research. Plasma Abeta40 and Abeta42 levels were measured in 481 Nurses' Health Study participants in late midlife (mean age, 63.6 years) and again 10 years later (mean age, 74.6 years). Cognitive testing also began 10 years after the initial blood draw. Participants completed 3 repeated telephone-based assessments (mean span, 4.1 years). Multivariable linear mixed-effects models were used to estimate relations of midlife plasma Abeta40 to Abeta42 ratios and Abeta42 levels to late-life cognitive decline, as well as relations of 10-year change in Abeta40 to Abeta42 ratios and Abeta42 levels to cognitive decline. The 3 primary outcomes were the Telephone Interview for Cognitive Status (TICS) findings, a global score averaging the results of all tests (TICS, immediate and delayed verbal recall, category fluency, and attention), and a verbal memory score averaging the results of 4 tests of verbal recall. Higher midlife plasma Abeta40 to Abeta42 ratios were associated with worse late-life decline on the global score (P = .04 for trend). Furthermore, increase in Abeta40 to Abeta42 ratios since midlife predicted greater decline in the global score (P = .03 for trend) and in the TICS (P = .02 for trend). There was no association of cognitive decline with midlife plasma Abeta42 levels alone or with change in Abeta42 levels since midlife. In this large community-dwelling sample, higher plasma Abeta40 to Abeta42 ratios in late midlife and increases in Abeta40 to Abeta42 ratios 10 years later were significantly associated with greater decline in global cognition at late life.

IQ as moderator of terminal decline in perceptual and motor speed, spatial, and verbal ability: Testing the cognitive reserve hypothesis in a population-based sample followed from age 70 until death.

PubMed

Thorvaldsson, Valgeir; Skoog, Ingmar; Johansson, Boo

2017-03-01

Terminal decline (TD) refers to acceleration in within-person cognitive decline prior to death. The cognitive reserve hypothesis postulates that individuals with higher IQ are able to better tolerate age-related increase in brain pathologies. On average, they will exhibit a later onset of TD, but once they start to decline, their trajectory is steeper relative to those with lower IQ. We tested these predictions using data from initially nondemented individuals (n = 179) in the H70-study repeatedly measured at ages 70, 75, 79, 81, 85, 88, 90, 92, 95, 97, 99, and 100, or until death, on cognitive tests of perceptual-and-motor-speed and spatial and verbal ability. We quantified IQ using the Raven's Coloured Progressive Matrices (RCPM) test administrated at age 70. We fitted random change point TD models to the data, within a Bayesian framework, conditioned on IQ, age of death, education, and sex. In line with predictions, we found that 1 additional standard deviation on the IQ scale was associated with a delay in onset of TD by 1.87 (95% highest density interval [HDI; 0.20, 4.08]) years on speed, 1.96 (95% HDI [0.15, 3.54]) years on verbal ability, but only 0.88 (95% HDI [-0.93, 3.49]) year on spatial ability. Higher IQ was associated with steeper rate of decline within the TD phase on measures of speed and verbal ability, whereas results on spatial ability were nonconclusive. Our findings provide partial support for the cognitive reserve hypothesis and demonstrate that IQ can be a significant moderator of cognitive change trajectories in old age. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Ethnoracial differences in brain structure change and cognitive change.

PubMed

Gavett, Brandon E; Fletcher, Evan; Harvey, Danielle; Farias, Sarah Tomaszewski; Olichney, John; Beckett, Laurel; DeCarli, Charles; Mungas, Dan

2018-04-12

The purpose of this study was to examine longitudinal associations between structural MRI and cognition in a diverse sample. Older adults (n = 444; Mage = 74.5)-121 African Americans, 212 Whites, and 111 Hispanics-underwent an average of 5.3 annual study visits. Approximately half were cognitively normal at baseline (global Clinical Dementia Rating M = 0.5). Of the patients with dementia, most (79%) were diagnosed with Alzheimer's disease (AD). MRI measures of gray matter volume (baseline and change), and hippocampal and white matter hyperintensity (WMH) volumes (baseline), were used to predict change in global cognition. Multilevel latent variable modeling was used to test the hypothesis that brain effects on cognitive change differed across ethnoracial groups. In a multivariable model, global gray matter change was the strongest predictor of cognitive decline in Whites and African Americans and specific temporal lobe change added incremental explanatory power in Whites. Baseline WMH volume was the strongest predictor of cognitive decline in Hispanics and made an incremental contribution in Whites. We found ethnoracial group differences in associations of brain variables with cognitive decline. The unique patterns in Whites appeared to suggest a greater influence of AD in this group. In contrast, cognitive decline in African Americans and Hispanics was most uniquely attributable to global gray matter change and baseline WMH, respectively. Brain changes underlying cognitive decline in older adults are heterogeneous and depend on fixed and modifiable risk factors that differ based on ethnicity and race. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

EEG correlates of visual short-term memory in older age vary with adult lifespan cognitive development.

PubMed

Wiegand, Iris; Lauritzen, Martin J; Osler, Merete; Mortensen, Erik Lykke; Rostrup, Egill; Rask, Lene; Richard, Nelly; Horwitz, Anna; Benedek, Krisztina; Vangkilde, Signe; Petersen, Anders

2018-02-01

Visual short-term memory (vSTM) is a cognitive resource that declines with age. This study investigated whether electroencephalography (EEG) correlates of vSTM vary with cognitive development over individuals' lifespan. We measured vSTM performance and EEG in a lateralized whole-report task in a healthy birth cohort, whose cognitive function (intelligence quotient) was assessed in youth and late-middle age. Higher vSTM capacity (K; measured by Bundesen's theory of visual attention) was associated with higher amplitudes of the contralateral delay activity (CDA) and the central positivity (CP). In addition, rightward hemifield asymmetry of vSTM (K λ ) was associated with lower CDA amplitudes. Furthermore, more severe cognitive decline from young adulthood to late-middle age predicted higher CDA amplitudes, and the relationship between K and the CDA was less reliable in individuals who show higher levels of cognitive decline compared to individuals with preserved abilities. By contrast, there was no significant effect of lifespan cognitive changes on the CP or the relationship between behavioral measures of vSTM and the CP. Neither the CDA, nor the CP, nor the relationships between K or K λ and the event-related potentials were predicted by individuals' current cognitive status. Together, our findings indicate complex age-related changes in processes underlying behavioral and EEG measures of vSTM and suggest that the K-CDA relationship might be a marker of cognitive lifespan trajectories. Copyright © 2017 Elsevier Inc. All rights reserved.

High-throughput, fully-automated volumetry for prediction of MMSE and CDR decline in mild cognitive impairment

PubMed Central

Kovacevic, Sanja; Rafii, Michael S.; Brewer, James B.

2008-01-01

Medial temporal lobe (MTL) atrophy is associated with increased risk for conversion to Alzheimer's disease (AD), but manual tracing techniques and even semi-automated techniques for volumetric assessment are not practical in the clinical setting. In addition, most studies that examined MTL atrophy in AD have focused only on the hippocampus. It is unknown the extent to which volumes of amygdala and temporal horn of the lateral ventricle predict subsequent clinical decline. This study examined whether measures of hippocampus, amygdala, and temporal horn volume predict clinical decline over the following 6-month period in patients with mild cognitive impairment (MCI). Fully-automated volume measurements were performed in 269 MCI patients. Baseline volumes of the hippocampus, amygdala, and temporal horn were evaluated as predictors of change in Mini-mental State Exam (MMSE) and Clinical Dementia Rating Sum of Boxes (CDR SB) over a 6-month interval. Fully-automated measurements of baseline hippocampus and amygdala volumes correlated with baseline delayed recall scores. Patients with smaller baseline volumes of the hippocampus and amygdala or larger baseline volumes of the temporal horn had more rapid subsequent clinical decline on MMSE and CDR SB. Fully-automated and rapid measurement of segmental MTL volumes may help clinicians predict clinical decline in MCI patients. PMID:19474571

Predicting functional decline in older emergency patients-the Safe Elderly Emergency Discharge (SEED) project.

PubMed

Lowthian, Judy A; Straney, Lahn D; Brand, Caroline A; Barker, Anna; Smit, P de Villiers; Newnham, Harvey; Hunter, Peter; Smith, Cathie; Cameron, Peter A

2017-03-01

to profile the trajectory of, and risk factors for, functional decline in older patients in the 30 days following Emergency Department (ED) discharge. prospective cohort study of community-dwelling patients aged ≥65 years, discharged home from a metropolitan Melbourne ED, 31 July 2012 to 30 November 2013. The primary outcome was functional decline, comprising either increased dependency in personal activities of daily living (ADL) or in skills required for living independently instrumental ADL (IADL), deterioration in cognitive function, nursing home admission or death. Univariate analyses were used to select risk factors and logistic regression models constructed to predict functional decline. at 30 days, 34.4% experienced functional decline; with 16.7% becoming more dependent in personal ADL, 17.5% more dependant in IADL and 18.4% suffering deterioration in cognitive function. Factors independently associated with decline were functional impairment prior to the visit in personal ADL (Odds Ratio [OR] 3.21, 95% confidence interval [CI] 2.26-4.53) or in IADL (OR 6.69, 95% CI 4.31-10.38). The relative odds were less for patients with moderately impaired cognition relative to those with normal cognition (OR 0.38, 95% CI 0.19-0.75). There was a 68% decline in the relative odds of functional decline for those with any impairment in IADL who used an aid for mobility (OR 0.32, 95% CI 0.14-0.7). older people with pre-existing ADL impairment were at high risk of functional decline in the 30 days following ED presentation. This effect was largely mitigated for those who used a mobility aid. Early intervention with functional assessments and appropriate implementation of support services and mobility aids could reduce functional decline after discharge. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

Auditory Processing of Older Adults with Probable Mild Cognitive Impairment

ERIC Educational Resources Information Center

Edwards, Jerri D.; Lister, Jennifer J.; Elias, Maya N.; Tetlow, Amber M.; Sardina, Angela L.; Sadeq, Nasreen A.; Brandino, Amanda D.; Bush, Aryn L. Harrison

2017-01-01

Purpose: Studies suggest that deficits in auditory processing predict cognitive decline and dementia, but those studies included limited measures of auditory processing. The purpose of this study was to compare older adults with and without probable mild cognitive impairment (MCI) across two domains of auditory processing (auditory performance in…

Predicting Reading Disability: Early Cognitive Risk and Protective Factors

ERIC Educational Resources Information Center

Eklund, Kenneth Mikael; Torppa, Minna; Lyytinen, Heikki

2013-01-01

This longitudinal study examined early cognitive risk and protective factors for Grade 2 reading disability (RD). We first examined the reading outcome of 198 children in four developmental cognitive subgroups that were identified in our previous analysis: dysfluent trajectory, declining trajectory, unexpected trajectory and typical trajectory. We…

Effects of age on a real-world What-Where-When memory task

PubMed Central

Mazurek, Adèle; Bhoopathy, Raja Meenakshi; Read, Jenny C. A.; Gallagher, Peter; Smulders, Tom V.

2015-01-01

Many cognitive abilities decline with aging, making it difficult to detect pathological changes against a background of natural changes in cognition. Most of the tests to assess cognitive decline are artificial tasks that have little resemblance to the problems faced by people in everyday life. This means both that people may have little practice doing such tasks (potentially contributing to the decline in performance) and that the tasks may not be good predictors of real-world cognitive problems. In this study, we test the performance of young people (18–25 years) and older people (60+-year-olds) on a novel, more ecologically valid test of episodic memory: the real-world What-Where-When (WWW) memory test. We also compare them on a battery of other cognitive tests, including working memory, psychomotor speed, executive function, and episodic memory. Older people show the expected age-related declines on the test battery. In the WWW memory task, older people were more likely to fail to remember any WWW combination than younger people were, although they did not significantly differ in their overall WWW score due to some older people performing as well as or better than most younger people. WWW memory performance was significantly predicted by other measures of episodic memory, such as the single-trial learning and long-term retention in the Rey Auditory Verbal Learning task and Combined Object Location Memory in the Object Relocation task. Self-reported memory complaints also predicted performance on the WWW task. These findings confirm that our real-world WWW memory task is a valid measure of episodic memory, with high ecological validity, which may be useful as a predictor of everyday memory abilities. The task will require a bit more development to improve its sensitivity to cognitive declines in aging and to potentially distinguish between mentally healthy older adults and those with early signs of cognitive pathologies. PMID:26042030

BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention

PubMed Central

Boots, Elizabeth A.; Schultz, Stephanie A.; Clark, Lindsay R.; Racine, Annie M.; Darst, Burcu F.; Koscik, Rebecca L.; Carlsson, Cynthia M.; Gallagher, Catherine L.; Hogan, Kirk J.; Bendlin, Barbara B.; Asthana, Sanjay; Sager, Mark A.; Hermann, Bruce P.; Christian, Bradley T.; Dubal, Dena B.; Engelman, Corinne D.; Johnson, Sterling C.

2017-01-01

Objective: To examine the influence of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on longitudinal cognitive trajectories in a large, cognitively healthy cohort enriched for Alzheimer disease (AD) risk and to understand whether β-amyloid (Aβ) burden plays a moderating role in this relationship. Methods: One thousand twenty-three adults (baseline age 54.94 ± 6.41 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention underwent BDNF genotyping and cognitive assessment at up to 5 time points (average follow-up 6.92 ± 3.22 years). A subset (n = 140) underwent 11C-Pittsburgh compound B (PiB) scanning. Covariate-adjusted mixed-effects regression models were used to elucidate the effect of BDNF on cognitive trajectories in 4 cognitive domains, including verbal learning and memory, speed and flexibility, working memory, and immediate memory. Secondary mixed-effects regression models were conducted to examine whether Aβ burden, indexed by composite PiB load, modified any observed BDNF-related cognitive trajectories. Results: Compared to BDNF Val/Val homozygotes, Met carriers showed steeper decline in verbal learning and memory (p = 0.002) and speed and flexibility (p = 0.017). In addition, Aβ burden moderated the relationship between BDNF and verbal learning and memory such that Met carriers with greater Aβ burden showed even steeper cognitive decline (p = 0.033). Conclusions: In a middle-aged cohort with AD risk, carriage of the BDNF Met allele was associated with steeper decline in episodic memory and executive function. This decline was exacerbated by greater Aβ burden. These results suggest that the BDNF Val66Met polymorphism may play an important role in cognitive decline and could be considered as a target for novel AD therapeutics. PMID:28468845

BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention.

PubMed

Boots, Elizabeth A; Schultz, Stephanie A; Clark, Lindsay R; Racine, Annie M; Darst, Burcu F; Koscik, Rebecca L; Carlsson, Cynthia M; Gallagher, Catherine L; Hogan, Kirk J; Bendlin, Barbara B; Asthana, Sanjay; Sager, Mark A; Hermann, Bruce P; Christian, Bradley T; Dubal, Dena B; Engelman, Corinne D; Johnson, Sterling C; Okonkwo, Ozioma C

2017-05-30

To examine the influence of the brain-derived neurotrophic factor ( BDNF ) Val66Met polymorphism on longitudinal cognitive trajectories in a large, cognitively healthy cohort enriched for Alzheimer disease (AD) risk and to understand whether β-amyloid (Aβ) burden plays a moderating role in this relationship. One thousand twenty-three adults (baseline age 54.94 ± 6.41 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention underwent BDNF genotyping and cognitive assessment at up to 5 time points (average follow-up 6.92 ± 3.22 years). A subset (n = 140) underwent 11 C-Pittsburgh compound B (PiB) scanning. Covariate-adjusted mixed-effects regression models were used to elucidate the effect of BDNF on cognitive trajectories in 4 cognitive domains, including verbal learning and memory, speed and flexibility, working memory, and immediate memory. Secondary mixed-effects regression models were conducted to examine whether Aβ burden, indexed by composite PiB load, modified any observed BDNF -related cognitive trajectories. Compared to BDNF Val/Val homozygotes, Met carriers showed steeper decline in verbal learning and memory ( p = 0.002) and speed and flexibility ( p = 0.017). In addition, Aβ burden moderated the relationship between BDNF and verbal learning and memory such that Met carriers with greater Aβ burden showed even steeper cognitive decline ( p = 0.033). In a middle-aged cohort with AD risk, carriage of the BDNF Met allele was associated with steeper decline in episodic memory and executive function. This decline was exacerbated by greater Aβ burden. These results suggest that the BDNF Val66Met polymorphism may play an important role in cognitive decline and could be considered as a target for novel AD therapeutics. © 2017 American Academy of Neurology.

Idea density measured in late life predicts subsequent cognitive trajectories: implications for the measurement of cognitive reserve.

PubMed

Farias, Sarah Tomaszewski; Chand, Vineeta; Bonnici, Lisa; Baynes, Kathleen; Harvey, Danielle; Mungas, Dan; Simon, Christa; Reed, Bruce

2012-11-01

The Nun Study showed that lower linguistic ability in young adulthood, measured by idea density (ID), increased the risk of dementia in late life. The present study examined whether ID measured in late life continues to predict the trajectory of cognitive change. ID was measured in 81 older adults who were followed longitudinally for an average of 4.3 years. Changes in global cognition and 4 specific neuropsychological domains (episodic memory, semantic memory, spatial abilities, and executive function) were examined as outcomes. Separate random effects models tested the effect of ID on longitudinal change in outcomes, adjusted for age and education. Lower ID was associated with greater subsequent decline in global cognition, semantic memory, episodic memory, and spatial abilities. When analysis was restricted to only participants without dementia at the time ID was collected, results were similar. Linguistic ability in young adulthood, as measured by ID, has been previously proposed as an index of neurocognitive development and/or cognitive reserve. The present study provides evidence that even when ID is measured in old age, it continues to be associated with subsequent cognitive decline and as such may continue to provide a marker of cognitive reserve.

The Effects of Sleep Deprivation on Item and Associative Recognition Memory

ERIC Educational Resources Information Center

Ratcliff, Roger; Van Dongen, Hans P. A.

2018-01-01

Sleep deprivation adversely affects the ability to perform cognitive tasks, but theories range from predicting an overall decline in cognitive functioning because of reduced stability in attentional networks to specific deficits in various cognitive domains or processes. We measured the effects of sleep deprivation on two memory tasks, item…

Does left ventricular hypertrophy affect cognition and brain structural integrity in type 2 diabetes? Study design and rationale of the Diabetes and Dementia (D2) study.

PubMed

Patel, Sheila K; Restrepo, Carolina; Werden, Emilio; Churilov, Leonid; Ekinci, Elif I; Srivastava, Piyush M; Ramchand, Jay; Wai, Bryan; Chambers, Brian; O'Callaghan, Christopher J; Darby, David; Hachinski, Vladimir; Cumming, Toby; Donnan, Geoff; Burrell, Louise M; Brodtmann, Amy

2017-04-07

Cognitive impairment is common in type 2 diabetes mellitus, and there is a strong association between type 2 diabetes and Alzheimer's disease. However, we do not know which type 2 diabetes patients will dement or which biomarkers predict cognitive decline. Left ventricular hypertrophy (LVH) is potentially such a marker. LVH is highly prevalent in type 2 diabetes and is a strong, independent predictor of cardiovascular events. To date, no studies have investigated the association between LVH and cognitive decline in type 2 diabetes. The Diabetes and Dementia (D2) study is designed to establish whether patients with type 2 diabetes and LVH have increased rates of brain atrophy and cognitive decline. The D2 study is a single centre, observational, longitudinal case control study that will follow 168 adult patients aged >50 years with type 2 diabetes: 50% with LVH (case) and 50% without LVH (control). It will assess change in cardiovascular risk, brain imaging and neuropsychological testing between two time-points, baseline (0 months) and 24 months. The primary outcome is brain volume change at 24 months. The co-primary outcome is the presence of cognitive decline at 24 months. The secondary outcome is change in left ventricular mass associated with brain atrophy and cognitive decline at 24 months. The D2 study will test the hypothesis that patients with type 2 diabetes and LVH will exhibit greater brain atrophy than those without LVH. An understanding of whether LVH contributes to cognitive decline, and in which patients, will allow us to identify patients at particular risk. Australian New Zealand Clinical Trials Registry ( ACTRN12616000546459 ), date registered, 28/04/2016.

Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease

PubMed Central

Small, Gary W.; Ercoli, Linda M.; Silverman, Daniel H. S.; Huang, S.-C.; Komo, Scott; Bookheimer, Susan Y.; Lavretsky, Helen; Miller, Karen; Siddarth, Prabha; Rasgon, Natalie L.; Mazziotta, John C.; Saxena, Sanjaya; Wu, H. M.; Mega, Michael S.; Cummings, Jeffrey L.; Saunders, Ann M.; Pericak-Vance, Margaret A.; Roses, Allen D.; Barrio, Jorge R.; Phelps, Michael E.

2000-01-01

The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by using positron emission tomography in middle-aged and older nondemented persons with normal memory performance. A single copy of the APOE-4 allele was associated with lowered inferior parietal, lateral temporal, and posterior cingulate metabolism, which predicted cognitive decline after 2 years of longitudinal follow-up. For the 20 nondemented subjects followed longitudinally, memory performance scores did not decline significantly, but cortical metabolic rates did. In APOE-4 carriers, a 4% left posterior cingulate metabolic decline was observed, and inferior parietal and lateral temporal regions demonstrated the greatest magnitude (5%) of metabolic decline after 2 years. These results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments. PMID:10811879

Subjective Cognitive Decline, Objective Cognition, and Depression in Older Hispanics Screened for Memory Impairment.

PubMed

Zlatar, Zvinka Z; Muniz, Martha C; Espinoza, Sarah G; Gratianne, Roberto; Gollan, Tamar H; Galasko, Douglas; Salmon, David P

2018-01-01

Subjective cognitive decline (SCD) is common in older adults and may be an early marker of future cognitive decline. Research suggest that SCD is more closely related to concurrent symptoms of depression than to objective cognitive performance in non-Hispanic Whites, but it is unknown whether the associations of SCD, cognition, and depression manifest differently in Hispanic older adults. We examined if SCD is associated with objective cognitive performance or with depression symptoms in 145 Hispanic individuals ages 60 or older referred by community health clinics for screening of cognitive complaints. All participants lived near the U.S.-Mexico border, spoke Spanish only, or were Spanish-English bilingual. Memory-only and global cognitive composites were created from scores on Spanish versions of several neuropsychological tests. The Geriatric Depression Scale (GDS) and a five-item SCD questionnaire developed by our group were also completed. Multiple regression analyses showed no significant associations between SCD and memory or global cognitive composite scores after adjusting for age, sex, education, and GDS score. In contrast, there was a significant association between GDS and SCD after adjusting for age, sex, education, global and memory composite scores. Findings suggest that SCD does not accurately reflect current cognitive status in older Hispanics who present to their primary care physician with cognitive complaints. Clinicians should interpret SCD in this population within the context of information about symptoms of depression. Longitudinal research is needed in older Hispanics to better characterize SCD in this population and to determine if it can predict future cognitive decline.

Early Recognition of Chronic Traumatic Encephalopathy Through FDDNP PET Imaging

DTIC Science & Technology

2017-10-01

imaging correlates with, and/or can predict, decline in cognitive function in those exposed to cumulative head trauma. 15. SUBJECT TERMS Traumatic...sheet-containing brain amyloid neuroaggregates. This project will examine whether FDDNP PET imaging correlates with, and/or can predict, decline in...with age. Table 1 - Regional uptake in ROIs with Age, Years of Pro Fighting, and Number of Pro Fights (Pearson’s correlations ; ns – non significant

Selective attrition and intraindividual variability in response time moderate cognitive change.

PubMed

Yao, Christie; Stawski, Robert S; Hultsch, David F; MacDonald, Stuart W S

2016-01-01

Selection of a developmental time metric is useful for understanding causal processes that underlie aging-related cognitive change and for the identification of potential moderators of cognitive decline. Building on research suggesting that time to attrition is a metric sensitive to non-normative influences of aging (e.g., subclinical health conditions), we examined reason for attrition and intraindividual variability (IIV) in reaction time as predictors of cognitive performance. Three hundred and four community dwelling older adults (64-92 years) completed annual assessments in a longitudinal study. IIV was calculated from baseline performance on reaction time tasks. Multilevel models were fit to examine patterns and predictors of cognitive change. We show that time to attrition was associated with cognitive decline. Greater IIV was associated with declines on executive functioning and episodic memory measures. Attrition due to personal health reasons was also associated with decreased executive functioning compared to that of individuals who remained in the study. These findings suggest that time to attrition is a useful metric for representing cognitive change, and reason for attrition and IIV are predictive of non-normative influences that may underlie instances of cognitive loss in older adults.

Selective Attrition and Intraindividual Variability in Response Time Moderate Cognitive Change

PubMed Central

Yao, Christie; Stawski, Robert S.; Hultsch, David F.; MacDonald, Stuart W.S.

2016-01-01

Objectives Selection of a developmental time metric is useful for understanding causal processes that underlie aging-related cognitive change, and for the identification of potential moderators of cognitive decline. Building on research suggesting that time to attrition is a metric sensitive to non-normative influences of aging (e.g., subclinical health conditions), we examined reason for attrition and intraindividual variability (IIV) in reaction time as predictors of cognitive performance. Method Three-hundred and four community dwelling older adults (64-92 years) completed annual assessments in a longitudinal study. IIV was calculated from baseline performance on reaction time tasks. Multilevel models were fit to examine patterns and predictors of cognitive change. Results We show that time to attrition was associated with cognitive decline. Greater IIV was associated with declines on executive functioning and episodic memory measures. Attrition due to personal health reasons was also associated with decreased executive functioning compared to individuals who remained in study. Discussion These findings suggest that time to attrition is a useful metric for representing cognitive change, and reason for attrition and IIV are predictive of non-normative influences that may underlie instances of cognitive loss in older adults. PMID:26647008

Including persistency of impairment in mild cognitive impairment classification enhances prediction of 5-year decline.

PubMed

Vandermorris, Susan; Hultsch, David F; Hunter, Michael A; MacDonald, Stuart W S; Strauss, Esther

2011-02-01

Although older adults with Mild Cognitive Impairment (MCI) show elevated rates of conversion to dementia as a group, heterogeneity of outcomes is common at the individual level. Using data from a prospective 5-year longitudinal investigation of cognitive change in healthy older adults (N = 262, aged 64-92 years), this study addressed limitations in contemporary MCI identification procedures which rely on single occasion assessment ("Single-Assessment [SA] MCI") by evaluating an alternate operational definition of MCI requiring evidence of persistent cognitive impairment over multiple-testing sessions ("Multiple-Assessment [MA] MCI"). As hypothesized, prevalence of SA-MCI exceeded that of MA-MCI. Further, the MA-MCI groups showed lower baseline cognitive and functional performance and steeper cognitive decline compared with Control and SA-MCI group. Results are discussed with reference to retest effects and clinical implications.

Openness as a buffer against cognitive decline: The Openness-Fluid-Crystallized-Intelligence (OFCI) model applied to late adulthood.

PubMed

Ziegler, Matthias; Cengia, Anja; Mussel, Patrick; Gerstorf, Denis

2015-09-01

Explaining cognitive decline in late adulthood is a major research area. Models using personality traits as possible influential variables are rare. This study tested assumptions based on an adapted version of the Openness-Fluid-Crystallized-Intelligence (OFCI) model. The OFCI model adapted to late adulthood predicts that openness is related to the decline in fluid reasoning (Gf) through environmental enrichment. Gf should be related to the development of comprehension knowledge (Gc; investment theory). It was also assumed that Gf predicts changes in openness as suggested by the environmental success hypothesis. Finally, the OFCI model proposes that openness has an indirect influence on the decline in Gc through its effect on Gf (mediation hypothesis). Using data from the Berlin Aging Study (N = 516, 70-103 years at T1), these predictions were tested using latent change score and latent growth curve models with indicators of each trait. The current findings and prior research support environmental enrichment and success, investment theory, and partially the mediation hypotheses. Based on a summary of all findings, the OFCI model for late adulthood is suggested. (c) 2015 APA, all rights reserved).

Mild cognitive impairment as a risk factor for Parkinson's disease dementia.

PubMed

Hoogland, Jeroen; Boel, Judith A; de Bie, Rob M A; Geskus, Ronald B; Schmand, Ben A; Dalrymple-Alford, John C; Marras, Connie; Adler, Charles H; Goldman, Jennifer G; Tröster, Alexander I; Burn, David J; Litvan, Irene; Geurtsen, Gert J

2017-07-01

The International Parkinson and Movement Disorder Society criteria for mild cognitive impairment in PD were recently formulated. The aim of this international study was to evaluate the predictive validity of the comprehensive (level II) version of these criteria by assessment of their contribution to the hazard of PD dementia. Individual patient data were selected from four separate studies on cognition in PD that provided information on demographics, motor examination, depression, neuropsychological examination suitable for application of level II criteria, and longitudinal follow-up for conversion to dementia. Survival analysis evaluated the predictive value of level II criteria for cognitive decline toward dementia as expressed by the relative hazard of dementia. A total of 467 patients were included. The analyses showed a clear contribution of impairment according to level II mild cognitive impairment criteria, age, and severity of PD motor symptoms to the hazard of dementia. There was a trend of increasing hazard of dementia with declining neuropsychological performance. This is the first large international study evaluating the predictive validity of level II mild cognitive impairment criteria for PD. The results showed a clear and unique contribution of classification according to level II criteria to the hazard of PD dementia. This finding supports their predictive validity and shows that they contribute important new information on the hazard of dementia, beyond known demographic and PD-specific factors of influence. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Ventral striatal volume is associated with cognitive decline in older people: a population based MR-study

PubMed Central

de Jong, L.W.; Wang, Y.; White, L.R.; Yu, B.; van Buchem, M.A.; Launer, L.J.

2012-01-01

Striatal degeneration may contribute to cognitive impairment in older people. Here, we examine the relation of degeneration of the striatum and substructures to cognitive decline and dementia in subjects with a wide range of cognitive function. Data are from the prospective community-based Honolulu Asia Aging Study of Japanese American men born 1900–1919. Brain MRI (1.5T) was acquired on a stratified sub-sample (n=477) that included four groups defined by cognitive status relative to the scan date: subjects without dementia (n=347), subjects identified as demented 2–3 years prior to brain scanning (n=30), at the time of scanning (n=58), and 3–5 years after scanning (n=42). Volumes of the striatum, including the accumbens, putamen, and caudate nucleus were automatically estimated from T1 MR images. Global cognitive function was measured with the CASI, at four exams spanning an 8 year interval. Trajectories of cognitive decline were estimated for each quartile of striatal volume using mixed models, controlling for demographic variables, measures of cerebro-vascular damage, global brain atrophy, and hippocampal volume. Diagnosis of dementia before, during, and after brain scanning was associated with smaller volumes of n. accumbens and putamen, but not with caudate nucleus volume. Subjects in the lowest quartile of n. accumbens, both in the total sample and in the subjects not diagnosed with dementia during the study, had a significantly (p < 0.0001) steeper decline in cognitive performance compared to those in the highest quartile. In conclusion, volumes of the n. accumbens and putamen are closely associated with the occurrence of dementia and n. accumbens volume predicts cognitive decline in older people. These associations were found independent of the magnitude of other pivotal markers of cognitive decline, i.e. cerebro-vascular damage and hippocampal volume. The present study suggests a role for the ventral striatum in the development of clinical dementia. PMID:21075480

Destination memory and cognitive theory of mind in normal ageing.

PubMed

El Haj, Mohamad; Raffard, Stéphane; Gély-Nargeot, Marie-Christine

2016-01-01

Destination memory is the ability to remember the destination to which a piece of information has been addressed (e.g., "Did I tell you about the promotion?"). This ability is found to be impaired in normal ageing. Our work aimed to link this deterioration to the decline in theory of mind. Forty younger adults (M age = 23.13 years, SD = 4.00) and 36 older adults (M age = 69.53 years, SD = 8.93) performed a destination memory task. They also performed the False-belief test addressing cognitive theory of mind and the Reading the mind in the eyes test addressing affective theory of mind. Results showed significant deterioration in destination memory, cognitive theory of mind and affective theory of mind in the older adults. The older adults' performance on destination memory was significantly correlated with and predicted by their performance on cognitive theory of mind. Difficulties in the ability to interpret and predict others' mental states are related to destination memory decline in older adults.

Association of subjective memory complaints with subsequent cognitive decline in community-dwelling elderly individuals with baseline cognitive impairment.

PubMed

Schofield, P W; Marder, K; Dooneief, G; Jacobs, D M; Sano, M; Stern, Y

1997-05-01

The validity of subjective memory complaints has been questioned by clinical studies that have shown little relationship between memory complaints and objective memory performance. These studies often have been cross-sectional in design, have excluded individuals with cognitive impairment, or have lacked a comparison group. The authors conducted a study that attempted to avoid these limitations. Memory complaints of 364 nondemented, community-dwelling elderly individuals were recorded as present or absent at the baseline evaluation. After 1 year, 169 subjects were reevaluated. Standardized neurologic and neuropsychological evaluations were used at each assessment to classify subjects as normal or cognitively impaired. At baseline, 31% of the normal subjects and 47% of those with cognitive impairment had memory complaints. Subjects with memory complaints had higher Hamilton depression scale scores than subjects without memory complaints but equivalent scores on a measure of total recall. At follow-up, multivariate analyses showed that subjects with baseline memory complaints had significantly greater decline in memory and cognition than subjects without memory complaints. Secondary analyses showed this effect to be confined to subjects with baseline cognitive impairment. Memory complaints may lack validity in subjects with normal cognition, but in nondemented individuals with cognitive impairment, memory complaints may predict subsequent cognitive decline.

Cognitive decline and quality of life in incident Parkinson's disease: The role of attention.

PubMed

Lawson, Rachael A; Yarnall, Alison J; Duncan, Gordon W; Breen, David P; Khoo, Tien K; Williams-Gray, Caroline H; Barker, Roger A; Collerton, Daniel; Taylor, John-Paul; Burn, David J

2016-06-01

Parkinson's disease dementia (PDD) is associated with poorer quality of life (QoL). Prior to the onset of PDD, many patients experience progressive cognitive impairment. There is a paucity of longitudinal studies investigating the effects of cognitive decline on QoL. This study aimed to determine the longitudinal impact of cognitive change on QoL in an incident PD cohort. Recently diagnosed patients with PD (n = 212) completed a schedule of neuropsychological assessments and QoL measures; these were repeated after 18 (n = 190) and 36 months (n = 158). Mild cognitive impairment (PD-MCI) was classified with reference to the Movement Disorder Society criteria. Principal component analysis was used to reduce 10 neuropsychological tests to three cognitive factors: attention, memory/executive function, and global cognition. Baseline PD-MCI was a significant contributor to QoL (β = 0.2, p < 0.01). For those subjects (9%) who developed dementia, cognitive function had a much greater impact on QoL (β = 10.3, p < 0.05). Multivariate modelling showed attentional deficits had the strongest predictive power (β = -2.3, p < 0.01); brief global tests only modestly predicted decline in QoL (β = -0.4, p < 0.01). PD-MCI was associated with poorer QoL over three years follow up. Cognitive impairment had a greater impact on QoL in individuals who developed dementia over follow-up. Impaired attention was a significant determinant of QoL in PD. Interventions which improve concentration and attention in those with PD could potentially improve QoL. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Physical Fitness and Aortic Stiffness Explain the Reduced Cognitive Performance Associated with Increasing Age in Older People.

PubMed

Kennedy, Greg; Meyer, Denny; Hardman, Roy J; Macpherson, Helen; Scholey, Andrew B; Pipingas, Andrew

2018-01-01

Greater physical fitness is associated with reduced rates of cognitive decline in older people; however, the mechanisms by which this occurs are still unclear. One potential mechanism is aortic stiffness, with increased stiffness resulting in higher pulsatile pressures reaching the brain and possibly causing progressive micro-damage. There is limited evidence that those who regularly exercise may have lower aortic stiffness. To investigate whether greater fitness and lower aortic stiffness predict better cognitive performance in older people and, if so, whether aortic stiffness mediates the relationship between fitness and cognition. Residents of independent living facilities, aged 60-90, participated in the study (N = 102). Primary measures included a computerized cognitive assessment battery, pulse wave velocity analysis to measure aortic stiffness, and the Six-Minute Walk test to assess fitness. Based on hierarchical regression analyses, structural equation modelling was used to test the mediation hypothesis. Both fitness and aortic stiffness independently predicted Spatial Working Memory (SWM) performance, however no mediating relationship was found. Additionally, the derived structural equation model shows that, in conjunction with BMI and sex, fitness and aortic stiffness explain 33% of the overall variation in SWM, with age no longer directly predicting any variation. Greater fitness and lower aortic stiffness both independently predict better SWM in older people. The strong effect of age on cognitive performance is totally mediated by fitness and aortic stiffness. This suggests that addressing both physical fitness and aortic stiffness may be important to reduce the rate of age associated cognitive decline.

[Functional impairment associated with cognitive impairment in hospitalised elderly].

PubMed

Ocampo-Chaparro, José Mauricio; Mosquera-Jiménez, José Ignacio; Davis, Annabelle S; Reyes-Ortiz, Carlos A

The aim of this study was to analyse the effect of cognitive impairment on functional decline in hospitalised patients aged ≥60 years. Measurements at admission included demographic data, Charlson's comorbidity index, and cognitive impairment (according to education level). Data were also collected on hospital length of stay, depression, and delirium developed during hospitalisation. The outcome, Barthel Index (BI), was measured at admission, discharge, and 1-month post-discharge. Patients with BI≤75 at admission (n=54) or with a missing BI value were excluded (n=1). Multivariate logistic regression analyses were conducted to explore predictive factors with functional decline (BI≤75) from admission to discharge, and 1-month later. Of the 133 patients included, 24.8% and 19.6% had a BI≤75 at discharge and at 1-month, respectively. Compared with men, women had more than double risk for functional decline at discharge and 1-month (P<.05). Compared with those without delirium and without cognitive impairment, those with delirium and cognitive impairment had an increased risk for functional decline (BI≤75) at discharge (OR 5.15, 95% CI; 1.94-13.67), and at 1-month (OR 6.26, 95% CI; 2.30-17.03). Similarly, those with comorbidity (≥2) had increased functional decline at discharge (OR 2.36, 95% CI; 1.14-4.87), and at 1-month after discharge (OR 2.71, 95% CI; 1.25-5.89). Delirium during hospitalisation, together with cognitive impairment on admission, was a strong predictor of functional decline. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Idea Density Measured in Late Life Predicts Subsequent Cognitive Trajectories: Implications for the Measurement of Cognitive Reserve

PubMed Central

Chand, Vineeta; Bonnici, Lisa; Baynes, Kathleen; Harvey, Danielle; Mungas, Dan; Simon, Christa; Reed, Bruce

2012-01-01

Objective. The Nun Study showed that lower linguistic ability in young adulthood, measured by idea density (ID), increased the risk of dementia in late life. The present study examined whether ID measured in late life continues to predict the trajectory of cognitive change. Method. ID was measured in 81 older adults who were followed longitudinally for an average of 4.3 years. Changes in global cognition and 4 specific neuropsychological domains (episodic memory, semantic memory, spatial abilities, and executive function) were examined as outcomes. Separate random effects models tested the effect of ID on longitudinal change in outcomes, adjusted for age and education. Results. Lower ID was associated with greater subsequent decline in global cognition, semantic memory, episodic memory, and spatial abilities. When analysis was restricted to only participants without dementia at the time ID was collected, results were similar. Discussion. Linguistic ability in young adulthood, as measured by ID, has been previously proposed as an index of neurocognitive development and/or cognitive reserve. The present study provides evidence that even when ID is measured in old age, it continues to be associated with subsequent cognitive decline and as such may continue to provide a marker of cognitive reserve. PMID:22357642

Mothers' depressive symptoms and children's cognitive and social agency: Predicting first-grade cognitive functioning.

PubMed

Yan, Ni; Dix, Theodore

2016-08-01

Using data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development (N = 1,364), the present study supports an agentic perspective; it demonstrates that mothers' depressive symptoms in infancy predict children's poor first-grade cognitive functioning because depressive symptoms predict children's low social and cognitive agency-low motivation to initiate social interaction and actively engage in activities. When mothers' depressive symptoms were high in infancy, children displayed poor first-grade cognitive functioning due to (a) tendencies to become socially withdrawn by 36 months and low in mastery motivation by 54 months and (b) tendencies for children's low agency to predict declines in mothers' sensitivity and cognitive stimulation. Findings suggest that mothers' depressive symptoms undermine cognitive development through bidirectional processes centered on children's low motivation to engage in social interaction and initiate and persist at everyday tasks. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Plasma apolipoprotein levels are associated with cognitive status and decline in a community cohort of older individuals.

PubMed

Song, Fei; Poljak, Anne; Crawford, John; Kochan, Nicole A; Wen, Wei; Cameron, Barbara; Lux, Ora; Brodaty, Henry; Mather, Karen; Smythe, George A; Sachdev, Perminder S

2012-01-01

Apolipoproteins have recently been implicated in the etiology of Alzheimer's disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort. 664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique. At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years. Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals.

Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals

PubMed Central

Song, Fei; Poljak, Anne; Crawford, John; Kochan, Nicole A.; Wen, Wei; Cameron, Barbara; Lux, Ora; Brodaty, Henry; Mather, Karen; Smythe, George A.; Sachdev, Perminder S.

2012-01-01

Objectives Apolipoproteins have recently been implicated in the etiology of Alzheimer’s disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort. Methods 664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique. Results At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years. Conclusions Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals. PMID:22701550

Decomposing the relationship between cognitive functioning and self-referent memory beliefs in older adulthood: What’s memory got to do with it?

PubMed Central

Payne, Brennan R.; Gross, Alden L.; Hill, Patrick L.; Parisi, Jeanine M.; Rebok, George W.; Stine-Morrow, Elizabeth A. L.

2018-01-01

With advancing age, episodic memory performance shows marked declines along with concurrent reports of lower subjective memory beliefs. Given that normative age-related declines in episodic memory co-occur with declines in other cognitive domains, we examined the relationship between memory beliefs and multiple domains of cognitive functioning. Confirmatory bi-factor structural equation models were used to parse the shared and independent variance among factors representing episodic memory, psychomotor speed, and executive reasoning in one large cohort study (Senior Odyssey, N = 462), and replicated using another large cohort of healthy older adults (ACTIVE, N = 2,802). Accounting for a general fluid cognitive functioning factor (comprised of the shared variance among measures of episodic memory, speed, and reasoning) attenuated the relationship between objective memory performance and subjective memory beliefs in both samples. Moreover, the general cognitive functioning factor was the strongest predictor of memory beliefs in both samples. These findings are consistent with the notion that dispositional memory beliefs may reflect perceptions of cognition more broadly. This may be one reason why memory beliefs have broad predictive validity for interventions that target fluid cognitive ability. PMID:27685541

Decomposing the relationship between cognitive functioning and self-referent memory beliefs in older adulthood: what's memory got to do with it?

PubMed

Payne, Brennan R; Gross, Alden L; Hill, Patrick L; Parisi, Jeanine M; Rebok, George W; Stine-Morrow, Elizabeth A L

2017-07-01

With advancing age, episodic memory performance shows marked declines along with concurrent reports of lower subjective memory beliefs. Given that normative age-related declines in episodic memory co-occur with declines in other cognitive domains, we examined the relationship between memory beliefs and multiple domains of cognitive functioning. Confirmatory bi-factor structural equation models were used to parse the shared and independent variance among factors representing episodic memory, psychomotor speed, and executive reasoning in one large cohort study (Senior Odyssey, N = 462), and replicated using another large cohort of healthy older adults (ACTIVE, N = 2802). Accounting for a general fluid cognitive functioning factor (comprised of the shared variance among measures of episodic memory, speed, and reasoning) attenuated the relationship between objective memory performance and subjective memory beliefs in both samples. Moreover, the general cognitive functioning factor was the strongest predictor of memory beliefs in both samples. These findings are consistent with the notion that dispositional memory beliefs may reflect perceptions of cognition more broadly. This may be one reason why memory beliefs have broad predictive validity for interventions that target fluid cognitive ability.

The Relation of Education and Income to Cognitive Function among Professional Women

PubMed Central

Lee, Sunmin; Buring, Julie E.; Cook, Nancy R.; Grodstein, Francine

2005-01-01

We investigated the relation of educational attainment and annual household income to cognitive function and cognitive decline in community-dwelling women aged 66 years or older. Subjects were 6,314 health professionals participating in the Women’s Health Study, among whom information on education and income was self-reported. From 1998 to 2000, we administered five cognitive tests, measuring general cognition, episodic memory and verbal fluency, using a validated telephone interview. Second cognitive assessments were conducted approximately two years later; information was complete for 5,573 women at the time of analysis, with 94% follow-up. We used linear and logistic regression to calculate multivariate-adjusted mean differences, and odds of cognitive impairment (defined as worst 10% of test distribution) and of substantial decline in performance (worst 10% of distribution), across various levels of education and income. After adjusting for numerous potential confounding factors, we found strong trends of increasing mean cognitive performance with increasing level of education (p-trend<0.0005 on all cognitive measures). Odds of cognitive impairment also consistently decreased with increasing education (eg, on summary score combining all tests, OR=0.6, 95% CI 0.3–0.9 comparing those with a doctoral degree to those with a 3-year associate’s degree). For income, we found significant trends of increasing mean cognitive performance with increasing income on the summary score and on episodic memory (p-trends<0.0001). For example, the OR was 0.6 (95% CI 0.4–0.8) comparing those with the highest income to the lowest income on the summary score. Results were generally similar for cognitive decline over two years, although somewhat weaker. Thus, in these well-educated, professional women, educational attainment and income both predicted cognitive function and decline. PMID:16352912

Intraindividual variability in basic reaction time predicts middle-aged and older pilots' flight simulator performance.

PubMed

Kennedy, Quinn; Taylor, Joy; Heraldez, Daniel; Noda, Art; Lazzeroni, Laura C; Yesavage, Jerome

2013-07-01

Intraindividual variability (IIV) is negatively associated with cognitive test performance and is positively associated with age and some neurological disorders. We aimed to extend these findings to a real-world task, flight simulator performance. We hypothesized that IIV predicts poorer initial flight performance and increased rate of decline in performance among middle-aged and older pilots. Two-hundred and thirty-six pilots (40-69 years) completed annual assessments comprising a cognitive battery and two 75-min simulated flights in a flight simulator. Basic and complex IIV composite variables were created from measures of basic reaction time and shifting and divided attention tasks. Flight simulator performance was characterized by an overall summary score and scores on communication, emergencies, approach, and traffic avoidance components. Although basic IIV did not predict rate of decline in flight performance, it had a negative association with initial performance for most flight measures. After taking into account processing speed, basic IIV explained an additional 8%-12% of the negative age effect on initial flight performance. IIV plays an important role in real-world tasks and is another aspect of cognition that underlies age-related differences in cognitive performance.

Intraindividual Variability in Basic Reaction Time Predicts Middle-Aged and Older Pilots’ Flight Simulator Performance

PubMed Central

2013-01-01

Objectives. Intraindividual variability (IIV) is negatively associated with cognitive test performance and is positively associated with age and some neurological disorders. We aimed to extend these findings to a real-world task, flight simulator performance. We hypothesized that IIV predicts poorer initial flight performance and increased rate of decline in performance among middle-aged and older pilots. Method. Two-hundred and thirty-six pilots (40–69 years) completed annual assessments comprising a cognitive battery and two 75-min simulated flights in a flight simulator. Basic and complex IIV composite variables were created from measures of basic reaction time and shifting and divided attention tasks. Flight simulator performance was characterized by an overall summary score and scores on communication, emergencies, approach, and traffic avoidance components. Results. Although basic IIV did not predict rate of decline in flight performance, it had a negative association with initial performance for most flight measures. After taking into account processing speed, basic IIV explained an additional 8%–12% of the negative age effect on initial flight performance. Discussion. IIV plays an important role in real-world tasks and is another aspect of cognition that underlies age-related differences in cognitive performance. PMID:23052365

Refining Mild-to-Moderate Alzheimer Disease Screening: A Tool for Clinicians.

PubMed

Del Campo, Natalia; Cesari, Matteo; Canevelli, Marco; Hoogendijk, Emiel O; Lilamand, Matthieu; Kelaiditi, Eirini; Soto, Maria E; Ousset, Pierre-Jean; Weiner, Michael W; Andrieu, Sandrine; Vellas, Bruno

2016-10-01

Recent evidence suggests that a substantial minority of people clinically diagnosed with probable Alzheimer disease (AD) in fact do not fulfill the neuropathological criteria for the disease. A clinical hallmark of these phenocopies of AD is that these individuals tend to remain cognitively stable for extended periods of time, in contrast to their peers with confirmed AD who show a progressive decline. We aimed to examine the prevalence of patients clinically diagnosed with mild-to-moderate AD who do not experience the expected clinically significant cognitive decline and identify markers easily available in routine medical practice predictive of a stable cognitive prognosis in this population. Data were obtained from two independent, longitudinal, observational multicenter studies in patients with mild-to-moderate AD. The two studies were the European "Impact of Cholinergic Treatment Use" (ICTUS) and the French "REseau sur la maladie d'Alzheimer FRançais" (REAL.FR). We used prospective data of 756 patients enrolled in ICTUS and 340 enrolled in REAL.FR. A prediction rule of cognitive decline was derived on ICTUS using classification and regression tree analysis and then cross-validated on REAL.FR. A range of demographic, clinical and cognitive variables were tested as predictor variables. Overall, 27.9% of patients in ICTUS and 20.9% in REAL.FR did not decline over 2 years. We identified optimized cut-points on the verbal memory items of the Alzheimer Disease Assessment Scale-Cognitive Subscale capable of classifying patients at baseline into those who went on to decline and those who remained stable or improved over the duration of the trial. The application of this simple rule would allow the identification of dementia cases where a more detailed differential diagnostic examination (eg, with biomarkers) is warranted. These findings are promising toward the refinement of AD screening in the clinic. For a further optimization of our classification rule, we encourage others to use our methodological approach on other episodic memory assessment tools designed to detect even small cognitive changes in patients with AD. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

APOE E4 status predicts age-related cognitive decline in the ninth decade: longitudinal follow-up of the Lothian Birth Cohort 1921.

PubMed

Schiepers, O J G; Harris, S E; Gow, A J; Pattie, A; Brett, C E; Starr, J M; Deary, I J

2012-03-01

Carriers of the APOE E4 allele have an increased risk of developing Alzheimer's disease. However, it is less clear whether APOE E4 status may also be involved in non-pathological cognitive ageing. The present study investigated the associations between APOE genotypes and cognitive change over 8 years in older community-dwelling individuals. APOE genotype was determined in 501 participants of the Lothian Birth Cohort 1921, whose intelligence had been measured in childhood in the Scottish Mental Survey 1932. A polymorphic variant of TOMM40 (rs10524523) was included to differentiate between the effects of the APOE E3 and E4 allelic variants. Cognitive performance on the domains of verbal memory, abstract reasoning and verbal fluency was assessed at mean age 79 years (n=501), and again at mean ages of 83 (n=284) and 87 (n=187). Using linear mixed models adjusted for demographic variables, vascular risk factors and IQ at age 11 years, possession of the APOE E4 allele was associated with a higher relative rate of cognitive decline over the subsequent 8 years for verbal memory and abstract reasoning. Individuals with the long allelic variant of TOMM40, which is linked to APOE E4, showed similar results. Verbal fluency was not affected by APOE E4 status. APOE E2 status was not associated with change in cognitive performance over 8 years. In non-demented older individuals, possession of the APOE E4 allele predicted a higher rate of cognitive decline on tests of verbal memory and abstract reasoning between 79 and 87 years. Thus, possession of the APOE E4 allele may not only predispose to Alzheimer's disease, but also appears to be a risk factor for non-pathological decline in verbal memory and abstract reasoning in the ninth decade of life.

Postoperative cognitive dysfunction and its relationship to cognitive reserve in elderly total joint replacement patients.

PubMed

Scott, J E; Mathias, J L; Kneebone, A C; Krishnan, J

2017-06-01

Whether total joint replacement (TJR) patients are susceptible to postoperative cognitive dysfunction (POCD) remains unclear due to inconsistencies in research methodologies. Moreover, cognitive reserve may moderate the development of POCD after TJR, but has not been investigated in this context. The current study investigated POCD after TJR, and its relationship with cognitive reserve, using a more rigorous methodology than has previously been utilized. Fifty-three older adults (aged 50+) scheduled for TJR were assessed pre and post surgery (6 months). Forty-five healthy controls matched for age, gender, and premorbid IQ were re-assessed after an equivalent interval. Cognition, cognitive reserve, and physical and mental health were all measured. Standardized regression-based methods were used to assess cognitive changes, while controlling for the confounding effect of repeated cognitive testing. TJR patients only demonstrated a significant decline in Trail Making Test Part B (TMT B) performance, compared to controls. Cognitive reserve only predicted change in TMT B scores among a subset of TJR patients. Specifically, patients who showed the most improvement pre to post surgery had significantly higher reserve than those who showed the greatest decline. The current study provides limited evidence of POCD after TJR when examined using a rigorous methodology, which controlled for practice effects. Cognitive reserve only predicted performance within a subset of the TJR sample. However, the role of reserve in more cognitively compromised patients remains to be determined.

Neuropsychiatric Symptoms and Alzheimer's Disease Biomarkers Predict Driving Decline: Brief Report.

PubMed

Babulal, Ganesh M; Stout, Sarah H; Head, Denise; Holtzman, David M; Fagan, Anne M; Morris, John C; Roe, Catherine M

2017-01-01

We examined whether neuropsychiatric symptoms (NPS) interact with cerebrospinal fluid (CSF) biomarkers (amyloid-β42 [Aβ42], tau, phosphorylated tau181 [ptau181], tau/Aβ42, and ptau181/Aβ42) of Alzheimer's disease pathology to predict driving decline among cognitively-normal older adults (N = 116) aged ≥65. Cox proportional hazards models examined time to receiving a rating of marginal or fail on the driving test. Age, education, and gender were adjusted in the models. Participants with more abnormal CSF (Aβ42, tau/Aβ42, ptau181/Aβ42) and NPS were faster to receive a marginal/fail on the road test compared to those without NPS. NPS interact with abnormal CSF biomarkers to impact driving performance among cognitively-normal older adults.

What physical performance measures predict incident cognitive decline among intact older adults? A 4.4year follow up study.

PubMed

Veronese, Nicola; Stubbs, Brendon; Trevisan, Caterina; Bolzetta, Francesco; De Rui, Marina; Solmi, Marco; Sartori, Leonardo; Musacchio, Estella; Zambon, Sabina; Perissinotto, Egle; Crepaldi, Gaetano; Manzato, Enzo; Sergi, Giuseppe

2016-08-01

Reductions in physical performance, cognitive impairment (CI) and decline (CD), are common in older age, but few prospective cohort studies have considered the relationship between these domains. In this study we investigated whether reduced physical performance and low handgrip/lower limbs strength, could predict a higher incidence of CI/CD during a 4-year follow-up among a cohort of elderly individuals. From 3099 older community-dwelling individuals initially enrolled in the Progetto Veneto Anziani (PRO.V.A.) study, 1249 participants without CI at the baseline were included (mean age 72.2years, 59.5% females). Physical performance measures included the Short Physical Performance Battery (SPPB), 4m gait speed, chair stands time, leg extension and flexion, handgrip strength, and 6-Minute Walking Test (6MWT), categorized in gender-specific tertiles. CI was defined as a Mini-Mental State Examination (MMSE) score below 24; CD a decline of 3 or more points in the MMSE without CI. At baseline, participants developing CI during follow-up scored significantly worse across all physical performance measures compared to those that retained normal cognitive status. After adjusting for potential confounders, a significant trend for MMSE changes was noted for all physical performance tests, except for the SPPB and chair stands time. Multinomial logistic regression revealed that slow gait speed at baseline significantly predicted CD at follow up. Poor SPPB performance and slower gait speed predicted the onset of CI at the follow-up. In conclusion, slow walking speed appears to be the best independent predictor of poor cognitive status over a 4.4-year follow-up, while other items of SPPB were also significantly associated with CI. Copyright © 2016 Elsevier Inc. All rights reserved.

The Gender Confidence Gap in Fractions Knowledge: Gender Differences in Student Belief-Achievement Relationships

ERIC Educational Resources Information Center

Ross, John A.; Scott, Garth; Bruce, Catherine D.

2012-01-01

Recent research demonstrates that in many countries gender differences in mathematics achievement have virtually disappeared. Expectancy-value theory and social cognition theory both predict that if gender differences in achievement have declined there should be a similar decline in gender differences in self-beliefs. Extant literature is…

Longitudinal decline of driving safety in Parkinson disease.

PubMed

Uc, Ergun Y; Rizzo, Matthew; O'Shea, Amy M J; Anderson, Steven W; Dawson, Jeffrey D

2017-11-07

To longitudinally assess and predict on-road driving safety in Parkinson disease (PD). Drivers with PD (n = 67) and healthy controls (n = 110) drove a standardized route in an instrumented vehicle and were invited to return 2 years later. A professional driving expert reviewed drive data and videos to score safety errors. At baseline, drivers with PD performed worse on visual, cognitive, and motor tests, and committed more road safety errors compared to controls (median PD 38.0 vs controls 30.5; p < 0.001). A smaller proportion of drivers with PD returned for repeat testing (42.8% vs 62.7%; p < 0.01). At baseline, returnees with PD made fewer errors than nonreturnees with PD (median 34.5 vs 40.0; p < 0.05) and performed similar to control returnees (median 33). Baseline global cognitive performance of returnees with PD was better than that of nonreturnees with PD, but worse than for control returnees ( p < 0.05). After 2 years, returnees with PD showed greater cognitive decline and larger increase in error counts than control returnees (median increase PD 13.5 vs controls 3.0; p < 0.001). Driving error count increase in the returnees with PD was predicted by greater error count and worse visual acuity at baseline, and by greater interval worsening of global cognition, Unified Parkinson's Disease Rating Scale activities of daily living score, executive functions, visual processing speed, and attention. Despite drop out of the more impaired drivers within the PD cohort, returning drivers with PD, who drove like controls without PD at baseline, showed many more driving safety errors than controls after 2 years. Driving decline in PD was predicted by baseline driving performance and deterioration of cognitive, visual, and functional abnormalities on follow-up. © 2017 American Academy of Neurology.

Social relationships and cognitive decline: a systematic review and meta-analysis of longitudinal cohort studies.

PubMed

Kuiper, Jisca S; Zuidersma, Marij; Zuidema, Sytse U; Burgerhof, Johannes Gm; Stolk, Ronald P; Oude Voshaar, Richard C; Smidt, Nynke

2016-08-01

Although poor social relationships are assumed to contribute to cognitive decline, meta-analytic approaches have not been applied. Individual study results are mixed and difficult to interpret due to heterogeneity in measures of social relationships. We conducted a systematic review and meta-analysis to investigate the relation between poor social relationships and cognitive decline. MEDLINE, Embase and PsycINFO were searched for longitudinal cohort studies examining various aspects of social relationships and cognitive decline in the general population. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random effects meta-analysis. Sources of heterogeneity were explored and likelihood of publication bias was assessed. We stratified analyses according to three aspects of social relationships: structural, functional and a combination of these. We identified 43 articles. Poor social relationships predicted cognitive decline; for structural (19 studies): pooled OR: 1.08 (95% CI: 1.05-1.11); functional (8 studies): pooled OR: 1.15 (95% CI: 1.00-1.32); and combined measures (7 studies): pooled OR: 1.12 (95% CI: 1.01-1.24). Meta-regression and subgroup analyses showed that the heterogeneity could be explained by the type of social relationship measurement and methodological quality of included studies. Despite heterogeneity in study design and measures, our meta-analyses show that multiple aspects of social relationships are associated with cognitive decline. As evidence for publication bias was found, the association might be overestimated and should therefore be interpreted with caution. Future studies are needed to better define the mechanisms underlying these associations. Potential causality of this prognostic association should be examined in future randomized controlled studies. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Spatial patterns of brain atrophy in MCI patients, identified via high-dimensional pattern classification, predict subsequent cognitive decline

PubMed Central

Fan, Yong; Batmanghelich, Nematollah; Clark, Chris M.; Davatzikos, Christos

2010-01-01

Spatial patterns of brain atrophy in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) were measured via methods of computational neuroanatomy. These patterns were spatially complex and involved many brain regions. In addition to the hippocampus and the medial temporal lobe gray matter, a number of other regions displayed significant atrophy, including orbitofrontal and medial-prefrontal grey matter, cingulate (mainly posterior), insula, uncus, and temporal lobe white matter. Approximately 2/3 of the MCI group presented patterns of atrophy that overlapped with AD, whereas the remaining 1/3 overlapped with cognitively normal individuals, thereby indicating that some, but not all, MCI patients have significant and extensive brain atrophy in this cohort of MCI patients. Importantly, the group with AD-like patterns presented much higher rate of MMSE decline in follow-up visits; conversely, pattern classification provided relatively high classification accuracy (87%) of the individuals that presented relatively higher MMSE decline within a year from baseline. High-dimensional pattern classification, a nonlinear multivariate analysis, provided measures of structural abnormality that can potentially be useful for individual patient classification, as well as for predicting progression and examining multivariate relationships in group analyses. PMID:18053747

Varying strength of cognitive markers and biomarkers to predict conversion and cognitive decline in an early-stage-enriched mild cognitive impairment sample.

PubMed

Egli, Simone C; Hirni, Daniela I; Taylor, Kirsten I; Berres, Manfred; Regeniter, Axel; Gass, Achim; Monsch, Andreas U; Sollberger, Marc

2015-01-01

Several cognitive, neuroimaging, and cerebrospinal fluid (CSF) markers predict conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. However, predictors might be more or less powerful depending on the characteristics of the MCI sample. To investigate which cognitive markers and biomarkers predict conversion to AD dementia and course of cognitive functioning in a MCI sample with a high proportion of early-stage MCI patients. Variables known to predict progression in MCI patients and hypothesized to predict progression in early-stage MCI patients were selected. Cognitive (long-delay free recall, regional primacy score), imaging (hippocampal and entorhinal cortex volumes, fornix fractional anisotropy), and CSF (Aβ1-42/t-tau, Aβ1-42) variables from 36 MCI patients were analyzed with Cox regression and mixed-effect models to determine their individual and combined abilities to predict time to conversion to AD dementia and course of global cognitive functioning, respectively. Those variables hypothesized to predict the course of early-stage MCI patients were most predictive for MCI progression. Specifically, regional primacy score (a measure of word-list position learning) most consistently predicted conversion to AD dementia and course of cognitive functioning. Both the prediction of conversion and course of cognitive functioning were maximized by including CSF Aβ1-42 and fornix integrity biomarkers, respectively, indicating the complementary information carried by cognitive variables and biomarkers. Predictors of MCI progression need to be interpreted in light of the characteristics of the respective MCI sample. Future studies should aim to compare predictive strengths of markers between early-stage and late-stage MCI patients.

CSF biomarkers of Alzheimer disease

PubMed Central

Fagan, Anne M.; Grant, Elizabeth A.; Holtzman, David M.; Morris, John C.

2013-01-01

Objectives: To test whether CSF Alzheimer disease biomarkers (β-amyloid 42 [Aβ42], tau, phosphorylated tau at threonine 181 [ptau181], tau/Aβ42, and ptau181/Aβ42) predict future decline in noncognitive outcomes among individuals cognitively normal at baseline. Methods: Longitudinal data from participants (N = 430) who donated CSF within 1 year of a clinical assessment indicating normal cognition and were aged 50 years or older were analyzed. Mixed linear models were used to test whether baseline biomarker values predicted future decline in function (instrumental activities of daily living), weight, behavior, and mood. Clinical Dementia Rating Sum of Boxes and Mini-Mental State Examination scores were also examined. Results: Abnormal levels of each biomarker were related to greater impairment with time in behavior (p < 0.035) and mood (p < 0.012) symptoms, and more difficulties with independent activities of daily living (p < 0.012). However, biomarker levels were unrelated to weight change with time (p > 0.115). As expected, abnormal biomarker values also predicted more rapidly changing Mini-Mental State Examination (p < 0.041) and Clinical Dementia Rating Sum of Boxes (p < 0.001) scores compared with normal values. Conclusions: CSF biomarkers among cognitively normal individuals are associated with future decline in some, but not all, noncognitive Alzheimer disease symptoms studied. Additional work is needed to determine the extent to which these findings generalize to other samples. PMID:24212387

CSF biomarkers of Alzheimer disease: "noncognitive" outcomes.

PubMed

Roe, Catherine M; Fagan, Anne M; Grant, Elizabeth A; Holtzman, David M; Morris, John C

2013-12-03

To test whether CSF Alzheimer disease biomarkers (β-amyloid 42 [Aβ42], tau, phosphorylated tau at threonine 181 [ptau181], tau/Aβ42, and ptau181/Aβ42) predict future decline in noncognitive outcomes among individuals cognitively normal at baseline. Longitudinal data from participants (N = 430) who donated CSF within 1 year of a clinical assessment indicating normal cognition and were aged 50 years or older were analyzed. Mixed linear models were used to test whether baseline biomarker values predicted future decline in function (instrumental activities of daily living), weight, behavior, and mood. Clinical Dementia Rating Sum of Boxes and Mini-Mental State Examination scores were also examined. Abnormal levels of each biomarker were related to greater impairment with time in behavior (p < 0.035) and mood (p < 0.012) symptoms, and more difficulties with independent activities of daily living (p < 0.012). However, biomarker levels were unrelated to weight change with time (p > 0.115). As expected, abnormal biomarker values also predicted more rapidly changing Mini-Mental State Examination (p < 0.041) and Clinical Dementia Rating Sum of Boxes (p < 0.001) scores compared with normal values. CSF biomarkers among cognitively normal individuals are associated with future decline in some, but not all, noncognitive Alzheimer disease symptoms studied. Additional work is needed to determine the extent to which these findings generalize to other samples.

Predicting loss of employment over three years in multiple sclerosis: clinically meaningful cognitive decline.

PubMed

Morrow, Sarah A; Drake, Allison; Zivadinov, Robert; Munschauer, Frederick; Weinstock-Guttman, Bianca; Benedict, Ralph H B

2010-10-01

Cognitive dysfunction is common in multiple sclerosis (MS), yet the magnitude of change on objective neuropsychological (NP) tests that is clinically meaningful is unclear. We endeavored to determine NP markers of the transition from employment to work disability in MS, as indicated by degree of decline on individual tests. Participants were 97 employed MS patients followed over 41.3 ± 17.6 months with a NP battery covering six domains of cognitive function. Deterioration at follow-up was designated as documented and paid disability benefits (conservative definition) or a reduction in hours/work responsibilities (liberal definition). Using the conservative definition, 28.9% reported deteriorated employment status and for the liberal definition, 45.4%. The Symbol Digit Modalities Test (SDMT) and California Verbal Learning Test, Total Learning (CVLT2-TL) measures distinguished employed and disabled patients at follow-up. Controlling for demographic and MS characteristics, the odds ratio of a deterioration based on a change of 2.0 on the CVLT2-TL was 3.7 (95% CI 1.2-11.4 and SDMT by 4.0 was 4.2 (95% CI 1.2-14.8), accounting for 86.7% of the area under the ROC curve. We conclude that decline on NP testing over time is predictive of deterioration in vocational status, establishing a magnitude of decline on NP tests that is clinically meaningful.

Decline in Literacy and Incident AD Dementia Among Community-Dwelling Older Persons.

PubMed

Yu, Lei; Wilson, Robert S; Han, S Duke; Leurgans, Sue; Bennett, David A; Boyle, Patricia A

2017-06-01

To quantify longitudinal change in financial and health literacy and examine the associations of declining literacy with incident Alzheimer's disease (AD) dementia and mild cognitive impairment (MCI). Data came from 799 participants of an ongoing cohort study. Literacy was measured using a battery of 32 questions. Clinical diagnoses were made annually following uniform structured procedures. The associations of declining literacy with incident AD dementia and MCI were tested using a joint model for longitudinal and time-to-event data. We observed an overall decline in total literacy score over up to 6 years of follow-up ( p < .001). Faster decline in literacy was associated with higher risks for incident AD dementia (hazard ratio = 4.526, 95% confidence interval = [2.993, 6.843], p < .001) and incident MCI (hazard ratio = 2.971, 95% confidence interval = [1.509, 5.849], p = .002). Declining literacy among community-dwelling older persons predicts adverse cognitive outcomes and serves as an early indicator of impending dementia.

Modeling Longitudinal Changes in Older Adults’ Memory for Spoken Discourse: Findings from the ACTIVE Cohort

PubMed Central

Payne, Brennan R.; Gross, Alden L.; Parisi, Jeanine M.; Sisco, Shannon M.; Stine-Morrow, Elizabeth A. L.; Marsiske, Michael; Rebok, George W.

2014-01-01

Episodic memory shows substantial declines with advancing age, but research on longitudinal trajectories of spoken discourse memory (SDM) in older adulthood is limited. Using parallel process latent growth curve models, we examined 10 years of longitudinal data from the no-contact control group (N = 698) of the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) randomized controlled trial in order to test (a) the degree to which SDM declines with advancing age, (b) predictors of these age-related declines, and (c) the within-person relationship between longitudinal changes in SDM and longitudinal changes in fluid reasoning and verbal ability over 10 years, independent of age. Individuals who were younger, White, had more years of formal education, were male, and had better global cognitive function and episodic memory performance at baseline demonstrated greater levels of SDM on average. However, only age at baseline uniquely predicted longitudinal changes in SDM, such that declines accelerated with greater age. Independent of age, within-person decline in reasoning ability over the 10-year study period was substantially correlated with decline in SDM (r = .87). An analogous association with SDM did not hold for verbal ability. The findings suggest that longitudinal declines in fluid cognition are associated with reduced spoken language comprehension. Unlike findings from memory for written prose, preserved verbal ability may not protect against developmental declines in memory for speech. PMID:24304364

Brain structure and verbal function across adulthood while controlling for cerebrovascular risks.

PubMed

Sanfratello, L; Lundy, S L; Qualls, C; Knoefel, J E; Adair, J C; Caprihan, A; Stephen, J M; Aine, C J

2017-04-08

The development and decline of brain structure and function throughout adulthood is a complex issue, with cognitive aging trajectories influenced by a host of factors including cerebrovascular risk. Neuroimaging studies of age-related cognitive decline typically reveal a linear decrease in gray matter (GM) volume/density in frontal regions across adulthood. However, white matter (WM) tracts mature later than GM, particularly in regions necessary for executive functions and memory. Therefore, it was predicted that a middle-aged group (MC: 35-45 years) would perform best on a verbal working memory task and reveal greater regional WM integrity, compared with both young (YC: 18-25 years) and elder groups (EC: 60+ years). Diffusion tensor imaging (DTI) and magnetoencephalography (MEG) were obtained from 80 healthy participants. Objective measures of cerebrovascular risk and cognition were also obtained. As predicted, MC revealed best verbal working memory accuracy overall indicating some maturation of brain function between YC and MC. However, contrary to the prediction fractional anisotropy values (FA), a measure of WM integrity, were not greater in MC (i.e., there were no significant differences in FA between YC and MC but both groups showed greater FA than EC). An overall multivariate model for MEG ROIs showed greater peak amplitudes for MC and YC, compared with EC. Subclinical cerebrovascular risk factors (systolic blood pressure and blood glucose) were negatively associated with FA in frontal callosal, limbic, and thalamic radiation regions which correlated with executive dysfunction and slower processing speed, suggesting their contribution to age-related cognitive decline. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Subjective cognitive decline and fall risk in community-dwelling older adults with or without objective cognitive decline.

PubMed

Shirooka, Hidehiko; Nishiguchi, Shu; Fukutani, Naoto; Tashiro, Yuto; Nozaki, Yuma; Aoyama, Tomoki

2018-05-01

The association between subjective cognitive decline and falls has not been clearly determined. Our aim was to explore the effect of subjective cognitive decline on falls in community-dwelling older adults with or without objective cognitive decline. We included 470 older adults (mean age 73.6 ± 5.2; 329 women) living in the community and obtained data on fall history directly from the participants. Subjective cognitive decline was assessed using a self-administered question. Objective cognitive function was measured using the Mini-Mental State Examination. Statistical analyses were carried out separately for participants with objective cognitive decline and those without. A multiple logistic regression analysis showed that, among participants without objective cognitive decline, subjective cognitive decline was positively associated with falls [OR 1.91; 95% confidence interval (CI) 1.17-3.12; p = 0.01). Conversely, among participants with objective cognitive decline, subjective cognitive decline was negatively associated with falls (OR 0.07; 95% CI 0.01-0.85, p = 0.04). The result suggests that the objective-subjective disparity may affect falls in community-dwelling older adults. The presence of subjective cognitive decline was significantly positively associated with falls among cognitively intact older adults. However, among their cognitively impaired peers, the absence of subjective cognitive decline was positively associated with falls.

Naturalistic distraction and driving safety in older drivers.

PubMed

Aksan, Nazan; Dawson, Jeffrey D; Emerson, Jamie L; Yu, Lixi; Uc, Ergun Y; Anderson, Steven W; Rizzo, Matthew

2013-08-01

In this study, we aimed to quantify and compare performance of middle-aged and older drivers during a naturalistic distraction paradigm (visual search for roadside targets) and to predict older drivers performance given functioning in visual, motor, and cognitive domains. Distracted driving can imperil healthy adults and may disproportionally affect the safety of older drivers with visual, motor, and cognitive decline. A total of 203 drivers, 120 healthy older (61 men and 59 women, ages 65 years and older) and 83 middle-aged drivers (38 men and 45 women, ages 40 to 64 years), participated in an on-road test in an instrumented vehicle. Outcome measures included performance in roadside target identification (traffic signs and restaurants) and concurrent driver safety. Differences in visual, motor, and cognitive functioning served as predictors. Older drivers identified fewer landmarks and drove slower but committed more safety errors than did middle-aged drivers. Greater familiarity with local roads benefited performance of middle-aged but not older drivers.Visual cognition predicted both traffic sign identification and safety errors, and executive function predicted traffic sign identification over and above vision. Older adults are susceptible to driving safety errors while distracted by common secondary visual search tasks that are inherent to driving. The findings underscore that age-related cognitive decline affects older drivers' management of driving tasks at multiple levels and can help inform the design of on-road tests and interventions for older drivers.

Normal cognitive decline or dementia?

PubMed

Ebmeier, Klaus P

2010-01-01

Cognitive speed, inhibitory function, and memory decline with age while crystallised, particularly verbal, abilities remain largely intact. Poor health, fewer years of education, lower activity, the presence of the APOE E4 allele, and high BP appear to predict faster cognitive decline. Dementia is diagnosed in the presence of objective cognitive impairment, both long- and short-term memory, plus at least one additional (cortical) cognitive deficit, such as dysphasia, dyspraxia, agnosia, or disturbance in executive functioning. In addition, patients have to show significant impairment in social or occupational functioning and a significant decline from previous levels. Both smoking and diabetes increase the risk of all types of dementia, not smoking or even stopping smoking reduces this risk, but better control of type 2 diabetes does not appear to have a measurable effect. Drinking small to moderate amounts of alcohol appears to confer some benefit in ameliorating cognitive decline. There is some evidence that HRT, DHEA, BP lowering in patients without prior cerebrovascular disease, statins, vitamin B6 and procaine are NOT helpful. There is insufficient evidence to establish or refute a beneficial effect for exercise, treatment of type 2 diabetes, omega-3 fatty acids, folic acid with/without vitamin B12, antioxidant vitamins, or ginkgo biloba. Depressive symptoms are more prevalent than dementia. Clinical (major) depression can present with cognitive deterioration, often associated with subjective complaints. Patients with subjective or objective memory impairment, but without functional deterioration, can be referred to the local memory clinic, while demented patients eligible for acetylcholinesterase inhibitor treatment, patients whose diagnosis is unclear and who may need some specific investigations, as well as patients who may benefit from a combined approach with psychotropic drugs and behavioural support should be referred to the local mental health team.

The Alzheimer's Disease Cooperative Study Prevention Instrument Project: Longitudinal Outcome of Behavioral Measures as Predictors of Cognitive Decline

PubMed Central

Banks, Sarah Jane; Raman, Rema; He, Feng; Salmon, David P.; Ferris, Steven; Aisen, Paul; Cummings, Jeffrey

2014-01-01

Background/Methods The Alzheimer's Disease Cooperative Study Prevention Instrument Project is a longitudinal study that recruited 644 cognitively healthy older subjects (aged between 75 and 93 years, 58% women) at baseline and evaluated their cognitive change over 4 years. The study was structured like a clinical trial to anticipate a prevention trial and to determine the performance of novel trial instruments in a longitudinal non-interventional trial framework. Behavioral symptoms were assessed at baseline. Results The existence of participant-reported behavioral symptoms at baseline predicted conversion to Clinical Dementia Rating scale score ≥0.5 over the 4-year period. Conclusions The results imply that early anxiety and depression may be harbingers of future cognitive decline, and that patients exhibiting such symptoms, even in the absence of co-occurring cognitive symptoms, should be closely followed over time. PMID:25685141

Preventing Cognitive Decline in Older African Americans with Mild Cognitive Impairment: Design and Methods of a Randomized Clinical Trial

PubMed Central

Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Leiby, Benjamin E.

2012-01-01

Mild Cognitive Impairment (MCI) affects 25% of older African Americans and predicts progression to Alzheimer's disease. An extensive epidemiologic literature suggests that cognitive, physical, and/or social activities may prevent cognitive decline. We describe the methods of a randomized clinical trial to test the efficacy of Behavior Activation to prevent cognitive decline in older African Americans with the amnestic multiple domain subtype of MCI. Community Health Workers deliver 6 initial in-home treatment sessions over 2-3 months and then 6 subsequent in-home booster sessions using language, materials, and concepts that are culturally relevant to older African Americans during this 24 month clinical trial. We are randomizing 200 subjects who are recruited from churches, senior centers, and medical clinics to Behavior Activation or Supportive Therapy, which controls for attention. The primary outcome is episodic memory as measured by the Hopkins Verbal Learning Test-Revised at baseline and at months 3, 12, 18, and 24. The secondary outcomes are general and domain-specific neuropsychological function, activities of daily living, depression, and quality-of-life. The negative results of recent clinical trials of drug treatments for MCI and Alzheimer's disease suggest that behavioral interventions may provide an alternative treatment approach to preserve cognition in an aging society. PMID:22406101

Audio-visual speech experience with age influences perceived audio-visual asynchrony in speech.

PubMed

Alm, Magnus; Behne, Dawn

2013-10-01

Previous research indicates that perception of audio-visual (AV) synchrony changes in adulthood. Possible explanations for these age differences include a decline in hearing acuity, a decline in cognitive processing speed, and increased experience with AV binding. The current study aims to isolate the effect of AV experience by comparing synchrony judgments from 20 young adults (20 to 30 yrs) and 20 normal-hearing middle-aged adults (50 to 60 yrs), an age range for which a decline of cognitive processing speed is expected to be minimal. When presented with AV stop consonant syllables with asynchronies ranging from 440 ms audio-lead to 440 ms visual-lead, middle-aged adults showed significantly less tolerance for audio-lead than young adults. Middle-aged adults also showed a greater shift in their point of subjective simultaneity than young adults. Natural audio-lead asynchronies are arguably more predictable than natural visual-lead asynchronies, and this predictability may render audio-lead thresholds more prone to experience-related fine-tuning.

Impact of Malnutrition on Physical, Cognitive Function and Mortality among Older Men Living in Veteran Homes by Minimum Data Set: A Prospective Cohort Study in Taiwan.

PubMed

Chen, L-Y; Liu, L-K; Hwang, A-C; Lin, M-H; Peng, L-N; Chen, L-K; Lan, C-F; Chang, P-L

2016-01-01

To evaluate the prevalence of malnutrition and its impact on mortality, functional decline and cognitive impairment among elder residents in long-term care settings. A prospective cohort study. Two veteran homes in Taiwan. A total of 1,248 male residents aged equal or more than 65 years. Charlson's comorbidity index (CCI), Minimum data set (MDS), resident assessment protocols (RAP), Activity of daily living-Hierarchy scale, Cognitive Performance Scale, MDS Social engagement scale. The mean age of participants is 83.1 ± 5.1 years, and the prevalence of malnutrition was 6.1%. Inadequate dietary content (57.9%) and unintentional weight loss (31.6%) account for the majority of malnutrition identified by MDS tool. Higher 18-month mortality rate (25% vs. 14.2%), higher baseline CCI (median 1 vs. 0), and higher baseline sum of RAP triggers (median 8.5 vs. 5) were noted among residents with malnutrition. Furthermore, malnutrition was shown predictive for functional decline (OR: 3.096, 95% CI: 1.715-5.587) and potential cognitive improvement (OR: 2.469, 95% CI: 1.188-5.128) among survivors after adjustment for age, body mass index and CCI. Malnutrition among elder men residing in veteran homes was associated with multimorbidities and higher care complexity, and was predictive for mortality and functional decline.

Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease.

PubMed

Caspell-Garcia, Chelsea; Simuni, Tanya; Tosun-Turgut, Duygu; Wu, I-Wei; Zhang, Yu; Nalls, Mike; Singleton, Andrew; Shaw, Leslie A; Kang, Ju-Hee; Trojanowski, John Q; Siderowf, Andrew; Coffey, Christopher; Lasch, Shirley; Aarsland, Dag; Burn, David; Chahine, Lana M; Espay, Alberto J; Foster, Eric D; Hawkins, Keith A; Litvan, Irene; Richard, Irene; Weintraub, Daniel

2017-01-01

To assess the neurobiological substrate of initial cognitive decline in Parkinson's disease (PD) to inform patient management, clinical trial design, and development of treatments. We longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aβ], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition. Additionally, longitudinal structural MRI and DAT scan data were included. Univariate analyses were run initially, with false discovery rate = 0.2, to select biomarker variables for inclusion in multivariable longitudinal mixed-effect models. By year 3, cognitive impairment was diagnosed in 15-38% participants depending on the criteria applied. Biomarkers, some longitudinal, predicting cognitive impairment in multivariable models were: (1) dopamine deficiency (decreased caudate and putamen DAT availability); (2) diffuse, cortical decreased brain volume or thickness (frontal, temporal, parietal, and occipital lobe regions); (3) co-morbid Alzheimer's disease Aβ amyloid pathology (lower CSF Aβ 1-42); and (4) genes (COMT val/val and BDNF val/val genotypes). Cognitive impairment in PD increases in frequency 50-200% in the first several years of disease, and is independently predicted by biomarker changes related to nigrostriatal or cortical dopaminergic deficits, global atrophy due to possible widespread effects of neurodegenerative disease, co-morbid Alzheimer's disease plaque pathology, and genetic factors.

Socioeconomic, emotional, and physical execution variables as predictors of cognitive performance in a Spanish sample of middle-aged and older community-dwelling participants.

PubMed

González, Mari Feli; Facal, David; Juncos-Rabadán, Onésimo; Yanguas, Javier

2017-10-01

Cognitive performance is not easily predicted, since different variables play an important role in the manifestation of age-related declines. The objective of this study is to analyze the predictors of cognitive performance in a Spanish sample over 50 years from a multidimensional perspective, including socioeconomic, affective, and physical variables. Some of them are well-known predictors of cognition and others are emergent variables in the study of cognition. The total sample, drawn from the "Longitudinal Study Aging in Spain (ELES)" project, consisted of 832 individuals without signs of cognitive impairment. Cognitive function was measured with tests evaluating episodic and working memory, visuomotor speed, fluency, and naming. Thirteen independent variables were selected as predictors belonging to socioeconomic, emotional, and physical execution areas. Multiple linear regressions, following the enter method, were calculated for each age group in order to study the influence of these variables in cognitive performance. Education is the variable which best predicts cognitive performance in the 50-59, 60-69, and 70-79 years old groups. In the 80+ group, the best predictor is objective economic status and education does not enter in the model. Age-related decline can be modified by the influence of educational and socioeconomic variables. In this context, it is relevant to take into account how easy is to modify certain variables, compared to others which depend on each person's life course.

Nutritional Status is Associated with Faster Cognitive Decline and Worse Functional Impairment in the Progression of Dementia: The Cache County Dementia Progression Study1

PubMed Central

Sanders, Chelsea; Behrens, Stephanie; Schwartz, Sarah; Wengreen, Heidi; Corcoran, Chris D.; Lyketsos, Constantine G.; Tschanz, JoAnn T.

2017-01-01

Nutritional status may be a modifiable factor in the progression of dementia. We examined the association of nutritional status and rate of cognitive and functional decline in a U.S. population-based sample. Study design was an observational longitudinal study with annual follow-ups up to 6 years of 292 persons with dementia (72% Alzheimer’s disease, 56% female) in Cache County, UT using the Mini-Mental State Exam (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-sb), and modified Mini Nutritional Assessment (mMNA). mMNA scores declined by approximately 0.50 points/year, suggesting increasing risk for malnutrition. Lower mMNA score predicted faster rate of decline on the MMSE at earlier follow-up times, but slower decline at later follow-up times, whereas higher mMNA scores had the opposite pattern (mMNA by time β = 0.22, p = 0.017; mMNA by time2 β = −0.04, p = 0.04). Lower mMNA score was associated with greater impairment on the CDR-sb over the course of dementia (β = 0.35, p < 0.001). Assessment of malnutrition may be useful in predicting rates of progression in dementia and may provide a target for clinical intervention. PMID:26967207

Nutritional Status is Associated with Faster Cognitive Decline and Worse Functional Impairment in the Progression of Dementia: The Cache County Dementia Progression Study1.

PubMed

Sanders, Chelsea; Behrens, Stephanie; Schwartz, Sarah; Wengreen, Heidi; Corcoran, Chris D; Lyketsos, Constantine G; Tschanz, JoAnn T

2016-02-27

Nutritional status may be a modifiable factor in the progression of dementia. We examined the association of nutritional status and rate of cognitive and functional decline in a U.S. population-based sample. Study design was an observational longitudinal study with annual follow-ups up to 6 years of 292 persons with dementia (72% Alzheimer's disease, 56% female) in Cache County, UT using the Mini-Mental State Exam (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-sb), and modified Mini Nutritional Assessment (mMNA). mMNA scores declined by approximately 0.50 points/year, suggesting increasing risk for malnutrition. Lower mMNA score predicted faster rate of decline on the MMSE at earlier follow-up times, but slower decline at later follow-up times, whereas higher mMNA scores had the opposite pattern (mMNA by time β= 0.22, p = 0.017; mMNA by time2 β= -0.04, p = 0.04). Lower mMNA score was associated with greater impairment on the CDR-sb over the course of dementia (β= 0.35, p <  0.001). Assessment of malnutrition may be useful in predicting rates of progression in dementia and may provide a target for clinical intervention.

Normal rates of cognitive change in successful aging: the freedom house study.

PubMed

Royall, Donald R; Palmer, Raymond; Chiodo, Laura K; Polk, Marsha J

2005-11-01

We determined the rates of cognitive change associated with twenty individual measures. Participants included 547 noninstitutionalized septuagenarians and octogenarian residents of a comprehensive care retirement community who were studied over three years. Latent growth curves (LGC) of multiple cognitive measures were compared to a LGC model of the rates of change in Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL). All curves were standardized relative to each variable's baseline distribution. Baseline scores were within their expected normal age-specific ranges. Most measures showed significant rates of change over time. There was also significant variability about those rates, suggesting clinical heterogeneity. Many deteriorated over time, as did ADLs and IADLs. However, performance on some measures improved, consistent with learning effects. The rates of change in two measures, the Executive Interview and the Trail Making Test, were closely related to decline in IADLs. These results suggest that age-related cognitive decline is a dynamic longitudinal process affecting multiple cognitive domains. Heterogeneity in the rates of cognitive change may reflect the summed effects of age and comorbid conditions affecting cognition. Some measures may be ill-suited for measuring age-related changes in cognition, either because they are insensitive to change, or hindered by learning effects. Nonverbal measures appear to be particularly well suited for the prediction of age-related functional decline. These observations are relevant to the definition and diagnosis of "dementing" conditions.

Cognitive and Language Skills in Adults with Autism: A 40-Year Follow-Up

ERIC Educational Resources Information Center

Howlin, Patricia; Savage, Sarah; Moss, Philippa; Tempier, Althea; Rutter, Michael

2013-01-01

Background: It is well established that very few individuals with autism spectrum disorders (ASD) and an IQ below 70 are able to live independently as adults. However, even amongst children with an IQ in the normal range, outcome is very variable. Childhood factors that predict later stability, improvement or decline in cognitive functioning…

Social disorder, APOE-E4 genotype, and change in cognitive function among older adults living in Chicago

PubMed Central

Boardman, Jason D.; Barnes, Lisa L.; Wilson, Robert S.; Evans, Denis A.; Mendes de Leon, Carlos F.

2013-01-01

The goal of this paper is to describe the simultaneous influence of social and genetic risk factors on declines in cognitive functioning among older American adults. We use detailed information about the social characteristics of older adults' neighborhoods from the Chicago Health and Aging Project (n = 1655; ages 65+) in conjunction with information about respondent's APOE genotype to predict changes in cognitive function over time. Results indicate that the presence of the ɛ4 allele is associated with a significantly lower cognitive function score at baseline and greater declines in cognitive function compared to those without this risk allele. Importantly, we also show significant variation in the effect of the ɛ4 allele across neighborhoods and our results indicate that this genotype is more strongly associated with cognitive function for residents of neighborhoods with the lowest levels of social disorder. Our findings support the non-causal social push gene–environment interaction model. PMID:22465377

Resting-State Functional Connectivity Predicts Cognitive Impairment Related to Alzheimer's Disease.

PubMed

Lin, Qi; Rosenberg, Monica D; Yoo, Kwangsun; Hsu, Tiffany W; O'Connell, Thomas P; Chun, Marvin M

2018-01-01

Resting-state functional connectivity (rs-FC) is a promising neuromarker for cognitive decline in aging population, based on its ability to reveal functional differences associated with cognitive impairment across individuals, and because rs-fMRI may be less taxing for participants than task-based fMRI or neuropsychological tests. Here, we employ an approach that uses rs-FC to predict the Alzheimer's Disease Assessment Scale (11 items; ADAS11) scores, which measure overall cognitive functioning, in novel individuals. We applied this technique, connectome-based predictive modeling, to a heterogeneous sample of 59 subjects from the Alzheimer's Disease Neuroimaging Initiative, including normal aging, mild cognitive impairment, and AD subjects. First, we built linear regression models to predict ADAS11 scores from rs-FC measured with Pearson's r correlation. The positive network model tested with leave-one-out cross validation (LOOCV) significantly predicted individual differences in cognitive function from rs-FC. In a second analysis, we considered other functional connectivity features, accordance and discordance, which disentangle the correlation and anticorrelation components of activity timecourses between brain areas. Using partial least square regression and LOOCV, we again built models to successfully predict ADAS11 scores in novel individuals. Our study provides promising evidence that rs-FC can reveal cognitive impairment in an aging population, although more development is needed for clinical application.

Anxiety symptoms and risk of cognitive decline in older community-dwelling men.

PubMed

Kassem, Ahmed M; Ganguli, Mary; Yaffe, Kristine; Hanlon, Joseph T; Lopez, Oscar L; Wilson, John W; Cauley, Jane A

2017-07-01

Previous research regarding anxiety as a predictor of future cognitive decline in older adults is limited and inconsistent. We examined the independent relationship between anxiety symptoms and subsequent cognitive decline. We included 2,818 community-dwelling older men (mean age = 76.1, SD ±5.3 years) who were followed on an average for 3.4 years. We assessed anxiety symptoms at baseline using the Goldberg Anxiety Scale (GAS; range = 0-9). We assessed cognitive function at baseline and at two subsequent visits using the Modified Mini-Mental State Examination (3MS; global cognition) and the Trails B test (executive function). At baseline, there were 690 (24%) men with mild anxiety symptoms (GAS 1-4) and 226 (8%) men with moderate/severe symptoms (GAS 5-9). Men with anxiety symptoms were more likely to have depressed mood, poor sleep, more chronic medical conditions, and more impairment in activities of daily living compared to those with no anxiety symptoms. Compared to those with no anxiety symptoms at baseline, men with any anxiety symptoms were more likely to have substantial worsening in Trails B completion time (OR = 1.56, 95% CI 1.19, 2.05). The association was attenuated after adjusting for potential confounders, including depression and poor sleep, but remained significant (OR = 1.40, 95% CI 1.04, 1.88). In cognitively healthy older men, mild anxiety symptoms may potentially predict future decline in executive functioning. Anxiety is likely a manifestation of an underlying neurodegenerative process rather than a cause.

Is age kinder to the initially more able?: Yes, and no

PubMed Central

Gow, Alan J.; Johnson, Wendy; Mishra, Gita; Richards, Marcus; Kuh, Diana; Deary, Ian J.

2012-01-01

Although a number of analyses have addressed whether initial cognitive ability level is associated with age-related cognitive decline, results have been inconsistent. Latent growth curve modeling was applied to two aging cohorts, extending previous analyses with a further wave of data collection, or as a more appropriate analytical methodology than used previously. In the Lothian Birth Cohort 1921, cognitive ability at age 11 was not associated with cognitive change from age 79 to 87, either in general cognitive ability, or in tests of reasoning, memory and executive function. However, data from the MRC National Survey of Health and Development suggested that higher cognitive ability at age 15 predicted less decline between ages 43 and 53 years in a latent cognitive factor from tests of verbal memory and search speed, and in search speed when considered separately. The results are discussed in terms of the differences between the cohorts and the interpretability of the analytical approach. Suggestions are made about when initial ability might be cognitively protective, and study requirements to bring about a clearer resolution. PMID:23690652

Moving Forward: Age Effects on the Cerebellum Underlie Cognitive and Motor Declines

PubMed Central

Bernard, Jessica A.; Seidler, Rachael D.

2014-01-01

Though the cortical contributions to age-related declines in motor and cognitive performance are well-known, the potential contributions of the cerebellum are less clear. The diverse functions of the cerebellum make it an important structure to investigate in aging. Here, we review the extant literature on this topic. To date, there is evidence to indicate that there are morphological age differences in the cerebellum that are linked to motor and cognitive behavior. Cerebellar morphology is often as good as -- or even better -- at predicting performance than the prefrontal cortex. We also touch on the few studies using functional neuroimaging and connectivity analyses that further implicate the cerebellum in age-related performance declines. Importantly, we provide a conceptual framework for the cerebellum influencing age differences in performance, centered on the notion of degraded internal models. The evidence indicating that cerebellar age differences associate with performance highlights the need for additional work in this domain to further elucidate the role of the cerebellum in age differences in movement control and cognitive function. PMID:24594194

Evolving Evidence for the Value of Neuroimaging Methods and Biological Markers in Subjects Categorized with Subjective Cognitive Decline.

PubMed

Lista, Simone; Molinuevo, Jose L; Cavedo, Enrica; Rami, Lorena; Amouyel, Philippe; Teipel, Stefan J; Garaci, Francesco; Toschi, Nicola; Habert, Marie-Odile; Blennow, Kaj; Zetterberg, Henrik; O'Bryant, Sid E; Johnson, Leigh; Galluzzi, Samantha; Bokde, Arun L W; Broich, Karl; Herholz, Karl; Bakardjian, Hovagim; Dubois, Bruno; Jessen, Frank; Carrillo, Maria C; Aisen, Paul S; Hampel, Harald

2015-09-24

There is evolving evidence that individuals categorized with subjective cognitive decline (SCD) are potentially at higher risk for developing objective and progressive cognitive impairment compared to cognitively healthy individuals without apparent subjective complaints. Interestingly, SCD, during advancing preclinical Alzheimer's disease (AD), may denote very early, subtle cognitive decline that cannot be identified using established standardized tests of cognitive performance. The substantial heterogeneity of existing SCD-related research data has led the Subjective Cognitive Decline Initiative (SCD-I) to accomplish an international consensus on the definition of a conceptual research framework on SCD in preclinical AD. In the area of biological markers, the cerebrospinal fluid signature of AD has been reported to be more prevalent in subjects with SCD compared to healthy controls; moreover, there is a pronounced atrophy, as demonstrated by magnetic resonance imaging, and an increased hypometabolism, as revealed by positron emission tomography, in characteristic brain regions affected by AD. In addition, SCD individuals carrying an apolipoprotein ɛ4 allele are more likely to display AD-phenotypic alterations. The urgent requirement to detect and diagnose AD as early as possible has led to the critical examination of the diagnostic power of biological markers, neurophysiology, and neuroimaging methods for AD-related risk and clinical progression in individuals defined with SCD. Observational studies on the predictive value of SCD for developing AD may potentially be of practical value, and an evidence-based, validated, qualified, and fully operationalized concept may inform clinical diagnostic practice and guide earlier designs in future therapy trials.

Diffusion Tensor Imaging of Normal-Appearing White Matter as Biomarker for Radiation-Induced Late Delayed Cognitive Decline

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, Christopher H., E-mail: chchap@umich.edu; Nagesh, Vijaya; Sundgren, Pia C.

Purpose: To determine whether early assessment of cerebral white matter degradation can predict late delayed cognitive decline after radiotherapy (RT). Methods and Materials: Ten patients undergoing conformal fractionated brain RT participated in a prospective diffusion tensor magnetic resonance imaging study. Magnetic resonance imaging studies were acquired before RT, at 3 and 6 weeks during RT, and 10, 30, and 78 weeks after starting RT. The diffusivity variables in the parahippocampal cingulum bundle and temporal lobe white matter were computed. A quality-of-life survey and neurocognitive function tests were administered before and after RT at the magnetic resonance imaging follow-up visits. Results:more » In both structures, longitudinal diffusivity ({lambda}{sub Double-Vertical-Line }) decreased and perpendicular diffusivity ({lambda}{sub Up-Tack }) increased after RT, with early changes correlating to later changes (p < .05). The radiation dose correlated with an increase in cingulum {lambda}{sub Up-Tack} at 3 weeks, and patients with >50% of cingula volume receiving >12 Gy had a greater increase in {lambda}{sub Up-Tack} at 3 and 6 weeks (p < .05). The post-RT changes in verbal recall scores correlated linearly with the late changes in cingulum {lambda}{sub Double-Vertical-Line} (30 weeks, p < .02). Using receiver operating characteristic curves, early cingulum {lambda}{sub Double-Vertical-Line} changes predicted for post-RT changes in verbal recall scores (3 and 6 weeks, p < .05). The neurocognitive test scores correlated significantly with the quality-of-life survey results. Conclusions: The correlation between early diffusivity changes in the parahippocampal cingulum and the late decline in verbal recall suggests that diffusion tensor imaging might be useful as a biomarker for predicting late delayed cognitive decline.« less

Relation between speech-in-noise threshold, hearing loss and cognition from 40-69 years of age.

PubMed

Moore, David R; Edmondson-Jones, Mark; Dawes, Piers; Fortnum, Heather; McCormack, Abby; Pierzycki, Robert H; Munro, Kevin J

2014-01-01

Healthy hearing depends on sensitive ears and adequate brain processing. Essential aspects of both hearing and cognition decline with advancing age, but it is largely unknown how one influences the other. The current standard measure of hearing, the pure-tone audiogram is not very cognitively demanding and does not predict well the most important yet challenging use of hearing, listening to speech in noisy environments. We analysed data from UK Biobank that asked 40-69 year olds about their hearing, and assessed their ability on tests of speech-in-noise hearing and cognition. About half a million volunteers were recruited through NHS registers. Respondents completed 'whole-body' testing in purpose-designed, community-based test centres across the UK. Objective hearing (spoken digit recognition in noise) and cognitive (reasoning, memory, processing speed) data were analysed using logistic and multiple regression methods. Speech hearing in noise declined exponentially with age for both sexes from about 50 years, differing from previous audiogram data that showed a more linear decline from <40 years for men, and consistently less hearing loss for women. The decline in speech-in-noise hearing was especially dramatic among those with lower cognitive scores. Decreasing cognitive ability and increasing age were both independently associated with decreasing ability to hear speech-in-noise (0.70 and 0.89 dB, respectively) among the population studied. Men subjectively reported up to 60% higher rates of difficulty hearing than women. Workplace noise history associated with difficulty in both subjective hearing and objective speech hearing in noise. Leisure noise history was associated with subjective, but not with objective difficulty hearing. Older people have declining cognitive processing ability associated with reduced ability to hear speech in noise, measured by recognition of recorded spoken digits. Subjective reports of hearing difficulty generally show a higher prevalence than objective measures, suggesting that current objective methods could be extended further.

Do apolipoprotein E genotype and educational attainment predict the rate of cognitive decline in normal aging? A 12-year follow-up of the Maastricht Aging Study.

PubMed

Van Gerven, Pascal W M; Van Boxtel, Martin P J; Ausems, Eleonora E B; Bekers, Otto; Jolles, Jelle

2012-07-01

We investigated suspected longitudinal interaction effects of apolipoprotein E (APOE) genotype and educational attainment on cognitive decline in normal aging. Our sample consisted of 571 healthy, nondemented adults aged between 49 and 82 years. Linear mixed-models analyses were performed with four measurement time points: baseline, 3-year, 6-year, and 12-year follow-up. Covariates included age at baseline, sex, and self-perceived physical and mental health. Dependent measures were global cognitive functioning (Mini-Mental State Examination; Folstein, Folstein, & McHugh, 1975), Stroop performance (Stroop Color-Word Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006a), set-shifting performance (Concept Shifting Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006b), cognitive speed (Letter-Digit Substitution Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006c), verbal learning (Verbal Learning Test: Sum of five trials; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2005), and long-term memory (Verbal Learning Test: Delayed recall). We found only faint evidence that older, high-educated carriers of the APOE-ε4 allele (irrespective of zygosity) show a more pronounced decline than younger, low-educated carriers and noncarriers (irrespective of educational attainment). Moreover, this outcome was confined to concept-shifting performance and was especially observable between 6- and 12-year follow-ups. No protective effects of higher education were found on any of the six cognitive measures. We conclude that the combination of APOE-ε4 allele and high educational attainment may be a risk factor for accelerated cognitive decline in older age, as has been reported before, but only to a very limited extent. Moreover, we conclude that, within the cognitive reserve framework, education does not have significant protective power against age-related cognitive decline.

Relation between Speech-in-Noise Threshold, Hearing Loss and Cognition from 40–69 Years of Age

PubMed Central

Moore, David R.; Edmondson-Jones, Mark; Dawes, Piers; Fortnum, Heather; McCormack, Abby; Pierzycki, Robert H.; Munro, Kevin J.

2014-01-01

Background Healthy hearing depends on sensitive ears and adequate brain processing. Essential aspects of both hearing and cognition decline with advancing age, but it is largely unknown how one influences the other. The current standard measure of hearing, the pure-tone audiogram is not very cognitively demanding and does not predict well the most important yet challenging use of hearing, listening to speech in noisy environments. We analysed data from UK Biobank that asked 40–69 year olds about their hearing, and assessed their ability on tests of speech-in-noise hearing and cognition. Methods and Findings About half a million volunteers were recruited through NHS registers. Respondents completed ‘whole-body’ testing in purpose-designed, community-based test centres across the UK. Objective hearing (spoken digit recognition in noise) and cognitive (reasoning, memory, processing speed) data were analysed using logistic and multiple regression methods. Speech hearing in noise declined exponentially with age for both sexes from about 50 years, differing from previous audiogram data that showed a more linear decline from <40 years for men, and consistently less hearing loss for women. The decline in speech-in-noise hearing was especially dramatic among those with lower cognitive scores. Decreasing cognitive ability and increasing age were both independently associated with decreasing ability to hear speech-in-noise (0.70 and 0.89 dB, respectively) among the population studied. Men subjectively reported up to 60% higher rates of difficulty hearing than women. Workplace noise history associated with difficulty in both subjective hearing and objective speech hearing in noise. Leisure noise history was associated with subjective, but not with objective difficulty hearing. Conclusions Older people have declining cognitive processing ability associated with reduced ability to hear speech in noise, measured by recognition of recorded spoken digits. Subjective reports of hearing difficulty generally show a higher prevalence than objective measures, suggesting that current objective methods could be extended further. PMID:25229622

Cerebral glucose metabolism and cognition in newly diagnosed Parkinson's disease: ICICLE-PD study.

PubMed

Firbank, M J; Yarnall, A J; Lawson, R A; Duncan, G W; Khoo, T K; Petrides, G S; O'Brien, J T; Barker, R A; Maxwell, R J; Brooks, D J; Burn, D J

2017-04-01

To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline. FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA. PD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (β=0.38, p=0.001) and MoCA (β=0.3, p=0.002) at 18 months controlling for baseline score. Reductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Poorer Visual Acuity Is Associated with Declines in Cognitive Performance Across Multiple Cognitive Domains: The Maine-Syracuse Longitudinal Study.

PubMed

Dearborn, Peter J; Elias, Merrill F; Sullivan, Kevin J; Sullivan, Cara E; Robbins, Michael A

2018-06-21

Prior studies have found associations between visual acuity (VA) and cognitive function. However, these studies used a limited range of cognitive measures and did not control for cardiovascular disease risk factors (CVD-RFs) and baseline function. The primary objective of this study was to analyze the associations of VA and cognitive performance using a thorough neuropsychological test battery. This study used community-dwelling sample data across the sixth (2001-2006) and seventh (2006-2010) waves of the Maine-Syracuse Longitudinal Study (n=655). Wave 6 VA as measured by the Snellen Eye Test was the primary predictor of wave 6 and wave 7 Global cognitive performance, Visual-Spatial Organization and Memory, Verbal Episodic Memory, Working Memory, Scanning and Tracking, and Executive Function. Additionally, VA was used to predict longitudinal changes in wave 7 cognitive performance (wave 6 performance adjusted). We analyzed these relationships with multiple linear and logistic regression models adjusted for age, sex, education, ethnicity, depressive symptoms, physical function deficits in addition to CVD-RFs, chronic kidney disease, homocysteine, continuous systolic blood pressure, and hypertension status. Adjusted for demographic covariates and CVD-RFs, poorer VA was associated with concurrent and approximate 5-year declines in Global cognitive function, Visual-Spatial Organization and Memory, and Verbal Episodic Memory. VA may be used in combination with other screening measures to determine risk for cognitive decline. (JINS, 2018, 24, 1-9).

Longitudinal association of hypertension and diabetes mellitus with cognitive functioning in a general 70-year-old population: the SONIC study.

PubMed

Ryuno, Hirochika; Kamide, Kei; Gondo, Yasuyuki; Kabayama, Mai; Oguro, Ryosuke; Nakama, Chikako; Yokoyama, Serina; Nagasawa, Motonori; Maeda-Hirao, Satomi; Imaizumi, Yuki; Takeya, Miyuki; Yamamoto, Hiroko; Takeda, Masao; Takami, Yoichi; Itoh, Norihisa; Takeya, Yasushi; Yamamoto, Koichi; Sugimoto, Ken; Nakagawa, Takeshi; Yasumoto, Saori; Ikebe, Kazunori; Inagaki, Hiroki; Masui, Yukie; Takayama, Michiyo; Arai, Yasumichi; Ishizaki, Tatsuro; Takahashi, Ryutaro; Rakugi, Hiromi

2017-07-01

Both hypertension and diabetes in middle-aged individuals have been suggested to be predictive indicators of cognitive decline. However, the association of hypertension, diabetes and their combination with cognitive functioning is still controversial in older people. The purpose of this study was to investigate the association between cognitive decline and hypertension, diabetes, and their combination in 70-year-old people based on a 3-year longitudinal analysis. Four hundred and fifty-four people aged 70 (±1) years who participated in the Japanese longitudinal cohort study of Septuagenarians, Octogenarians and Nonagenarians Investigation with Centenarians (SONIC) were recruited randomly from a general population and were monitored for 3 years. The data, including most of the demographics, cognitive functioning measured by the Montreal Cognitive Assessment Japanese version (MoCA-J), blood pressure, blood chemistry and other medical histories, were collected at baseline and during the follow-up. The prevalence of hypertension noted in the follow-up survey was significantly higher than than noted at baseline. The mean MoCA-J score at follow-up was not significantly different from the score obtained at baseline. However, the participants with diabetes, especially combined with hypertension at baseline, had significantly lower MoCA-J scores than those without lifestyle-related diseases. The combination of hypertension and diabetes was still a significant risk factor for cognitive decline, considering the MoCA-J scores obtained during the follow-up after adjustments at baseline, relative to sex, body mass index, dyslipidemia, smoking, excessive alcohol intake, antihypertensive treatment and education level (β=-0.14; P<0.01). Our findings indicate that diabetes and the combination of hypertension and diabetes are clear risk factors for future cognitive decline in elderly individuals who are 70 years of age.

Naturalistic distraction and driving safety in older drivers

PubMed Central

Aksan, Nazan; Dawson, Jeffrey D.; Emerson, Jamie L.; Yu, Lixi; Uc, Ergun Y.; Anderson, Steven W.; Rizzo, Matthew

2013-01-01

Objective This study aimed to quantify and compare performance of middle-aged and older drivers during a naturalistic distraction paradigm (visual search for roadside targets) and predict older driver performance given functioning in visual, motor, and cognitive domains. Background Distracted driving can imperil healthy adults and may disproportionally affect the safety of older drivers with visual, motor, and cognitive decline. Methods Two hundred and three drivers, 120 healthy older (61 men and 59 women, ages 65 years or greater) and 83 middle-aged drivers (38 men and 45 women, ages 40–64 years), participated in an on-road test in an instrumented vehicle. Outcome measures included performance in roadside target identification (traffic signs and restaurants) and concurrent driver safety. Differences in visual, motor, and cognitive functioning served as predictors. Results Older drivers identified fewer landmarks and drove slower but committed more safety errors than middle-aged drivers. Greater familiarity with local roads benefited performance of middle-aged but not older drivers. Visual cognition predicted both traffic sign identification and safety errors while executive function predicted traffic sign identification over and above vision. Conclusion Older adults are susceptible to driving safety errors while distracted by common secondary visual search tasks that are inherent to driving. The findings underscore that age-related cognitive decline affects older driver management of driving tasks at multiple levels, and can help inform the design of on-road tests and interventions for older drivers. PMID:23964422

Positive affect and cognitive decline: a 12-year follow-up of the Maastricht Aging Study.

PubMed

Berk, Lotte; van Boxtel, Martin; Köhler, Sebastian; van Os, Jim

2017-12-01

In cross-sectional studies, positive affect (PA) has been associated with higher levels of cognitive functioning. This study examined whether positive affect (PA) is associated with change in cognitive function over 12 years in an adult population sample. Participants (n = 258), aged 40 to 82 years, were drawn from a subsample of the Maastricht Aging Study (MAAS) and assessed at baseline, 6 years and 12 years. PA was measured at baseline with a Dutch translation of the Positive and Negative Affect Schedule (PANAS). PA scores and associations with cognitive decline were tested in random-effects models. Controlling for demographics and depressive symptoms, there was no significant association with PA scores and decline in memory (χ 2  = 1.52; df = 2; P = 0.47), executive functions (χ 2  = 0.99; df = 2; P = 0.61), and information processing speed (χ 2  = 0.52; df = 2; P = 0.77) at 6- and 12-year follow-up. PA did not predict cognitive change over time. These findings question the extent of protective effects of PA on cognitive aging in adulthood, and are discussed in terms of age range and types of measures used for PA and cognition. Copyright © 2016 John Wiley & Sons, Ltd.

Loneliness, depression and cognitive function in older U.S. adults.

PubMed

Donovan, Nancy J; Wu, Qiong; Rentz, Dorene M; Sperling, Reisa A; Marshall, Gad A; Glymour, M Maria

2017-05-01

To examine reciprocal relations of loneliness and cognitive function in older adults. Data were analyzed from 8382 men and women, age 65 and older, participating in the US Health and Retirement Study from 1998 to 2010. Participants underwent biennial assessments of loneliness and depression (classified as no, low or high depression) determined by the Center for Epidemiologic Studies Depression scale (8-item version), cognition (a derived memory score based on a word list memory task and proxy-rated memory and global cognitive function), health status and social and demographic characteristics from 1998 to 2010. We used repeated measures analysis to examine the reciprocal relations of loneliness and cognitive function in separate models controlling sequentially and cumulatively for socio-demographic factors, social network, health conditions and depression. Loneliness at baseline predicted accelerated cognitive decline over 12 years independent of baseline socio-demographic factors, social network, health conditions and depression (β = -0.2, p = 0.002). After adjustment for depression interacting with time, both low and high depression categories were related to faster cognitive decline and the estimated effect of loneliness became marginally significant. Reciprocally, poorer cognition at baseline was associated with greater odds of loneliness over time in adjusted analyses (OR 1.3, 95% CI (1.1-1.5) p = 0.005), but not when controlling for baseline depression. Furthermore, cognition did not predict change in loneliness over time. Examining longitudinal data across a broad range of cognitive abilities, loneliness and depressive symptoms appear to be related risk factors for worsening cognition but low cognitive function does not lead to worsening loneliness over time. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease

PubMed Central

Caspell-Garcia, Chelsea; Simuni, Tanya; Tosun-Turgut, Duygu; Wu, I-Wei; Zhang, Yu; Nalls, Mike; Singleton, Andrew; Shaw, Leslie A.; Kang, Ju-Hee; Trojanowski, John Q.; Siderowf, Andrew; Coffey, Christopher; Lasch, Shirley; Aarsland, Dag; Burn, David; Chahine, Lana M.; Espay, Alberto J.; Foster, Eric D.; Hawkins, Keith A.; Litvan, Irene; Richard, Irene; Weintraub, Daniel

2017-01-01

Objectives To assess the neurobiological substrate of initial cognitive decline in Parkinson’s disease (PD) to inform patient management, clinical trial design, and development of treatments. Methods We longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aβ], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition. Additionally, longitudinal structural MRI and DAT scan data were included. Univariate analyses were run initially, with false discovery rate = 0.2, to select biomarker variables for inclusion in multivariable longitudinal mixed-effect models. Results By year 3, cognitive impairment was diagnosed in 15–38% participants depending on the criteria applied. Biomarkers, some longitudinal, predicting cognitive impairment in multivariable models were: (1) dopamine deficiency (decreased caudate and putamen DAT availability); (2) diffuse, cortical decreased brain volume or thickness (frontal, temporal, parietal, and occipital lobe regions); (3) co-morbid Alzheimer’s disease Aβ amyloid pathology (lower CSF Aβ 1–42); and (4) genes (COMT val/val and BDNF val/val genotypes). Conclusions Cognitive impairment in PD increases in frequency 50–200% in the first several years of disease, and is independently predicted by biomarker changes related to nigrostriatal or cortical dopaminergic deficits, global atrophy due to possible widespread effects of neurodegenerative disease, co-morbid Alzheimer’s disease plaque pathology, and genetic factors. PMID:28520803

Only White Matter Hyperintensities Predicts Post-Stroke Cognitive Performances Among Cerebral Small Vessel Disease Markers: Results from the TABASCO Study.

PubMed

Molad, Jeremy; Kliper, Efrat; Korczyn, Amos D; Ben Assayag, Einor; Ben Bashat, Dafna; Shenhar-Tsarfaty, Shani; Aizenstein, Orna; Shopin, Ludmila; Bornstein, Natan M; Auriel, Eitan

2017-01-01

White matter hyperintensities (WMH) were shown to predict cognitive decline following stroke or transient ischemic attack (TIA). However, WMH are only one among other radiological markers of cerebral small vessel disease (SVD). The aim of this study was to determine whether adding other SVD markers to WMH improves prediction of post-stroke cognitive performances. Consecutive first-ever stroke or TIA patients (n = 266) from the Tel Aviv Acute Brain Stroke Cohort (TABASCO) study were enrolled. MRI scans were performed within seven days of stroke onset. We evaluated the relationship between cognitive performances one year following stroke, and previously suggested total SVD burden score including WMH, lacunes, cerebral microbleeds (CMB), and perivascular spaces (PVS). Significant negative associations were found between WMH and cognition (p < 0.05). Adding other SVD markers (lacunes, CMB, PVS) to WMH did not improve predication of post-stroke cognitive performances. Negative correlations between SVD burden score and cognitive scores were observed for global cognitive, memory, and visual spatial scores (all p < 0.05). However, following an adjustment for confounders, no associations remained significant. WMH score was associated with poor post-stroke cognitive performance. Adding other SVD markers or SVD burden score, however, did not improve prediction.

Working memory overload: fronto-limbic interactions and effects on subsequent working memory function.

PubMed

Yun, Richard J; Krystal, John H; Mathalon, Daniel H

2010-03-01

The human working memory system provides an experimentally useful model for examination of neural overload effects on subsequent functioning of the overloaded system. This study employed functional magnetic resonance imaging in conjunction with a parametric working memory task to characterize the behavioral and neural effects of cognitive overload on subsequent cognitive performance, with particular attention to cognitive-limbic interactions. Overloading the working memory system was associated with varying degrees of subsequent decline in performance accuracy and reduced activation of brain regions central to both task performance and suppression of negative affect. The degree of performance decline was independently predicted by three separate factors operating during the overload condition: the degree of task failure, the degree of amygdala activation, and the degree of inverse coupling between the amygdala and dorsolateral prefrontal cortex. These findings suggest that vulnerability to overload effects in cognitive functioning may be mediated by reduced amygdala suppression and subsequent amygdala-prefrontal interaction.

Hypothetical Preclinical Alzheimer Disease Groups and Longitudinal Cognitive Change.

PubMed

Soldan, Anja; Pettigrew, Corinne; Cai, Qing; Wang, Mei-Cheng; Moghekar, Abhay R; O'Brien, Richard J; Selnes, Ola A; Albert, Marilyn S

2016-06-01

Clinical trials testing treatments for Alzheimer disease (AD) are increasingly focused on cognitively normal individuals in the preclinical phase of the disease. To optimize observing a treatment effect, such trials need to enroll cognitively normal individuals likely to show cognitive decline over the duration of the trial. To identify which group of cognitively normal individuals shows the greatest cognitive decline over time based on their cerebrospinal fluid biomarker profile. In this cohort study, cognitively normal participants were classified into 1 of the following 4 hypothetical preclinical AD groups using baseline cerebrospinal fluid levels of Aβ and tau or Aβ and phosphorylated tau (p-tau): stage 0 (high Aβ and low tau), stage 1 (low Aβ and low tau), stage 2 (low Aβ and high tau), and suspected non-AD pathology (SNAP) (high Aβ and high tau). The data presented herein were collected between August 1995 and August 2014. An a priori cognitive composite score based on the following 4 tests previously shown to predict progression from normal cognition to symptom onset of mild cognitive impairment or dementia: Paired Associates immediate recall, Logical Memory delayed recall, Boston Naming, and Digit-Symbol Substitution. Linear mixed-effects models were used to compare the cognitive composite scores across the 4 groups over time, adjusting for baseline age, sex, education, and their interactions with time. Two hundred twenty-two cognitively normal participants were included in the analyses (mean follow-up, 11.0 years [range, 0-18.3 years] and mean baseline age, 56.9 years [range, 22.1-85.8 years]). Of these, 102 were stage 0, 46 were stage 1, 28 were stage 2, and 46 were SNAP. Individuals in stage 2 (low Aβ and high tau [or p-tau]) had lower baseline cognitive scores and a greater decline in the cognitive composite score relative to the other 3 groups (β ≤ -0.06 for all and P ≤ .001 for the rate of decline for all). Individuals in stage 0, stage 1, and SNAP did not differ from one another in cognitive performance at baseline or over time (11.0 years) and showed practice-related improvement in performance. The APOE ε4 genotype was not associated with baseline cognitive composite score or the rate of change in the cognitive composite score. These results suggest that, to optimize observing a treatment effect, clinical trials enrolling cognitively normal individuals should selectively recruit participants with abnormal levels of both amyloid and tau (ie, stage 2) because this group would be expected to show the greatest cognitive decline over time if untreated.

The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study.

PubMed

Samaras, Katherine; Lutgers, Helen L; Kochan, Nicole A; Crawford, John D; Campbell, Lesley V; Wen, Wei; Slavin, Melissa J; Baune, Bernard T; Lipnicki, Darren M; Brodaty, Henry; Trollor, Julian N; Sachdev, Perminder S

2014-04-01

Type 2 diabetes predicts accelerated cognitive decline and brain atrophy. We hypothesized that impaired fasting glucose (IFG) and incident glucose disorders have detrimental effects on global cognition and brain volume. We further hypothesized that metabolic and inflammatory derangements accompanying hyperglycaemia contribute to change in brain structure and function. This was a longitudinal study of a community-dwelling elderly cohort with neuropsychological testing (n = 880) and brain volumes by magnetic resonance imaging (n = 312) measured at baseline and 2 years. Primary outcomes were global cognition and total brain volume. Secondary outcomes were cognitive domains (processing speed, memory, language, visuospatial and executive function) and brain volumes (hippocampal, parahippocampal, precuneus and frontal lobe). Participants were categorised as normal, impaired fasting glucose at both assessments (stable IFG), baseline diabetes or incident glucose disorders (incident diabetes or IFG at 2 years). Measures included inflammatory cytokines and oxidative metabolites. Covariates were age, sex, education, non-English speaking background, smoking, blood pressure, lipid-lowering or antihypertensive medications, mood score, apolipoprotein E genotype and baseline cognition or brain volume. Participants with incident glucose disorders had greater decline in global cognition and visuospatial function compared to normal, similar to that observed in baseline diabetes. Homocysteine was independently associated with the observed effect of diabetes on executive function. Apolipoprotein E genotype did not influence the observed effects of diabetes on cognition. Incident glucose disorders and diabetes were also associated with greater 2-year decline in total brain volume, compared to normal (40.0 ± 4.2 vs. 46.7 ± 5.7 mm(3) vs. 18.1 ± 6.2, respectively, p < 0.005). Stable IFG did not show greater decline in global cognition or brain volumes compared to normal. Incident glucose disorders, like diabetes, are associated with accelerated decline in global cognition and brain volumes in non-demented elderly, whereas stable IFG is not. Preventing deterioration in glucose metabolism in the elderly may help preserve brain structure and function.

COMPASS: A computational model to predict changes in MMSE scores 24-months after initial assessment of Alzheimer's disease.

PubMed

Zhu, Fan; Panwar, Bharat; Dodge, Hiroko H; Li, Hongdong; Hampstead, Benjamin M; Albin, Roger L; Paulson, Henry L; Guan, Yuanfang

2016-10-05

We present COMPASS, a COmputational Model to Predict the development of Alzheimer's diSease Spectrum, to model Alzheimer's disease (AD) progression. This was the best-performing method in recent crowdsourcing benchmark study, DREAM Alzheimer's Disease Big Data challenge to predict changes in Mini-Mental State Examination (MMSE) scores over 24-months using standardized data. In the present study, we conducted three additional analyses beyond the DREAM challenge question to improve the clinical contribution of our approach, including: (1) adding pre-validated baseline cognitive composite scores of ADNI-MEM and ADNI-EF, (2) identifying subjects with significant declines in MMSE scores, and (3) incorporating SNPs of top 10 genes connected to APOE identified from functional-relationship network. For (1) above, we significantly improved predictive accuracy, especially for the Mild Cognitive Impairment (MCI) group. For (2), we achieved an area under ROC of 0.814 in predicting significant MMSE decline: our model has 100% precision at 5% recall, and 91% accuracy at 10% recall. For (3), "genetic only" model has Pearson's correlation of 0.15 to predict progression in the MCI group. Even though addition of this limited genetic model to COMPASS did not improve prediction of progression of MCI group, the predictive ability of SNP information extended beyond well-known APOE allele.

Cognitive Performance in Healthy Women During Induced Hypogonadism and Ovarian Steroid Addback

PubMed Central

Schmidt, Peter J.; Keenan, PA; Schenkel, Linda A; Berlin, Kate; Gibson, Carolyn; Rubinow, David R.

2012-01-01

Background Gynecology clinic-based studies have consistently demonstrated that induced hypogonadism is accompanied by a decline in cognitive test performance. However, a recent study in healthy asymptomatic controls observed that neither induced hypogonadism nor estradiol replacement influenced cognitive performance. Thus the effects of induced hypogonadism on cognition might not be uniformly experienced across individual women. Moreover, discrepancies in the effects of hypogonadism on cognition also could suggest the existence of specific risk phenotypes that predict a woman’s symptomatic experience during the menopause. In this study, we examined the effects of induced hypogonadism and ovarian steroid replacement on cognitive performance in healthy premenopausal women. Methods Ovarian suppression was induced with a GnRH agonist (Lupron) and then physiologic levels of estradiol and progesterone were re-introduced in 23 women. Cognitive tests were administered during each hormone condition. To evaluate possible practice effects arising during repeated testing, an identical battery of tests was administered at the same time intervals in 11 untreated women. Results With the exception of an improved performance on mental rotation during estradiol, we observed no significant effects of estradiol or progesterone on measures of attention, concentration, or memory compared with hypogonadism. Conclusions In contrast to studies in which a decline in cognitive performance was observed in women receiving ovarian suppression therapy for an underlying gynecologic condition, we confirm a prior report demonstrating that short term changes in gonadal steroids have a limited effect on cognition in young, healthy, women. Differences in the clinical characteristics of the women receiving GnRH agonists could predict a risk for ovarian steroid-related changes in cognitive performance during induced, and possibly, natural menopause. Key Words: estradiol, hypogonadism, progesterone, cognition. PMID:23188540

Cognitive Flexibility in Juvenile Anorexia Nervosain Relation to Comorbid Symptoms of Depression, Obsessive Compulsive Symptoms and Duration of Illness.

PubMed

Rößner, Anne; Juniak, Izabela; van Noort, Betteke Maria; Pfeiffer, Ernst; Lehmkuhl, Ulrike; Kappel, Viola

2017-09-01

Whereas the evidence in adolescents is inconsistent, anorexia nervosa (AN) in adults is characterized by weak cognitive flexibility. This study investigates cognitive flexibility in adolescents with AN and its potential associations with symptoms of depression, obsessive compulsive disorder (OCD), and duration of illness. 69 patients and 63 age-matched healthy controls (HC) from 9 till 19 years of age were assessed using the Trail-Making Test (TMT) and self-report questionnaires. In hierarchical regression analyses, set-shifting ability did not differ between AN and HC, whereas AN patients reported significantly higher rates of depression symptoms and OCD symptoms. Age significantly predicted set-shifting in the total sample. Only among AN patients aged 14 years and older did set-shifting decline with increasing age. The presence of AN with depression or OCD symptoms or the duration of illness do not influence cognitive flexibility in children and adolescents. Early interventions may be helpful to prevent a decline in cognitive flexibility in adolescent AN with increasing age.

Loneliness and Cognitive Function in Older Adults: Findings From the Chinese Longitudinal Healthy Longevity Survey

PubMed Central

Chen, Shu-Lin; Tu, Xin; Conwell, Yeates

2017-01-01

Objectives: To examine the relationship between loneliness and cognitive function and to explore the mediating role of physical health on the loneliness–cognition relationship in Chinese older adults (OAs). Method: Data came from a nationally representative sample of 14,199 Chinese OAs (aged 65+) from 2002, 2005, 2008, and 2011 waves of the Chinese Longitudinal Healthy Longevity Survey. A latent variable cross-lagged panel model combined with mediation analysis was used to determine the relationship between loneliness and cognitive function and the mediating effect of increase in the number of chronic conditions (ΔNCCs) on the ascertained loneliness–cognition relationship. Results: Severe loneliness at prior assessment points was significantly associated with poorer cognitive function at subsequent assessments, and vice versa. The ΔNCCs partially mediated this prospective reciprocal relationships, accounting for 2.58% of the total effect of loneliness on cognition and 4.44% of the total effect of cognition on loneliness, respectively. Discussion: Loneliness may predict subsequent cognitive decline, and vice versa. This loneliness–cognition relationship is partially explained by their impact on physical health. Multidisciplinary interventions aimed at reducing loneliness and cognitive decline per se and their associated risk factors as well as improving chronic illness management would be beneficial for emotional well-being and cognitive health in OAs. PMID:27013536

Nucleus basalis of Meynert degeneration precedes and predicts cognitive impairment in Parkinson's disease.

PubMed

Schulz, Jonathan; Pagano, Gennaro; Fernández Bonfante, Juan Alberto; Wilson, Heather; Politis, Marios

2018-05-01

Currently, no reliable predictors of cognitive impairment in Parkinson's disease exist. We hypothesized that microstructural changes at grey matter T1-weighted MRI and diffusion tensor imaging in the cholinergic system nuclei and associated limbic pathways underlie cognitive impairment in Parkinson's disease. We performed a cross-sectional comparison between patients with Parkinson's disease with and without cognitive impairment. We also performed a longitudinal 36-month follow-up study of cognitively intact Parkinson's disease patients, comparing patients who remained cognitively intact to those who developed cognitive impairment. Patients with Parkinson's disease with cognitive impairment showed lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert, compared to patients with Parkinson's disease without cognitive impairment. These results were confirmed both with region of interest and voxel-based analyses, and after partial volume correction. Lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert was predictive for developing cognitive impairment in cognitively intact patients with Parkinson's disease, independent of other clinical and non-clinical markers of the disease. Structural and microstructural alterations in entorhinal cortex, amygdala, hippocampus, insula, and thalamus were not predictive for developing cognitive impairment in Parkinson's disease. Our findings provide evidence that degeneration of the nucleus basalis of Meynert precedes and predicts the onset of cognitive impairment, and might be used in a clinical setting as a reliable biomarker to stratify patients at higher risk of cognitive decline.

Lacunar Infarcts, but Not Perivascular Spaces, Are Predictors of Cognitive Decline in Cerebral Small-Vessel Disease

PubMed Central

Trippier, Sarah; Lawrence, Andrew J.; Lambert, Christian; Zeestraten, Eva; Williams, Owen A.; Patel, Bhavini; Morris, Robin G.; Barrick, Thomas R.; MacKinnon, Andrew D.; Markus, Hugh S.

2018-01-01

Background and Purpose— Cerebral small-vessel disease is a major cause of cognitive impairment. Perivascular spaces (PvS) occur in small-vessel disease, but their relationship to cognitive impairment remains uncertain. One reason may be difficulty in distinguishing between lacunes and PvS. We determined the relationship between baseline PvS score and PvS volume with change in cognition over a 5-year follow-up. We compared this to the relationship between baseline lacune count and total lacune volume with cognition. In addition, we examined change in PvS volume over time. Methods— Data from the prospective SCANS study (St Georges Cognition and Neuroimaging in Stroke) of patients with symptomatic lacunar stroke and confluent leukoaraiosis were used (n=121). Multimodal magnetic resonance imaging was performed annually for 3 years and neuropsychological testing annually for 5 years. Lacunes were manually identified and distinguished from PvS. PvS were rated using a validated visual rating scale, and PvS volumes calculated using T1-weighted images. Linear mixed-effect models were used to determine the impact of PvS and lacunes on cognition. Results— Baseline PvS scores or volumes showed no association with cognitive indices. No change was detectable in PvS volumes over the 3 years. In contrast, baseline lacunes associated with all cognitive indices and predicted cognitive decline over the 5-year follow-up. Conclusions— Although a feature of small-vessel disease, PvS are not a predictor of cognitive decline, in contrast to lacunes. This study highlights the importance of carefully differentiating between lacunes and PvS in studies investigating vascular cognitive impairment. PMID:29438074

Using Neuropsychological Process Scores to Identify Subtle Cognitive Decline and Predict Progression to Mild Cognitive Impairment.

PubMed

Thomas, Kelsey R; Edmonds, Emily C; Eppig, Joel; Salmon, David P; Bondi, Mark W

2018-05-26

We previously operationally-defined subtle cognitive decline (SCD) in preclinical Alzheimer's disease (AD) using total scores on neuropsychological (NP) tests. NP process scores (i.e., provide information about how a total NP score was achieved) may be a useful tool for identifying early cognitive inefficiencies prior to objective impairment seen in mild cognitive impairment (MCI) and dementia. We aimed to integrate process scores into the SCD definition to identify stages of SCD and improve early detection of those at risk for decline. Cognitively "normal" participants from the Alzheimer's Disease Neuroimaging Initiative were classified as "early" SCD (E-SCD; >1 SD below mean on 2 process scores or on 1 process score plus 1 NP total score), "late" SCD (L-SCD; existing SCD criteria of >1 SD below norm-adjusted mean on 2 NP total scores in different domains), or "no SCD" (NC). Process scores considered in the SCD criteria were word-list intrusion errors, retroactive interference, and learning slope. Cerebrospinal fluid AD biomarkers were used to examine pathologic burden across groups. E-SCD and L-SCD progressed to MCI 2.5-3.4 times faster than the NC group. Survival curves for E-SCD and L-SCD converged at 7-8 years after baseline. The combined (E-SCD+L-SCD) group had improved sensitivity to detect progression to MCI relative to L-SCD only. AD biomarker positivity increased across NC, SCD, and MCI groups. Process scores can be integrated into the SCD criteria to allow for increased sensitivity and earlier identification of cognitively normal older adults at risk for decline prior to frank impairment on NP total scores.

Video games as a means to reduce age-related cognitive decline: attitudes, compliance, and effectiveness.

PubMed

Boot, Walter R; Champion, Michael; Blakely, Daniel P; Wright, Timothy; Souders, Dustin J; Charness, Neil

2013-01-01

Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a "brain fitness" game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants' ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why.

Video Games as a Means to Reduce Age-Related Cognitive Decline: Attitudes, Compliance, and Effectiveness

PubMed Central

Boot, Walter R.; Champion, Michael; Blakely, Daniel P.; Wright, Timothy; Souders, Dustin J.; Charness, Neil

2013-01-01

Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a “brain fitness” game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants’ ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why. PMID:23378841

Longitudinal change of biomarkers in cognitive decline.

PubMed

Lo, Raymond Y; Hubbard, Alan E; Shaw, Leslie M; Trojanowski, John Q; Petersen, Ronald C; Aisen, Paul S; Weiner, Michael W; Jagust, William J

2011-10-01

To delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD). Cohort study. The 59 study sites for the Alzheimer's Disease Neuroimaging Initiative. A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007. Rates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease's Assessment Scale-cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker. Reductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease's Assessment Scale-cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD. Trajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent.

Association of cytomegalovirus and Epstein-Barr virus with cognitive functioning and risk of dementia in the general population: 11-year follow-up study.

PubMed

Torniainen-Holm, Minna; Suvisaari, Jaana; Lindgren, Maija; Härkänen, Tommi; Dickerson, Faith; Yolken, Robert H

2018-03-01

Earlier studies have documented an association between cytomegalovirus and cognitive impairment, but results have been inconsistent. Few studies have investigated the association of cytomegalovirus and Epstein-Barr virus with cognitive decline longitudinally. Our aim was to examine whether cytomegalovirus and Epstein-Barr virus are associated with cognitive decline in adults. The study sample is from the Finnish Health 2000 Survey (BRIF8901, n = 7112), which is representative of the Finnish adult population. The sample was followed up after 11 years in the Health 2011 Survey. In addition, persons with dementia were identified from healthcare registers. In the Finnish population aged 30 and over, the seroprevalence of cytomegalovirus was estimated to be 84% and the seroprevalence of Epstein-Barr virus 98%. Seropositivity of the viruses and antibody levels were mostly not associated with cognitive performance. In the middle-aged adult group, cytomegalovirus serointensity was associated with impaired performance in verbal learning. However, the association disappeared when corrected for multiple testing. No interactions between infection and time or between the two infections were significant when corrected for multiple testing. Seropositivity did not predict dementia diagnosis. The results suggest that adult levels of antibodies to cytomegalovirus and Epstein-Barr virus may not be associated with a significant decline in cognitive function or with dementia at population level. Copyright © 2018. Published by Elsevier Inc.

Enrichment Effects on Adult Cognitive Development: Can the Functional Capacity of Older Adults Be Preserved and Enhanced?

PubMed

Hertzog, Christopher; Kramer, Arthur F; Wilson, Robert S; Lindenberger, Ulman

2008-10-01

In this monograph, we ask whether various kinds of intellectual, physical, and social activities produce cognitive enrichment effects-that is, whether they improve cognitive performance at different points of the adult life span, with a particular emphasis on old age. We begin with a theoretical framework that emphasizes the potential of behavior to influence levels of cognitive functioning. According to this framework, the undeniable presence of age-related decline in cognition does not invalidate the view that behavior can enhance cognitive functioning. Instead, the course of normal aging shapes a zone of possible functioning, which reflects person-specific endowments and age-related constraints. Individuals influence whether they function in the higher or lower ranges of this zone by engaging in or refraining from beneficial intellectual, physical, and social activities. From this point of view, the potential for positive change, or plasticity, is maintained in adult cognition. It is an argument that is supported by newer research in neuroscience showing neural plasticity in various aspects of central nervous system functioning, neurochemistry, and architecture. This view of human potential contrasts with static conceptions of cognition in old age, according to which decline in abilities is fixed and individuals cannot slow its course. Furthermore, any understanding of cognition as it occurs in everyday life must make a distinction between basic cognitive mechanisms and skills (such as working-memory capacity) and the functional use of cognition to achieve goals in specific situations. In practice, knowledge and expertise are critical for effective functioning, and the available evidence suggests that older adults effectively employ specific knowledge and expertise and can gain new knowledge when it is required. We conclude that, on balance, the available evidence favors the hypothesis that maintaining an intellectually engaged and physically active lifestyle promotes successful cognitive aging. First, cognitive-training studies have demonstrated that older adults can improve cognitive functioning when provided with intensive training in strategies that promote thinking and remembering. The early training literature suggested little transfer of function from specifically trained skills to new cognitive tasks; learning was highly specific to the cognitive processes targeted by training. Recently, however, a new generation of studies suggests that providing structured experience in situations demanding executive coordination of skills-such as complex video games, task-switching paradigms, and divided attention tasks-train strategic control over cognition that does show transfer to different task environments. These studies suggest that there is considerable reserve potential in older adults' cognition that can be enhanced through training. Second, a considerable number of studies indicate that maintaining a lifestyle that is intellectually stimulating predicts better maintenance of cognitive skills and is associated with a reduced risk of developing Alzheimer's disease in late life. Our review focuses on longitudinal evidence of a connection between an active lifestyle and enhanced cognition, because such evidence admits fewer rival explanations of observed effects (or lack of effects) than does cross-sectional evidence. The longitudinal evidence consistently shows that engaging in intellectually stimulating activities is associated with better cognitive functioning at later points in time. Other studies show that meaningful social engagement is also predictive of better maintenance of cognitive functioning in old age. These longitudinal findings are also open to important rival explanations, but overall, the available evidence suggests that activities can postpone decline, attenuate decline, or provide prosthetic benefit in the face of normative cognitive decline, while at the same time indicating that late-life cognitive changes can result in curtailment of activities. Given the complexity of the dynamic reciprocal relationships between stimulating activities and cognitive function in old age, additional research will be needed to address the extent to which observed effects validate a causal influence of an intellectually engaged lifestyle on cognition. Nevertheless, the hypothesis that an active lifestyle that requires cognitive effort has long-term benefits for older adults' cognition is at least consistent with the available data. Furthermore, new intervention research that involves multimodal interventions focusing on goal-directed action requiring cognition (such as reading to children) and social interaction will help to address whether an active lifestyle enhances cognitive function. Third, there is a parallel literature suggesting that physical activity, and aerobic exercise in particular, enhances older adults' cognitive function. Unlike the literature on an active lifestyle, there is already an impressive array of work with humans and animal populations showing that exercise interventions have substantial benefits for cognitive function, particularly for aspects of fluid intelligence and executive function. Recent neuroscience research on this topic indicates that exercise has substantial effects on brain morphology and function, representing a plausible brain substrate for the observed effects of aerobic exercise and other activities on cognition. Our review identifies a number of areas where additional research is needed to address critical questions. For example, there is considerable epidemiological evidence that stress and chronic psychological distress are negatively associated with changes in cognition. In contrast, less is known about how positive attributes, such as self-efficacy, a sense of control, and a sense of meaning in life, might contribute to preservation of cognitive function in old age. It is well known that certain personality characteristics such as conscientiousness predict adherence to an exercise regimen, but we do not know whether these attributes are also relevant to predicting maintenance of cognitive function or effective compensation for cognitive decline when it occurs. Likewise, more information is needed on the factors that encourage maintenance of an active lifestyle in old age in the face of elevated risk for physiological decline, mechanical wear and tear on the body, and incidence of diseases with disabling consequences, and whether efforts to maintain an active lifestyle are associated with successful aging, both in terms of cognitive function and psychological and emotional well-being. We also discuss briefly some interesting issues for society and public policy regarding cognitive-enrichment effects. For example, should efforts to enhance cognitive function be included as part of a general prevention model for enhancing health and vitality in old age? We also comment on the recent trend of business marketing interventions claimed to build brain power and prevent age-related cognitive decline, and the desirability of direct research evidence to back claims of effectiveness for specific products. © 2009 Association for Psychological Science.

Depressive symptoms predict cognitive decline and dementia in older people independently of cerebral white matter changes: the LADIS study.

PubMed

Verdelho, Ana; Madureira, Sofia; Moleiro, Carla; Ferro, José M; O'Brien, John T; Poggesi, Anna; Pantoni, Leonardo; Fazekas, Franz; Scheltens, Philip; Waldemar, Gunhild; Wallin, Anders; Erkinjuntti, Timo; Inzitari, Domenico

2013-11-01

Depressive symptoms (DS) have been associated with increased risk of cognitive decline. Our aim was to evaluate the longitudinal influence of DS on cognition in independent older people, accounting for the severity of white matter changes (WMC). The LADIS (Leukoaraiosis And DISability in the elderly) prospective study evaluated the impact of WMC on the transition of independent older subjects into disability. Subjects were evaluated annually over a 3 year period with a comprehensive clinical and neuropsychological evaluation. Previous episodes of depression and current DS were assessed during each interview. Severity of DS was assessed using the self-rated 15 item Geriatric Depression Scale. A neuropsychological battery and clinical criteria for cognitive impairments were applied in all clinical visits, and cognitive compound measures were made based on neuropsychological results. MRI was performed at baseline and at year 3. 639 subjects were included (74.1 ± 5 years old, 55% women, 9.6 ± 3.8 years of schooling). Dementia was diagnosed in 90 patients and cognitive impairment not dementia in 147 patients at the last clinical evaluation. DS were an independent predictor of cognitive impairment (dementia and not dementia) during follow-up, independent of the effect of the severity of WMC, medial temporal lobe atrophy, age, education or global cognitive function at baseline. DS are associated with an increase risk of cognitive decline, independent of the effect of WMC, probably due to an additive or synergistic effect. In this context, DS probably represent a subtle ongoing organic dysfunction.

Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB.

PubMed

Resnick, S M; Sojkova, J; Zhou, Y; An, Y; Ye, W; Holt, D P; Dannals, R F; Mathis, C A; Klunk, W E; Ferrucci, L; Kraut, M A; Wong, D F

2010-03-09

To investigate whether longitudinal declines in cognition are associated with higher fibrillar amyloid-beta (Abeta) deposition in vivo in individuals without dementia. [(11)C]PiB images were obtained to measure fibrillar Abeta burden in 57 participants without dementia from the Baltimore Longitudinal Study of Aging. Participants (33 men, 24 women) had a mean (SD) age of 78.7 (6.2) years. Six participants (4 men, 2 women) had mild cognitive impairment defined as Clinical Dementia Rating = 0.5. To measure [(11)C]PiB retention, distribution volume ratios (DVR) for 15 regions of interest were estimated by fitting a simplified reference tissue model to the measured time activity curves. Mixed effects regression was used to predict cognitive trajectories over time using data before and including time of PiB (mean follow-up 10.8 years), with mean cortical DVR, age at baseline, sex, and education as independent predictors. Voxel-based analysis identified local associations. [(11)C]PiB retention was higher in older individuals. Greater declines over time in mental status and verbal learning and memory, but not visual memory, were associated significantly with higher PiB retention. Voxel-based analysis showed significant associations in frontal and lateral temporal regions. Higher Abeta deposition is associated with greater longitudinal decline in mental status and verbal memory in the preceding years. The differential association for verbal but not visual memory may reflect the greater reliance of verbal word list learning on prefrontal regions, which show early Abeta deposition. Prospective imaging may help distinguish between individuals with evolving neuropathology who develop accelerated cognitive decline vs those with normal aging.

Education amplifies brain atrophy effect on cognitive decline: implications for cognitive reserve.

PubMed

Mungas, Dan; Gavett, Brandon; Fletcher, Evan; Farias, Sarah Tomaszewski; DeCarli, Charles; Reed, Bruce

2018-08-01

Level of education is often regarded as a proxy for cognitive reserve in older adults. This implies that brain degeneration has a smaller effect on cognitive decline in those with more education, but this has not been directly tested in previous research. We examined how education, quantitative magnetic resonance imaging-based measurement of brain degeneration, and their interaction affect cognitive decline in diverse older adults spanning the spectrum from normal cognition to dementia. Gray matter atrophy was strongly related to cognitive decline. While education was not related to cognitive decline, brain atrophy had a stronger effect on cognitive decline in those with more education. Importantly, high education was associated with slower decline in individuals with lesser atrophy but with faster decline in those with greater atrophy. This moderation effect was observed in Hispanics (who had high heterogeneity of education) but not in African-Americans or Caucasians. These results suggest that education is an indicator of cognitive reserve in individuals with low levels of brain degeneration, but the protective effect of higher education is rapidly depleted as brain degeneration progresses. Copyright © 2018 Elsevier Inc. All rights reserved.

Consumption of alcoholic beverages and cognitive decline at middle age: the Doetinchem Cohort Study.

PubMed

Nooyens, Astrid C J; Bueno-de-Mesquita, H Bas; van Gelder, Boukje M; van Boxtel, Martin P J; Verschuren, W M Monique

2014-02-01

Accelerated cognitive decline increases the risk of dementia. Slowing down the rate of cognitive decline leads to the preservation of cognitive functioning in the elderly, who can live independently for a longer time. Alcohol consumption may influence the rate of cognitive decline. The aim of the present study was to evaluate the associations between the total consumption of alcoholic beverages and different types of alcoholic beverages and cognitive decline at middle age. In 2613 men and women of the Doetinchem Cohort Study, aged 43-70 years at baseline (1995-2002), cognitive function (global cognitive function and the domains memory, speed and flexibility) was assessed twice, with a 5-year time interval. In linear regression analyses, the consumption of different types of alcoholic beverages was analysed in relation to cognitive decline, adjusting for confounders. We observed that, in women, the total consumption of alcoholic beverages was inversely associated with the decline in global cognitive function over a 5-year period (P for trend = 0·02), while no association was observed in men. Regarding the consumption of different types of alcoholic beverages in men and women together, red wine consumption was inversely associated with the decline in global cognitive function (P for trend < 0·01) as well as memory (P for trend < 0·01) and flexibility (P for trend = 0·03). Smallest declines were observed at a consumption of about 1·5 glasses of red wine per d. No other types of alcoholic beverages were associated with cognitive decline. In conclusion, only (moderate) red wine consumption was consistently associated with less strong cognitive decline. Therefore, it is most likely that non-alcoholic substances in red wine are responsible for any cognition-preserving effects.

Higher brain BDNF gene expression is associated with slower cognitive decline in older adults.

PubMed

Buchman, Aron S; Yu, Lei; Boyle, Patricia A; Schneider, Julie A; De Jager, Philip L; Bennett, David A

2016-02-23

We tested whether brain-derived neurotrophic factor (BDNF) gene expression levels are associated with cognitive decline in older adults. Five hundred thirty-five older participants underwent annual cognitive assessments and brain autopsy at death. BDNF gene expression was measured in the dorsolateral prefrontal cortex. Linear mixed models were used to examine whether BDNF expression was associated with cognitive decline adjusting for age, sex, and education. An interaction term was added to determine whether this association varied with clinical diagnosis proximate to death (no cognitive impairment, mild cognitive impairment, or dementia). Finally, we examined the extent to which the association of Alzheimer disease (AD) pathology with cognitive decline varied by BDNF expression. Higher brain BDNF expression was associated with slower cognitive decline (p < 0.001); cognitive decline was about 50% slower with the 90th percentile BDNF expression vs 10th. This association was strongest in individuals with dementia. The level of BDNF expression was lower in individuals with pathologic AD (p = 0.006), but was not associated with macroscopic infarcts, Lewy body disease, or hippocampal sclerosis. BDNF expression remained associated with cognitive decline in a model adjusting for age, sex, education, and neuropathologies (p < 0.001). Furthermore, the effect of AD pathology on cognitive decline varied by BDNF expression such that the effect was strongest for high levels of AD pathology (p = 0.015); thus, in individuals with high AD pathology (90th percentile), cognitive decline was about 40% slower with the 90th percentile BDNF expression vs 10th. Higher brain BDNF expression is associated with slower cognitive decline and may also reduce the deleterious effects of AD pathology on cognitive decline. © 2016 American Academy of Neurology.

The impact of retirement on age related cognitive decline - a systematic review.

PubMed

Meng, Annette; Nexø, Mette Andersen; Borg, Vilhelm

2017-07-21

Knowledge on factors affecting the rate of cognitive decline and how to maintain cognitive functioning in old age becomes increasingly relevant. The purpose of the current study was to systematically review the evidence for the impact of retirement on cognitive functioning and on age related cognitive decline. We conducted a systematic literature review, following the principles of the PRISMA statement, of longitudinal studies on the association between retirement and cognition. Only seven studies fulfilled the inclusion criteria. We found weak evidence that retirement accelerates the rate of cognitive decline in crystallised abilities, but only for individuals retiring from jobs high in complexity with people. The evidence of the impact of retirement on the rate of decline in fluid cognitive abilities is conflicting. The review revealed a major knowledge gap in regards to the impact of retirement on cognitive decline. More knowledge on the association between retirement and age related cognitive decline as well as knowledge on the mechanisms behind these associations is needed.

The mediational effects of FDG hypometabolism on the association between cerebrospinal fluid biomarkers and neurocognitive function.

PubMed

Dowling, N Maritza; Johnson, Sterling C; Gleason, Carey E; Jagust, William J

2015-01-15

Positive cerebrospinal fluid (CSF) biomarkers of tau and amyloid beta42 suggest possible active underlying Alzheimer's disease (AD) including neurometabolic dysfunction and neurodegeneration leading to eventual cognitive decline. But the temporal relationship between CSF, imaging markers of neural function, and cognition has not been described. Using a statistical mediation model, we examined relationships between cerebrospinal fluid (CSF) analytes (hyperphosphorylated tau (p-Tau(181p)), β-amyloid peptides 1-42 (Aβ(1-42)), total tau (t-Tau), and their ratios); change in cognitive function; and change in [18F]fluorodeoxyglucose (FDG) uptake using positron emission tomography (PET). We hypothesized that a) abnormal CSF protein values at baseline, result in cognitive declines by decreasing neuronal glucose metabolism across time, and b) the role of altered glucose metabolism in the assumed causal chain varies by brain region and the nature of CSF protein alteration. Data from 412 individuals participating in Alzheimer's Disease Neuroimaging (ADNI) cohort studies were included in analyses. At baseline, individuals were cognitively normal (N = 82), or impaired: 241 with mild cognitive impairment, and 89 with Alzheimer's disease. A parallel-process latent growth curve model was used to test mediational effects of changes in regional FDG-PET uptake over time in relation to baseline CSF biomarkers and changes in cognition, measured with the 13-item Alzheimer Disease's Assessment Scale-cognitive subscale (ADAS-Cog). Findings suggested a causal sequence of events; specifically, FDG hypometabolism acted as a mediator between antecedent CSF biomarker alterations and subsequent cognitive impairment. Higher baseline concentrations of t-Tau, and p-Tau(181p) were more predictive of decline in cerebral glucose metabolism than lower baseline concentrations of Aβ(1-42). FDG-PET changes appeared to mediate t-Tau or t-Tau/Aβ(1-42)-associated cognitive change across all brain regions examined. Significant direct effects of alterations in Aβ(1-42) levels on hypometabolism were observed in a single brain region: middle/inferior temporal gyrus. Results support a temporal framework model in which reduced CSF amyloid-related biomarkers occur earlier in the pathogenic pathway, ultimately leading to detrimental cognitive effects. Also consistent with this temporal framework model, baseline markers of neurofibrillary degeneration predicted changes in brain glucose metabolism in turn causing longitudinal cognitive changes, suggesting that tau-related burden precedes neurometabolic dysfunction. While intriguing, the hypothesized mediational relationships require further validation. Published by Elsevier Inc.

The association between cognitive decline and incident depressive symptoms in a sample of older Puerto Rican adults with diabetes.

PubMed

Bell, Tyler; Dávila, Ana Luisa; Clay, Olivio; Markides, Kyriakos S; Andel, Ross; Crowe, Michael

2017-08-01

Older Puerto Rican adults have particularly high risk of diabetes compared to the general US population. Diabetes is associated with both higher depressive symptoms and cognitive decline, but less is known about the longitudinal relationship between cognitive decline and incident depressive symptoms in those with diabetes. This study investigated the association between cognitive decline and incident depressive symptoms in older Puerto Rican adults with diabetes over a four-year period. Households across Puerto Rico were visited to identify a population-based sample of adults aged 60 years and over for the Puerto Rican Elderly: Health Conditions study (PREHCO); 680 participants with diabetes at baseline and no baseline cognitive impairment were included in analyses. Cognitive decline and depressive symptoms were measured using the Mini-Mental Cabán (MMC) and Geriatric Depression Scale (GDS), respectively. We examined predictors of incident depressive symptoms (GDS ≥ 5 at follow-up but not baseline) and cognitive decline using regression modeling. In a covariate-adjusted logistic regression model, cognitive decline, female gender, and greater diabetes-related complications were each significantly associated with increased odds of incident depressive symptoms (p < 0.05). In a multiple regression model adjusted for covariates, incident depressive symptoms and older age were associated with greater cognitive decline, and higher education was related to less cognitive decline (p < 0.05). Incident depressive symptoms were more common for older Puerto Ricans with diabetes who also experienced cognitive decline. Efforts are needed to optimize diabetes management and monitor for depression and cognitive decline in this population.

Personality Predicts Cognitive Function Over Seven Years in Older Persons

PubMed Central

Chapman, Benjamin; Duberstein, Paul; Tindle, Hilary A; Sink, Kaycee M; Robbins, John; Tancredi, Daniel J.; Franks, Peter

2011-01-01

Objectives To determine whether Neuroticism, as well as the less-studied dimensions the Five Factor Model of personality (Extraversion, Openness to Experience, Agreeableness, and Conscientiousness) were associated with 7-year trajectories of cognitive functioning in older persons. Design Primary analysis of existing clinical trial data. Participants 602 persons of average age 79 at baseline. Measurements The NEO-Five Factor Inventory of personality, completed at baseline, and the modified Mini Mental Status Exam (3MSE) measured every 6 months for 7 years. Results Controlling for demographics, baseline morbidities including depression, health behaviors, Apolipoprotein E4 genotype, and self-rated health, higher Neuroticism was associated with worse average cognitive functioning and a steeper rate of decline over follow-up. Higher Extraversion and lower Openness were both associated with worse average cognitive functioning prospectively, while persons higher in Conscientiousness showed a slower rate of cognitive decline. Conclusions In addition to Neuroticism, other dispositional tendencies appear prognostically relevant for cognitive functioning in older persons. More work is needed to understand the mechanisms by which traits operate, as well as whether mitigation of certain dispositional tendencies can facilitate a better course of cognitive function. PMID:22735597

Neural Plastic Effects of Cognitive Training on Aging Brain

PubMed Central

Leung, Natalie T. Y.; Tam, Helena M. K.; Chu, Leung W.; Kwok, Timothy C. Y.; Chan, Felix; Lam, Linda C. W.; Woo, Jean; Lee, Tatia M. C.

2015-01-01

Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n = 109) and the Active Control Group (n = 100). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age. PMID:26417460

Association between functional alterations of senescence and senility and disorders of gait and balance

PubMed Central

Teixeira-Leite, Homero; Manhães, Alex C.

2012-01-01

OBJECTIVES: Declines in cognition and mobility are frequently observed in the elderly, and it has been suggested that the appearance of gait disorders in older individuals may constitute a marker of cognitive decline that precedes significant findings in functional performance screening tests. This study sought to evaluate the relationship between functional capacities and gait and balance in an elderly community monitored by the Preventive and Integrated Care Unit of the Hospital Adventista Silvestre in Rio de Janeiro, RJ, Brazil. METHODS: Elderly individuals (193 females and 90 males) were submitted to a broad geriatric evaluation, which included the following tests: 1) a performance-oriented mobility assessment (POMA) to evaluate gait; 2) a mini-mental state examination (MMSE); 3) the use of Katz and Lawton scales to assess functional capacity; 4) the application of the geriatric depression scale (GDS); and 5) a mini-nutritional assessment (MNA) scale. RESULTS: Reductions in MMSE, Katz and Lawton scores were associated with reductions in POMA scores, and we also observed that significant reductions in POMA scores were present in persons for whom the MMSE and Katz scores did not clearly indicate cognitive dysfunction. We also demonstrated that a decline in the scores obtained with the GDS and MNA scales was associated with a decline in the POMA scores. CONCLUSIONS: Considering that significant alterations in the POMA scores were observed prior to the identification of significant alterations in cognitive capacity using either the MMSE or the Katz systems, a prospective study seems warranted to assess the predictive capacity of POMA scores regarding the associated decline in functional capacity. PMID:22892914

Association between functional alterations of senescence and senility and disorders of gait and balance.

PubMed

Teixeira-Leite, Homero; Manhães, Alex C

2012-07-01

Declines in cognition and mobility are frequently observed in the elderly, and it has been suggested that the appearance of gait disorders in older individuals may constitute a marker of cognitive decline that precedes significant findings in functional performance screening tests. This study sought to evaluate the relationship between functional capacities and gait and balance in an elderly community monitored by the Preventive and Integrated Care Unit of the Hospital Adventista Silvestre in Rio de Janeiro, RJ, Brazil. Elderly individuals (193 females and 90 males) were submitted to a broad geriatric evaluation, which included the following tests: 1) a performance-oriented mobility assessment (POMA) to evaluate gait; 2) a mini-mental state examination (MMSE); 3) the use of Katz and Lawton scales to assess functional capacity; 4) the application of the geriatric depression scale (GDS); and 5) a mini-nutritional assessment (MNA) scale. Reductions in MMSE, Katz and Lawton scores were associated with reductions in POMA scores, and we also observed that significant reductions in POMA scores were present in persons for whom the MMSE and Katz scores did not clearly indicate cognitive dysfunction. We also demonstrated that a decline in the scores obtained with the GDS and MNA scales was associated with a decline in the POMA scores. Considering that significant alterations in the POMA scores were observed prior to the identification of significant alterations in cognitive capacity using either the MMSE or the Katz systems, a prospective study seems warranted to assess the predictive capacity of POMA scores regarding the associated decline in functional capacity.

Texture Analysis of T1-Weighted and Fluid-Attenuated Inversion Recovery Images Detects Abnormalities That Correlate With Cognitive Decline in Small Vessel Disease.

PubMed

Tozer, Daniel J; Zeestraten, Eva; Lawrence, Andrew J; Barrick, Thomas R; Markus, Hugh S

2018-06-04

Magnetic resonance imaging may be useful to assess disease severity in cerebral small vessel disease (SVD), identify those individuals who are most likely to progress to dementia, monitor disease progression, and act as surrogate markers to test new therapies. Texture analysis extracts information on the relationship between signal intensities of neighboring voxels. A potential advantage over techniques, such as diffusion tensor imaging, is that it can be used on clinically obtained magnetic resonance sequences. We determined whether texture parameters (TP) were abnormal in SVD, correlated with cognitive impairment, predicted cognitive decline, or conversion to dementia. In the prospective SCANS study (St George's Cognition and Neuroimaging in Stroke), we assessed TP in 121 individuals with symptomatic SVD at baseline, 99 of whom attended annual cognitive testing for 5 years. Conversion to dementia was recorded for all subjects during the 5-year period. Texture analysis was performed on fluid-attenuated inversion recovery and T1-weighted images. The TP obtained from the SVD cohort were cross-sectionally compared with 54 age-matched controls scanned on the same magnetic resonance imaging system. There were highly significant differences in several TP between SVD cases and controls. Within the SVD population, TP were highly correlated to other magnetic resonance imaging parameters (brain volume, white matter lesion volume, lacune count). TP correlated with executive function and global function at baseline and predicted conversion to dementia, after controlling for age, sex, premorbid intelligence quotient, and magnetic resonance parameters. TP, which can be obtained from routine clinical images, are abnormal in SVD, and the degree of abnormality correlates with executive dysfunction and global cognition at baseline and decline during 5 years. TP may be useful to assess disease severity in clinically collected data. This needs testing in data clinically acquired across multiple sites. © 2018 The Authors.

Trajectories of age-related cognitive decline and potential associated factors of cognitive function in senior citizens of Beijing.

PubMed

Li, He; Lv, Chenlong; Zhang, Ting; Chen, Kewei; Chen, Chuansheng; Gai, Guozhong; Hu, Liangping; Wang, Yongyan; Zhang, Zhanjun

2014-01-01

With a longer life expectancy and an increased prevalence of neurodegenerative diseases, investigations on trajectories of cognitive aging have become exciting and promising. This study aimed to estimate the patterns of age-related cognitive decline and the potential associated factors of cognitive function in community-dwelling residents of Beijing, China. In this study, 1248 older adults aged 52-88 years [including 175 mild cognitive impairment (MCI) subjects] completed a battery of neuropsychological scales. The personal information, including demographic information, medical history, eating habits, lifestyle regularity and leisure activities, was also collected. All cognitive function exhibited an agerelated decline in normal volunteers. Piece-wise linear fitting results suggested that performance on the Auditory Verbal Learning Test remained stable until 58 years of age and continued to decline thereafter. The decline in processing speed and executive function began during the early 50's. Scores on visual-spatial and language tests declined after 66 years of age. The decline stage of the general mental status ranged from 63 to 70 years of age. However, the MCI group did not exhibit an obvious age-related decline in most cognitive tests. Multivariate linear regression analyses indicated that education, gender, leisure activities, diabetes and eating habits were associated with cognitive abilities. These results indicated various trajectories of age-related decline across multiple cognitive domains. We also found different patterns of agerelated cognitive decline between MCI and normal elderly. These findings could help improve the guidance of cognitive intervention program and have implications for public policy issues.

The Contribution of Generative Leisure Activities to Cognitive Function among Sri Lankan Elderly

PubMed Central

Maselko, Joanna; Sebranek, Matthew; Mun, Mirna Hodzic; Perera, Bilesha; Ahs, Jill; Østbye, Truls

2014-01-01

OBJECTIVES Although a substantive body of research has shown a protective association between leisure activities and cognitive function, consistent evidence is lacking about which specific types of activities should be promoted. The objective of this analysis was to examine the unique contribution of generative leisure activities, defined as activities motivated by “a concern for others and a need to contribute something to the next generation” (Erikson). DESIGN Cross-sectional survey. SETTING Peri-urban and rural area in southern Sri Lanka. PARTICIPANTS Community dwelling adults aged 60+ (n=252). MEASUREMENTS Main predictors were leisure activities grouped into generative, social, or solitary. Main outcome was cognitive function assessed with Montreal Cognitive Assessment (MoCA) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS We found that more frequent engagement in generative leisure activities was associated with higher levels of cognitive function, independent of the impact of other social and solitary leisure activities. In a fully adjusted model combining all three leisure activities, generative activities independently predicted cognitive function as measured with the MoCA (β =0.47 (0.11 to 0.83) and the IQCODE (β = -0.81 (-1.54 to -0.09)). In this combined model, solitary activities were also independently associated with slower cognitive decline with the MoCA (β =0.40 (0.16, 0.64), but not with IQCODE (β =-0.38 (-0.88, 0.12)); the association with social activities did not reach statistical significance with either measure. These associations did not differ meaningfully by gender. CONCLUSION Generative leisure activities are a promising area for the development of interventions aimed at reducing cognitive decline among the elderly. PMID:25139145

A decline in prosocial language helps explain public disapproval of the US Congress.

PubMed

Frimer, Jeremy A; Aquino, Karl; Gebauer, Jochen E; Zhu, Luke Lei; Oakes, Harrison

2015-05-26

Talking about helping others makes a person seem warm and leads to social approval. This work examines the real world consequences of this basic, social-cognitive phenomenon by examining whether record-low levels of public approval of the US Congress may, in part, be a product of declining use of prosocial language during Congressional debates. A text analysis of all 124 million words spoken in the House of Representatives between 1996 and 2014 found that declining levels of prosocial language strongly predicted public disapproval of Congress 6 mo later. Warm, prosocial language still predicted public approval when removing the effects of societal and global factors (e.g., the September 11 attacks) and Congressional efficacy (e.g., passing bills), suggesting that prosocial language has an independent, direct effect on social approval.

Cerebrospinal fluid neurogranin: relation to cognition and neurodegeneration in Alzheimer's disease.

PubMed

Portelius, Erik; Zetterberg, Henrik; Skillbäck, Tobias; Törnqvist, Ulrika; Andreasson, Ulf; Trojanowski, John Q; Weiner, Michael W; Shaw, Leslie M; Mattsson, Niklas; Blennow, Kaj

2015-11-01

Synaptic dysfunction is linked to cognitive symptoms in Alzheimer's disease. Thus, measurement of synapse proteins in cerebrospinal fluid may be useful biomarkers to monitor synaptic degeneration. Cerebrospinal fluid levels of the postsynaptic protein neurogranin are increased in Alzheimer's disease, including in the predementia stage of the disease. Here, we tested the performance of cerebrospinal fluid neurogranin to predict cognitive decline and brain injury in the Alzheimer's Disease Neuroimaging Initiative study. An in-house immunoassay was used to analyse neurogranin in cerebrospinal fluid samples from a cohort of patients who at recruitment were diagnosed as having Alzheimer's disease with dementia (n = 95) or mild cognitive impairment (n = 173), as well as in cognitively normal subjects (n = 110). Patients with mild cognitive impairment were grouped into those that remained cognitively stable for at least 2 years (stable mild cognitive impairment) and those who progressed to Alzheimer's disease dementia during follow-up (progressive mild cognitive impairment). Correlations were tested between baseline cerebrospinal fluid neurogranin levels and baseline and longitudinal cognitive impairment, brain atrophy and glucose metabolism within each diagnostic group. Cerebrospinal fluid neurogranin was increased in patients with Alzheimer's disease dementia (P < 0.001), progressive mild cognitive impairment (P < 0.001) and stable mild cognitive impairment (P < 0.05) compared with controls, and in Alzheimer's disease dementia (P < 0.01) and progressive mild cognitive impairment (P < 0.05) compared with stable mild cognitive impairment. In the mild cognitive impairment group, high baseline cerebrospinal fluid neurogranin levels predicted cognitive decline as reflected by decreased Mini-Mental State Examination (P < 0.001) and increased Alzheimer's Disease Assessment Scale-cognitive subscale (P < 0.001) scores at clinical follow-up. In addition, high baseline cerebrospinal fluid neurogranin levels in the mild cognitive impairment group correlated with longitudinal reductions in cortical glucose metabolism (P < 0.001) and hippocampal volume (P < 0.001) at clinical follow-up. Furthermore, within the progressive mild cognitive impairment group, elevated cerebrospinal fluid neurogranin levels were associated with accelerated deterioration in Alzheimer's Disease Assessment Scale-cognitive subscale (β = 0.0017, P = 0.01). These data demonstrate that cerebrospinal fluid neurogranin is increased already at the early clinical stage of Alzheimer's disease and predicts cognitive deterioration and disease-associated changes in metabolic and structural biomarkers over time. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Associations between a neurophysiological marker of central cholinergic activity and cognitive functions in young and older adults

PubMed Central

2012-01-01

Background The deterioration of the central cholinergic system in aging is hypothesized to underlie declines in several cognitive domains, including memory and executive functions. However, there is surprisingly little direct evidence regarding acetylcholine’s specific role(s) in normal human cognitive aging. Methods We used short-latency afferent inhibition (SAI) with transcranial magnetic stimulation (TMS) as a putative marker of cholinergic activity in vivo in young (n = 24) and older adults (n = 31). Results We found a significant age difference in SAI, concordant with other evidence of cholinergic decline in normal aging. We also found clear age differences on several of the memory and one of the executive function measures. Individual differences in SAI levels predicted memory but not executive functions. Conclusion Individual differences in SAI levels were better predictors of memory than executive functions. We discuss cases in which the relations between SAI and cognition might be even stronger, and refer to other age-related biological changes that may interact with cholinergic activity in cognitive aging. PMID:22537877

The role of vascular endothelial growth factor in neurodegeneration and cognitive decline: exploring interactions with biomarkers of Alzheimer disease.

PubMed

Hohman, Timothy J; Bell, Susan P; Jefferson, Angela L

2015-05-01

A subset of older adults present post mortem with Alzheimer disease (AD) pathologic features but without any significant clinical manifestation of dementia. Vascular endothelial growth factor (VEGF) has been implicated in staving off AD-related neurodegeneration. To evaluate whether VEGF levels are associated with brain aging outcomes (hippocampal volume and cognition) and to further evaluate whether VEGF modifies relations between AD biomarkers and brain aging outcomes. Biomarker analysis using neuroimaging and neuropsychological outcomes from the Alzheimer's Disease Neuroimaging Initiative. This prospective longitudinal study across North America included individuals with normal cognition (n = 90), mild cognitive impairment (n = 130), and AD (n = 59) and began in October 2004, with follow-up ongoing. Cerebrospinal fluid VEGF was cross-sectionally related to brain aging outcomes (hippocampal volume, episodic memory, and executive function) using a general linear model and longitudinally using mixed-effects regression. Alzheimer disease biomarker (cerebrospinal fluid β-amyloid 42 and total tau)-by-VEGF interactions evaluated the effect of VEGF on brain aging outcomes in the presence of enhanced AD biomarkers. Vascular endothelial growth factor was associated with baseline hippocampal volume (t277 = 2.62; P = .009), longitudinal hippocampal atrophy (t858 = 2.48; P = .01), and longitudinal decline in memory (t1629 = 4.09; P < .001) and executive function (t1616 = 3.00; P = .003). Vascular endothelial growth factor interacted with tau in predicting longitudinal hippocampal atrophy (t845 = 4.17; P < .001), memory decline (t1610 = 2.49; P = .01), and executive function decline (t1597 = 3.71; P < .001). Vascular endothelial growth factor interacted with β-amyloid 42 in predicting longitudinal memory decline (t1618 = -2.53; P = .01). Elevated cerebrospinal fluid VEGF was associated with more optimal brain aging in vivo. The neuroprotective effect appeared strongest in the presence of enhanced AD biomarkers, suggesting that VEGF may be particularly beneficial in individuals showing early hallmarks of the AD cascade. Future work should evaluate the interaction between VEGF expression in vitro and pathologic burden to address potential mechanisms.

Predictors of cognitive impairment in an early stage Parkinson's disease cohort.

PubMed

Hu, Michele T M; Szewczyk-Królikowski, Konrad; Tomlinson, Paul; Nithi, Kannan; Rolinski, Michal; Murray, Clara; Talbot, Kevin; Ebmeier, Klaus P; Mackay, Clare E; Ben-Shlomo, Yoav

2014-03-01

The impact of Parkinson's disease (PD) dementia is substantial and has major functional and socioeconomic consequences. Early prediction of future cognitive impairment would help target future interventions. The Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), and fluency tests were administered to 486 patients with PD within 3.5 years of diagnosis, and the results were compared with those from 141 controls correcting for age, sex, and educational years. Eighteen-month longitudinal assessments were performed in 155 patients with PD. The proportion of patients classified with normal cognition, mild cognitive impairment (MCI), and dementia varied considerably, depending on the MoCA and MMSE thresholds used. With the MoCA total score at screening threshold, 47.7%, 40.5%, and 11.7% of patients with PD were classified with normal cognition, MCI, and dementia, respectively; by comparison, 78.7% and 21.3% of controls had normal cognition and MCI, respectively. Cognitive impairment was predicted by lower education, increased age, male sex, and quantitative motor and non-motor (smell, depression, and anxiety) measures. Longitudinal data from 155 patients with PD over 18 months showed significant reductions in MoCA scores, but not in MMSE scores, with 21.3% of patients moving from normal cognition to MCI and 4.5% moving from MCI to dementia, although 13.5% moved from MCI to normal; however, none of the patients with dementia changed their classification. The MoCA may be more sensitive than the MMSE in detecting early baseline and longitudinal cognitive impairment in PD, because it identified 25.8% of those who experienced significant cognitive decline over 18 months. Cognitive decline was associated with worse motor and non-motor features, suggesting that this reflects a faster progressive phenotype. © 2014 The Authors. International Parkinson and Movement Disorder Society published by Wiley Periodicals, Inc.

Olfaction Is Related to Motor Function in Older Adults.

PubMed

Tian, Qu; Resnick, Susan M; Studenski, Stephanie A

2017-08-01

Among older adults, both olfaction and motor function predict future cognitive decline and dementia, suggesting potential shared causal pathways. However, it is not known whether olfactory and motor function are independently related in late life. We assessed cross-sectional associations of olfaction with motor and cognitive function, using concurrent data on olfactory function, mobility, balance, fine motor function, manual dexterity, and cognition in 163 Baltimore Longitudinal Study of Aging participants aged 60 and older without common neurological diseases (n = 114 with available cognitive data). Using multiple linear regression, we adjusted for age, sex, race, smoking history, height, and weight for mobility and balance, and education for cognition. We used multiple linear regression to test whether olfaction-motor associations were independent of cognition and depressive symptoms. Olfactory scores were significantly associated with mobility (usual gait speed, rapid gait speed, 400-m walk time, and Health ABC Physical Performance Battery score), balance, fine motor function, and manual dexterity (all p < .05). In those with available cognitive data, additional adjustment for depressive symptoms, verbal memory, or visuoperceptual speed demonstrated especially strong independent relationships with challenging motor tasks such as 400-m walk and nondominant hand manual dexterity (p < .005). This study demonstrates for the first time that, in older adults, olfactory function is associated with mobility, balance, fine motor function, and manual dexterity, and independent of cognitive function, with challenging upper and lower extremity motor function tasks. Longitudinal studies are needed to determine if olfactory performance predicts future mobility and functional decline. Published by Oxford University Press on behalf of The Gerontological Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Total daily physical activity and the risk of AD and cognitive decline in older adults

PubMed Central

Boyle, P.A.; Yu, L.; Shah, R.C.; Wilson, R.S.; Bennett, D.A.

2012-01-01

Objective: Studies examining the link between objective measures of total daily physical activity and incident Alzheimer disease (AD) are lacking. We tested the hypothesis that an objective measure of total daily physical activity predicts incident AD and cognitive decline. Methods: Total daily exercise and nonexercise physical activity was measured continuously for up to 10 days with actigraphy (Actical®; Philips Healthcare, Bend, OR) from 716 older individuals without dementia participating in the Rush Memory and Aging Project, a prospective, observational cohort study. All participants underwent structured annual clinical examination including a battery of 19 cognitive tests. Results: During an average follow-up of about 4 years, 71 subjects developed clinical AD. In a Cox proportional hazards model adjusting for age, sex, and education, total daily physical activity was associated with incident AD (hazard ratio = 0.477; 95% confidence interval 0.273–0.832). The association remained after adjusting for self-report physical, social, and cognitive activities, as well as current level of motor function, depressive symptoms, chronic health conditions, and APOE allele status. In a linear mixed-effect model, the level of total daily physical activity was associated with the rate of global cognitive decline (estimate 0.033, SE 0.012, p = 0.007). Conclusions: A higher level of total daily physical activity is associated with a reduced risk of AD. PMID:22517108

Total daily physical activity and the risk of AD and cognitive decline in older adults.

PubMed

Buchman, A S; Boyle, P A; Yu, L; Shah, R C; Wilson, R S; Bennett, D A

2012-04-24

Studies examining the link between objective measures of total daily physical activity and incident Alzheimer disease (AD) are lacking. We tested the hypothesis that an objective measure of total daily physical activity predicts incident AD and cognitive decline. Total daily exercise and nonexercise physical activity was measured continuously for up to 10 days with actigraphy (Actical®; Philips Healthcare, Bend, OR) from 716 older individuals without dementia participating in the Rush Memory and Aging Project, a prospective, observational cohort study. All participants underwent structured annual clinical examination including a battery of 19 cognitive tests. During an average follow-up of about 4 years, 71 subjects developed clinical AD. In a Cox proportional hazards model adjusting for age, sex, and education, total daily physical activity was associated with incident AD (hazard ratio = 0.477; 95% confidence interval 0.273-0.832). The association remained after adjusting for self-report physical, social, and cognitive activities, as well as current level of motor function, depressive symptoms, chronic health conditions, and APOE allele status. In a linear mixed-effect model, the level of total daily physical activity was associated with the rate of global cognitive decline (estimate 0.033, SE 0.012, p = 0.007). A higher level of total daily physical activity is associated with a reduced risk of AD.

The effects of sleep deprivation on item and associative recognition memory.

PubMed

Ratcliff, Roger; Van Dongen, Hans P A

2018-02-01

Sleep deprivation adversely affects the ability to perform cognitive tasks, but theories range from predicting an overall decline in cognitive functioning because of reduced stability in attentional networks to specific deficits in various cognitive domains or processes. We measured the effects of sleep deprivation on two memory tasks, item recognition ("was this word in the list studied") and associative recognition ("were these two words studied in the same pair"). These tasks test memory for information encoded a few minutes earlier and so do not address effects of sleep deprivation on working memory or consolidation after sleep. A diffusion model was used to decompose accuracy and response time distributions to produce parameter estimates of components of cognitive processing. The model assumes that over time, noisy evidence from the task stimulus is accumulated to one of two decision criteria, and parameters governing this process are extracted and interpreted in terms of distinct cognitive processes. Results showed that sleep deprivation reduces drift rate (evidence used in the decision process), with little effect on the other components of the decision process. These results contrast with the effects of aging, which show little decline in item recognition but large declines in associative recognition. The results suggest that sleep deprivation degrades the quality of information stored in memory and that this may occur through degraded attentional processes. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Predicting impending death: inconsistency in speed is a selective and early marker.

PubMed

Macdonald, Stuart W S; Hultsch, David F; Dixon, Roger A

2008-09-01

Among older adults, deficits in both level and variability of speeded performance are linked to neurological impairment. This study examined whether and when speed (rate), speed (inconsistency), and traditional accuracy-based markers of cognitive performance foreshadow terminal decline and impending death. Victoria Longitudinal Study data spanning 12 years (5 waves) of measurement were assembled for 707 adults aged 59 to 95 years. Whereas 442 survivors completed all waves and relevant measures, 265 decedents participated on at least 1 occasion and subsequently died. Four main results were observed. First, Cox regressions evaluating the 3 cognitive predictors of mortality replicated previous results for cognitive accuracy predictors. Second, level (rate) of speeded performance predicted survival independent of demographic indicators, cardiovascular health, and cognitive performance level. Third, inconsistency in speed predicted survival independent of all influences combined. Fourth, follow-up random-effects models revealed increases in inconsistency in speed per year closer to death, with advancing age further moderating the accelerated growth. Hierarchical prediction patterns support the view that inconsistency in speed is an early behavioral marker of neurological dysfunction associated with impending death. (c) 2008 APA, all rights reserved

Predicting Impending Death: Inconsistency in Speed is a Selective and Early Marker

PubMed Central

MacDonald, Stuart W.S.; Hultsch, David F.; Dixon, Roger A.

2008-01-01

Among older adults, deficits in both level and variability of speeded performance are linked to neurological impairment. This study examined whether and when speed (rate), speed (inconsistency), and traditional accuracy-based markers of cognitive performance foreshadow terminal decline and impending death. Victoria Longitudinal Study data spanning 12 years (5 waves) of measurement were assembled for 707 adults aged 59 to 95 years. Whereas 442 survivors completed all waves and relevant measures, 265 decedents participated on at least one occasion and subsequently died. Four main results were observed. First, Cox regressions evaluating the three cognitive predictors of mortality replicated previous results for cognitive accuracy predictors. Second, level (rate) of speeded performance predicted survival independent of demographic indicators, cardiovascular health, and cognitive performance level. Third, inconsistency in speed predicted survival independent of all influences combined. Fourth, follow-up random-effects models revealed increases in inconsistency in speed per year closer to death, with advancing age further moderating the accelerated growth. Hierarchical prediction patterns support the view that inconsistency in speed is an early behavioral marker of neurological dysfunction associated with impending death. PMID:18808249

Divided attention in computer game play: analysis utilizing unobtrusive health monitoring.

PubMed

McKanna, James A; Jimison, Holly; Pavel, Misha

2009-01-01

Divided attention is a vital cognitive ability used in important daily activities (e.g., driving), which tends to deteriorate with age. As with Alzheimer's and other neural degenerative conditions, treatment for divided attention problems is likely to be more effective the earlier it is detected. Thus, it is important that a method be found to detect changes in divided attention early on in the process, for both safety and health care reasons. We present here a new method for detecting divided attention unobtrusively, using performance on a computer game designed to force players to attend to different dimensions simultaneously in order to succeed. Should this model prove to predict scores on a standard test for divided attention, it could help to detect cognitive decline earlier in our increasingly computer-involved aging population, providing treatment efficacy benefits to those who will experience cognitive decline.

A prospective cohort study of long-term cognitive changes in older Medicare beneficiaries.

PubMed

Wolinsky, Fredric D; Bentler, Suzanne E; Hockenberry, Jason; Jones, Michael P; Weigel, Paula A; Kaskie, Brian; Wallace, Robert B

2011-09-20

Promoting cognitive health and preventing its decline are longstanding public health goals, but long-term changes in cognitive function are not well-documented. Therefore, we first examined long-term changes in cognitive function among older Medicare beneficiaries in the Survey on Assets and Health Dynamics among the Oldest Old (AHEAD), and then we identified the risk factors associated with those changes in cognitive function. We conducted a secondary analysis of a prospective, population-based cohort using baseline (1993-1994) interview data linked to 1993-2007 Medicare claims to examine cognitive function at the final follow-up interview which occurred between 1995-1996 and 2006-2007. Besides traditional risk factors (i.e., aging, age, race, and education) and adjustment for baseline cognitive function, we considered the reason for censoring (entrance into managed care or death), and post-baseline continuity of care and major health shocks (hospital episodes). Residual change score multiple linear regression analysis was used to predict cognitive function at the final follow-up using data from telephone interviews among 3,021 to 4,251 (sample size varied by cognitive outcome) baseline community-dwelling self-respondents that were ≥ 70 years old, not in managed Medicare, and had at least one follow-up interview as self-respondents. Cognitive function was assessed using the 7-item Telephone Interview for Cognitive Status (TICS-7; general mental status), and the 10-item immediate and delayed (episodic memory) word recall tests. Mean changes in the number of correct responses on the TICS-7, and 10-item immediate and delayed word recall tests were -0.33, -0.75, and -0.78, with 43.6%, 54.9%, and 52.3% declining and 25.4%, 20.8%, and 22.9% unchanged. The main and most consistent risks for declining cognitive function were the baseline values of cognitive function (reflecting substantial regression to the mean), aging (a strong linear pattern of increased decline associated with greater aging, but with diminishing marginal returns), older age at baseline, dying before the end of the study period, lower education, and minority status. In addition to aging, age, minority status, and low education, substantial and differential risks for cognitive change were associated with sooner vs. later subsequent death that help to clarify the terminal drop hypothesis. No readily modifiable protective factors were identified.

Longitudinal Modeling of Functional Decline Associated with Pathologic Alzheimer's Disease in Older Persons without Cognitive Impairment.

PubMed

Wang, Dai; Schultz, Tim; Novak, Gerald P; Baker, Susan; Bennett, David A; Narayan, Vaibhav A

2018-01-01

Therapeutic research on Alzheimer's disease (AD) has moved to intercepting the disease at the preclinical phase. Most drugs in late development have focused on the amyloid hypothesis. To understand the magnitude of amyloid-related functional decline and to identify the functional domains sensitive to decline in a preclinical AD population. Data were from the Religious Orders Study and the Rush Memory and Aging Project. Cognitive decline was measured by a modified version of the Alzheimer's Disease Cooperative Study Preclinical Alzheimer Cognitive Composite. The trajectories of functional decline, as measured by the instrumental and basic activities of daily living, were longitudinally modeled in 484 participants without cognitive impairment at baseline and having both a final clinical and a postmortem neuropathology assessment of AD. Individuals with different final clinical diagnoses had different trajectories of cognitive and functional decline. Individuals with AD dementia, minor cognitive impairment, and no cognitive impairment had the most, intermediate, and least declines. While individuals with pathologic AD had significantly more cognitive decline over time than those without, the magnitude of difference in functional decline between these two groups was small. Functional domains such as handling finance and handling medications were more sensitive to decline. Demonstrating the functional benefit of an amyloid-targeting drug represents a significant challenge as elderly people experience functional decline due to a wide range of reasons with limited manifestation attributable to AD neuropathology. More sensitive functional scales focusing on the functional domains sensitive to decline in preclinical AD are needed.

Cognitive Function Before and After Left Heart Catheterization.

PubMed

Scott, David A; Evered, Lisbeth; Maruff, Paul; MacIsaac, Andrew; Maher, Sarah; Silbert, Brendan S

2018-03-10

Hospital procedures have been associated with cognitive change in older patients. This study aimed to document the prevalence of mild cognitive impairment in individuals undergoing left heart catheterization (LHC) before the procedure and the incidence of cognitive decline to 3 months afterwards. We conducted a prospective, observational, clinical investigation of elderly participants undergoing elective LHC. Cognition was assessed using a battery of written tests and a computerized cognitive battery before the LHC and then at 3 months afterwards. The computerized tests were also administered at 24 hours (or discharge) and 7 days after LHC. A control group of 51 community participants was recruited to calculate cognitive decline using the Reliable Change Index. Of 437 participants, mild cognitive impairment was identified in 226 (51.7%) before the procedure. Computerized tests detected an incidence of cognitive decline of 10.0% at 24 hours and 7.5% at 7 days. At 3 months, written tests detected an incidence of cognitive decline of 13.1% and computerized tests detected an incidence of 8.5%. Cognitive decline at 3 months using written tests was associated with increasing age, whereas computerized tests showed cognitive decline was associated with baseline amnestic mild cognitive impairment, diabetes mellitus, and prior coronary stenting. More than half the patients aged >60 years presenting for LHC have mild cognitive impairment. LHC is followed by cognitive decline in 8% to 13% of individuals at 3 months after the procedure. Subtle cognitive decline both before and after LHC is common and may have important clinical implications. URL: www.anzctr.org.au. Unique identifier: ACTRN12607000051448. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Erythrocyte polyunsaturated fatty acid status, memory, cognition and mood in older adults with mild cognitive impairment and healthy controls.

PubMed

Milte, Catherine M; Sinn, Natalie; Street, Steven J; Buckley, Jonathan D; Coates, Alison M; Howe, Peter R C

2011-01-01

Polyunsaturated fatty acid (PUFA) levels are altered in adults with cognitive decline and also depression. Depression facilitates progression from mild cognitive impairment (MCI) to dementia. We investigated associations between omega-3 (n-3) and omega-6 (n-6) PUFAs and cognition, memory and depression in 50 adults ≥65 years with MCI and 29 controls. Memory, depressive symptoms and erythrocyte PUFAs (% total fatty acids) were assessed. Eicosapentaenoic acid (EPA) was lower in MCI vs controls (.94% vs 1.26%, p<.01); n-6 PUFAs were higher: dihomo-gamma-linolenic acid (1.51% vs 1.32%, p<.01), arachidonic acid (11.54% vs 10.70%, p<.01), n-6 docosapentaenoic acid (DPA:.46% vs.34%, p<.01), and total n-6 PUFA (24.14% vs 23.37%, p<.05). Higher n-6 DPA predicted poorer mental health. Lower n-3 DPA was associated with higher self-reported bodily pain. Adults with MCI had higher depression scores (3.05±.39 vs 1.33±.24, p<.01). Depressive symptoms associated with elevated n-6 PUFA may contribute to cognitive decline in this population. Copyright © 2011 Elsevier Ltd. All rights reserved.

Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer's disease.

PubMed

Zhang, Xiuming; Mormino, Elizabeth C; Sun, Nanbo; Sperling, Reisa A; Sabuncu, Mert R; Yeo, B T Thomas

2016-10-18

We used a data-driven Bayesian model to automatically identify distinct latent factors of overlapping atrophy patterns from voxelwise structural MRIs of late-onset Alzheimer's disease (AD) dementia patients. Our approach estimated the extent to which multiple distinct atrophy patterns were expressed within each participant rather than assuming that each participant expressed a single atrophy factor. The model revealed a temporal atrophy factor (medial temporal cortex, hippocampus, and amygdala), a subcortical atrophy factor (striatum, thalamus, and cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal, and lateral occipital cortices). To explore the influence of each factor in early AD, atrophy factor compositions were inferred in beta-amyloid-positive (Aβ+) mild cognitively impaired (MCI) and cognitively normal (CN) participants. All three factors were associated with memory decline across the entire clinical spectrum, whereas the cortical factor was associated with executive function decline in Aβ+ MCI participants and AD dementia patients. Direct comparison between factors revealed that the temporal factor showed the strongest association with memory, whereas the cortical factor showed the strongest association with executive function. The subcortical factor was associated with the slowest decline for both memory and executive function compared with temporal and cortical factors. These results suggest that distinct patterns of atrophy influence decline across different cognitive domains. Quantification of this heterogeneity may enable the computation of individual-level predictions relevant for disease monitoring and customized therapies. Factor compositions of participants and code used in this article are publicly available for future research.

Linking perceived control, physical activity, and biological health to memory change.

PubMed

Infurna, Frank J; Gerstorf, Denis

2013-12-01

Perceived control plays an important role for remaining cognitively fit across adulthood and old age. However, much less is known about the role of perceived control over and above common correlates of cognition, and possible factors that underlie such control-cognition associations. Our study examined whether perceived control was predictive of individual differences in subsequent 4-year changes in episodic memory, and explored the mediating role of physical activity and indicators of physical fitness, cardiovascular, and metabolic health for control-memory associations. To do so, we used longitudinal data from the nationwide Health and Retirement Study (HRS; N = 4,177; ages 30 to 97 years; 59% women). Our results show that perceiving more control over one's life predicted less memory declines, and this protective effect was similar in midlife and old age. We additionally observed that higher levels and maintenance of physical activity over 2 years, better pulmonary function, lower systolic blood pressure (SPB), lower hemoglobin A1c, and higher high-density lipoprotein cholesterol (HDL-C) also predicted less memory declines. Mediation analyses revealed that levels of, and 2-year changes in, physical activity, as well as levels of pulmonary function and hemoglobin A1c and HDL-C, each uniquely mediated control-memory change associations. Our findings illustrate that perceived control, physical activity, and indicators of physical fitness and cardiovascular and metabolic health moderate changes in memory, and add to the literature on antecedents of cognitive aging by conjointly targeting perceived control and some of its mediating factors. We discuss possible pathways underlying the role of control for memory change and consider future routes of inquiry to further our understanding of control-cognition associations in adulthood and old age. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Lifestyle Markers Predict Cognitive Function.

PubMed

Masley, Steven C; Roetzheim, Richard; Clayton, Gwendolyn; Presby, Angela; Sundberg, Kelley; Masley, Lucas V

2017-01-01

Rates of mild cognitive impairment and Alzheimer's disease are increasing rapidly. None of the current treatment regimens for Alzheimer's disease are effective in arresting progression. Lifestyle choices may prevent cognitive decline. This study aims to clarify which factors best predict cognitive function. This was a prospective cross-sectional analysis of 799 men and women undergoing health and cognitive testing every 1 to 3 years at an outpatient center. This study utilizes data collected from the first patient visit. Participant ages were 18 to 88 (mean = 50.7) years and the sample was 26.6% female and 73.4% male. Measurements were made of body composition, fasting laboratory and anthropometric measures, strength and aerobic fitness, nutrient and dietary intake, and carotid intimal media thickness (IMT). Each participant was tested with a computerized neurocognitive test battery. Cognitive outcomes were assessed in bivariate analyses using t-tests and correlation coefficients and in multivariable analysis (controlling for age) using multiple linear regression. The initial bivariate analyses showed better Neurocognitive Index (NCI) scores with lower age, greater fitness scores (push-up strength, VO 2 max, and exercise duration during treadmill testing), and lower fasting glucose levels. Better cognitive flexibility scores were also noted with younger age, lower systolic blood pressure, lower body fat, lower carotid IMT scores, greater fitness, and higher alcohol intake. After controlling for age, factors that remained associated with better NCI scores include no tobacco use, lower fasting glucose levels, and better fitness (aerobic and strength). Higher cognitive flexibility scores remained associated with greater aerobic and strength fitness, lower body fat, and higher intake of alcohol. Modifiable biomarkers that impact cognitive performance favorably include greater aerobic fitness and strength, lower blood sugar levels, greater alcohol intake, lower body fat, and avoidance of tobacco. Further studies are warranted to study whether modifying these lifestyle factors improves cognitive function and slows cognitive decline.

Plasma proteins predict conversion to dementia from prodromal disease

PubMed Central

Hye, Abdul; Riddoch-Contreras, Joanna; Baird, Alison L.; Ashton, Nicholas J.; Bazenet, Chantal; Leung, Rufina; Westman, Eric; Simmons, Andrew; Dobson, Richard; Sattlecker, Martina; Lupton, Michelle; Lunnon, Katie; Keohane, Aoife; Ward, Malcolm; Pike, Ian; Zucht, Hans Dieter; Pepin, Danielle; Zheng, Wei; Tunnicliffe, Alan; Richardson, Jill; Gauthier, Serge; Soininen, Hilkka; Kłoszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon

2014-01-01

Background The study aimed to validate previously discovered plasma biomarkers associated with AD, using a design based on imaging measures as surrogate for disease severity and assess their prognostic value in predicting conversion to dementia. Methods Three multicenter cohorts of cognitively healthy elderly, mild cognitive impairment (MCI), and AD participants with standardized clinical assessments and structural neuroimaging measures were used. Twenty-six candidate proteins were quantified in 1148 subjects using multiplex (xMAP) assays. Results Sixteen proteins correlated with disease severity and cognitive decline. Strongest associations were in the MCI group with a panel of 10 proteins predicting progression to AD (accuracy 87%, sensitivity 85%, and specificity 88%). Conclusions We have identified 10 plasma proteins strongly associated with disease severity and disease progression. Such markers may be useful for patient selection for clinical trials and assessment of patients with predisease subjective memory complaints. PMID:25012867

Plasma proteins predict conversion to dementia from prodromal disease.

PubMed

Hye, Abdul; Riddoch-Contreras, Joanna; Baird, Alison L; Ashton, Nicholas J; Bazenet, Chantal; Leung, Rufina; Westman, Eric; Simmons, Andrew; Dobson, Richard; Sattlecker, Martina; Lupton, Michelle; Lunnon, Katie; Keohane, Aoife; Ward, Malcolm; Pike, Ian; Zucht, Hans Dieter; Pepin, Danielle; Zheng, Wei; Tunnicliffe, Alan; Richardson, Jill; Gauthier, Serge; Soininen, Hilkka; Kłoszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon

2014-11-01

The study aimed to validate previously discovered plasma biomarkers associated with AD, using a design based on imaging measures as surrogate for disease severity and assess their prognostic value in predicting conversion to dementia. Three multicenter cohorts of cognitively healthy elderly, mild cognitive impairment (MCI), and AD participants with standardized clinical assessments and structural neuroimaging measures were used. Twenty-six candidate proteins were quantified in 1148 subjects using multiplex (xMAP) assays. Sixteen proteins correlated with disease severity and cognitive decline. Strongest associations were in the MCI group with a panel of 10 proteins predicting progression to AD (accuracy 87%, sensitivity 85%, and specificity 88%). We have identified 10 plasma proteins strongly associated with disease severity and disease progression. Such markers may be useful for patient selection for clinical trials and assessment of patients with predisease subjective memory complaints. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Occupational cognitive requirements and late-life cognitive aging.

PubMed

Pool, Lindsay R; Weuve, Jennifer; Wilson, Robert S; Bültmann, Ute; Evans, Denis A; Mendes de Leon, Carlos F

2016-04-12

To examine whether occupational cognitive requirements, as a marker of adulthood cognitive activity, are associated with late-life cognition and cognitive decline. Main lifetime occupation information for 7,637 participants aged >65 years of the Chicago Health and Aging Project (CHAP) was linked with standardized data on worker attributes and job characteristics from the Occupational Information Network (O*NET). Ratings of cognitive processes required in 10 work-related tasks were used to create a summary measure of occupational cognitive requirements (possible range 0-7). Multivariable-adjusted linear mixed models were used to estimate the association of occupational cognitive requirements score (OCRS) with cognitive function and rate of cognitive decline. Higher OCRS corresponded to significantly better late-life cognitive performance at baseline in 1993 (p < 0.001) and to slower decline in global cognitive function over time (p = 0.004). Within a genotyped subsample (n = 4,104), the associations of OCRS with rate of cognitive decline did not differ significantly by APOE ε4 carriership (p = 0.11). Findings suggest that occupational cognitive requirements are associated with better cognition and a slower rate of cognitive decline in older age. Adulthood cognitive activity may contribute to cognitive reserve in late life. © 2016 American Academy of Neurology.

Bereavement and behavioral changes as risk factors for cognitive decline in adults with Down syndrome.

PubMed

Fonseca, Luciana Mascarenhas; de Oliveira, Melaine Cristina; de Figueiredo Ferreira Guilhoto, Laura Maria; Cavalheiro, Esper Abrao; Bottino, Cássio Mc

2014-01-01

Cognitive decline and Alzheimer's disease often affect older adults with Down syndrome (DS) much earlier than those in the general population. There is also growing evidence of the effects of negative life events on the mental health and behavior of individuals with intellectual disability. However, to our knowledge, this is the first study investigating objective cognitive decline following bereavement in aging individuals with DS. The objective of this study was to determine whether cognitive decline correlates with bereavement following the recent loss of a caregiver or with behavioral changes in a sample of adult individuals with DS who do not meet the criteria for dementia or depression, using the longitudinal assessment of the Cambridge Cognitive Examination (CAMCOG), together with the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). We evaluated 18 subjects at baseline and over a follow-up period of 14-22 months, attempting to determine whether cognitive decline correlates with bereavement following the recent loss of the main caregiver or with behavioral changes (as assessed with the Neuropsychiatric Inventory). The mean rate of change in CAMCOG was -1.83 (standard deviation 4.51). Behavioral changes had a significant direct influence on cognitive decline. When bereavement was accompanied by behavioral changes, the probability of cognitive decline was 87% (odds ratio 3.82). The occurrence of behavioral changes attributed to bereavement following the loss of the primary caregiver significantly increases the probability of cognitive decline in individuals with DS. Longitudinal comparison of the CAMCOG and use of the IQCODE appear to enrich the analysis of cognitive decline in individuals with DS. Further studies involving larger samples are needed in order to corroborate and expand upon our findings, which can have implications for the clinical management of older adults with DS.

Aging and the shape of cognitive change before death: terminal decline or terminal drop?

PubMed

MacDonald, Stuart W S; Hultsch, David F; Dixon, Roger A

2011-05-01

Relative to typical age-related cognitive decrements, the terms "terminal decline" and "terminal drop" refer to the phenomenon of increased cognitive decline in proximity to death. Given that these terms are not necessarily synonymous, we examined the important theoretical distinction between the two alternative trajectories or shapes of changes they imply. We used 12-year (5-wave) data from the Victoria Longitudinal Study to directly test whether pre-death cognitive decrements follow a terminal decline (generally gradual) or a terminal drop (more abrupt) shape. Pre-death trajectories of cognitive decline for n=265 decedents (Mage = 72.67 years, SD = 6.44) were examined separately for 5 key cognitive constructs (verbal speed, working memory, episodic memory, semantic memory, and crystallized ability). Several classes of linear mixed models evaluated whether cognitive decline increased per additional year closer to death. Findings indicated that the shape of pre-death cognitive change was predominantly characterized by decline that is steeper as compared with typical aging-related change, but still best described as slow and steady decline, especially as compared with precipitous drop. The present findings suggest that terminal decline and terminal drop trajectories may not be mutually exclusive but could rather reflect distinct developmental trajectories within the same individual.

Semantic Memory in the Clinical Progression of Alzheimer Disease.

PubMed

Tchakoute, Christophe T; Sainani, Kristin L; Henderson, Victor W

2017-09-01

Semantic memory measures may be useful in tracking and predicting progression of Alzheimer disease. We investigated relationships among semantic memory tasks and their 1-year predictive value in women with Alzheimer disease. We conducted secondary analyses of a randomized clinical trial of raloxifene in 42 women with late-onset mild-to-moderate Alzheimer disease. We assessed semantic memory with tests of oral confrontation naming, category fluency, semantic recognition and semantic naming, and semantic density in written narrative discourse. We measured global cognition (Alzheimer Disease Assessment Scale, cognitive subscale), dementia severity (Clinical Dementia Rating sum of boxes), and daily function (Activities of Daily Living Inventory) at baseline and 1 year. At baseline and 1 year, most semantic memory scores correlated highly or moderately with each other and with global cognition, dementia severity, and daily function. Semantic memory task performance at 1 year had worsened one-third to one-half standard deviation. Factor analysis of baseline test scores distinguished processes in semantic and lexical retrieval (semantic recognition, semantic naming, confrontation naming) from processes in lexical search (semantic density, category fluency). The semantic-lexical retrieval factor predicted global cognition at 1 year. Considered separately, baseline confrontation naming and category fluency predicted dementia severity, while semantic recognition and a composite of semantic recognition and semantic naming predicted global cognition. No individual semantic memory test predicted daily function. Semantic-lexical retrieval and lexical search may represent distinct aspects of semantic memory. Semantic memory processes are sensitive to cognitive decline and dementia severity in Alzheimer disease.

Neighborhoods, sleep quality, and cognitive decline: Does where you live and how well you sleep matter?

PubMed

Hunter, Jaimie C; Handing, Elizabeth P; Casanova, Ramon; Kuchibhatla, Maragatha; Lutz, Michael W; Saldana, Santiago; Plassman, Brenda L; Hayden, Kathleen M

2018-04-01

We evaluated the association between neighborhood socioeconomic status (NSES) and sleep quality on cognitive decline in the Health and Retirement Study. Health and Retirement Study participants (n = 8090), aged 65+ with DNA and multiple biennial cognitive observations (abbreviated Telephone Interview for Cognitive Status), were included. Participants were grouped into quartiles of NSES and sleep quality scores. We adjusted for apolipoprotein E ε4, demographic, and cardiovascular risk factors. Random effects modeling evaluated cognitive change over time. NSES and sleep were significantly associated with cognitive decline, and there was a significant interaction between them (P = .02). Significant differences between high/low NSES and high/low sleep quality (P < .0001) were found. Sleep and NSES were associated with cognitive decline; the association between sleep and cognition appeared stronger among those with low NSES. The association between low NSES, poor sleep quality, and cognitive decline was roughly equivalent to the association between apolipoprotein E ε4 and cognitive decline. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

The relationship between long-term sunlight radiation and cognitive decline in the REGARDS cohort study

NASA Astrophysics Data System (ADS)

Kent, Shia T.; Kabagambe, Edmond K.; Wadley, Virginia G.; Howard, Virginia J.; Crosson, William L.; Al-Hamdan, Mohammad Z.; Judd, Suzanne E.; Peace, Fredrick; McClure, Leslie A.

2014-04-01

Sunlight may be related to cognitive function through vitamin D metabolism or circadian rhythm regulation. The analysis presented here sought to test whether ground and satellite measures of solar radiation are associated with cognitive decline. The study used a 15-year residential history merged with satellite and ground monitor data to determine sunlight (solar radiation) and air temperature exposure for a cohort of 19,896 cognitively intact black and white participants aged 45+ from the 48 contiguous United States. Exposures of 15, 10, 5, 2, and 1-year were used to predict cognitive status at the most recent assessment in logistic regression models; 1-year insolation and maximum temperatures were chosen as exposure measures. Solar radiation interacted with temperature, age, and gender in its relationships with incident cognitive impairment. After adjustment for covariates, the odds ratio (OR) of cognitive decline for solar radiation exposure below the median vs above the median in the 3rd tertile of maximum temperatures was 1.88 (95 % CI: 1.24, 2.85), that in the 2nd tertile was 1.33 (95 % CI: 1.09, 1.62), and that in the 1st tertile was 1.22 (95 % CI: 0.92, 1.60). We also found that participants under 60 years old had an OR = 1.63 (95 % CI: 1.20, 2.22), those 60-80 years old had an OR = 1.18 (95 % CI: 1.02, 1.36), and those over 80 years old had an OR = 1.05 (0.80, 1.37). Lastly, we found that males had an OR = 1.43 (95 % CI: 1.22, 1.69), and females had an OR = 1.02 (0.87, 1.20). We found that lower levels of solar radiation were associated with increased odds of incident cognitive impairment.

Interleukin-6 and C-Reactive Protein Levels and 9-Year Cognitive Decline in Community-Dwelling Older Women: The Women's Health and Aging Study II.

PubMed

Palta, Priya; Xue, Qian-Li; Deal, Jennifer A; Fried, Linda P; Walston, Jeremy D; Carlson, Michelle C

2015-07-01

Elevated inflammation is a proposed mechanism relating chronic diseases to cognitive dysfunction. The objective of this study was to test the hypothesis that greater levels of inflammation, as measured by the proinflammatory cytokine interleukin-6 (IL-6) and C-reactive protein, are associated with faster rates of cognitive decline among cognitively intact community-dwelling older women. We analyzed 336 women from the Women's Health and Aging Study II. Cognitive assessments were performed at baseline and every 18-36 months, and included the following domains: immediate and delayed memory (Hopkins Verbal Learning Test), psychomotor speed (Trail Making Test, Part A), and executive function (Trail Making Test, Part B). Aggregate measures of IL-6 and C-reactive protein, based on the average from visits one and two, were analyzed categorically. Random effects models were employed to test the relationship between tertiles of each inflammatory marker and changes in cognitive domain scores over 9 years. Moderate and high levels of IL-6 predicted early declines in psychomotor speed by 1.0 connection/min per year. There were no differences in baseline scores or rates of change across tertiles of IL-6 in memory or executive function. No differences were observed across tertiles of C-reactive protein for all cognitive domains. Higher levels of serum IL-6 were associated with greater declines in psychomotor speed over 9 years. This finding could suggest that elevated IL-6 may result in microvascular changes that may lead to damage of myelin sheaths that line neuronal axons, leading to decreased neuron propagation and impaired processing speed; however, mechanistic studies are needed to evaluate these hypotheses. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Nuclear Radiation Damages Minds!

ERIC Educational Resources Information Center

Blai, Boris, Jr.

Professors Ernest Sternglass (University of Pittsburgh) and Steven Bell (Berry College) have assembled cogent, conclusive evidence indicating that nuclear radiation is associated with impaired cognition. They suggest that Scholastic Aptitude Scores (SATs), which have declined steadily for 19 years, will begin to rise. Their prediction is based on…

Dysfunctional beliefs in group and individual cognitive behavioral therapy for obsessive compulsive disorder.

PubMed

Jónsson, Hjalti; Hougaard, Esben; Bennedsen, Birgit E

2011-05-01

The primary aim of the study was to investigate dysfunctional beliefs in the form of inflated responsibility (IR) and thought action fusion (TAF) as predictive and mediating variables in individual (n=33) and group (n=37) cognitive behavioral therapy (CBT) for obsessive compulsive disorder (OCD). IR and TAF declined significantly during CBT, and the decline was positively associated with change in OCD symptoms. However, when controlling for change in depressive symptoms, only change in IR remained significantly associated with OCD symptom change. The moral subtype of TAF predicted poorer treatment outcome, but only in group CBT. Both treatments produced a similar amount of change in the dysfunctional beliefs. The results provide some, preliminary evidence that IR, but not TAF, may be specifically involved in the change mechanisms of both individual and group CBT for OCD, although the design of the study with pre- and post-therapy measurements only does not allow for a causal mediator analysis. Copyright © 2010 Elsevier Ltd. All rights reserved.

Old Brains Come Uncoupled in Sleep: Slow Wave-Spindle Synchrony, Brain Atrophy, and Forgetting.

PubMed

Helfrich, Randolph F; Mander, Bryce A; Jagust, William J; Knight, Robert T; Walker, Matthew P

2018-01-03

The coupled interaction between slow-wave oscillations and sleep spindles during non-rapid-eye-movement (NREM) sleep has been proposed to support memory consolidation. However, little evidence in humans supports this theory. Moreover, whether such dynamic coupling is impaired as a consequence of brain aging in later life, contributing to cognitive and memory decline, is unknown. Combining electroencephalography (EEG), structural MRI, and sleep-dependent memory assessment, we addressed these questions in cognitively normal young and older adults. Directional cross-frequency coupling analyses demonstrated that the slow wave governs a precise temporal coordination of sleep spindles, the quality of which predicts overnight memory retention. Moreover, selective atrophy within the medial frontal cortex in older adults predicted a temporal dispersion of this slow wave-spindle coupling, impairing overnight memory consolidation and leading to forgetting. Prefrontal-dependent deficits in the spatiotemporal coordination of NREM sleep oscillations therefore represent one pathway explaining age-related memory decline. Copyright © 2017 Elsevier Inc. All rights reserved.

Longitudinal Change of Biomarkers in Cognitive Decline

PubMed Central

Lo, Raymond Y.; Hubbard, Alan E.; Shaw, Leslie M.; Trojanowski, John Q.; Petersen, Ronald C.; Aisen, Paul S.; Weiner, Michael W.; Jagust, William J.

2017-01-01

Objective To delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD). Design Cohort study. Setting The 59 study sites for the Alzheimer’s Disease Neuroimaging Initiative. Participants A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007. Main Outcome Measures Rates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease’s Assessment Scale–cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker. Results Reductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease’s Assessment Scale–cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD. Conclusion Trajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent. PMID:21670386

Biomarkers for cognitive decline in patients with diabetes mellitus: evidence from clinical studies

PubMed Central

Zhao, Xue; Han, Qing; Lv, You; Sun, Lin; Gang, Xiaokun; Wang, Guixia

2018-01-01

Diabetes mellitus is considered as an important factor for cognitive decline and dementia in recent years. However, cognitive impairment in diabetic patients is often underestimated and kept undiagnosed, leading to thousands of diabetic patients suffering from worsening memory. Available reviews in this field were limited and not comprehensive enough. Thus, the present review aimed to summarize all available clinical studies on diabetic patients with cognitive decline, and to find valuable biomarkers that might be applied as diagnostic and therapeutic targets of cognitive impairment in diabetes. The biomarkers or risk factors of cognitive decline in diabetic patients could be classified into the following three aspects: serum molecules or relevant complications, functional or metabolic changes by neuroimaging tools, and genetic variants. Specifically, factors related to poor glucose metabolism, insulin resistance, inflammation, comorbid depression, micro-/macrovascular complications, adipokines, neurotrophic molecules and Tau protein presented significant changes in diabetic patients with cognitive decline. Besides, neuroimaging platform could provide more clues on the structural, functional and metabolic changes during the cognitive decline progression of diabetic patients. Genetic factors related to cognitive decline showed inconsistency based on the limited studies. Future studies might apply above biomarkers as diagnostic and treatment targets in a large population, and regulation of these parameters might shed light on a more valuable, sensitive and specific strategy for the diagnosis and treatment of cognitive decline in diabetic patients. PMID:29484146

Differences in quantitative methods for measuring subjective cognitive decline - results from a prospective memory clinic study.

PubMed

Vogel, Asmus; Salem, Lise Cronberg; Andersen, Birgitte Bo; Waldemar, Gunhild

2016-09-01

Cognitive complaints occur frequently in elderly people and may be a risk factor for dementia and cognitive decline. Results from studies on subjective cognitive decline are difficult to compare due to variability in assessment methods, and little is known about how different methods influence reports of cognitive decline. The Subjective Memory Complaints Scale (SMC) and The Memory Complaint Questionnaire (MAC-Q) were applied in 121 mixed memory clinic patients with mild cognitive symptoms (mean MMSE = 26.8, SD 2.7). The scales were applied independently and raters were blinded to results from the other scale. Scales were not used for diagnostic classification. Cognitive performances and depressive symptoms were also rated. We studied the association between the two measures and investigated the scales' relation to depressive symptoms, age, and cognitive status. SMC and MAC-Q were significantly associated (r = 0.44, N = 121, p = 0.015) and both scales had a wide range of scores. In this mixed cohort of patients, younger age was associated with higher SMC scores. There were no significant correlations between cognitive test performances and scales measuring subjective decline. Depression scores were significantly correlated to both scales measuring subjective decline. Linear regression models showed that age did not have a significant contribution to the variance in subjective memory beyond that of depressive symptoms. Measures for subjective cognitive decline are not interchangeable when used in memory clinics and the application of different scales in previous studies is an important factor as to why studies show variability in the association between subjective cognitive decline and background data and/or clinical results. Careful consideration should be taken as to which questions are relevant and have validity when operationalizing subjective cognitive decline.

Perception and Cognition in the Ageing Brain: A Brief Review of the Short- and Long-Term Links between Perceptual and Cognitive Decline

PubMed Central

Roberts, Katherine L.; Allen, Harriet A.

2016-01-01

Ageing is associated with declines in both perception and cognition. We review evidence for an interaction between perceptual and cognitive decline in old age. Impoverished perceptual input can increase the cognitive difficulty of tasks, while changes to cognitive strategies can compensate, to some extent, for impaired perception. While there is strong evidence from cross-sectional studies for a link between sensory acuity and cognitive performance in old age, there is not yet compelling evidence from longitudinal studies to suggest that poor perception causes cognitive decline, nor to demonstrate that correcting sensory impairment can improve cognition in the longer term. Most studies have focused on relatively simple measures of sensory (visual and auditory) acuity, but more complex measures of suprathreshold perceptual processes, such as temporal processing, can show a stronger link with cognition. The reviewed evidence underlines the importance of fully accounting for perceptual deficits when investigating cognitive decline in old age. PMID:26973514

Loneliness and Cognitive Function in Older Adults: Findings From the Chinese Longitudinal Healthy Longevity Survey.

PubMed

Zhong, Bao-Liang; Chen, Shu-Lin; Tu, Xin; Conwell, Yeates

2017-01-01

To examine the relationship between loneliness and cognitive function and to explore the mediating role of physical health on the loneliness-cognition relationship in Chinese older adults (OAs). Data came from a nationally representative sample of 14,199 Chinese OAs (aged 65+) from 2002, 2005, 2008, and 2011 waves of the Chinese Longitudinal Healthy Longevity Survey. A latent variable cross-lagged panel model combined with mediation analysis was used to determine the relationship between loneliness and cognitive function and the mediating effect of increase in the number of chronic conditions (ΔNCCs) on the ascertained loneliness-cognition relationship. Severe loneliness at prior assessment points was significantly associated with poorer cognitive function at subsequent assessments, and vice versa. The ΔNCCs partially mediated this prospective reciprocal relationships, accounting for 2.58% of the total effect of loneliness on cognition and 4.44% of the total effect of cognition on loneliness, respectively. Loneliness may predict subsequent cognitive decline, and vice versa. This loneliness-cognition relationship is partially explained by their impact on physical health. Multidisciplinary interventions aimed at reducing loneliness and cognitive decline per se and their associated risk factors as well as improving chronic illness management would be beneficial for emotional well-being and cognitive health in OAs. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Grit in Adolescence Is Protective of Late-Life Cognition: Non-Cognitive Factors and Cognitive Reserve

PubMed Central

Rhodes, Emma; Devlin, Kathryn N.; Steinberg, Laurence

2018-01-01

Various psychological assets have been shown to protect against late-life cognitive impairment by promoting cognitive reserve. While factors such as educational attainment and IQ are well-established contributors to cognitive reserve, non-cognitive factors, such as grit, have not been studied in this regard. We examined the contribution of adolescent grit, indexed by high school class rank controlling for IQ, to late-life cognition and its decline among approximately 4,000 participants in the Wisconsin Longitudinal Study, a random sample of high school graduates followed from 1957 to 2011. Adolescent grit significantly predicted both immediate and delayed memory at ages 64 and 71, over and above the contribution of IQ. While the relative contributions of IQ and grit to immediate memory were comparable, grit was a stronger predictor of delayed memory. Cognitive reserve has non-cognitive, as well as cognitive, components. PMID:27428038

Social activity, cognitive decline and dementia risk: a 20-year prospective cohort study.

PubMed

Marioni, Riccardo E; Proust-Lima, Cecile; Amieva, Helene; Brayne, Carol; Matthews, Fiona E; Dartigues, Jean-Francois; Jacqmin-Gadda, Helene

2015-10-24

Identifying modifiable lifestyle correlates of cognitive decline and risk of dementia is complex, particularly as few population-based longitudinal studies jointly model these interlinked processes. Recent methodological developments allow us to examine statistically defined sub-populations with separate cognitive trajectories and dementia risks. Engagement in social, physical, or intellectual pursuits, social network size, self-perception of feeling well understood, and degree of satisfaction with social relationships were assessed in 2854 participants from the Paquid cohort (mean baseline age 77 years) and related to incident dementia and cognitive change over 20-years of follow-up. Multivariate repeated cognitive information was exploited by defining the global cognitive functioning as the latent common factor underlying the tests. In addition, three latent homogeneous sub-populations of cognitive change and dementia were identified and contrasted according to social environment variables. In the whole population, we found associations between increased engagement in social, physical, or intellectual pursuits and increased cognitive ability (but not decline) and decreased risk of incident dementia, and between feeling understood and slower cognitive decline. There was evidence for three sub-populations of cognitive aging: fast, medium, and no cognitive decline. The social-environment measures at baseline did not help explain the heterogeneity of cognitive decline and incident dementia diagnosis between these sub-populations. We observed a complex series of relationships between social-environment variables and cognitive decline and dementia. In the whole population, factors such as increased engagement in social, physical, or intellectual pursuits were related to a decreased risk of dementia. However, in a sub-population analysis, the social-environment variables were not linked to the heterogeneous patterns of cognitive decline and dementia risk that defined the sub-groups.

Widowhood Status as a Risk Factor for Cognitive Decline among Older Adults.

PubMed

Shin, Su Hyun; Kim, Giyeon; Park, Soohyun

2018-07-01

This study investigated whether widowhood status has an effect on cognitive decline among older adults in the United States. Longitudinal analysis of existing secondary data. The 1996-2012 waves of the Health and Retirement Study. A total of 6,766 individuals (28,420 observations) aged 50 years and older who responded to all questions. Widow/widower status, cognitive functioning score, and various covariates. Growth-curve models show that after controlling for covariates, widowhood status was related to cognitive decline (95% CI: -0.8090, -0.4674). We also found a linear relationship between time since spousal loss and cognitive decline. Conditional upon spousal bereavement status, higher education and having at least one living sibling were found to be protective factors against cognitive decline. Widowhood status accelerated cognitive decline over time among widowed older adults. Findings suggest that extra support is needed to monitor cognitive functioning for those experiencing widowhood. Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Identifying elderly people at risk for cognitive decline by using the 2-step test.

PubMed

Maruya, Kohei; Fujita, Hiroaki; Arai, Tomoyuki; Hosoi, Toshiki; Ogiwara, Kennichi; Moriyama, Shunnichiro; Ishibashi, Hideaki

2018-01-01

[Purpose] The purpose is to verify the effectiveness of the 2-step test in predicting cognitive decline in elderly individuals. [Subjects and Methods] One hundred eighty-two participants aged over 65 years underwent the 2-step test, cognitive function tests and higher level competence testing. Participants were classified as Robust, <1.3, and <1.1 using criteria regarding the locomotive syndrome risk stage for the 2-step test, variables were compared between groups. In addition, ordered logistic analysis was used to analyze cognitive functions as independent variables in the three groups, using the 2-step test results as the dependent variable, with age, gender, etc. as adjustment factors. [Results] In the crude data, the <1.3 and <1.1 groups were older and displayed lower motor and cognitive functions than did the Robust group. Furthermore, the <1.3 group exhibited significantly lower memory retention than did the Robust group. The 2-step test was related to the Stroop test (β: 0.06, 95% confidence interval: 0.01-0.12). [Conclusion] The finding is that the risk stage of the 2-step test is related to cognitive functions, even at an initial risk stage. The 2-step test may help with earlier detection and implementation of prevention measures for locomotive syndrome and mild cognitive impairment.

Age and Vascular Burden Determinants of Cortical Hemodynamics Underlying Verbal Fluency.

PubMed

Heinzel, Sebastian; Metzger, Florian G; Ehlis, Ann-Christine; Korell, Robert; Alboji, Ahmed; Haeussinger, Florian B; Wurster, Isabel; Brockmann, Kathrin; Suenkel, Ulrike; Eschweiler, Gerhard W; Maetzler, Walter; Berg, Daniela; Fallgatter, Andreas J

2015-01-01

Aging processes and several vascular burden factors have been shown to increase the risk of dementia including Alzheimer's disease. While pathological alterations in dementia precede diagnosis by many years, reorganization of brain processing might temporarily delay cognitive decline. We hypothesized that in healthy elderly individuals both age-related neural and vascular factors known to be related to the development of dementia impact functional cortical hemodynamics during increased cognitive demands. Vascular burden factors and cortical functional hemodynamics during verbal fluency were assessed in 1052 non-demented elderly individuals (51 to 83 years; cross-sectional data of the longitudinal TREND study) using functional near-infrared spectroscopy (fNIRS). The prediction of functional hemodynamic responses by age in multiple regressions and the impact of single and cumulative vascular burden factors including hypertension, diabetes, obesity, smoking and atherosclerosis were investigated. Replicating and extending previous findings we could show that increasing age predicted functional hemodynamics to be increased in right prefrontal and bilateral parietal cortex, and decreased in bilateral inferior frontal junction during phonological fluency. Cumulative vascular burden factors, with hypertension in particular, decreased left inferior frontal junction hemodynamic responses during phonological fluency. However, age and vascular burden factors showed no statistical interaction on functional hemodynamics. Based on these findings, one might hypothesize that increased fronto-parietal processing may represent age-related compensatory reorganization during increased cognitive demands. Vascular burden factors, such as hypertension, may contribute to regional cerebral hypoperfusion. These neural and vascular hemodynamic determinants should be investigated longitudinally and combined with other markers to advance the prediction of future cognitive decline and dementia.

Coordinated Analysis of Age, Sex, and Education Effects on Change in MMSE Scores

PubMed Central

2013-01-01

Objectives. We describe and compare the expected performance trajectories of older adults on the Mini-Mental Status Examination (MMSE) across six independent studies from four countries in the context of a collaborative network of longitudinal studies of aging. A coordinated analysis approach is used to compare patterns of change conditional on sample composition differences related to age, sex, and education. Such coordination accelerates evaluation of particular hypotheses. In particular, we focus on the effect of educational attainment on cognitive decline. Method. Regular and Tobit mixed models were fit to MMSE scores from each study separately. The effects of age, sex, and education were examined based on more than one centering point. Results. Findings were relatively consistent across studies. On average, MMSE scores were lower for older individuals and declined over time. Education predicted MMSE score, but, with two exceptions, was not associated with decline in MMSE over time. Conclusion. A straightforward association between educational attainment and rate of cognitive decline was not supported. Thoughtful consideration is needed when synthesizing evidence across studies, as methodologies adopted and sample characteristics, such as educational attainment, invariably differ. PMID:23033357

Coordinated analysis of age, sex, and education effects on change in MMSE scores.

PubMed

Piccinin, Andrea M; Muniz-Terrera, Graciela; Clouston, Sean; Reynolds, Chandra A; Thorvaldsson, Valgeir; Deary, Ian J; Deeg, Dorly J H; Johansson, Boo; Mackinnon, Andrew; Spiro, Avron; Starr, John M; Skoog, Ingmar; Hofer, Scott M

2013-05-01

We describe and compare the expected performance trajectories of older adults on the Mini-Mental Status Examination (MMSE) across six independent studies from four countries in the context of a collaborative network of longitudinal studies of aging. A coordinated analysis approach is used to compare patterns of change conditional on sample composition differences related to age, sex, and education. Such coordination accelerates evaluation of particular hypotheses. In particular, we focus on the effect of educational attainment on cognitive decline. Regular and Tobit mixed models were fit to MMSE scores from each study separately. The effects of age, sex, and education were examined based on more than one centering point. Findings were relatively consistent across studies. On average, MMSE scores were lower for older individuals and declined over time. Education predicted MMSE score, but, with two exceptions, was not associated with decline in MMSE over time. A straightforward association between educational attainment and rate of cognitive decline was not supported. Thoughtful consideration is needed when synthesizing evidence across studies, as methodologies adopted and sample characteristics, such as educational attainment, invariably differ.

Extrinsic and Intrinsic Help-Seeking Motivation in the Assessment of Cognitive Decline.

PubMed

Haussmann, Robert; Mayer-Pelinski, René; Borchardt, Maike; Beier, Fabrice; Helling, Franziska; Buthut, Maria; Meissner, Gisa; Lange, Jan; Zweiniger, Anne; Donix, Markus

2018-06-01

Diagnostic assessments for dementia include the evaluation of subjective memory impairment, dementia worries, or depressive symptoms. Data on the predictive value of these factors remain unclear, and varying help-seeking behavior may contribute to this finding. We investigate whether differentiating help-seeking motivation from other psychological factors associated with cognitive impairment would enhance the prediction of diagnostic outcomes in a memory clinic. We obtained information on help-seeking motivation from 171 patients who underwent routine diagnostic assessments. Utilizing a discriminant correspondence analysis, our results indicate that extrinsic motivation increases the likelihood of receiving a dementia diagnosis, whereas depression or the duration of deficits carries discriminatory information to further guide the differentiation of prodromal dementia. Recognizing motivational aspects of help-seeking behavior can complement the clinical evaluation of cognitive performance.

A decline in prosocial language helps explain public disapproval of the US Congress

PubMed Central

Frimer, Jeremy A.; Aquino, Karl; Gebauer, Jochen E.; Zhu, Luke (Lei); Oakes, Harrison

2015-01-01

Talking about helping others makes a person seem warm and leads to social approval. This work examines the real world consequences of this basic, social-cognitive phenomenon by examining whether record-low levels of public approval of the US Congress may, in part, be a product of declining use of prosocial language during Congressional debates. A text analysis of all 124 million words spoken in the House of Representatives between 1996 and 2014 found that declining levels of prosocial language strongly predicted public disapproval of Congress 6 mo later. Warm, prosocial language still predicted public approval when removing the effects of societal and global factors (e.g., the September 11 attacks) and Congressional efficacy (e.g., passing bills), suggesting that prosocial language has an independent, direct effect on social approval. PMID:25964358

Effects of Sex and Education on Cognitive Change Over a 27-Year Period in Older Adults: The Rancho Bernardo Study.

PubMed

Reas, Emilie T; Laughlin, Gail A; Bergstrom, Jaclyn; Kritz-Silverstein, Donna; Barrett-Connor, Elizabeth; McEvoy, Linda K

2017-08-01

This study investigated how cognitive function changes with age and whether rates of decline vary by sex or education in a large, homogenous longitudinal cohort characterized by high participation rates, long duration of follow-up, and minimal loss to follow-up. Between 1988 and 2016, 2,225 community-dwelling participants of the Rancho Bernardo Study, aged 31 to 99 years at their initial cognitive assessment, completed neuropsychological testing approximately every 4 years, over a maximum 27-year follow-up. Linear mixed effects regression models defined sex-specific cognitive trajectories, adjusting for education and retest effects. Significant decline across all cognitive domains began around age 65 years and accelerated after age 80 years. Patterns of decline were generally similar between sexes, although men declined more rapidly than women on the global function test. Higher education was associated with slower decline on the tests of executive and global functions. After excluding 517 participants with evidence of cognitive impairment, accelerating decline with age remained for all tests, and women declined more rapidly than men on the executive function test. Accelerating decline with advancing age occurs across multiple cognitive domains in community-dwelling older adults, with few differences in rates of decline between men and women. Higher education may provide some protection against executive and global function decline with age. These findings better characterize normal cognitive aging, a critical prerequisite for identifying individuals at risk for cognitive impairment, and lay the groundwork for future studies of health and behavioral factors that affect age-related decline in this cohort. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies

PubMed Central

Arvanitakis, Z.; Yu, L.; Boyle, P. A.; Leurgans, S. E.; Bennett, D. A.

2012-01-01

Lewy bodies are common in the ageing brain and often co-occur with Alzheimer’s disease pathology. There is little known regarding the independent role of Lewy body pathology in cognition impairment, decline and fluctuations in community-dwelling older persons. We examined the contribution of Lewy body pathology to dementia, global cognition, cognitive domains, cognitive decline and fluctuations in 872 autopsied subjects (mean age = 87.9 years) from the Rush Religious Order Study (n = 491) and Memory and Aging Project (n = 381) longitudinal community-based clinical–pathological studies. Dementia was based on a clinical evaluation; annual cognitive performance tests were used to create a measure of global cognition and five cognitive domains. Lewy body type was determined by using α-synuclein immunostained sections of substantia nigra, limbic and neocortical regions. Statistical models included multiple regression models for dementia and cognition and mixed effects models for decline. Cognitive fluctuations were estimated by comparing standard deviations of individual residuals from mean trajectories of decline in those with and without Lewy bodies. All models controlled for age, sex, education, Alzheimer’s disease pathology and infarcts. One hundred and fifty-seven subjects (18%) exhibited Lewy body pathology (76 neocortical-type, 54 limbic-type and 27 nigra-predominant). One hundred and three (66%) subjects with Lewy body pathology had a pathologic diagnosis of Alzheimer’s disease. Neocortical-type, but not nigral-predominant or limbic-type Lewy body pathology was related to an increased odds of dementia (odds ratio = 3.21; 95% confidence interval = 1.78–5.81) and lower cognition (P < 0.001) including episodic memory function (P < 0.001) proximate to death. Neocortical-type Lewy body pathology was also related to a faster decline in global cognition (P < 0.001), decline in all five specific cognitive domains (all P-values < 0.001), and to fluctuations in decline of working and semantic memory (P-values < 0.001). Limbic-type Lewy body pathology was related to lower and faster decline in visuospatial skills (P = 0.042). The relationship of Lewy body pathology to cognition and dementia was not modified by Alzheimer’s disease pathology. Neocortical-type Lewy body pathology is associated with increased odds of dementia; lower and more rapid decline in all cognitive domains including episodic memory and fluctuations in decline in semantic and working memory. Limbic-type Lewy body pathology is specifically associated with lower and more rapid decline in visuospatial skills. The effect of Lewy body pathology on cognition appears to be independent of Alzheimer’s disease pathology. PMID:23065790

Terminal decline and practice effects in older adults without dementia: the MoVIES project.

PubMed

Dodge, Hiroko H; Wang, Chia-Ning; Chang, Chung-Chou H; Ganguli, Mary

2011-08-23

To track cognitive change over time in dementia-free older adults and to examine terminal cognitive decline. A total of 1,230 subjects who remained free from dementia over 14 years of follow-up were included in a population-based epidemiologic cohort study. First, we compared survivors and decedents on their trajectories of 5 cognitive functions (learning, memory, language, psychomotor speed, executive functions), dissociating practice effects which can mask clinically significant decline from age-associated cognitive decline. We used longitudinal mixed-effects models with penalized linear spline. Second, limiting the sample to 613 subjects who died during follow-up, we identified the inflection points at which the rate of cognitive decline accelerated, in relation to time of death, controlling for practice effects. We used mixed-effects model with a change point. Age-associated cognitive trajectories were similar between decedents and survivors without dementia. However, substantial differences were observed between the trajectories of practice effects of survivors and decedents, resembling those usually observed between normal and mildly cognitively impaired elderly. Executive and language functions showed the earliest terminal declines, more than 9 years prior to death, independent of practice effects. Terminal cognitive decline in older adults without dementia may reflect presymptomatic disease which does not cross the clinical threshold during life. Alternatively, cognitive decline attributed to normal aging may itself represent underlying neurodegenerative or vascular pathology. Although we cannot conclude definitively from this study, the separation of practice effects from age-associated decline could help identify preclinical dementia.

The quality of life of patients developed delirium after coronary artery bypass grafting is determined by cognitive function after discharge: A cross-sectional study.

PubMed

Chen, Yuling; Ding, Shu; Tao, Xiangjun; Feng, Xinwei; Lu, Sai; Shen, Yuzhi; Wu, Ying; An, Xiangguang

2017-10-01

Postoperative delirium (POD) and declined cognitive function were common in patients (especially elderly patients) who underwent coronary artery bypass grafting (CABG), which may affect quality of life (QoL). The aim of this study was to determine the relationships among age, POD, declined cognitive function, and QoL in patients who underwent CABG. Consecutive patients who underwent first time elective CABG and assessed for POD using Confusion Assessment Method for intensive care unit for 5 postoperative days from November 2013 to March 2015 were recruited. A cross-sectional study was conducted during April 2015 to assess their cognitive function and QoL, using the Telephone Interview for Cognitive Status Scale and Medical Outcomes Study 36-Item Short Form Health Survey. The relationships among age, POD, declined cognitive function, and QoL were tested using path analysis. Declined cognitive function was associated with poorer QoL. POD was associated with declined cognitive function but was not associated with poorer QoL. Ageing was not associated with QoL but was associated with POD and declined cognitive function. The QoL of patients developed delirium after CABG is determined by cognitive function after discharge. Necessary strategies should be implemented to prevent POD and declined cognitive function, especially in elderly patients. © 2017 John Wiley & Sons Australia, Ltd.

Long-term trajectories of self-reported cognitive function in a cohort of older survivors of breast cancer: CALGB 369901 (Alliance).

PubMed

Mandelblatt, Jeanne S; Clapp, Jonathan D; Luta, Gheorghe; Faul, Leigh Anne; Tallarico, Michelle D; McClendon, Trina D; Whitley, Jessica A; Cai, Ling; Ahles, Tim A; Stern, Robert A; Jacobsen, Paul B; Small, Brent J; Pitcher, Brandelyn N; Dura-Fernandis, Estrella; Muss, Hyman B; Hurria, Arti; Cohen, Harvey J; Isaacs, Claudine

2016-07-22

The number of survivors of breast cancer aged ≥65 years ("older") is growing, but to the authors' knowledge, little is known regarding the cognitive outcomes of these individuals. A cohort of cognitively intact older survivors with nonmetastatic, invasive breast cancer was recruited from 78 sites from 2004 through 2011; approximately 83.7% of the survivors (1280 survivors) completed baseline assessments. Follow-up data were collected at 6 months and annually for up to 7 years (median, 4.1 years). Cognitive function was self-reported using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30); scores ranged from 0 to 100, with a higher score indicating better function. Group-based trajectory modeling determined trajectories; women were assigned to a trajectory group based on the highest predicted probability of membership. Multinomial logistic regression evaluated the association between receipt of chemotherapy (with or without hormonal treatment) and trajectory group. Survivors were aged 65 to 91 years; approximately 41% received chemotherapy. There were 3 cognitive trajectories: "maintained high" (42.3% of survivors); "phase shift" (50.1% of survivors), with scores slightly below but parallel to maintained high; and "accelerated decline" (7.6% of survivors), with the lowest baseline scores and greatest decline (from 71.7 [standard deviation, 19.8] to 58.3 [standard deviation, 21.9]). The adjusted odds of being in the accelerated decline group (vs the maintained high group) were 2.1 times higher (95% confidence interval, 1.3-3.5) for survivors who received chemotherapy (with or without hormonal therapy) versus those treated with hormonal therapy alone. Greater comorbidity and frailty also were found to be associated with accelerated decline. Trajectory group analysis demonstrated that the majority of older survivors maintained good long-term self-reported cognitive function, and that only a small subset who were exposed to chemotherapy manifested accelerated cognitive decline. Future research is needed to determine factors that place some older survivors at risk of experiencing cognitive decline. Cancer 2016. 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Education and Cognitive Decline in Older Americans: Results From the AHEAD Sample

PubMed Central

Alley, Dawn; Suthers, Kristen; Crimmins, Eileen

2009-01-01

Although education is consistently related to better cognitive performance, findings on the relationship between education and age-associated cognitive change have been conflicting. Using measures of multiple cognitive domains from four waves of the Asset and Health Dynamics of the Oldest Old study, a representative sample of Americans aged 70 years and older, the authors performed growth curve modeling to examine the relationships between education, initial cognitive score, and the rate of decline in cognitive function. More years of education were linked to better initial performance on each of the cognitive tests, and higher levels of education were linked to slower decline in mental status. However, more education was unrelated to the rate of decline in working memory, and education was associated with somewhat faster cognitive decline on measures of verbal memory. These findings highlight the role of early-life experiences not only in long-term cognitive performance but also in old-age cognitive trajectories. PMID:19830260

Demonstration of cognitive decline in Parkinson's disease using the Cambridge Cognitive Assessment (Revised) (CAMCOG-R).

PubMed

Athey, Richard J; Walker, Richard W

2006-10-01

Cognitive impairment is well recognised in Parkinson's Disease (PD) but few studies have examined cognitive decline over time in such subjects. Standard clinical assessments of cognitive function, such as the MMSE, do not measure all cognitive domains and often have a ceiling effect. CAMCOG-R provides a more comprehensive cognitive assessment allowing several different domains of cognition to be compared. It also features the ability to test 'executive function'. CAMCOG-R has only been reported on one previous occasion in PD subjects and this is the first study to report a follow-up CAMCOG-R to assess cognitive decline. In a previously published study CAMCOG-R was administered to a prevalent community-based population of 94 subjects with PD with a MMSE of 25 or above. In this subsequent study 85 of the subjects (two declined and seven were deceased) underwent a follow-up CAMCOG-R after a mean delay of 13.1 months. The initial, and follow-up mean total CAMCOG-R scores were 88.65/104 and 84.75/104 respectively, demonstrating a significant decline (p < 0.05). Significant cognitive decline (p < 0.05) was also seen across every CAMCOG-R cognitive domain and in the executive function scores. A wide range of cognitive ability was again demonstrated using CAMCOG-R in this PD population. The decline of 3.9 CAMCOG-R points over the 13-month period compares to other previous studies showing an annual decline of 1.6 CAMCOG points in normal elderly individuals and 12 CAMCOG points annually in those with established dementia. This study suggests that CAMCOG-R is a useful and appropriate tool for use in follow-up cognitive screening in PD subjects. Copyright (c) 2006 John Wiley & Sons, Ltd.

Aging and the Shape of Cognitive Change Before Death: Terminal Decline Or Terminal Drop?

PubMed Central

Hultsch, David F.; Dixon, Roger A.

2011-01-01

Objectives. Relative to typical age-related cognitive decrements, the terms “terminal decline” and “terminal drop” refer to the phenomenon of increased cognitive decline in proximity to death. Given that these terms are not necessarily synonymous, we examined the important theoretical distinction between the two alternative trajectories or shapes of changes they imply. Methods. We used 12-year (5-wave) data from the Victoria Longitudinal Study to directly test whether pre-death cognitive decrements follow a terminal decline (generally gradual) or a terminal drop (more abrupt) shape. Pre-death trajectories of cognitive decline for n = 265 decedents (Mage = 72.67 years, SD = 6.44) were examined separately for 5 key cognitive constructs (verbal speed, working memory, episodic memory, semantic memory, and crystallized ability). Results. Several classes of linear mixed models evaluated whether cognitive decline increased per additional year closer to death. Findings indicated that the shape of pre-death cognitive change was predominantly characterized by decline that is steeper as compared with typical aging-related change, but still best described as slow and steady decline, especially as compared with precipitous drop. Discussion. The present findings suggest that terminal decline and terminal drop trajectories may not be mutually exclusive but could rather reflect distinct developmental trajectories within the same individual. PMID:21300703

Insulin-like Growth Factor 1 (IGF-1) as a marker of cognitive decline in normal ageing: A review.

PubMed

Frater, Julanne; Lie, David; Bartlett, Perry; McGrath, John J

2018-03-01

Insulin-like Growth Factor 1 (IGF-1) and its signaling pathway play a primary role in normal growth and ageing, however serum IGF-1 is known to reduce with advancing age. Recent findings suggest IGF-1 is essential for neurogenesis in the adult brain, and this reduction of IGF-1 with ageing may contribute to age-related cognitive decline. Experimental studies have shown manipulation of the GH/GF-1 axis can slow rates of cognitive decline in animals, making IGF-1 a potential biomarker of cognition, and/or its signaling pathway a possible therapeutic target to prevent or slow age-related cognitive decline. A systematic literature review and qualitative narrative summary of current evidence for IGF-1 as a biomarker of cognitive decline in the ageing brain was undertaken. Results indicate IGF-1 concentrations do not confer additional diagnostic information for those with cognitive decline, and routine clinical measurement of IGF-1 is not currently justified. In cases of established cognitive impairment, it remains unclear whether increasing circulating or brain IGF-1 may reverse or slow down the rate of further decline. Advances in neuroimaging, genetics, neuroscience and the availability of large well characterized biobanks will facilitate research exploring the role of IGF-1 in both normal ageing and age-related cognitive decline. Copyright © 2017 Elsevier B.V. All rights reserved.

[Cognitive impairment, nutritional status and clinical profile in chronic obstructive pulmonary disease].

PubMed

López Torres, Isabel; Torres-Sánchez, Irene; Martín Salvador, Adelina; Ortiz Rubio, Araceli; Rodríguez Alzueta, Elisabeth; Valenza, Marie Carmen

2014-11-01

Chronic obstructive pulmonary disease (COPD) is a progressive disease with a prevalence that increases with the aging of the subject. It presents a high prevalence of comorbidities, such as cognitive decline, which is gaining great clinical relevance in recent years. Factors such as pulmonary function, hypoxemia, hypercapnia or exacerbations contribute to the decline of cognitive functions. The nutritional status has been added to these factors as contributing to cognitive function decline when presenting in COPD. To evidence the relationship between cognitive decline, nutritional status and the clinical profile of patients admitted because of an acute exacerbation of COPD (AECOPD). 110 subjects hospitalized because of COPD, divided in two groups according to their nutritional status and assessment of cognitive decline at admittance, nutritional status and clinical profile. Significant differences between groups concerning nutritional status in anthropometric variables (sex and IMC), functional ability (Barthel index and Daily Life Activities Scale), quality of life (Euroqol- 5D y SGRQ), sleep quality (Pittsburgh), mood (HAD) and cognitive decline (MoCa attention, MoCa abstraction). (p<0.05). Cognitive function is affected in COPD patients with an altered nutritional status when compared to those with a normal nutritional status. The nutritional decline is a factor contributing to the impairment of cognitive functions in this kind of patients, particularly a decline in attention and abstraction ability. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Recent and past musical activity predicts cognitive aging variability: direct comparison with general lifestyle activities.

PubMed

Hanna-Pladdy, Brenda; Gajewski, Byron

2012-01-01

Studies evaluating the impact of modifiable lifestyle factors on cognition offer potential insights into sources of cognitive aging variability. Recently, we reported an association between extent of musical instrumental practice throughout the life span (greater than 10 years) on preserved cognitive functioning in advanced age. These findings raise the question of whether there are training-induced brain changes in musicians that can transfer to non-musical cognitive abilities to allow for compensation of age-related cognitive declines. However, because of the relationship between engagement in general lifestyle activities and preserved cognition, it remains unclear whether these findings are specifically driven by musical training or the types of individuals likely to engage in greater activities in general. The current study controlled for general activity level in evaluating cognition between musicians and nomusicians. Also, the timing of engagement (age of acquisition, past versus recent) was assessed in predictive models of successful cognitive aging. Seventy age and education matched older musicians (>10 years) and non-musicians (ages 59-80) were evaluated on neuropsychological tests and general lifestyle activities. Musicians scored higher on tests of phonemic fluency, verbal working memory, verbal immediate recall, visuospatial judgment, and motor dexterity, but did not differ in other general leisure activities. Partition analyses were conducted on significant cognitive measures to determine aspects of musical training predictive of enhanced cognition. The first partition analysis revealed education best predicted visuospatial functions in musicians, followed by recent musical engagement which offset low education. In the second partition analysis, early age of musical acquisition (<9 years) predicted enhanced verbal working memory in musicians, while analyses for other measures were not predictive. Recent and past musical activity, but not general lifestyle activities, predicted variability across both verbal and visuospatial domains in aging. These findings are suggestive of different use-dependent adaptation periods depending on cognitive domain. Furthermore, they imply that early age of musical acquisition, sustained and maintained during advanced age, may enhance cognitive functions and buffer age and education influences.

Is low cognitive functioning a predictor or consequence of major depressive disorder? A test in two longitudinal birth cohorts.

PubMed

Schaefer, Jonathan D; Scult, Matthew A; Caspi, Avshalom; Arseneault, Louise; Belsky, Daniel W; Hariri, Ahmad R; Harrington, Honalee; Houts, Renate; Ramrakha, Sandhya; Poulton, Richie; Moffitt, Terrie E

2017-11-16

Cognitive impairment has been identified as an important aspect of major depressive disorder (MDD). We tested two theories regarding the association between MDD and cognitive functioning using data from longitudinal cohort studies. One theory, the cognitive reserve hypothesis, suggests that higher cognitive ability in childhood decreases risk of later MDD. The second, the scarring hypothesis, instead suggests that MDD leads to persistent cognitive deficits following disorder onset. We tested both theories in the Dunedin Study, a population-representative cohort followed from birth to midlife and assessed repeatedly for both cognitive functioning and psychopathology. We also used data from the Environmental Risk Longitudinal Twin Study to test whether childhood cognitive functioning predicts future MDD risk independent of family-wide and genetic risk using a discordant twin design. Contrary to both hypotheses, we found that childhood cognitive functioning did not predict future risk of MDD, nor did study members with a past history of MDD show evidence of greater cognitive decline unless MDD was accompanied by other comorbid psychiatric conditions. Our results thus suggest that low cognitive functioning is related to comorbidity, but is neither an antecedent nor an enduring consequence of MDD. Future research may benefit from considering cognitive deficits that occur during depressive episodes from a transdiagnostic perspective.

Hypertension is associated with cognitive decline in elderly people at high risk for dementia.

PubMed

Wysocki, Michael; Luo, Xiaodong; Schmeidler, James; Dahlman, Karen; Lesser, Gerson T; Grossman, Hillel; Haroutunian, Vahram; Beeri, Michal Schnaider

2012-02-01

Cardiovascular risk factors including hypertension (HTN) have been shown to increase the risk of Alzheimer disease. The current study investigated whether individuals with HTN are more susceptible to increased cognitive decline and whether the influence of HTN on cognitive decline varied as a function of dementia severity. A total of 224 nursing home and assisted living residents, with a mean age of 84.9 (±7.6) years, were assessed longitudinally with Mini Mental State Exams (MMSEs) and Clinical Dementia Ratings (CDR). Baseline dementia status was defined by the CDR score. As described in , MMSE scores in persons with HTN and questionable dementia (CDR = 0.5) declined significantly faster than nonhypertensive questionably demented persons. Hypertensive participants did not decline significantly faster than nonhypertensive participants in persons with intact cognition (CDR = 0) or frank dementia (CDR ≥ 1). These results suggest an increased risk of subsequent cognitive decline in hypertensive individuals who are especially vulnerable to developing dementia and raises the possibility that avoiding or controlling HTN might reduce the rate of cognitive decline in cognitively vulnerable individuals, potentially delaying their conversion to full-fledged dementia.

Vitamin D Levels and the Risk of Cognitive Decline in Chinese Elderly People: the Chinese Longitudinal Healthy Longevity Survey.

PubMed

Matchar, David B; Chei, Choy-Lye; Yin, Zhao-Xue; Koh, Victoria; Chakraborty, Bibhas; Shi, Xiao-Ming; Zeng, Yi

2016-10-01

Vitamin D has a neuroprotective function, potentially important for the prevention of cognitive decline. Prospective studies from Western countries support an association between lower vitamin D level and future cognitive decline in elderly people. No prospective study has examined this association in Asia. This community-based cohort study of elderly people in China follows 1,202 cognitively intact adults aged ≥60 years for a mean duration of 2 years. Plasma vitamin D level was measured at the baseline. Cognitive state of participants was assessed using the Mini-Mental State Examination (MMSE). Cognitive impairment was defined as an MMSE score <18. Cognitive decline was defined as ≥3 points decline from baseline. Multivariable logistic regression models were used to examine the association between quartiles of vitamin D levels with cognitive decline and incidence of cognitive impairment. Participants with low vitamin D level had an increased risk of cognitive decline. Compared with the highest quartile of vitamin D levels, the multivariable odds ratios (ORs; 95% confidence interval) for cognitive decline were 2.1 (1.3-3.4) for the second highest quartile, 2.2 (1.4-3.6) for the third highest quartile, and 2.0 (1.2-3.3) for the lowest quartile. The multivariable ORs of incident cognitive impairment for the second highest, third highest, and lowest versus highest quartiles of vitamin D levels were 1.9 (0.9-4.1), 2.6 (1.2-5.6), and 3.2 (1.5-6.6), respectively. This first follow-up study of elderly people, including the oldest-old, in Asia shows that low vitamin D levels were associated with increased risk of subsequent cognitive decline and impairment. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Personality and Cognitive Decline in Older Adults: Data From a Longitudinal Sample and Meta-Analysis

PubMed Central

Terracciano, Antonio; Stephan, Yannick; Sutin, Angelina R.

2016-01-01

Objectives: Personality traits are associated with risk of dementia; less is known about their association with the trajectory of cognitive functioning. This research examines the association between the 5 major dimensions of personality and cognitive function and decline in older adulthood and includes a meta-analysis of published studies. Method: Personality traits, objective and subjective memory, and cognitive status were collected in a large national sample (N = 13,987) with a 4-year follow-up period. For each trait, the meta-analysis pooled results from up to 5 prospective studies to examine personality and change in global cognition. Results: Higher Neuroticism was associated with worse performance on all cognitive measures and greater decline in memory, whereas higher Conscientiousness and Openness were associated with better memory performance concurrently and less decline over time. All traits were associated with subjective memory. Higher Conscientiousness and lower Extraversion were associated with better cognitive status and less decline. Although modest, these associations were generally larger than that of hypertension, diabetes, history of psychological treatment, obesity, smoking, and physical inactivity. The meta-analysis supported the association between Neuroticism and Conscientiousness and cognitive decline. Discussion: Personality is associated with cognitive decline in older adults, with effects comparable to established clinical and lifestyle risk factors. PMID:25583598

Metabolic Syndrome and 16-year Cognitive Decline in Community-Dwelling Older Adults

PubMed Central

McEvoy, Linda K.; Laughlin, Gail A.; Barrett-Connor, Elizabeth; Bergstrom, Jaclyn; Kritz-Silverstein, Donna; Der-Martirosian, Claudia; von Mühlen, Denise

2012-01-01

PURPOSE To determine whether metabolic syndrome is associated with accelerated cognitive decline in community-dwelling older adults. METHODS Longitudinal study of 993 adults (mean 66.8 ± 8.7 years) from the Rancho Bernardo Study. Metabolic syndrome components, defined by 2001 NCEP-ATP III criteria, were measured in 1984–87. Cognitive function was first assessed in 1988–92. Cognitive assessments were repeated approximately every four years, for a maximum 16-year follow-up. Mixed-effects models examined longitudinal rate of cognitive decline by metabolic syndrome status, controlling for factors plausibly associated with cognitive function (diabetes, inflammation). RESULTS Metabolic syndrome was more common in men than women (14% vs. 9%, p=0.01). In women, metabolic syndrome was associated with greater executive function and long term memory decline. These associations did not differ by inflammatory biomarker levels. Diabetes did not alter the association of metabolic syndrome with long-term recall but modified the association with executive function: metabolic syndrome was associated with accelerated executive function decline in diabetic women only. Metabolic syndrome was not related to rate of decline on any cognitive measure in men. CONCLUSIONS Metabolic syndrome was a risk factor for accelerated cognitive decline, but only in women. Prevention of metabolic syndrome may aid in maintenance of cognitive function with age. PMID:22285865

Changes in physical activity and cognitive decline in older adults living in the community.

PubMed

Lee, Yunhwan; Kim, Jinhee; Han, Eun Sook; Chae, Songi; Ryu, Mikyung; Ahn, Kwang Ho; Park, Eun Ju

2015-01-01

Accumulating evidence suggests that physical activity may be beneficial in preserving cognition in late life. This study examined the association between baseline and changes in physical activity and cognitive decline in community-dwelling older people. Data were from the Korean Longitudinal Study of Aging, with 2605 aged 65 years and older subjects interviewed in 2006 and followed up for 2 years. Cognitive decline was defined by calculating the Reliable Change Index using the Mini-Mental State Examination. Physical activity levels were categorized as sedentary, low, or high. Changes in physical activity were classified as inactive, decreaser, increaser, or active. Logistic regression analysis of baseline and changes in physical activity with cognitive decline was performed. Compared with the sedentary group at baseline, both the low and high activity groups were less likely to experience cognitive decline. The active (odds ratio [OR] = 0.40, 95 % confidence interval [CI] 0.23-0.68) and increaser (OR = 0.45, 95 % CI 0.27-0.74) group, compared with the inactive counterpart, demonstrated a significantly lower likelihood of cognitive decline. Older adults who remained active or increased activity over time had a reduced risk of cognitive decline. Engagement in physical activity in late life may have cognitive health benefits.

Depressed Mood Mediates Decline in Cognitive Processing Speed in Caregivers

ERIC Educational Resources Information Center

Vitaliano, Peter P.; Zhang, Jianping; Young, Heather M.; Caswell, Lisa W.; Scanlan, James M.; Echeverria, Diana

2009-01-01

Purpose: Very few studies have examined cognitive decline in caregivers versus noncaregivers, and only 1 study has examined mediators of such decline. We evaluated the relationship between caregiver status and decline on the digit symbol test (DST; a measure of processing speed, attention, cognitive-motor translation, and visual scanning) and…

Grit in adolescence is protective of late-life cognition: non-cognitive factors and cognitive reserve.

PubMed

Rhodes, Emma; Devlin, Kathryn N; Steinberg, Laurence; Giovannetti, Tania

2017-05-01

Various psychological assets have been shown to protect against late-life cognitive impairment by promoting cognitive reserve. While factors such as educational attainment and IQ are well-established contributors to cognitive reserve, noncognitive factors, such as grit, have not been studied in this regard. We examined the contribution of adolescent grit, indexed by high school class rank controlling for IQ, to late-life cognition and its decline among approximately 4000 participants in the Wisconsin Longitudinal Study, a random sample of high school graduates followed from 1957 to 2011. Adolescent grit significantly predicted both immediate and delayed memory at ages 64 and 71, over and above the contribution of IQ. While the relative contributions of IQ and grit to immediate memory were comparable, grit was a stronger predictor of delayed memory. Cognitive reserve has noncognitive, as well as cognitive, components.

Sleep duration, cognitive decline, and dementia risk in older women

PubMed Central

Chen, Jiu-Chiuan; Espeland, Mark A.; Brunner, Robert L.; Lovato, Laura C.; Wallace, Robert B.; Leng, Xiaoyan; Phillips, Lawrence S.; Robinson, Jennifer G.; Kotchen, Jane M.; Johnson, Karen C.; Manson, JoAnn E.; Stefanick, Marcia L.; Sarto, Gloria E.; Mysiw, W. Jerry

2015-01-01

Background Consistent evidence linking habitual sleep duration with risks of mild cognitive impairment (MCI) and dementia is lacking. Methods We conducted a prospective study on 7444 community-dwelling women (aged 65–80) with self-reported sleep duration, within the Women’s Health Initiative Memory Study in 1995–2008. Incident MCI/dementia cases were ascertained by validated protocols. Cox models were used to adjust for multiple sociodemographic and lifestyle factors, depression, cardiovascular disease (CVD), and other clinical characteristics. Results We found a statistically significant (p=0.03) V-shaped association, with a higher MCI/dementia risk in women with either short (≤6 hours/night) or long (≥8 hours/night) sleep duration (vs.7 hours/night). The multicovariate-adjusted hazard for MCI/dementia was increased by 36% in short sleepers irrespective of CVD, and by 35% in long sleepers without CVD. A similar V-shaped association was found with cognitive decline. Conclusion In older women, habitual sleep duration predicts the future risk for cognitive impairments including dementia, independent of vascular risk factors. PMID:26086180

Mild Cognitive Impairment (MCI)

MedlinePlus

Mild cognitive impairment (MCI) Overview Mild cognitive impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and the more-serious decline of dementia. It ...

Behavioral and Neural Markers of Flexible Attention over Working Memory in Aging.

PubMed

Mok, Robert M; Myers, Nicholas E; Wallis, George; Nobre, Anna Christina

2016-04-01

Working memory (WM) declines as we age and, because of its fundamental role in higher order cognition, this can have highly deleterious effects in daily life. We investigated whether older individuals benefit from flexible orienting of attention within WM to mitigate cognitive decline. We measured magnetoencephalography (MEG) in older adults performing a WM precision task with cues during the maintenance period that retroactively predicted the location of the relevant items for performance (retro-cues). WM performance of older adults significantly benefitted from retro-cues. Whereas WM maintenance declined with age, retro-cues conferred strong attentional benefits. A model-based analysis revealed an increase in the probability of recalling the target, a lowered probability of retrieving incorrect items or guessing, and an improvement in memory precision. MEG recordings showed that retro-cues induced a transient lateralization of alpha (8-14 Hz) and beta (15-30 Hz) oscillatory power. Interestingly, shorter durations of alpha/beta lateralization following retro-cues predicted larger cueing benefits, reinforcing recent ideas about the dynamic nature of access to WM representations. Our results suggest that older adults retain flexible control over WM, but individual differences in control correspond to differences in neural dynamics, possibly reflecting the degree of preservation of control in healthy aging. © The Author 2016. Published by Oxford University Press.

Behavioral and Neural Markers of Flexible Attention over Working Memory in Aging

PubMed Central

Mok, Robert M.; Myers, Nicholas E.; Wallis, George; Nobre, Anna Christina

2016-01-01

Working memory (WM) declines as we age and, because of its fundamental role in higher order cognition, this can have highly deleterious effects in daily life. We investigated whether older individuals benefit from flexible orienting of attention within WM to mitigate cognitive decline. We measured magnetoencephalography (MEG) in older adults performing a WM precision task with cues during the maintenance period that retroactively predicted the location of the relevant items for performance (retro-cues). WM performance of older adults significantly benefitted from retro-cues. Whereas WM maintenance declined with age, retro-cues conferred strong attentional benefits. A model-based analysis revealed an increase in the probability of recalling the target, a lowered probability of retrieving incorrect items or guessing, and an improvement in memory precision. MEG recordings showed that retro-cues induced a transient lateralization of alpha (8–14 Hz) and beta (15–30 Hz) oscillatory power. Interestingly, shorter durations of alpha/beta lateralization following retro-cues predicted larger cueing benefits, reinforcing recent ideas about the dynamic nature of access to WM representations. Our results suggest that older adults retain flexible control over WM, but individual differences in control correspond to differences in neural dynamics, possibly reflecting the degree of preservation of control in healthy aging. PMID:26865653

Brain reserve and cognitive reserve in multiple sclerosis

PubMed Central

Rocca, Maria A.; Leavitt, Victoria M.; Riccitelli, Gianna; Comi, Giancarlo; DeLuca, John; Filippi, Massimo

2013-01-01

Objective: We first tested the brain reserve (BR) hypothesis in multiple sclerosis (MS) by examining whether larger maximal lifetime brain volume (MLBV; determined by genetics) protects against disease-related cognitive impairment, and then investigated whether cognitive reserve (CR) gained through life experience (intellectually enriching leisure activities) protects against cognitive decline independently of MLBV (BR). Methods: Sixty-two patients with MS (41 relapsing-remitting MS, 21 secondary progressive MS) received MRIs to estimate BR (MLBV, estimated with intracranial volume [ICV]) and disease burden (T2 lesion load; atrophy of gray matter, white matter, thalamus, and hippocampus). Early-life cognitive leisure was measured as a source of CR. We assessed cognitive status with tasks of cognitive efficiency and memory. Hierarchical regressions were used to investigate whether higher BR (ICV) protects against cognitive impairment, and whether higher CR (leisure) independently protects against cognitive impairment over and above BR. Results: Cognitive status was positively associated with ICV (R2 = 0.066, p = 0.017). An ICV × disease burden interaction (R2 = 0.050, p = 0.030) revealed that larger ICV attenuated the impact of disease burden on cognition. Controlling for BR, higher education (R2 = 0.047, p = 0.030) and leisure (R2 = 0.090, p = 0.001) predicted better cognition. A leisure × disease burden interaction (R2 = 0.037, p = 0.030) showed that leisure independently attenuated the impact of disease burden on cognition. Follow-up analyses revealed that BR protected against cognitive inefficiency, not memory deficits, whereas CR was more protective against memory deficits than cognitive inefficiency. Conclusion: We provide evidence of BR in MS, and show that CR independently protects against disease-related cognitive decline over and above BR. Lifestyle choices protect against cognitive impairment independently of genetic factors outside of one's control. PMID:23667062

Cognitive domains that predict time to diagnosis in prodromal Huntington disease.

PubMed

Harrington, Deborah Lynn; Smith, Megan M; Zhang, Ying; Carlozzi, Noelle E; Paulsen, Jane S

2012-06-01

Prodromal Huntington's disease (prHD) is associated with a myriad of cognitive changes but the domains that best predict time to clinical diagnosis have not been studied. This is a notable gap because some domains may be more sensitive to cognitive decline, which would inform clinical trials. The present study sought to characterise cognitive domains underlying a large test battery and for the first time, evaluate their ability to predict time to diagnosis. Participants included gene negative and gene positive prHD participants who were enrolled in the PREDICT-HD study. The CAG-age product (CAP) score was the measure of an individual's genetic signature. A factor analysis of 18 tests was performed to identify sets of measures or latent factors that elucidated core constructs of tests. Factor scores were then fit to a survival model to evaluate their ability to predict time to diagnosis. Six factors were identified: (1) speed/inhibition, (2) verbal working memory, (3) motor planning/speed, (4) attention-information integration, (5) sensory-perceptual processing and (6) verbal learning/memory. Factor scores were sensitive to worsening of cognitive functioning in prHD, typically more so than performances on individual tests comprising the factors. Only the motor planning/speed and sensory-perceptual processing factors predicted time to diagnosis, after controlling for CAP scores and motor symptoms. Conclusions The results suggest that motor planning/speed and sensory-perceptual processing are important markers of disease prognosis. The findings also have implications for using composite indices of cognition in preventive Huntington's disease trials where they may be more sensitive than individual tests.

Functional Magnetic Resonance Imaging of Semantic Memory as a Presymptomatic Biomarker of Alzheimer’s Disease Risk

PubMed Central

Sugarman, Michael A.; Woodard, John L.; Nielson, Kristy A.; Seidenberg, Michael; Smith, J. Carson; Durgerian, Sally; Rao, Stephen M.

2011-01-01

Extensive research efforts have been directed toward strategies for predicting risk of developing Alzheimer’s disease (AD) prior to the appearance of observable symptoms. Existing approaches for early detection of AD vary in terms of their efficacy, invasiveness, and ease of implementation. Several non-invasive magnetic resonance imaging strategies have been developed for predicting decline in cognitively healthy older adults. This review will survey a number of studies, beginning with the development of a famous name discrimination task used to identify neural regions that participate in semantic memory retrieval and to test predictions of several key theories of the role of the hippocampus in memory. This task has revealed medial temporal and neocortical contributions to recent and remote memory retrieval, and it has been used to demonstrate compensatory neural recruitment in older adults, apolipoprotein E ε4 carriers, and amnestic mild cognitive impairment patients. Recently, we have also found that the famous name discrimination task provides predictive value for forecasting episodic memory decline among asymptomatic older adults. Other studies investigating the predictive value of semantic memory tasks will also be presented. We suggest several advantages associated with the use of semantic processing tasks, particularly those based on person identification, in comparison to episodic memory tasks to study AD risk. Future directions for research and potential clinical uses of semantic memory paradigms are also discussed. PMID:21996618

Analysis of neuron–astrocyte metabolic cooperation in the brain of db/db mice with cognitive decline using 13C NMR spectroscopy

PubMed Central

Zheng, Hong; Zheng, Yongquan; Wang, Dan; Cai, Aimin; Lin, Qiuting; Zhao, Liangcai; Chen, Minjiang; Deng, Mingjie; Ye, Xinjian

2016-01-01

Type 2 diabetes has been linked to cognitive impairment, but its potential metabolic mechanism is still unclear. The present study aimed to explore neuron–astrocyte metabolic cooperation in the brain of diabetic (db/db, BKS.Cg-m+/+ Leprdb/J) mice with cognitive decline using 13C NMR technique in combination with intravenous [2-13C]-acetate and [3-13C]-lactate infusions. We found that the 13C-enrichment from [2-13C]-acetate into tricarboxylic acid cycle intermediate, succinate, was significantly decreased in db/db mice with cognitive decline compared with wild-type (WT, C57BLKS/J) mice, while an opposite result was obtained after [3-13C]-lactate infusion. Relative to WT mice, db/db mice with cognitive decline had significantly lower 13C labeling percentages in neurotransmitters including glutamine, glutamate, and γ-aminobutyric acid after [2-13C]-acetate infusion. However, [3-13C]-lactate resulted in increased 13C-enrichments in neurotransmitters in db/db mice with cognitive decline. This may indicate that the disturbance of neurotransmitter metabolism occurred during the development of cognitive decline. In addition, a reduction in 13C-labeling of lactate and an increase in gluconeogenesis were found from both labeled infusions in db/db mice with cognitive decline. Therefore, our results suggest that the development of cognitive decline in type 2 diabetes may be implicated to an unbalanced metabolism in neuron–astrocyte cooperation and an enhancement of gluconeogenesis. PMID:26762505

Healthy eating and reduced risk of cognitive decline

PubMed Central

Dehghan, Mahshid; O'Donnell, Martin; Anderson, Craig; Teo, Koon; Gao, Peggy; Sleight, Peter; Dagenais, Gilles; Probstfield, Jeffrey L.; Mente, Andrew; Yusuf, Salim

2015-01-01

Objective: We sought to determine the association of dietary factors and risk of cognitive decline in a population at high risk of cardiovascular disease. Methods: Baseline dietary intake and measures of the Mini-Mental State Examination were recorded in 27,860 men and women who were enrolled in 2 international parallel trials of the ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease) studies. We measured diet quality using the modified Alternative Healthy Eating Index. Cox proportional hazards regression was used to determine the association between diet quality and risk of ≥3-point decline in Mini-Mental State Examination score, and reported as hazard ratio with 95% confidence intervals with adjustment for covariates. Results: During 56 months of follow-up, 4,699 cases of cognitive decline occurred. We observed lower risk of cognitive decline among those in the healthiest dietary quintile of modified Alternative Healthy Eating Index compared with lowest quintile (hazard ratio 0.76, 95% confidence interval 0.66–0.86, Q5 vs Q1). Lower risk of cognitive decline was consistent regardless of baseline cognitive level. Conclusion: We found that higher diet quality was associated with a reduced risk of cognitive decline. Improved diet quality represents an important potential target for reducing the global burden of cognitive decline. PMID:25948720

Examining age-related shared variance between face cognition, vision, and self-reported physical health: a test of the common cause hypothesis for social cognition

PubMed Central

Olderbak, Sally; Hildebrandt, Andrea; Wilhelm, Oliver

2015-01-01

The shared decline in cognitive abilities, sensory functions (e.g., vision and hearing), and physical health with increasing age is well documented with some research attributing this shared age-related decline to a single common cause (e.g., aging brain). We evaluate the extent to which the common cause hypothesis predicts associations between vision and physical health with social cognition abilities specifically face perception and face memory. Based on a sample of 443 adults (17–88 years old), we test a series of structural equation models, including Multiple Indicator Multiple Cause (MIMIC) models, and estimate the extent to which vision and self-reported physical health are related to face perception and face memory through a common factor, before and after controlling for their fluid cognitive component and the linear effects of age. Results suggest significant shared variance amongst these constructs, with a common factor explaining some, but not all, of the shared age-related variance. Also, we found that the relations of face perception, but not face memory, with vision and physical health could be completely explained by fluid cognition. Overall, results suggest that a single common cause explains most, but not all age-related shared variance with domain specific aging mechanisms evident. PMID:26321998

Mechanisms of Age-Related Decline in Memory Search Across the Adult Life Span

PubMed Central

Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.

2013-01-01

Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis). We investigated these 3 hypotheses by formally modeling the semantic recall patterns of 185 adults between 27 to 99 years of age in the animal fluency task (Thurstone, 1938). The results indicate that people switch between global frequency-based retrieval cues and local item-based retrieval cues to navigate their semantic memory. Contrary to the global slowing hypothesis that predicts no qualitative differences in dynamic search processes and the cluster-switching hypothesis that predicts reduced switching between retrieval cues, the results indicate that as people age, they tend to switch more often between local and global cues per item recalled, supporting the cue-maintenance hypothesis. Additional support for the cue-maintenance hypothesis is provided by a negative correlation between switching and digit span scores and between switching and total items recalled, which suggests that cognitive control may be involved in cue maintenance and the effective search of memory. Overall, the results are consistent with age-related decline in memory search being a consequence of reduced cognitive control, consistent with models suggesting that working memory is related to goal perseveration and the ability to inhibit distracting information. PMID:23586941

From Subjective Cognitive Decline to Alzheimer's Disease: The Predictive Role of Neuropsychological Assessment, Personality Traits, and Cognitive Reserve. A 7-Year Follow-Up Study.

PubMed

Bessi, Valentina; Mazzeo, Salvatore; Padiglioni, Sonia; Piccini, Carolina; Nacmias, Benedetta; Sorbi, Sandro; Bracco, Laura

2018-01-01

The aim of this study was to evaluate the accuracy of neuropsychological assessment in predicting conversion from subjective cognitive decline (SCD) and mild cognitive impairment (MCI) to Alzheimer's disease (AD) and the effect of personality traits and cognitive reserve in progression from SCD to MCI. As part of a longitudinal, clinical-neuropsychological-genetic survey on SCD and MCI, 284 patients referred to our hospital between 1990 and 2017 were included. All patients underwent clinical-extensive neuropsychological evaluation and Apolipoprotein E genotyping; personality traits were assessed in a subgroup. Each patient underwent clinical-neuropsychological follow-up. Subjects with a follow-up shorter than two years were excluded. A total of 212 subjects were, after exclusions, considered: 26 out of 109 SCD subjects progressed to MCI (SCD-p), 15 converted to AD (SCD-c), and 68 remained stable (SCD-s). Of 103 MCI subjects, 39 converted to AD (MCI-c) and 64 remained stable (MCI-s). At baseline, SCD-c performed significantly worse than SCD-s in tests assessing long-term verbal memory. MCI-c showed worse performance on neuropsychological tests for short- and long-term verbal memory and for ecological evaluation of memory (RBMT). These tests provided good accuracy in distinguishing MCI-c and MCI-s. Emotional stability was significantly lower in SCD-s than in SCD-p while higher intellectual activities were associated with a lower risk of conversion to MCI. Our results suggest that memory neuropsychological tests may represent a reliable tool to estimate the risk of progression to AD. Personality and lifestyle factors could provide useful information to identify SCD subjects who may develop an objective cognitive impairment.

Association between Cerebrospinal Fluid Biomarkers for Alzheimer's Disease, APOE Genotypes and Auditory Verbal Learning Task in Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Disease.

PubMed

Mandecka, Monika; Budziszewska, Magdalena; Barczak, Anna; Pepłońska, Beata; Chodakowska-Żebrowska, Małgorzata; Filipek-Gliszczyńska, Anna; Nesteruk, Marta; Styczyńska, Maria; Barcikowska, Maria; Gabryelewicz, Tomasz

2016-07-29

In the course of Alzheimer's disease (AD), early pathological changes in the brain start decades before any clinical manifestation. The concentration levels of AD cerebrospinal fluid (CSF) biomarkers, such as amyloid-β1-42 (Aβ1-42), total tau (T-tau), and phosphorylated tau (P-tau), may reflect a cerebral pathology facilitating an early diagnosis of the disease and predicting a cognitive deterioration. The aim of this study was to estimate the prevalence of AD CSF biomarkers in those individuals with a subjective cognitive decline (SCD), a mild cognitive impairment (MCI), and Alzheimer's dementia (AD-D), together with the relationships between the biomarkers, an APOE ɛ4 presence, and a verbal episodic memory performance. We included 252 patients from the memory clinic with a diagnosis of SCD (n = 85), MCI (n = 87), and AD-D (n = 80). A verbal episodic memory performance level was assessed and was based on a delayed recall trial from the 10-word list of an auditory verbal learning task (AVLT). We found that the patients with more severe cognitive impairments had significantly lower levels of Aβ1-42 and higher levels of T-tau and P-tau. This pattern was also typical for the APOE ɛ4 carriers, who had lower levels of Aβ1-42 than the noncarriers in the AD-D and MCI groups. The levels of T-tau and P-tau were significantly higher in the APOE ɛ4 carriers than in the noncarriers, but only in the MCI patients. The AVLT performance in the whole study samples was predicted by age, Aβ1-42, and the T-tau CSF biomarkers, but not by the APOE genotyping.

A Retrospective Belgian Multi-Center MRI Biomarker Study in Alzheimer's Disease (REMEMBER).

PubMed

Niemantsverdriet, Ellis; Ribbens, Annemie; Bastin, Christine; Benoit, Florence; Bergmans, Bruno; Bier, Jean-Christophe; Bladt, Roxanne; Claes, Lene; De Deyn, Peter Paul; Deryck, Olivier; Hanseeuw, Bernard; Ivanoiu, Adrian; Lemper, Jean-Claude; Mormont, Eric; Picard, Gaëtane; Salmon, Eric; Segers, Kurt; Sieben, Anne; Smeets, Dirk; Struyfs, Hanne; Thiery, Evert; Tournoy, Jos; Triau, Eric; Vanbinst, Anne-Marie; Versijpt, Jan; Bjerke, Maria; Engelborghs, Sebastiaan

2018-01-01

Magnetic resonance imaging (MRI) acquisition/processing techniques assess brain volumes to explore neurodegeneration in Alzheimer's disease (AD). We examined the clinical utility of MSmetrix and investigated if automated MRI volumes could discriminate between groups covering the AD continuum and could be used as a predictor for clinical progression. The Belgian Dementia Council initiated a retrospective, multi-center study and analyzed whole brain (WB), grey matter (GM), white matter (WM), cerebrospinal fluid (CSF), cortical GM (CGM) volumes, and WM hyperintensities (WMH) using MSmetrix in the AD continuum. Baseline (n = 887) and follow-up (FU, n = 95) T1-weighted brain MRIs and time-linked neuropsychological data were available. The cohort consisted of cognitively healthy controls (HC, n = 93), subjective cognitive decline (n = 102), mild cognitive impairment (MCI, n = 379), and AD dementia (n = 313). Baseline WB and GM volumes could accurately discriminate between clinical diagnostic groups and were significantly decreased with increasing cognitive impairment. MCI patients had a significantly larger change in WB, GM, and CGM volumes based on two MRIs (n = 95) compared to HC (FU>24months, p = 0.020). Linear regression models showed that baseline atrophy of WB, GM, CGM, and increased CSF volumes predicted cognitive impairment. WB and GM volumes extracted by MSmetrix could be used to define the clinical spectrum of AD accurately and along with CGM, they are able to predict cognitive impairment based on (decline in) MMSE scores. Therefore, MSmetrix can support clinicians in their diagnostic decisions, is able to detect clinical disease progression, and is of help to stratify populations for clinical trials.

Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology.

PubMed

Insel, Philip S; Mattsson, Niklas; Mackin, R Scott; Schöll, Michael; Nosheny, Rachel L; Tosun, Duygu; Donohue, Michael C; Aisen, Paul S; Jagust, William J; Weiner, Michael W

2016-05-17

To estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloid positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ42. Future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline. © 2016 American Academy of Neurology.

Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

PubMed Central

Mattsson, Niklas; Mackin, R. Scott; Schöll, Michael; Nosheny, Rachel L.; Tosun, Duygu; Donohue, Michael C.; Aisen, Paul S.; Jagust, William J.; Weiner, Michael W.

2016-01-01

Objective: To estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. Methods: In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloid positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. Conclusions: A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ42. Future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline. PMID:27164667

Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Insel, Philip S.; Mattsson, Niklas; Mackin, R. Scott

Objective: Our objective is to estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. Methods: In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ 42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloidmore » positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. Conclusions: A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ 42. Lastly, future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline.« less

Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

DOE PAGES

Insel, Philip S.; Mattsson, Niklas; Mackin, R. Scott; ...

2016-04-15

Objective: Our objective is to estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. Methods: In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ 42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloidmore » positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. Conclusions: A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ 42. Lastly, future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline.« less

Diagnostic and Prognostic Utility of the Synaptic Marker Neurogranin in Alzheimer Disease.

PubMed

Tarawneh, Rawan; D'Angelo, Gina; Crimmins, Dan; Herries, Elizabeth; Griest, Terry; Fagan, Anne M; Zipfel, Gregory J; Ladenson, Jack H; Morris, John C; Holtzman, David M

2016-05-01

Synaptic loss is an early pathologic substrate of Alzheimer disease (AD). Neurogranin is a postsynaptic neuronal protein that has demonstrated utility as a cerebrospinal fluid (CSF) marker of synaptic loss in AD. To investigate the diagnostic and prognostic utility of CSF neurogranin levels in a large, well-characterized cohort of individuals with symptomatic AD and cognitively normal controls. A cross-sectional and longitudinal observational study of cognitive decline in patients with symptomatic AD and cognitively normal controls was performed. Participants were individuals with a clinical diagnosis of early symptomatic AD and cognitively normal controls who were enrolled in longitudinal studies of aging and dementia at the Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, from January 21, 2000, through March 21, 2011. Data analysis was performed from November 1, 2013, to March 31, 2015. Correlations between baseline CSF biomarker levels and future cognitive decline in patients with symptomatic AD and cognitively normal controls over time. A total of 302 individuals (mean [SE] age, 73.1 [0.4] years) were included in this study (95 patients [52 women and 43 men] with AD and 207 controls [125 women and 82 men]). The CSF neurogranin levels differentiated patients with early symptomatic AD from controls with comparable diagnostic utility (mean [SE] area under the receiver operating characteristic curve, 0.71 [0.03]; 95% CI, 0.64-0.77) to the other CSF biomarkers. The CSF neurogranin levels correlated with brain atrophy (normalized whole-brain volumes: adjusted r = -0.38, P = .02; hippocampal volumes: adjusted r = -0.36, P = .03; entorhinal volumes: adjusted r = -0.46, P = .006; and parahippocampal volumes: adjusted r = -0.47, P = .005, n = 38) in AD and with amyloid load (r = 0.39, P = .02, n = 36) in preclinical AD. The CSF neurogranin levels predicted future cognitive impairment (adjusted hazard ratio, 1.89; 95% CI, 1.29-2.78; P = .001 as a continuous measure, and adjusted hazard ratio, 2.78; 95% CI, 1.13-5.99; P = .02 as a categorical measure using the 85th percentile cutoff value) in controls and rates of cognitive decline (Clinical Dementia Rating sum of boxes score: β estimate, 0.29; P = .001; global composite scores: β estimate, -0.11; P = .001; episodic memory scores: β estimate, -0.18; P < .001; and semantic memory scores: β estimate, -0.06; P = .04, n = 57) in patients with symptomatic AD over time, similarly to the CSF proteins VILIP-1, tau, and p-tau181. The CSF levels of the synaptic marker neurogranin offer diagnostic and prognostic utility for early symptomatic AD that is comparable to other CSF markers of AD. Importantly, CSF neurogranin complements the collective ability of these markers to predict future cognitive decline in cognitively normal individuals and, therefore, will be a useful addition to the current panel of AD biomarkers.

Initial Cognitive Performance Predicts Longitudinal Aviator Performance

PubMed Central

Jo, Booil; Adamson, Maheen M.; Kennedy, Quinn; Noda, Art; Hernandez, Beatriz; Zeitzer, Jamie M.; Friedman, Leah F.; Fairchild, Kaci; Scanlon, Blake K.; Murphy, Greer M.; Taylor, Joy L.

2011-01-01

Objectives. The goal of the study was to improve prediction of longitudinal flight simulator performance by studying cognitive factors that may moderate the influence of chronological age. Method. We examined age-related change in aviation performance in aircraft pilots in relation to baseline cognitive ability measures and aviation expertise. Participants were aircraft pilots (N = 276) aged 40–77.9. Flight simulator performance and cognition were tested yearly; there were an average of 4.3 (± 2.7; range 1–13) data points per participant. Each participant was classified into one of the three levels of aviation expertise based on Federal Aviation Administration pilot proficiency ratings: least, moderate, or high expertise. Results. Addition of measures of cognitive processing speed and executive function to a model of age-related change in aviation performance significantly improved the model. Processing speed and executive function performance interacted such that the slowest rate of decline in flight simulator performance was found in aviators with the highest scores on tests of these abilities. Expertise was beneficial to pilots across the age range studied; however, expertise did not show evidence of reducing the effect of age. Discussion. These data suggest that longitudinal performance on an important real-world activity can be predicted by initial assessment of relevant cognitive abilities. PMID:21586627

Cognitive Aging Research: What Does It Say about Cognition? Aging?

ERIC Educational Resources Information Center

Glucksberg, Sam

Cognitive aging research needs to clarify whether or not there are functional or ability declines with aging and, if so, to understand and mediate these declines. Recent research which has demonstrated declines in cognitive functioning with age has involved episodic memory and rehearsal-independent forms of such memory. It is not known how much of…

Development and assessment of a composite score for memory in the Alzheimer's Disease Neuroimaging Initiative (ADNI).

PubMed

Crane, Paul K; Carle, Adam; Gibbons, Laura E; Insel, Philip; Mackin, R Scott; Gross, Alden; Jones, Richard N; Mukherjee, Shubhabrata; Curtis, S McKay; Harvey, Danielle; Weiner, Michael; Mungas, Dan

2012-12-01

We sought to develop and evaluate a composite memory score from the neuropsychological battery used in the Alzheimer's Disease (AD) Neuroimaging Initiative (ADNI). We used modern psychometric approaches to analyze longitudinal Rey Auditory Verbal Learning Test (RAVLT, 2 versions), AD Assessment Schedule - Cognition (ADAS-Cog, 3 versions), Mini-Mental State Examination (MMSE), and Logical Memory data to develop ADNI-Mem, a composite memory score. We compared RAVLT and ADAS-Cog versions, and compared ADNI-Mem to RAVLT recall sum scores, four ADAS-Cog-derived scores, the MMSE, and the Clinical Dementia Rating Sum of Boxes. We evaluated rates of decline in normal cognition, mild cognitive impairment (MCI), and AD, ability to predict conversion from MCI to AD, strength of association with selected imaging parameters, and ability to differentiate rates of decline between participants with and without AD cerebrospinal fluid (CSF) signatures. The second version of the RAVLT was harder than the first. The ADAS-Cog versions were of similar difficulty. ADNI-Mem was slightly better at detecting change than total RAVLT recall scores. It was as good as or better than all of the other scores at predicting conversion from MCI to AD. It was associated with all our selected imaging parameters for people with MCI and AD. Participants with MCI with an AD CSF signature had somewhat more rapid decline than did those without. This paper illustrates appropriate methods for addressing the different versions of word lists, and demonstrates the additional power to be gleaned with a psychometrically sound composite memory score.

Integration of Multilocus Genetic Risk into the Default Mode Network Longitudinal Trajectory during the Alzheimer's Disease Process.

PubMed

Su, Fan; Shu, Hao; Ye, Qing; Xie, Chunming; Yuan, Baoyu; Zhang, Zhijun; Bai, Feng

2017-01-01

The aim of the study was to investigate the cognitive significance of the changes in default mode network (DMN) during the process of Alzheimer's disease (AD) and the genetic basis that drives the alteration. Eighty-seven subjects with mild cognitive impairment (MCI) and 131 healthy controls (HC) were employed at baseline, and they had the genetic risk scores (GRS) based on the GWAS-validated AD-related top loci. Eleven MCIs who converted to AD (c-MCIs), 32 subjects who remained stable (nc-MCIs), and 56 HCs participated in the follow-up analyses after an average of 35 months. Decreased functional connectivity (FC) within temporal cortex was identified for MCIs at baseline, which was partially determined by the GRS; moreover, compensations may occur within the frontal-parietal brain to maintain relatively intact cognition. During the follow-ups, c-MCIs exhibited more FC declines within the prefrontal-parietal lobes and parahippocampal gyrus/hippocampus than the HCs and nc-MCIs. The GRS did not significantly vary among the three groups, whereas associations were identified at risky alleles and FC declines in all AD spectra. Interestingly, the influence of APOEɛ4 varied as the disease progressed; APOEɛ4 was associated with longitudinal FC decreases only for HCs in the single variance-based analyses and deteriorated DMN integration in nc-MCIs by combining the effects of other loci. However, the GRS without APOEɛ4 predicted FC decline for converters. It is suggested that the integration of multilocus genetic risk predicted the longitudinal trajectory of DMN and may be used as a clinical strategy to track AD progression.

Cognitive Decline in a Colombian Kindred With Autosomal Dominant Alzheimer Disease: A Retrospective Cohort Study.

PubMed

Aguirre-Acevedo, Daniel C; Lopera, Francisco; Henao, Eliana; Tirado, Victoria; Muñoz, Claudia; Giraldo, Margarita; Bangdiwala, Shrikant I; Reiman, Eric M; Tariot, Pierre N; Langbaum, Jessica B; Quiroz, Yakeel T; Jaimes, Fabian

2016-04-01

Data from an autosomal dominant Alzheimer disease (ADAD) kindred were used to track the longitudinal trajectory of cognitive decline associated with preclinical ADAD and explore factors that may modify the rate of cognitive decline. To evaluate the onset and rate of cognitive decline during preclinical ADAD and the effect of socioeconomic, vascular, and genetic factors on the cognitive decline. We performed a retrospective cohort study from January 1, 1995, through June 31, 2012, of individuals from Antioquia, Colombia, who tested positive for the ADAD-associated PSEN1 E280A mutation. Data analysis was performed from August 20, 2014, through November 30, 2015. A mixed-effects model was used to estimate annual rates of change in cognitive test scores and to mark the onset of cognitive decline. Memory, language, praxis, and total scores from the Consortium to Establish a Registry for Alzheimer Disease test battery. Chronologic age was used as a time scale in the models. We explore the effects of sex; educational level; socioeconomic status; residence area; occupation type; marital status; history of hypertension, diabetes mellitus, and dyslipidemia; tobacco and alcohol use; and APOE ε4 on the rates of cognitive decline. A total of 493 carriers met the inclusion criteria and were analyzed. A total of 256 carriers had 2 or more assessments. At the time of the initial assessment, participants had a mean (SD) age of 33.4 (11.7) years and a mean (SD) educational level of 7.2 (4.2) years. They were predominantly female (270 [54.8%]), married (293 [59.4%]), and of low socioeconomic status (322 [65.3%]). Word list recall scores provided the earliest indicator of preclinical cognitive decline at 32 years of age, 12 and 17 years before the kindred's respective median ages at mild cognitive impairment and dementia onset. After the change point, carriers had a statistically significant cognitive decline with a loss of 0.24 (95% CI, -0.26 to -0.22) points per year for the word list recall test and 2.13 (95% CI, -2.29 to -1.96) points per year for total scores. Carriers with high educational levels had an increase of approximately 36% in the rate of cognitive decline after the change point when compared with those with low educational levels (-2.89 vs -2.13 points per year, respectively). Onset of cognitive decline was delayed by 3 years in individuals with higher educational levels compared with those with lower educational levels. Those with higher educational level, middle/high socioeconomic status, history of diabetes and hypertension, and tobacco and alcohol use had a steeper cognitive decline after onset. Preclinical cognitive decline was evident in PSEN1 E280A mutation carriers 12 years before the onset of clinical impairment. Educational level may be a protective factor against the onset of cognitive impairment.

Cognitive Decline in a Colombian Kindred With Autosomal Dominant Alzheimer Disease

PubMed Central

Aguirre-Acevedo, Daniel C.; Lopera, Francisco; Henao, Eliana; Tirado, Victoria; Muñoz, Claudia; Giraldo, Margarita; Bangdiwala, Shrikant I.; Reiman, Eric M.; Tariot, Pierre N.; Langbaum, Jessica B.; Quiroz, Yakeel T.; Jaimes, Fabian

2017-01-01

IMPORTANCE Data from an autosomal dominant Alzheimer disease (ADAD) kindred were used to track the longitudinal trajectory of cognitive decline associated with preclinical ADAD and explore factors that may modify the rate of cognitive decline. OBJECTIVES To evaluate the onset and rate of cognitive decline during preclinical ADAD and the effect of socioeconomic, vascular, and genetic factors on the cognitive decline. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective cohort study from January 1, 1995, through June 31, 2012, of individuals from Antioquia, Colombia, who tested positive for the ADAD-associated PSEN1 E280A mutation. Data analysis was performed from August 20, 2014, through November 30, 2015. A mixed-effects model was used to estimate annual rates of change in cognitive test scores and to mark the onset of cognitive decline. MAIN OUTCOMES AND MEASURES Memory, language, praxis, and total scores from the Consortium to Establish a Registry for Alzheimer Disease test battery. Chronologic age was used as a time scale in the models. We explore the effects of sex; educational level; socioeconomic status; residence area; occupation type; marital status; history of hypertension, diabetes mellitus, and dyslipidemia; tobacco and alcohol use; and APOE ε4 on the rates of cognitive decline. RESULTS A total of 493 carriers met the inclusion criteria and were analyzed. A total of 256 carriers had 2 or more assessments. At the time of the initial assessment, participants had a mean (SD) age of 33.4 (11.7) years and a mean (SD) educational level of 7.2 (4.2) years. They were predominantly female (270 [54.8%]), married (293 [59.4%]), and of low socioeconomic status (322 [65.3%]). Word list recall scores provided the earliest indicator of preclinical cognitive decline at 32 years of age, 12 and 17 years before the kindred’s respective median ages at mild cognitive impairment and dementia onset. After the change point, carriers had a statistically significant cognitive decline with a loss of 0.24 (95% CI, −0.26 to −0.22) points per year for the word list recall test and 2.13 (95% CI, −2.29 to −1.96) points per year for total scores. Carriers with high educational levels had an increase of approximately 36% in the rate of cognitive decline after the change point when compared with those with low educational levels (−2.89 vs −2.13 points per year, respectively). Onset of cognitive decline was delayed by 3 years in individuals with higher educational levels compared with those with lower educational levels. Those with higher educational level, middle/high socioeconomic status, history of diabetes and hypertension, and tobacco and alcohol use had a steeper cognitive decline after onset. CONCLUSIONS AND RELEVANCE Preclinical cognitive decline was evident in PSEN1 E280A mutation carriers 12 years before the onset of clinical impairment. Educational level may be a protective factor against the onset of cognitive impairment. PMID:26902171

Determinants of poor cognitive function using A-IQCODE among Lebanese older adults: a cross-sectional study.

PubMed

Bou-Orm, Ibrahim R; Khamis, Assem M; Chaaya, Monique

2018-06-01

Dementia characterized by gradual cognitive decline is an increasing public health problem due to population ageing. This study aims at assessing the prevalence and determinants of cognitive decline among Lebanese older adults. Secondary analysis of data from a cross-sectional sample of 502 elders from two Lebanese governorates was conducted. Cognitive decline was assessed using the Arabic Version of 16-item Informant Questionnaire on Cognitive Decline for the older adults (A-IQCODE 16). A multivariable logistic regression model assessed the associations of socio-demographic, clinical and behavioral factors with the presence of cognitive decline. Almost one of six Lebanese older adults (14.8%) scored below 3.34. Higher odds of cognitive decline were associated with higher age, being female, having heart disease and suffering from depression. Pack-years of cigarette smoking showed a protective effect and this relationship seems to be only statistically significant among older adults aged more than 75 years. Screening programs of cardiovascular risk factors and early detection of depression are 'best buy' public health interventions that could prevent cognitive decline among Lebanese older adults. Differential survival bias seems the reasonable explanation for the protective effect of smoking that is not the common finding from the literature.

Central obesity, leptin and cognitive decline: the Sacramento Area Latino Study on Aging.

PubMed

Zeki Al Hazzouri, Adina; Haan, Mary N; Whitmer, Rachel A; Yaffe, Kristine; Neuhaus, John

2012-01-01

Central obesity is a risk factor for cognitive decline. Leptin is secreted by adipose tissue and has been associated with better cognitive function. Aging Mexican Americans have higher levels of obesity than non-Hispanic Whites, but no investigations examined the relationship between leptin and cognitive decline among them or the role of central obesity in this association. We analyzed 1,480 dementia-free older Mexican Americans who were followed over 10 years. Cognitive function was assessed every 12-15 months with the Modified Mini Mental State Exam (3MSE) and the Spanish and English Verbal Learning Test (SEVLT). For females with a small waist circumference (≤35 inches), an interquartile range difference in leptin was associated with 35% less 3MSE errors and 22% less decline in the SEVLT score over 10 years. For males with a small waist circumference (≤40 inches), an interquartile range difference in leptin was associated with 44% less 3MSE errors and 30% less decline in the SEVLT score over 10 years. There was no association between leptin and cognitive decline among females or males with a large waist circumference. Leptin interacts with central obesity in shaping cognitive decline. Our findings provide valuable information about the effects of metabolic risk factors on cognitive function. Copyright © 2012 S. Karger AG, Basel.

Cognitive activities delay onset of memory decline in persons who develop dementia

PubMed Central

Hall, C B.; Lipton, R B.; Sliwinski, M; Katz, M J.; Derby, C A.; Verghese, J

2009-01-01

Background: Persons destined to develop dementia experience an accelerated rate of decline in cognitive ability, particularly in memory. Early life education and participation in cognitively stimulating leisure activities later in life are 2 factors thought to reflect cognitive reserve, which may delay the onset of the memory decline in the preclinical stages of dementia. Methods: We followed 488 initially cognitively intact community residing individuals with epidemiologic, clinical, and cognitive assessments every 12 to 18 months in the Bronx Aging Study. We assessed the influence of self-reported participation in cognitively stimulating leisure activities on the onset of accelerated memory decline as measured by the Buschke Selective Reminding Test in 101 individuals who developed incident dementia using a change point model. Results: Each additional self-reported day of cognitive activity at baseline delayed the onset of accelerated memory decline by 0.18 years. Higher baseline levels of cognitive activity were associated with more rapid memory decline after that onset. Inclusion of education did not significantly add to the fit of the model beyond the effect of cognitive activities. Conclusions: Our findings show that late life cognitive activities influence cognitive reserve independently of education. The effect of early life education on cognitive reserve may be mediated by cognitive activity later in life. Alternatively, early life education may be a determinant of cognitive reserve, and individuals with more education may choose to participate in cognitive activities without influencing reserve. Future studies should examine the efficacy of increasing participation in cognitive activities to prevent or delay dementia. GLOSSARY AD = Alzheimer disease; BL = baseline; CAS = Cognitive Activity Scale; CI = confidence interval; DSM = Diagnostic and Statistical Manual of Mental Disorders; dx = diagnosis; NIA = National Institute on Aging; SRT = Selective Reminding Test; WAIS VIQ = Wechsler Adult Intelligence Scale Verbal IQ. PMID:19652139

Effects of Diabetes Mellitus on Cognitive Decline in Patients with Alzheimer Disease: A Systematic Review.

PubMed

Li, Jun; Cesari, Matteo; Liu, Fei; Dong, Birong; Vellas, Bruno

2017-02-01

Basic and clinical research support a link between diabetes mellitus and Alzheimer disease (AD). However, the relationship with AD progression is unclear. This review focuses on the association between diabetes and cognitive decline in patients with AD. The literature published through May 2015 was searched in 3 databases: PubMed, Embase and Cochrane. Studies evaluating the effects of diabetes on patients with AD or cognitive decline were included, and extracted data were analyzed. A total of 10 articles met the inclusion criteria for review. The results of these studies were inconsistent in terms of the association between diabetes and cognitive decline. Only 2 studies demonstrated that the presence of diabetes was independently related to the progression of cognitive decline in the patients with AD, and 3 studies suggested that histories of diabetes were not correlated with the changes in cognitive function in patients with AD. Half of the included studies even indicated that histories of diabetes were associated with lesser declines in cognitive function in patients with AD. Current evidence indicates that the link between diabetes and cognitive decline in patients with AD is uncertain. Further clinical studies are needed, with larger samples, long-term follow up and an extended battery of cognitive assessments. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Personality and Cognitive Decline in Older Adults: Data From a Longitudinal Sample and Meta-Analysis.

PubMed

Luchetti, Martina; Terracciano, Antonio; Stephan, Yannick; Sutin, Angelina R

2016-07-01

Personality traits are associated with risk of dementia; less is known about their association with the trajectory of cognitive functioning. This research examines the association between the 5 major dimensions of personality and cognitive function and decline in older adulthood and includes a meta-analysis of published studies. Personality traits, objective and subjective memory, and cognitive status were collected in a large national sample (N = 13,987) with a 4-year follow-up period. For each trait, the meta-analysis pooled results from up to 5 prospective studies to examine personality and change in global cognition. Higher Neuroticism was associated with worse performance on all cognitive measures and greater decline in memory, whereas higher Conscientiousness and Openness were associated with better memory performance concurrently and less decline over time. All traits were associated with subjective memory. Higher Conscientiousness and lower Extraversion were associated with better cognitive status and less decline. Although modest, these associations were generally larger than that of hypertension, diabetes, history of psychological treatment, obesity, smoking, and physical inactivity. The meta-analysis supported the association between Neuroticism and Conscientiousness and cognitive decline. Personality is associated with cognitive decline in older adults, with effects comparable to established clinical and lifestyle risk factors. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Role of APOE ε4 Allele and Incident Stroke on Cognitive Decline and Mortality.

PubMed

Rajan, Kumar B; Aggarwal, Neelum T; Schneider, Julie A; Wilson, Robert S; Everson-Rose, Susan A; Evans, Denis A

2016-01-01

The apolipoprotein E (APOE) ε4 allele and stroke increase the risk of cognitive decline. However, the association of the APOE ε4 allele before and after stroke is not well understood. Using a prospective sample of 3444 (66% African Americans, 61% females, mean age=71.9 y) participants, we examined cognitive decline relative to stroke among those with and without the APOE ε4 allele. In our sample, 505 (15%) had incident stroke. Among participants without stroke, the ε4 allele was associated with increased cognitive decline compared to noncarriers (0.080 vs. 0.036 units/year; P<0.0001). Among participants without the ε4 allele, cognitive decline increased significantly after stroke compared to before stroke (0.115 vs. 0.039 units/year; P<0.0001). Interestingly, cognitive decline before and after stroke was not significantly different among those with the ε4 allele (0.091 vs. 0.102 units/year; P=0.32). Poor cognitive function was associated with higher risk of stroke (hazard ratio=1.41, 95% confidence interval, 1.25-1.58), but the APOE ε4 allele was not (P=0.66). The APOE ε4 allele, cognitive function, and incident stroke were associated with mortality. The association of stroke with cognitive decline appears to differ by the presence of the APOE ε4 allele, but no such interaction was observed for mortality.

Personalized long-term prediction of cognitive function: Using sequential assessments to improve model performance.

PubMed

Chi, Chih-Lin; Zeng, Wenjun; Oh, Wonsuk; Borson, Soo; Lenskaia, Tatiana; Shen, Xinpeng; Tonellato, Peter J

2017-12-01

Prediction of onset and progression of cognitive decline and dementia is important both for understanding the underlying disease processes and for planning health care for populations at risk. Predictors identified in research studies are typically accessed at one point in time. In this manuscript, we argue that an accurate model for predicting cognitive status over relatively long periods requires inclusion of time-varying components that are sequentially assessed at multiple time points (e.g., in multiple follow-up visits). We developed a pilot model to test the feasibility of using either estimated or observed risk factors to predict cognitive status. We developed two models, the first using a sequential estimation of risk factors originally obtained from 8 years prior, then improved by optimization. This model can predict how cognition will change over relatively long time periods. The second model uses observed rather than estimated time-varying risk factors and, as expected, results in better prediction. This model can predict when newly observed data are acquired in a follow-up visit. Performances of both models that are evaluated in10-fold cross-validation and various patient subgroups show supporting evidence for these pilot models. Each model consists of multiple base prediction units (BPUs), which were trained using the same set of data. The difference in usage and function between the two models is the source of input data: either estimated or observed data. In the next step of model refinement, we plan to integrate the two types of data together to flexibly predict dementia status and changes over time, when some time-varying predictors are measured only once and others are measured repeatedly. Computationally, both data provide upper and lower bounds for predictive performance. Copyright © 2017 Elsevier Inc. All rights reserved.

Late Life Leisure Activities and Risk of Cognitive Decline

PubMed Central

2013-01-01

Background. Studies concerning the effect of different types of leisure activities on various cognitive domains are limited. This study tests the hypothesis that mental, physical, and social activities have a domain-specific protection against cognitive decline. Methods. A cohort of a geographically defined population in China was examined in 2003–2005 and followed for an average of 2.4 years. Leisure activities were assessed in 1,463 adults aged 65 years and older without cognitive or physical impairment at baseline, and their cognitive performances were tested at baseline and follow-up examinations. Results. High level of mental activity was related to less decline in global cognition (β = −.23, p < .01), language (β = −.11, p < .05), and executive function (β = −.13, p < .05) in ANCOVA models adjusting for age, gender, education, history of stroke, body mass index, Apolipoprotein E genotype, and baseline cognition. High level of physical activity was related to less decline in episodic memory (β = −.08, p < .05) and language (β = −.15, p < .01). High level of social activity was associated with less decline in global cognition (β = −.11, p < .05). Further, a dose-response pattern was observed: although participants who did not engage in any of the three activities experienced a significant global cognitive decline, those who engaged in any one of the activities maintained their cognition, and those who engaged in two or three activities improved their cognition. The same pattern was observed in men and in women. Conclusions. Leisure activities in old age may protect against cognitive decline for both women and men, and different types of activities seem to benefit different cognitive domains. PMID:22879456

Distinct aspects of frontal lobe structure mediate age-related differences in fluid intelligence and multitasking

PubMed Central

Kievit, Rogier A.; Davis, Simon W.; Mitchell, Daniel J.; Taylor, Jason R.; Duncan, John; Tyler, Lorraine K.; Brayne, Carol; Bullmore, Ed; Calder, Andrew; Cusack, Rhodri; Dalgleish, Tim; Matthews, Fiona; Marslen-Wilson, William; Rowe, James; Shafto, Meredith; Campbell, Karen; Cheung, Teresa; Geerligs, Linda; McCarrey, Anna; Tsvetanov, Kamen; Williams, Nitin; Bates, Lauren; Emery, Tina; Erzinçlioglu, Sharon; Gadie, Andrew; Gerbase, Sofia; Georgieva, Stanimira; Hanley, Claire; Parkin, Beth; Troy, David; Allen, Jodie; Amery, Gillian; Amunts, Liana; Barcroft, Anne; Castle, Amanda; Dias, Cheryl; Dowrick, Jonathan; Fair, Melissa; Fisher, Hayley; Goulding, Anna; Grewal, Adarsh; Hale, Geoff; Hilton, Andrew; Johnson, Frances; Johnston, Patricia; Kavanagh-Williamson, Thea; Kwasniewska, Magdalena; McMinn, Alison; Norman, Kim; Penrose, Jessica; Roby, Fiona; Rowland, Diane; Sargeant, John; Squire, Maggie; Stevens, Beth; Stoddart, Aldabra; Stone, Cheryl; Thompson, Tracy; Yazlik, Ozlem; Barnes, Dan; Dixon, Marie; Hillman, Jaya; Mitchell, Joanne; Villis, Laura; Henson, Richard N.A.

2014-01-01

Ageing is characterized by declines on a variety of cognitive measures. These declines are often attributed to a general, unitary underlying cause, such as a reduction in executive function owing to atrophy of the prefrontal cortex. However, age-related changes are likely multifactorial, and the relationship between neural changes and cognitive measures is not well-understood. Here we address this in a large (N=567), population-based sample drawn from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data. We relate fluid intelligence and multitasking to multiple brain measures, including grey matter in various prefrontal regions and white matter integrity connecting those regions. We show that multitasking and fluid intelligence are separable cognitive abilities, with differential sensitivities to age, which are mediated by distinct neural subsystems that show different prediction in older versus younger individuals. These results suggest that prefrontal ageing is a manifold process demanding multifaceted models of neurocognitive ageing. PMID:25519467

Fish consumption, intake of fats and cognitive decline at middle and older age: the Doetinchem Cohort Study.

PubMed

Nooyens, Astrid C J; van Gelder, Boukje M; Bueno-de-Mesquita, H Bas; van Boxtel, Martin P J; Verschuren, W M Monique

2018-06-01

To get insight in the impact of fish and fat intake in the prevention of accelerated cognitive decline with ageing, we tested associations between fish and different fat intakes and 5-year change in cognitive functions. In 2612 men and women of the Doetinchem Cohort Study, aged 43-70 years at baseline, dietary intake (including fish consumption) and cognitive function were assessed at baseline and at 5-year follow-up. Average fish consumption (frequency) and intakes (as energy percentages) of total fat, saturated, mono unsaturated, and polyunsaturated fatty acids (PUFA), linoleic, docosahexaenoic, eicosapentaenoic, and a-linolenic acid (ALA), and cholesterol were averaged over baseline and follow-up. Intakes were studied in relation to 5-year change in global cognitive function, memory, information processing speed, and cognitive flexibility, using ANCOVA and multivariate linear regression analyses. No consistent association between (fatty) fish consumption and cognitive decline was observed. Higher cholesterol intake was associated with faster cognitive decline (p < 0.05). Higher n-3 PUFA (especially ALA) intake was associated with slower decline in global cognitive function and memory (p < 0.01). Intakes of other fatty acids were not associated with cognitive decline. Higher cholesterol intake was detrimental, while higher ALA intake was beneficial for maintaining cognitive function with ageing, already at middle age.

Recent publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing progress toward improved AD clinical trials.

PubMed

Weiner, Michael W; Veitch, Dallas P; Aisen, Paul S; Beckett, Laurel A; Cairns, Nigel J; Green, Robert C; Harvey, Danielle; Jack, Clifford R; Jagust, William; Morris, John C; Petersen, Ronald C; Saykin, Andrew J; Shaw, Leslie M; Toga, Arthur W; Trojanowski, John Q

2017-04-01

The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the over 400 publications using ADNI data during 2014 and 2015. We used standard searches to find publications using ADNI data. (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses. Models of prion-like spreading of Aβ pathology along WM tracts predict known patterns of cortical Aβ deposition and declines in glucose metabolism; (7) New AD risk and protective gene loci have been identified using biologically informed approaches; (8) Cognitively normal and mild cognitive impairment (MCI) subjects are heterogeneous and include groups typified not only by "classic" AD pathology but also by normal biomarkers, accelerated decline, and suspected non-Alzheimer's pathology; (9) Selection of subjects at risk of imminent decline on the basis of one or more pathologies improves the power of clinical trials; (10) Sensitivity of cognitive outcome measures to early changes in cognition has been improved and surrogate outcome measures using longitudinal structural magnetic resonance imaging may further reduce clinical trial cost and duration; (11) Advances in machine learning techniques such as neural networks have improved diagnostic and prognostic accuracy especially in challenges involving MCI subjects; and (12) Network connectivity measures and genetic variants show promise in multimodal classification and some classifiers using single modalities are rivaling multimodal classifiers. Taken together, these studies fundamentally deepen our understanding of AD progression and its underlying genetic basis, which in turn informs and improves clinical trial design. Copyright © 2017. Published by Elsevier Inc.

T-Tau is Associated with Objective Memory Decline Over Two Years in Persons Seeking Help for Subjective Cognitive Decline: A Report from the Gothenburg-Oslo MCI Study.

PubMed

Hessen, Erik; Nordlund, Arto; Stålhammar, Jacob; Eckerström, Marie; Bjerke, Maria; Eckerström, Carl; Göthlin, Mattias; Fladby, Tormod; Reinvang, Ivar; Wallin, Anders

2015-01-01

There is a need to find very early markers for pre-clinical Alzheimer's disease as interventions early in the disease process are thought to be most effective. The present study aimed to address the potential relation between cerebrospinal fluid (CSF) biomarkers and reduced cognitive function in a relatively young cohort of memory clinic patients with subjective cognitive decline. 122 patients (mean age 63 years) with subjective cognitive decline were recruited from two university memory clinics and followed for two years. The main finding was that the subgroup with objective memory decline during the study period had significantly higher T-tau at baseline than the group with improved memory. Baseline CSF variables showed a trend toward more pathological values in the patients with memory decline compared to those who improved or remained stable. The baseline memory score of those who declined was significantly better than the baseline score of those who improved over two years. The general trend for the whole group was improved memory and executive test scores. There were no differences in cognitive scores based on CSF quartiles at baseline, nor were there differences in cognitive outcome for patients with early amnestic mild cognitive impairment versus average cognitive function at baseline. The main finding that T-tau rather than amyloid-β was associated with memory decline do not support the prevailing opinion about the chain of events assumed to take place in Alzheimer's disease. In addition, memory decline was not associated with poor baseline memory score. Thus, a memory cut-off indicating low baseline memory would not would have identified the declining group.

Multi-modal imaging predicts memory performance in normal aging and cognitive decline.

PubMed

Walhovd, K B; Fjell, A M; Dale, A M; McEvoy, L K; Brewer, J; Karow, D S; Salmon, D P; Fennema-Notestine, C

2010-07-01

This study (n=161) related morphometric MR imaging, FDG-PET and APOE genotype to memory scores in normal controls (NC), mild cognitive impairment (MCI) and Alzheimer's disease (AD). Stepwise regression analyses focused on morphometric and metabolic characteristics of the episodic memory network: hippocampus, entorhinal, parahippocampal, retrosplenial, posterior cingulate, precuneus, inferior parietal, and lateral orbitofrontal cortices. In NC, hippocampal metabolism predicted learning; entorhinal metabolism predicted recognition; and hippocampal metabolism predicted recall. In MCI, thickness of the entorhinal and precuneus cortices predicted learning, while parahippocampal metabolism predicted recognition. In AD, posterior cingulate cortical thickness predicted learning, while APOE genotype predicted recognition. In the total sample, hippocampal volume and metabolism, cortical thickness of the precuneus, and inferior parietal metabolism predicted learning; hippocampal volume and metabolism, parahippocampal thickness and APOE genotype predicted recognition. Imaging methods appear complementary and differentially sensitive to memory in health and disease. Medial temporal and parietal metabolism and morphometry best explained memory variance. Medial temporal characteristics were related to learning, recall and recognition, while parietal structures only predicted learning. Copyright 2008. Published by Elsevier Inc.

Feasibility of Predicting MCI/AD Using Neuropsychological Tests and Serum β-Amyloid

PubMed Central

Luis, Cheryl A.; Abdullah, Laila; Ait-Ghezala, Ghania; Mouzon, Benoit; Keegan, Andrew P.; Crawford, Fiona; Mullan, Michael

2011-01-01

We examined the usefulness of brief neuropsychological tests and serum Aβ as a predictive test for detecting MCI/AD in older adults. Serum Aβ levels were measured from 208 subjects who were cognitively normal at enrollment and blood draw. Twenty-eight of the subjects subsequently developed MCI (n = 18) or AD (n = 10) over the follow-up period. Baseline measures of global cognition, memory, language fluency, and serum Aβ1–42 and the ratio of serum Aβ1–42/Aβ1–40 were significant predictors for future MCI/AD using Cox regression with demographic variables, APOE ε4, vascular risk factors, and specific medication as covariates. An optimal sensitivity of 85.2% and specificity of 86.5% for predicting MCI/AD was achieved using ROC analyses. Brief neuropsychological tests and measurements of Aβ1–42 obtained via blood warrants further study as a practical and cost effective method for wide-scale screening for identifying older adults who may be at-risk for pathological cognitive decline. PMID:21660215

Amyloid and tau signatures of brain metabolic decline in preclinical Alzheimer's disease.

PubMed

Pascoal, Tharick A; Mathotaarachchi, Sulantha; Shin, Monica; Park, Ah Yeon; Mohades, Sara; Benedet, Andrea L; Kang, Min Su; Massarweh, Gassan; Soucy, Jean-Paul; Gauthier, Serge; Rosa-Neto, Pedro

2018-06-01

We aimed to determine the amyloid (Aβ) and tau biomarker levels associated with imminent Alzheimer's disease (AD) - related metabolic decline in cognitively normal individuals. A threshold analysis was performed in 120 cognitively normal elderly individuals by modelling 2-year declines in brain glucose metabolism measured with [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) as a function of [ 18 F]florbetapir Aβ positron emission tomography (PET) and cerebrospinal fluid phosphorylated tau biomarker thresholds. Additionally, using a novel voxel-wise analytical framework, we determined the sample sizes needed to test an estimated 25% drugeffect with 80% of power on changes in FDG uptake over 2 years at every brain voxel. The combination of [ 18 F]florbetapir standardized uptake value ratios and phosphorylated-tau levels more than one standard deviation higher than their respective thresholds for biomarker abnormality was the best predictor of metabolic decline in individuals with preclinical AD. We also found that a clinical trial using these thresholds would require as few as 100 individuals to test a 25% drug effect on AD-related metabolic decline over 2 years. These results highlight the new concept that combined Aβ and tau thresholds can predict imminent neurodegeneration as an alternative framework with a high statistical power for testing the effect of disease-modifying therapies on [ 18 F]FDG uptake decline over a typical 2-year clinical trial period in individuals with preclinical AD.

Analysis of neuron-astrocyte metabolic cooperation in the brain of db/db mice with cognitive decline using 13C NMR spectroscopy.

PubMed

Zheng, Hong; Zheng, Yongquan; Wang, Dan; Cai, Aimin; Lin, Qiuting; Zhao, Liangcai; Chen, Minjiang; Deng, Mingjie; Ye, Xinjian; Gao, Hongchang

2017-01-01

Type 2 diabetes has been linked to cognitive impairment, but its potential metabolic mechanism is still unclear. The present study aimed to explore neuron-astrocyte metabolic cooperation in the brain of diabetic (db/db, BKS.Cg-m +/+ Leprdb/J) mice with cognitive decline using 13 C NMR technique in combination with intravenous [2- 13 C]-acetate and [3- 13 C]-lactate infusions. We found that the 13 C-enrichment from [2- 13 C]-acetate into tricarboxylic acid cycle intermediate, succinate, was significantly decreased in db/db mice with cognitive decline compared with wild-type (WT, C57BLKS/J) mice, while an opposite result was obtained after [3- 13 C]-lactate infusion. Relative to WT mice, db/db mice with cognitive decline had significantly lower 13 C labeling percentages in neurotransmitters including glutamine, glutamate, and γ-aminobutyric acid after [2- 13 C]-acetate infusion. However, [3- 13 C]-lactate resulted in increased 13 C-enrichments in neurotransmitters in db/db mice with cognitive decline. This may indicate that the disturbance of neurotransmitter metabolism occurred during the development of cognitive decline. In addition, a reduction in 13 C-labeling of lactate and an increase in gluconeogenesis were found from both labeled infusions in db/db mice with cognitive decline. Therefore, our results suggest that the development of cognitive decline in type 2 diabetes may be implicated to an unbalanced metabolism in neuron-astrocyte cooperation and an enhancement of gluconeogenesis. © The Author(s) 2016.

Novel Virtual User Models of Mild Cognitive Impairment for Simulating Dementia

PubMed Central

Segkouli, Sofia; Tzovaras, Dimitrios; Tsakiris, Thanos; Tsolaki, Magda; Karagiannidis, Charalampos

2015-01-01

Virtual user modeling research has attempted to address critical issues of human-computer interaction (HCI) such as usability and utility through a large number of analytic, usability-oriented approaches as cognitive models in order to provide users with experiences fitting to their specific needs. However, there is demand for more specific modules embodied in cognitive architecture that will detect abnormal cognitive decline across new synthetic task environments. Also, accessibility evaluation of graphical user interfaces (GUIs) requires considerable effort for enhancing ICT products accessibility for older adults. The main aim of this study is to develop and test virtual user models (VUM) simulating mild cognitive impairment (MCI) through novel specific modules, embodied at cognitive models and defined by estimations of cognitive parameters. Well-established MCI detection tests assessed users' cognition, elaborated their ability to perform multitasks, and monitored the performance of infotainment related tasks to provide more accurate simulation results on existing conceptual frameworks and enhanced predictive validity in interfaces' design supported by increased tasks' complexity to capture a more detailed profile of users' capabilities and limitations. The final outcome is a more robust cognitive prediction model, accurately fitted to human data to be used for more reliable interfaces' evaluation through simulation on the basis of virtual models of MCI users. PMID:26339282

Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future "Non-Cognitive" Outcomes of Alzheimer's Disease.

PubMed

Ingber, Adam P; Hassenstab, Jason; Fagan, Anne M; Benzinger, Tammie L S; Grant, Elizabeth A; Holtzman, David M; Morris, John C; Roe, Catherine M

2016-01-01

The influence of reserve variables and Alzheimer's disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on "non-cognitive" outcomes, including functional abilities and mood. We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior. Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants. Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers. The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD.

Interaction between personality traits and cerebrospinal fluid biomarkers of Alzheimer's disease pathology modulates cognitive performance.

PubMed

Tautvydaitė, Domilė; Kukreja, Deepti; Antonietti, Jean-Philippe; Henry, Hugues; von Gunten, Armin; Popp, Julius

2017-02-02

During adulthood, personality characteristics may contribute to the individual capacity to compensate the impact of developing cerebral Alzheimer's disease (AD) pathology on cognitive impairment in later life. In this study we aimed to investigate whether and how premorbid personality traits interact with cerebrospinal fluid (CSF) markers of AD pathology to predict cognitive performance in subjects with mild cognitive impairment or mild AD dementia and in participants with normal cognition. One hundred and ten subjects, of whom 66 were patients with mild cognitive impairment or mild AD dementia and 44 were healthy controls, had a comprehensive medical and neuropsychological examination as well as lumbar puncture to measure CSF biomarkers of AD pathology (amyloid beta 1-42 , phosphorylated tau and total-tau). Participants' proxies completed the Revised NEO Personality Inventory, Form R to retrospectively assess subjects' premorbid personality. In hierarchical multivariate regression analyses, including age, gender, education, APOEε4 status and cognitive level, premorbid neuroticism, conscientiousness and agreeableness modulated the effect of CSF biomarkers on cognitive performance. Low premorbid openness independently predicted lower levels of cognitive functioning after controlling for biomarker concentrations. Our findings suggest that specific premorbid personality traits are associated with cerebral AD pathology and modulate its impact on cognitive performance. Considering personality characteristics may help to appraise a person's cognitive reserve and the risk of cognitive decline in later life.

Transverse Diffusivity of Cerebral Parenchyma Predicts Visual Tracking Performance in Relapsing-Remitting Multiple Sclerosis

ERIC Educational Resources Information Center

Warlop, Nele P.; Achten, Eric; Fieremans, Els; Debruyne, Jan; Vingerhoets, Guy

2009-01-01

This study investigated the relation between cerebral damage related to multiple sclerosis (MS) and cognitive decline as determined by two classical mental tracking tests. Cerebral damage in 15 relapsing-remitting MS patients was measured by diffusion tensor imaging (DTI). Fractional anisotropy, longitudinal and transverse diffusivity were defined…

Hypertension, Dietary Sodium, and Cognitive Decline: Results From the Women’s Health Initiative Memory Study

PubMed Central

Wu, Chunyuan; Coker, Laura H.; Seth, Arjun; Snetselaar, Linda; Manson, JoAnn E.; Rossouw, Jacques E.; Wassertheil-Smoller, Sylvia

2016-01-01

BACKGROUND To investigate the relationships of hypertension, antihypertensive treatment, and sodium intake on cognitive decline in older women. METHODS Prospective follow-up of 6,426 cognitively intact women aged 65–79 years enrolled in the Women’s Health Initiative Memory Study (WHIMS) with a median follow-up of 9.1 years. Dietary sodium intake was determined by food frequency questionnaires. Hypertension was defined as self-report of current drug therapy for hypertension. Blood pressure (BP) control was assessed by treatment for hypertension and clinic measurement of systolic BP ≥ 140mm Hg or diastolic BP ≥ 90mm Hg at baseline. Cognitive functioning was assessed annually by global cognitive screening, neurocognitive, and neuropsychiatric evaluations. Cognitive decline was identified by the incidence of mild cognitive impairment (MCI) or probable dementia (PD). Cox proportional hazards analyses were used to calculate hazard ratios (HRs). RESULTS Hypertension was associated with an increased risk for cognitive decline (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P = 0.02). Among women with antihypertensive medication, those with BP ≥140/90mm Hg (uncontrolled BP) were at highest risk for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment and BP <140/90mm Hg (controlled BP). Sodium intake >1,500mg/day did not alter the risk for cognitive decline in hypertensive women or women with antihypertensive treatment (P for interaction = 0.96 or 0.97). CONCLUSIONS Women with antihypertensive treatment and uncontrolled BP showed highest risk estimates for developing cognitive decline compared to non-hypertensive women. Sodium intake did not modify the risk for cognitive decline in women with hypertension or receiving antihypertensive medication. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov. Unique identifier: NCT00685009 and NCT00745056 PMID:26137952

Hypertension, Dietary Sodium, and Cognitive Decline: Results From the Women's Health Initiative Memory Study.

PubMed

Haring, Bernhard; Wu, Chunyuan; Coker, Laura H; Seth, Arjun; Snetselaar, Linda; Manson, JoAnn E; Rossouw, Jacques E; Wassertheil-Smoller, Sylvia

2016-02-01

To investigate the relationships of hypertension, antihypertensive treatment, and sodium intake on cognitive decline in older women. Prospective follow-up of 6,426 cognitively intact women aged 65-79 years enrolled in the Women's Health Initiative Memory Study (WHIMS) with a median follow-up of 9.1 years. Dietary sodium intake was determined by food frequency questionnaires. Hypertension was defined as self-report of current drug therapy for hypertension. Blood pressure (BP) control was assessed by treatment for hypertension and clinic measurement of systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg at baseline. Cognitive functioning was assessed annually by global cognitive screening, neurocognitive, and neuropsychiatric evaluations. Cognitive decline was identified by the incidence of mild cognitive impairment (MCI) or probable dementia (PD). Cox proportional hazards analyses were used to calculate hazard ratios (HRs). Hypertension was associated with an increased risk for cognitive decline (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P = 0.02). Among women with antihypertensive medication, those with BP ≥140/90 mm Hg (uncontrolled BP) were at highest risk for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment and BP <140/90mm Hg (controlled BP). Sodium intake >1,500 mg/day did not alter the risk for cognitive decline in hypertensive women or women with antihypertensive treatment (P for interaction = 0.96 or 0.97). Women with antihypertensive treatment and uncontrolled BP showed highest risk estimates for developing cognitive decline compared to non-hypertensive women. Sodium intake did not modify the risk for cognitive decline in women with hypertension or receiving antihypertensive medication. http://www.clinicaltrials.gov. Unique identifier: NCT00685009 and NCT00745056. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Compensatory mechanisms in higher-educated subjects with Alzheimer's disease: a study of 20 years of cognitive decline.

PubMed

Amieva, Hélène; Mokri, Hind; Le Goff, Mélanie; Meillon, Céline; Jacqmin-Gadda, Hélène; Foubert-Samier, Alexandra; Orgogozo, Jean-Marc; Stern, Yaakov; Dartigues, Jean-François

2014-04-01

A better knowledge of long-term trajectories of cognitive decline is a central feature of the study of the process leading to Alzheimer's dementia. Several factors may mitigate such decline, among which is education, a major risk factor for Alzheimer's disease. The aim of our work was to compare the pattern and duration of clinical trajectories before Alzheimer's dementia in individuals with low and high education within the PAQUID cohort involving 20 years of follow-up. The sample comprises 442 participants with incident Alzheimer's disease (27.2% were male)--171 with low education (mean age=86.2 years; standard deviation=5.3 years) and 271 with higher education (mean age=86.5; standard deviation=5.4)--and 442 control subjects matched according to age, sex and education. At each visit and up to the 20-year follow-up visit, several cognitive and clinical measures were collected and incident cases of Alzheimer's disease clinically diagnosed. The evolution of clinical measures in pre-demented subjects and matched controls was analysed with a semi-parametric extension of the mixed effects linear model. The results show that the first signs of cognitive decline occurred 15 to 16 years before achieving dementia threshold in higher-educated subjects whereas signs occurred at 7 years before dementia in low-educated subjects. There seemed to be two successive periods of decline in higher-educated subjects. Decline started ∼15 to 16 years before dementia with subtle impairment restricted to some cognitive tests and with no impact during the first 7 to 8 years on global cognition, cognitive complaints, or activities of daily living scales. Then, ∼7 years before dementia, global cognitive abilities begin to deteriorate, along with difficulties dealing with complex activities of daily living, the increase in self-perceived difficulties and depressive symptoms. By contrast, lower-educated subjects presented a single period of decline lasting ∼7 years, characterized by decline concomitantly affecting specific and more global cognitive function along with alteration in functional abilities. This study demonstrates how early cognitive symptoms may emerge preceding Alzheimer's dementia particularly in higher-educated individuals, for whom decline occurred up to 16 years before dementia. It also demonstrates the protective role of education in the clinical trajectory preceding Alzheimer's dementia. We suggest that the initial decline in cognition occurs at the onset of comparable Alzheimer's disease pathology in both groups, and is associated with immediate decline to dementia in the lower education group. In contrast, higher education protects against further cognitive decline for ∼7 years until pathology becomes more severe.

Carotid disease at age 73 and cognitive change from age 70 to 76 years: A longitudinal cohort study

PubMed Central

Allerhand, Michael; Eadie, Elizabeth; Thomas, Avril; Corley, Janey; Pattie, Alison; Taylor, Adele; Shenkin, Susan D; Cox, Simon; Gow, Alan; Starr, John M; Deary, Ian J

2016-01-01

Cognitive decline and carotid artery atheroma are common at older ages. In community-dwelling subjects, we assessed cognition at ages 70, 73 and 76 and carotid Doppler ultrasound at age 73, to determine whether carotid stenosis was related to cognitive decline. We used latent growth curve models to examine associations between four carotid measures (internal carotid artery stenosis, velocity, pulsatility and resistivity indices) and four cognitive ability domains (memory, visuospatial function, crystallised intelligence, processing speed) adjusted for cognitive ability at age 11, current age, gender and vascular risk factors. Amongst 866 participants, carotid stenosis (median 12.96%) was not associated with cognitive abilities at age 70 or cognitive decline from age 70 to 76. Increased ICA pulsatility and resistivity indices were associated with slower processing speed (both P < 0.001) and worse visuospatial function (P = 0.036, 0.031, respectively) at age 70, and declining crystallised intelligence from ages 70 to 76 (P = 0.008, 0.006, respectively). The findings suggest that vascular stiffening, rather than carotid luminal narrowing, adversely influences cognitive ageing and provides a potential target for ameliorating age-related cognitive decline. PMID:28155579

Carotid disease at age 73 and cognitive change from age 70 to 76 years: A longitudinal cohort study.

PubMed

Wardlaw, Joanna M; Allerhand, Michael; Eadie, Elizabeth; Thomas, Avril; Corley, Janey; Pattie, Alison; Taylor, Adele; Shenkin, Susan D; Cox, Simon; Gow, Alan; Starr, John M; Deary, Ian J

2017-08-01

Cognitive decline and carotid artery atheroma are common at older ages. In community-dwelling subjects, we assessed cognition at ages 70, 73 and 76 and carotid Doppler ultrasound at age 73, to determine whether carotid stenosis was related to cognitive decline. We used latent growth curve models to examine associations between four carotid measures (internal carotid artery stenosis, velocity, pulsatility and resistivity indices) and four cognitive ability domains (memory, visuospatial function, crystallised intelligence, processing speed) adjusted for cognitive ability at age 11, current age, gender and vascular risk factors. Amongst 866 participants, carotid stenosis (median 12.96%) was not associated with cognitive abilities at age 70 or cognitive decline from age 70 to 76. Increased ICA pulsatility and resistivity indices were associated with slower processing speed (both P < 0.001) and worse visuospatial function ( P = 0.036, 0.031, respectively) at age 70, and declining crystallised intelligence from ages 70 to 76 ( P = 0.008, 0.006, respectively). The findings suggest that vascular stiffening, rather than carotid luminal narrowing, adversely influences cognitive ageing and provides a potential target for ameliorating age-related cognitive decline.

Contribution of cognitive performance and cognitive decline to associations between socioeconomic factors and dementia: A cohort study.

PubMed

Rusmaully, Jennifer; Dugravot, Aline; Moatti, Jean-Paul; Marmot, Michael G; Elbaz, Alexis; Kivimaki, Mika; Sabia, Séverine; Singh-Manoux, Archana

2017-06-01

Socioeconomic disadvantage is a risk factor for dementia, but longitudinal studies suggest that it does not affect the rate of cognitive decline. Our objective is to understand the manner in which socioeconomic disadvantage shapes dementia risk by examining its associations with midlife cognitive performance and cognitive decline from midlife to old age, including cognitive decline trajectories in those with dementia. Data are drawn from the Whitehall II study (N = 10,308 at study recruitment in 1985), with cognitive function assessed at 4 waves (1997, 2002, 2007, and 2012). Sociodemographic, behavioural, and cardiometabolic risk factors from 1985 and chronic conditions until the end of follow-up in 2015 (N dementia/total = 320/9,938) allowed the use of inverse probability weighting to take into account data missing because of loss to follow-up between the study recruitment in 1985 and the introduction of cognitive tests to the study in 1997. Generalized estimating equations and Cox regression were used to assess associations of socioeconomic markers (height, education, and midlife occupation categorized as low, intermediate, and high to represent hierarchy in the socioeconomic marker) with cognitive performance, cognitive decline, and dementia (N dementia/total = 195/7,499). In those with dementia, we examined whether retrospective trajectories of cognitive decline (backward timescale) over 18 years prior to diagnosis differed as a function of socioeconomic markers. Socioeconomic disadvantage was associated with poorer cognitive performance (all p < 0.001). Using point estimates for the effect of age, the differences between the high and low socioeconomic groups corresponded to an age effect of 4, 15, and 26 years, for height, education, and midlife occupation, respectively. There was no evidence of faster cognitive decline in socioeconomically disadvantaged groups. Low occupation, but not height or education, was associated with risk of dementia (hazard ratio [HR] = 2.03 [95% confidence interval (CI) 1.23-3.36]) in an analysis adjusted for sociodemographic factors; the excess risk was unchanged after adjustment for cognitive decline but was completely attenuated after adjustment for cognitive performance. In further analyses restricted to those with dementia, retrospective cognitive trajectories over 18 years prior to dementia diagnosis showed faster cognitive decline in the high education (p = 0.006) and occupation (p = 0.001) groups such that large differences in cognitive performance in midlife were attenuated at dementia diagnosis. A major limitation of our study is the use of electronic health records rather than comprehensive dementia ascertainment. Our results support the passive or threshold cognitive reserve hypothesis, in that high cognitive reserve is associated with lower risk for dementia because of its association with cognitive performance, which provides a buffer against clinical expression of dementia.

Neighborhood socioeconomic context and cognitive decline among older Mexican Americans: results from the Sacramento Area Latino Study on Aging.

PubMed

Zeki Al Hazzouri, Adina; Haan, Mary N; Osypuk, Theresa; Abdou, Cleopatra; Hinton, Ladson; Aiello, Allison E

2011-08-15

In 1 previous study, it was shown that neighborhood socioeconomic disadvantage is associated with cognitive decline among Latinos. No studies have explored whether and to what extent individual-level socioeconomic factors account for the relation between neighborhood disadvantage and cognitive decline. The purpose of the present study was to assess the influence of neighborhood socioeconomic position (SEP) on cognitive decline and examine how individual-level SEP factors (educational level, annual income, and occupation) influenced neighborhood associations over the course of 10 years. Participants (n = 1,789) were community-dwelling older Mexican Americans from the Sacramento Area Latino Study on Aging. Neighborhood SEP was derived by linking the participant's individual data to the 2000 decennial census. The authors assessed cognitive function with the Modified Mini-Mental State Examination. Analyses used 3-level hierarchical linear mixed models of time within individuals within neighborhoods. After adjustment for individual-level sociodemographic characteristics, higher neighborhood SEP was significantly associated with cognitive function (β = -0.033; P < 0.05) and rates of decline (β = -0.0009; P < 0.10). After adjustment for individual educational level, neighborhood SEP remained associated with baseline cognition but not with rates of decline. Differences in individual educational levels explained most of the intra- and interneighborhood variance. These results suggest that the effect of neighborhood SEP on cognitive decline among Latinos is primarily accounted for by education.

Amyloid-Related Memory Decline in Preclinical Alzheimer's Disease Is Dependent on APOE ε4 and Is Detectable over 18-Months.

PubMed

Thai, Christine; Lim, Yen Ying; Villemagne, Victor L; Laws, Simon M; Ames, David; Ellis, Kathryn A; Rainey-Smith, Stephanie R; Martins, Ralph N; Masters, Colin L; Rowe, Christopher C; Maruff, Paul

2015-01-01

High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. However, the relationship between these two biomarkers and cognitive decline is unclear. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 months, in 317 cognitively healthy (CN) older adults (47.6% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SD = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE ε4 non-carriers, high Aβ was unrelated to cognitive decline in learning and working memory. Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer's disease.

Polygenic hazard scores in preclinical Alzheimer disease.

PubMed

Tan, Chin Hong; Hyman, Bradley T; Tan, Jacinth J X; Hess, Christopher P; Dillon, William P; Schellenberg, Gerard D; Besser, Lilah M; Kukull, Walter A; Kauppi, Karolina; McEvoy, Linda K; Andreassen, Ole A; Dale, Anders M; Fan, Chun Chieh; Desikan, Rahul S

2017-09-01

Identifying asymptomatic older individuals at elevated risk for developing Alzheimer disease (AD) is of clinical importance. Among 1,081 asymptomatic older adults, a recently validated polygenic hazard score (PHS) significantly predicted time to AD dementia and steeper longitudinal cognitive decline, even after controlling for APOE ɛ4 carrier status. Older individuals in the highest PHS percentiles showed the highest AD incidence rates. PHS predicted longitudinal clinical decline among older individuals with moderate to high Consortium to Establish a Registry for Alzheimer's Disease (amyloid) and Braak (tau) scores at autopsy, even among APOE ɛ4 noncarriers. Beyond APOE, PHS may help identify asymptomatic individuals at highest risk for developing Alzheimer neurodegeneration. Ann Neurol 2017;82:484-488. © 2017 American Neurological Association.

Can psychosocial work conditions protect against age-related cognitive decline? Results from a systematic review

PubMed Central

Nexø, Mette Andersen; Meng, Annette; Borg, Vilhelm

2016-01-01

According to the use it or lose it hypothesis, intellectually stimulating activities postpone age-related cognitive decline. A previous systematic review concluded that a high level of mental work demands and job control protected against cognitive decline. However, it did not distinguish between outcomes that were measured as cognitive function at one point in time or as cognitive decline. Our study aimed to systematically review which psychosocial working conditions were prospectively associated with high levels of cognitive function and/or changes in cognitive function over time. Articles were identified by a systematic literature search (MEDLINE, Web of Science (WOS), PsycNET, Occupational Safety and Health (OSH)). We included only studies with longitudinal designs examining the impact of psychosocial work conditions on outcomes defined as cognitive function or changes in cognitive function. Two independent reviewers compared title-abstract screenings, full-text screenings and quality assessment ratings. Eleven studies were included in the final synthesis and showed that high levels of mental work demands, occupational complexity or job control at one point in time were prospectively associated with higher levels of cognitive function in midlife or late life. However, the evidence to clarify whether these psychosocial factors also affected cognitive decline was insufficient, conflicting or weak. It remains speculative whether job control, job demands or occupational complexity can protect against cognitive decline. Future studies using methodological advancements can reveal whether workers gain more cognitive reserve in midlife and late life than the available evidence currently suggests. The public health implications of a previous review should thereby be redefined accordingly. PMID:27178844

PET staging of amyloidosis using striatum.

PubMed

Hanseeuw, Bernard J; Betensky, Rebecca A; Mormino, Elizabeth C; Schultz, Aaron P; Sepulcre, Jorge; Becker, John A; Jacobs, Heidi I L; Buckley, Rachel F; LaPoint, Molly R; Vanini, Patrizia; Donovan, Nancy J; Chhatwal, Jasmeer P; Marshall, Gad A; Papp, Kathryn V; Amariglio, Rebecca E; Rentz, Dorene M; Sperling, Reisa A; Johnson, Keith A

2018-05-21

Amyloid PET data are commonly expressed as binary measures of cortical deposition. However, not all individuals with high cortical amyloid will experience rapid cognitive decline. Motivated by postmortem data, we evaluated a three-stage PET classification: low cortical; high cortical, low striatal; and high cortical, high striatal amyloid; hypothesizing this model could better reflect Alzheimer's dementia progression than a model based only on cortical measures. We classified PET data from 1433 participants (646 normal, 574 mild cognitive impairment, and 213 AD), explored the successive involvement of cortex and striatum using 3-year follow-up PET data, and evaluated the associations between PET stages, hippocampal volumes, and cognition. Follow-up data indicated that PET detects amyloid first in cortex and then in striatum. Our three-category staging including striatum better predicted hippocampal volumes and subsequent cognition than a three-category staging including only cortical amyloid. PET can evaluate amyloid expansion from cortex to subcortex. Using striatal signal as a marker of advanced amyloidosis may increase predictive power in Alzheimer's dementia research. Copyright © 2018. Published by Elsevier Inc.

Adolescent Self-Organization Predicts Midlife Memory in a Prospective Birth Cohort Study

PubMed Central

2013-01-01

Childhood and adolescent mental health have a lasting impact on adult life chances, with strong implications for subsequent health, including cognitive aging. Using the British 1946 birth cohort, the authors tested associations between adolescent conduct problems, emotional problems and aspects of self-organization, and verbal memory at 43 years and rate of decline in verbal memory from 43 to 60–64 years. After controlling for childhood intelligence, adolescent self-organization was positively associated with verbal memory at 43 years, mainly through educational attainment, although not with rate of memory decline. Associations between adolescent conduct and emotional problems and future memory were of negligible magnitude. It has been suggested that interventions to improve self-organization may save a wide range of societal costs; this study also suggests that this might also benefit cognitive function in later life. PMID:24364401

Apolipoprotein E e4 allele is associated with more rapid motor decline in older persons.

PubMed

Buchman, Aron S; Boyle, Patricia A; Wilson, Robert S; Beck, Todd L; Kelly, Jeremiah F; Bennett, David A

2009-01-01

We tested the hypothesis that apolipoprotein E allele status predicts the rate of motor decline in the elderly. Eight hundred seventy-six older participants without dementia underwent baseline and annual motor testing for up to 10 years. In a generalized estimating equation controlling for age, sex, and education, motor function declined by about 0.03 U/y. The presence of epsilon4 allele was associated with a 2-fold increase in rate of motor decline epsilon4 allele x time: estimate=-0.027 (SE 0.012, P=0.025)]. The association of epsilon4 allele with motor decline persisted even after controlling for cognitive status, race, body mass index, vascular risk factors, and diseases. Further analyses suggested that the association of epsilon4 with motor decline was for the most part explained by the association between epsilon4 allele and change in muscle strength. These results suggest that the presence of epsilon4 allele is a risk factor for more rapid motor decline in the elderly.

To Switch or Not to Switch: Role of Cognitive Control in Working Memory Training in Older Adults.

PubMed

Basak, Chandramallika; O'Connell, Margaret A

2016-01-01

It is currently not known what are the best working memory training strategies to offset the age-related declines in fluid cognitive abilities. In this randomized clinical double-blind trial, older adults were randomly assigned to one of two types of working memory training - one group was trained on a predictable memory updating task (PT) and another group was trained on a novel, unpredictable memory updating task (UT). Unpredictable memory updating, compared to predictable, requires greater demands on cognitive control (Basak and Verhaeghen, 2011a). Therefore, the current study allowed us to evaluate the role of cognitive control in working memory training. All participants were assessed on a set of near and far transfer tasks at three different testing sessions - before training, immediately after the training, and 1.5 months after completing the training. Additionally, individual learning rates for a comparison working memory task (performed by both groups) and the trained task were computed. Training on unpredictable memory updating, compared to predictable, significantly enhanced performance on a measure of episodic memory, immediately after the training. Moreover, individuals with faster learning rates showed greater gains in this episodic memory task and another new working memory task; this effect was specific to UT. We propose that the unpredictable memory updating training, compared to predictable memory updating training, may a better strategy to improve selective cognitive abilities in older adults, and future studies could further investigate the role of cognitive control in working memory training.

Longitudinal relationships between resources, motivation, and functioning.

PubMed

Hess, Thomas M; Emery, Lisa; Neupert, Shevaun D

2012-05-01

We investigated how fluctuations and linear changes in health and cognitive resources influence the motivation to engage in complex cognitive activity and the extent to which motivation mediated the relationship between changing resources and cognitively demanding activities. Longitudinal data from 332 adults aged 20-85 years were examined. Motivation was assessed using a composite of Need for Cognition and Personal Need for Structure and additional measures of health, sensory functioning, cognitive ability, and self-reported activity engagement. Multilevel modeling revealed that age-typical changes in health, sensory functions, and ability were associated with changes in motivation, with the impact of declining health on motivation being particularly strong in older adulthood. Changes in motivation, in turn, predicted involvement in cognitive and social activities as well as changes in cognitive ability. Finally, motivation was observed to partially mediate the relationship between changes in resources and cognitively demanding activities. Our results suggest that motivation may play an important role in determining the course of cognitive change and involvement in cognitively demanding everyday activities in adulthood.

The nonlinear relationship between cerebrospinal fluid Aβ42 and tau in preclinical Alzheimer's disease.

PubMed

de Leon, Mony J; Pirraglia, Elizabeth; Osorio, Ricardo S; Glodzik, Lidia; Saint-Louis, Les; Kim, Hee-Jin; Fortea, Juan; Fossati, Silvia; Laska, Eugene; Siegel, Carole; Butler, Tracy; Li, Yi; Rusinek, Henry; Zetterberg, Henrik; Blennow, Kaj

2018-01-01

Cerebrospinal fluid (CSF) studies consistently show that CSF levels of amyloid-beta 1-42 (Aβ42) are reduced and tau levels increased prior to the onset of cognitive decline related to Alzheimer's disease (AD). However, the preclinical prediction accuracy for low CSF Aβ42 levels, a surrogate for brain Aβ42 deposits, is not high. Moreover, the pathology data suggests a course initiated by tauopathy contradicting the contemporary clinical view of an Aβ initiated cascade. CSF Aβ42 and tau data from 3 normal aging cohorts (45-90 years) were combined to test both cross-sectional (n = 766) and longitudinal (n = 651) hypotheses: 1) that the relationship between CSF levels of Aβ42 and tau are not linear over the adult life-span; and 2) that non-linear models improve the prediction of cognitive decline. Supporting the hypotheses, the results showed that a u-shaped quadratic fit (Aβ2) best describes the relationship for CSF Aβ42 with CSF tau levels. Furthermore we found that the relationship between Aβ42 and tau changes with age-between 45 and 70 years there is a positive linear association, whereas between 71 and 90 years there is a negative linear association between Aβ42 and tau. The quadratic effect appears to be unique to Aβ42, as Aβ38 and Aβ40 showed only positive linear relationships with age and CSF tau. Importantly, we observed the prediction of cognitive decline was improved by considering both high and low levels of Aβ42. Overall, these data suggest an earlier preclinical stage than currently appreciated, marked by CSF elevations in tau and accompanied by either elevations or reductions in Aβ42. Future studies are needed to examine potential mechanisms such as failing CSF clearance as a common factor elevating CSF Aβxx analyte levels prior to Aβ42 deposition in brain.

Cognitive Control Signals in Posterior Cingulate Cortex

PubMed Central

Hayden, Benjamin Y.; Smith, David V.; Platt, Michael L.

2010-01-01

Efficiently shifting between tasks is a central function of cognitive control. The role of the default network – a constellation of areas with high baseline activity that declines during task performance – in cognitive control remains poorly understood. We hypothesized that task switching demands cognitive control to shift the balance of processing toward the external world, and therefore predicted that switching between the two tasks would require suppression of activity of neurons within the posterior cingulate cortex (CGp). To test this idea, we recorded the activity of single neurons in CGp, a central node in the default network, in monkeys performing two interleaved tasks. As predicted, we found that basal levels of neuronal activity were reduced following a switch from one task to another and gradually returned to pre-switch baseline on subsequent trials. We failed to observe these effects in lateral intraparietal cortex, part of the dorsal fronto-parietal cortical attention network directly connected to CGp. These findings indicate that suppression of neuronal activity in CGp facilitates cognitive control, and suggest that activity in the default network reflects processes that directly compete with control processes elsewhere in the brain. PMID:21160560

The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis.

PubMed

Debette, Stéphanie; Markus, H S

2010-07-26

To review the evidence for an association of white matter hyperintensities with risk of stroke, cognitive decline, dementia, and death. Systematic review and meta-analysis. PubMed from 1966 to 23 November 2009. Prospective longitudinal studies that used magnetic resonance imaging and assessed the impact of white matter hyperintensities on risk of incident stroke, cognitive decline, dementia, and death, and, for the meta-analysis, studies that provided risk estimates for a categorical measure of white matter hyperintensities, assessing the impact of these lesions on risk of stroke, dementia, and death. Population studied, duration of follow-up, method used to measure white matter hyperintensities, definition of the outcome, and measure of the association of white matter hyperintensities with the outcome. 46 longitudinal studies evaluated the association of white matter hyperintensities with risk of stroke (n=12), cognitive decline (n=19), dementia (n=17), and death (n=10). 22 studies could be included in a meta-analysis (nine of stroke, nine of dementia, eight of death). White matter hyperintensities were associated with an increased risk of stroke (hazard ratio 3.3, 95% confidence interval 2.6 to 4.4), dementia (1.9, 1.3 to 2.8), and death (2.0, 1.6 to 2.7). An association of white matter hyperintensities with a faster decline in global cognitive performance, executive function, and processing speed was also suggested. White matter hyperintensities predict an increased risk of stroke, dementia, and death. Therefore white matter hyperintensities indicate an increased risk of cerebrovascular events when identified as part of diagnostic investigations, and support their use as an intermediate marker in a research setting. Their discovery should prompt detailed screening for risk factors of stroke and dementia.

A new approach to the characterization of subtle errors in everyday action: implications for mild cognitive impairment.

PubMed

Seligman, Sarah C; Giovannetti, Tania; Sestito, John; Libon, David J

2014-01-01

Mild functional difficulties have been associated with early cognitive decline in older adults and increased risk for conversion to dementia in mild cognitive impairment, but our understanding of this decline has been limited by a dearth of objective methods. This study evaluated the reliability and validity of a new system to code subtle errors on an established performance-based measure of everyday action and described preliminary findings within the context of a theoretical model of action disruption. Here 45 older adults completed the Naturalistic Action Test (NAT) and neuropsychological measures. NAT performance was coded for overt errors, and subtle action difficulties were scored using a novel coding system. An inter-rater reliability coefficient was calculated. Validity of the coding system was assessed using a repeated-measures ANOVA with NAT task (simple versus complex) and error type (overt versus subtle) as within-group factors. Correlation/regression analyses were conducted among overt NAT errors, subtle NAT errors, and neuropsychological variables. The coding of subtle action errors was reliable and valid, and episodic memory breakdown predicted subtle action disruption. Results suggest that the NAT can be useful in objectively assessing subtle functional decline. Treatments targeting episodic memory may be most effective in addressing early functional impairment in older age.

Age trajectories of everyday cognition in African American and White older adults under prompted and unprompted conditions

PubMed Central

Thomas, Kelsey R.; Marsiske, Michael

2016-01-01

We investigated how race and verbal prompting interacted with age to predict age trajectories on a performance-based measure of everyday cognition. African American (n = 727) and White (n = 2052) older adults from the ACTIVE clinical trial were given the Observed Tasks of Daily Living (OTDL; a performance-based measure of medication management/finances/telephone use) at baseline and 1-, 2-, 3-, 5-, and 10-year follow-ups. When participants said “I don't know” or did not respond, they received a standardised verbal prompt, which served only as a cue to initiate the first step. At each occasion, unprompted (sum of items correct without prompting) and prompted (sum of correct prompted and unprompted items) scores were derived for each participant. Mixed effects models for change were used to determine the age trajectories of OTDL performance by race. When not prompted, African Americans demonstrated more rapid decline in OTDL performance than Whites, especially after age 80. When prompted, both groups had improved performance and evinced shallower decline, although African Americans continued to demonstrate a slightly more rapid decline. Simple prompting attenuated age-related changes of African Americans and Whites on a measure of everyday cognition. Prompting may be especially helpful for older African Americans. PMID:26480946

Age trajectories of everyday cognition in African American and White older adults under prompted and unprompted conditions.

PubMed

Thomas, Kelsey R; Marsiske, Michael

2017-06-01

We investigated how race and verbal prompting interacted with age to predict age trajectories on a performance-based measure of everyday cognition. African American (n = 727) and White (n = 2052) older adults from the ACTIVE clinical trial were given the Observed Tasks of Daily Living (OTDL; a performance-based measure of medication management/finances/telephone use) at baseline and 1-, 2-, 3-, 5-, and 10-year follow-ups. When participants said "I don't know" or did not respond, they received a standardised verbal prompt, which served only as a cue to initiate the first step. At each occasion, unprompted (sum of items correct without prompting) and prompted (sum of correct prompted and unprompted items) scores were derived for each participant. Mixed effects models for change were used to determine the age trajectories of OTDL performance by race. When not prompted, African Americans demonstrated more rapid decline in OTDL performance than Whites, especially after age 80. When prompted, both groups had improved performance and evinced shallower decline, although African Americans continued to demonstrate a slightly more rapid decline. Simple prompting attenuated age-related changes of African Americans and Whites on a measure of everyday cognition. Prompting may be especially helpful for older African Americans.

Plasma Klotho and Cognitive Decline in Older Adults: Findings From the InCHIANTI Study

PubMed Central

Semba, Richard D.; Rosano, Caterina; Kalyani, Rita R.; Bandinelli, Stefania; Chia, Chee W.; Ferrucci, Luigi

2016-01-01

Background. The hormone klotho, encoded by the gene klotho, is primarily expressed in the kidney and choroid plexus of the brain. Higher klotho concentrations and certain genetic variants of klotho have been linked to better cognition; however, it is unknown whether klotho relates prospectively to slower cognitive decline in older adults. Methods: Plasma klotho was measured in 833 participants aged 55 or older without dementia enrolled in InCHIANTI, a prospective cohort study comprising Italian adults. Cognition was measured by Mini-Mental State Examination (MMSE) and Trail-Making Tests A and B (Trails A and Trails B) at enrollment and at 3 and 6 years after enrollment. We assessed whether klotho concentrations measured at the 3-year visit related to cognition and cognitive decline. Results: Each additional natural logarithm of klotho (pg/mL) was associated with 35% lower risk of meaningful decline in MMSE, defined as decline exceeding three points (relative risk = 0.65; 95% confidence interval 0.45, 0.95; p value = .02), and 0.75-point smaller average 3-year decline (baseline to 3-year visit) in MMSE (95% confidence interval 0.02, 1.48; p value = .04). No statistically significant associations were found between klotho and declining Trails A (relative risk = 0.99; 95% confidence interval 0.75, 1.32; p value = .97) and B (relative risk = 1.02; 95% confidence interval 0.84, 1.24; p value = .82). Conclusions: Higher plasma klotho concentrations were associated with lower risk of meaningful decline and smaller average decline in MMSE. We did not observe such findings with Trails A and B, perhaps because they test executive function and motor skills, whereas MMSE measures global cognition. Future studies should investigate mechanisms through which klotho may affect domain-specific cognitive changes. PMID:26297657

Self-Reported Decline in Everyday Function, Cognitive Symptoms, and Cognitive Function in People With HIV.

PubMed

Laverick, Rosanna; Haddow, Lewis; Daskalopoulou, Marina; Lampe, Fiona; Gilson, Richard; Speakman, Andrew; Antinori, Andrea; Bruun, Tina; Vassilenko, Anna; Collins, Simon; Rodger, Alison

2017-11-01

We determined factors associated with self-reported decline in activities of daily living (ADLs) and symptoms of cognitive impairment in HIV positive adults in 5 European clinics. HIV+ adults underwent computerized and pen-and-paper neuropsychological tests and questionnaires of cognitive symptoms and ADLs. We considered cognitive function in 5 domains, psychosocial factors, and clinical parameters as potentially associated with symptoms. Separate regression analyses were used to determine factors associated with a decline in ADL (defined as self-reported decline affecting ≥2 ADLs and attributed to cognitive difficulties) and self-reported frequency of symptoms of cognitive impairment. We also estimated the diagnostic accuracy of both questionnaires as tests for cognitive impairment. Four hundred forty-eight patients completed the assessments [mean age 45.8 years, 84% male, 87% white, median CD4 count 550 cells/mm, median time since HIV diagnosis 9.9 years, 81% virologically suppressed (HIV-1 plasma RNA <50 copies/mL)]. Ninety-six (21.4%) reported decline in ADLs and attributed this to cognitive difficulties. Self-reported decline in ADLs and increased symptoms of cognitive impairment were both associated with worse performance on some cognitive tests. There were also strong associations with financial difficulties, depressive and anxiety symptoms, unemployment, and longer time since HIV diagnosis. Both questionnaires performed poorly as diagnostic tests for cognitive impairment. Patients' own assessments of everyday function and symptoms were associated with objectively measured cognitive function. However, there were strong associations with other psychosocial issues including mood and anxiety disorders and socioeconomic hardship. This should be considered when assessing HIV-associated cognitive impairment in clinical care or research studies.

Affective problems and decline in cognitive state in older adults: a systematic review and meta-analysis.

PubMed

John, A; Patel, U; Rusted, J; Richards, M; Gaysina, D

2018-05-24

Evidence suggests that affective problems, such as depression and anxiety, increase risk for late-life dementia. However, the extent to which affective problems influence cognitive decline, even many years prior to clinical diagnosis of dementia, is not clear. The present study systematically reviews and synthesises the evidence for the association between affective problems and decline in cognitive state (i.e., decline in non-specific cognitive function) in older adults. An electronic search of PubMed, PsycInfo, Cochrane, and ScienceDirect was conducted to identify studies of the association between depression and anxiety separately and decline in cognitive state. Key inclusion criteria were prospective, longitudinal designs with a minimum follow-up period of 1 year. Data extraction and methodological quality assessment using the STROBE checklist were conducted independently by two raters. A total of 34 studies (n = 71 244) met eligibility criteria, with 32 studies measuring depression (n = 68 793), and five measuring anxiety (n = 4698). A multi-level meta-analysis revealed that depression assessed as a binary predictor (OR 1.36, 95% CI 1.05-1.76, p = 0.02) or a continuous predictor (B = -0.008, 95% CI -0.015 to -0.002, p = 0.012; OR 0.992, 95% CI 0.985-0.998) was significantly associated with decline in cognitive state. The number of anxiety studies was insufficient for meta-analysis, and they are described in a narrative review. Results of the present study improve current understanding of the temporal nature of the association between affective problems and decline in cognitive state. They also suggest that cognitive function may need to be monitored closely in individuals with affective disorders, as these individuals may be at particular risk of greater cognitive decline.

Genetic influences on cognitive decline in Parkinson's disease

PubMed Central

Morley, J.F.; Xie, S.X.; Hurtig, H.I.; Stern, M.B.; Colcher, A.; Horn, S.; Dahodwala, N.; Duda, J.E.; Weintraub, D.; Chen-Plotkin, A.S.; Van Deerlin, V.; Falcone, D.; Siderowf, A.

2012-01-01

Background The role of genetic factors in cognitive decline associated with Parkinson's disease is unclear. We examined whether variations in apolipoprotein E, microtubule-associated protein tau or catechol-O-methytransferase genotypes are associated with cognitive decline in Parkinson's disease. Methods We performed a prospective cohort study of 212 patients with a clinical diagnosis of Parkinson's disease. The primary outcome was change in Mattis Dementia Rating Scale version 2 score. Linear mixed-effects models and survival analysis were used to test for associations between genotypes and change in cognitive function over time. Results The ε4 allele of apoliporotein E was associated with more rapid decline (loss of 2.9 (95% CI, 1.7–4.1) more points/year, p<0.001) in total score and an increased risk of a ≥10 pointdrop during the follow-up period (HR 2.8, 95% CI 1.4–5.4, p=0.003). Microtubule-associated protein tau haplotype and catechol-O-methytransferase genotype were associated with measures of memory and attention, respectively, over the entire followup period but not with the overall rate of cognitive decline. Conclusion These results confirm and extend previously described genetic associations with cognitive decline in Parkinson's disease and imply that individual genes may exert effects on specific cognitive domains or at different disease stages. Carrying at least one apolipoprotein E ε4 allele is associated with more rapid cognitive decline in Parkinson's disease, supporting the idea of a component of shared etiology between Parkinson's disease dementia and Alzheimer disease. Clinically, these results suggest genotyping can provide information about the risk of future cognitive decline for Parkinson's disease patients. PMID:22344634

Linking late cognitive outcome with glioma surgery location using resection cavity maps.

PubMed

Hendriks, Eef J; Habets, Esther J J; Taphoorn, Martin J B; Douw, Linda; Zwinderman, Aeilko H; Vandertop, W Peter; Barkhof, Frederik; Klein, Martin; De Witt Hamer, Philip C

2018-05-01

Patients with a diffuse glioma may experience cognitive decline or improvement upon resective surgery. To examine the impact of glioma location, cognitive alteration after glioma surgery was quantified and related to voxel-based resection probability maps. A total of 59 consecutive patients (range 18-67 years of age) who had resective surgery between 2006 and 2011 for a supratentorial nonenhancing diffuse glioma (grade I-III, WHO 2007) were included in this observational cohort study. Standardized neuropsychological examination and MRI were obtained before and after surgery. Intraoperative stimulation mapping guided resections towards neurological functions (language, sensorimotor function, and visual fields). Maps of resected regions were constructed in standard space. These resection cavity maps were compared between patients with and without new cognitive deficits (z-score difference >1.5 SD between baseline and one year after resection), using a voxel-wise randomization test and calculation of false discovery rates. Brain regions significantly associated with cognitive decline were classified in standard cortical and subcortical anatomy. Cognitive improvement in any domain occurred in 10 (17%) patients, cognitive decline in any domain in 25 (42%), and decline in more than one domain in 10 (17%). The most frequently affected subdomains were attention in 10 (17%) patients and information processing speed in 9 (15%). Resection regions associated with decline in more than one domain were predominantly located in the right hemisphere. For attention decline, no specific region could be identified. For decline in information speed, several regions were found, including the frontal pole and the corpus callosum. Cognitive decline after resective surgery of diffuse glioma is prevalent, in particular, in patients with a tumor located in the right hemisphere without cognitive function mapping. © The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

The Relationship of Bilingualism Compared to Monolingualism to the Risk of Cognitive Decline or Dementia: A Systematic Review and Meta-Analysis.

PubMed

Mukadam, Naaheed; Sommerlad, Andrew; Livingston, Gill

2017-01-01

Bilingualism may contribute to cognitive reserve, protect against cognitive decline, and delay the onset of dementia. We systematically reviewed evidence about the effect of bilingualism on subsequent cognitive decline or dementia. We searched electronic databases and references for longitudinal studies comparing cognitive decline in people who were bilingual with those who were monolingual and evaluated study quality. We conducted meta-analyses using random effects models to calculate pooled odds ratio of incident dementia. We included 13/1,156 eligible articles. Meta-analysis of prospective studies of the effects of bilingualism on future dementia gave a combined Odds Ratio of dementia of 0.96 (95% CI 0.74-1.23) in bilingual participants (n = 5,527) compared to monolinguals. Most retrospective studies found that bilingual people were reported to develop symptoms of cognitive decline at a later age than monolingual participants. We did not find that bilingualism protects from cognitive decline or dementia from prospective studies. Retrospective studies are more prone to confounding by education, or cultural differences in presentation to dementia services and are therefore not suited to establishing causative links between risk factors and outcomes.

Does a patent foramen ovale influence cognitive function in dialysis patients?

PubMed

George, Sudhakar; Holt, Stephen; Medford, Nick; Hildick-Smith, David

2013-01-01

Patients with chronic kidney disease on dialysis treatment have poorer cognitive function than age- and sex-matched controls. One proposed mechanism is cerebral microembolisation due to material from the dialysis circuit crossing a patent foramen ovale (PFO). Cognitive testing was carried out in haemodialysis (HD) patients and peritoneal dialysis (PD) patients. Transthoracic echocardiography was used to identify PFO. Follow-up testing 1 year later enabled comparison of cognitive decline between patients with and without a PFO, and between those undergoing different dialysis modalities. 80 patients (aged 60.4 ± 15.0 years) were recruited (51 HD patients and 29 PD controls). A PFO was found in 21% of patients. 83% of dialysis patients suffered a decline in one or more cognitive function tests over 1 year. There was a significant difference in only one test between HD patients with or without a PFO. PD patients showed a more rapid cognitive decline than those on HD. Cognitive decline in dialysis patients is rapid and affects most patients. The presence of a PFO made only subtle differences to the rates of cognitive decline during 1 year of follow-up. Patients with a PFO should not be prevented from considering HD because of concerns of cerebral decline due to microembolisation. Copyright © 2013 S. Karger AG, Basel.

Daily Stress Magnifies the Association between Cognitive Decline and Everyday Memory Problems: An Integration of Longitudinal and Diary Methods

PubMed Central

Rickenbach, Elizabeth H.; Almeida, David M.; Seeman, Teresa E.; Lachman, Margie E.

2014-01-01

We examined whether long-term fluid cognitive decline was associated with memory problems in everyday life, and whether stress plays a moderating role. We expected that the association between cognitive decline and everyday memory problems would be magnified in the context of self-reported and physiological stress. Data are from the Boston Longitudinal Study, a subsample of the Midlife in the United States study. Participants in the current study (n=112) completed a battery of tests measuring fluid cognitive functioning at Time 1 (T1) and 2 (T2) over ten years. At T2, participants completed weekly diaries of self-reported daily stressors and everyday memory problems for twelve consecutive weeks. Also at T2, participants provided four saliva samples over the course of one day to assess physiological stress using diurnal cortisol profiles [cortisol awakening response (CAR) and diurnal cortisol slope (DCS)]. Self-reported daily stressors and a less healthy DCS were associated with more everyday memory problems, and participants with greater cognitive decline reported more memory problems compared to those with less or no decline. Self-reported daily stressors and CAR moderated the relationship of cognitive decline and memory problems. As expected, more cognitive decline was associated with greater increases in memory problems on weeks when individuals reported more daily stressors and for individuals with a less healthy CAR. The current findings can inform interventions aimed to identify factors, such as daily stress, that contribute to daily functioning in the context of cognitive decline. PMID:25365691

Anxiety symptoms in amnestic mild cognitive impairment are associated with medial temporal atrophy and predict conversion to Alzheimer disease.

PubMed

Mah, Linda; Binns, Malcolm A; Steffens, David C

2015-05-01

To test the hypothesis that anxiety in amnestic mild cognitive impairment (aMCI) increases rates of conversion to Alzheimer disease (AD) and to identify potential neural mechanisms underlying such an association. Participants (N = 376) with aMCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were studied over a median period of 36 months. A Cox proportional-hazards model was used to assess the association between anxiety severity ratings on the Neuropsychiatric Inventory Questionnaire and AD risk. Other variables were depression, memory loss, and MRI-derived AD-related regions of interest (ROIs), including hippocampal, amygdalar, entorhinal cortical (EC) volumes, and EC thickness, In addition, a linear regression model was used to determine the effect of anxiety in aMCI on rates of atrophy within ROIs. Anxiety severity increased rate of aMCI conversion to AD, after controlling for depression and cognitive decline. The association between anxiety and AD remained significant even with inclusion of ROI baseline values or atrophy rates as explanatory variables. Further, anxiety status predicted greater rates of decrease in EC volume. An association between anxiety and EC thickness missed significance. Anxiety symptoms in aMCI predict conversion to AD, over and beyond the effects of depression, memory loss, or atrophy within AD neuroimaging biomarkers. These findings, together with the greater EC atrophy rate predicted by anxiety, are compatible with the hypothesis that anxiety is not a prodromal noncognitive feature of AD but may accelerate decline toward AD through direct or indirect effects on EC. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Corpus callosum atrophy as a predictor of age-related cognitive and motor impairment: a 3-year follow-up of the LADIS study cohort.

PubMed

Ryberg, C; Rostrup, E; Paulson, O B; Barkhof, F; Scheltens, P; van Straaten, E C W; van der Flier, W M; Fazekas, F; Schmidt, R; Ferro, J M; Baezner, H; Erkinjuntti, T; Jokinen, H; Wahlund, L-O; Poggesi, A; Pantoni, L; Inzitari, D; Waldemar, G

2011-08-15

The aim of this 3-year follow-up study was to investigate whether corpus callosum (CC) atrophy may predict future motor and cognitive impairment in an elderly population. On baseline MRI from 563 subjects with age-related white matter changes (ARWMC) from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented and subdivided into five anterior-posterior regions (CC1-CC5). Associations between the CC areas and decline in motor performance and cognitive functions over a 3-year period were analyzed. CC atrophy at baseline was significantly associated with impaired cognitive performance (p<0.01 for CC1, p<0.05 for CC5), motor function (p<0.05 for CC2 and CC5), and walking speed (p<0.01 for CC2 and CC5, p<0.05 for CC3 and total CC), and with development of dementia at 3 years (p<0.05 for CC1) after correction for appropriate confounders (ARWMC volume, atrophy, age, gender and handedness). In conclusion, CC atrophy, an indicator of reduced functional connectivity between cortical areas, seems to contribute, independently of ARWMC load, to future cognitive and motor decline in the elderly. Copyright © 2011 Elsevier B.V. All rights reserved.

Cognitive decline following incident and preexisting diabetes mellitus in a population sample.

PubMed

Rajan, Kumar B; Arvanitakis, Zoe; Lynch, Elizabeth B; McAninch, Elizabeth A; Wilson, Robert S; Weuve, Jennifer; Barnes, Lisa L; Bianco, Antonio C; Evans, Denis A

2016-10-18

To examine if incident and preexisting diabetes mellitus (DM) were associated with cognitive decline among African Americans (AAs) and European Americans (EAs). Based on a prospective study of 7,740 older adults (mean age 72.3 years, 64% AA, 63% female), DM was ascertained by hypoglycemic medication use and Medicare claims during physician or hospital visits, and cognition by performance on a brief battery for executive functioning, episodic memory, and Mini-Mental State Examination (MMSE). Decline in composite and individual tests among those with incident DM, with preexisting DM, and without DM was studied using a linear mixed effects model with and without change point. At baseline, 737 (15%) AAs and 269 (10%) EAs had preexisting DM. Another 721 (17%) AAs and 289 (12%) EAs had incident DM in old age. Following incident DM, cognitive decline increased by 36% among AAs and by 40% among EAs compared to those without DM. No significant difference was observed between AAs and EAs (p = 0.64). However, cognitive decline increased by 17% among AAs with preexisting DM compared to those without DM, but no increased decline was observed among EAs with preexisting DM. In secondary analyses, faster decline in executive functioning and episodic memory was observed following incident DM. In old age, faster cognitive decline was present among AAs and EAs following incident DM, compared to cognitive decline prior to DM, and among those without DM. This underscores the need for stronger prevention and control of DM in old age. © 2016 American Academy of Neurology.

Association of Crossword Puzzle Participation with Memory Decline in Persons Who Develop Dementia

PubMed Central

Pillai, Jagan A.; Hall, Charles B.; Dickson, Dennis W.; Buschke, Herman; Lipton, Richard B.; Verghese, Joe

2013-01-01

Participation in cognitively stimulating leisure activities such as crossword puzzles may delay onset of the memory decline in the preclinical stages of dementia, possibly via its effect on improving cognitive reserve. We followed 488 initially cognitively intact community residing individuals with clinical and cognitive assessments every 12–18 months in the Bronx Aging Study. We assessed the influence of crossword puzzle participation on the onset of accelerated memory decline as measured by the Buschke Selective Reminding Test in 101 individuals who developed incident dementia using a change point model. Crossword puzzle participation at baseline delayed onset of accelerated memory decline by 2.54 years. Inclusion of education or participation in other cognitively stimulating activities did not significantly add to the fit of the model beyond the effect of puzzles. Our findings show that late life crossword puzzle participation, independent of education, was associated with delayed onset of memory decline in persons who developed dementia. Given the wide availability and accessibility of crossword puzzles, their role in preventing cognitive decline should be validated in future clinical trials. PMID:22040899

Associations between cognitively stimulating leisure activities, cognitive function and age-related cognitive decline.

PubMed

Ferreira, Nicola; Owen, Adrian; Mohan, Anita; Corbett, Anne; Ballard, Clive

2015-04-01

Emerging literature suggests that lifestyle factors may play an important role in reducing age-related cognitive decline. There have, however, been few studies investigating the role of cognitively stimulating leisure activities in maintaining cognitive health. This study sought to identify changes in cognitive performance with age and to investigate associations of cognitive performance with several key cognitively stimulating leisure activities. Over 65,000 participants provided demographic and lifestyle information and completed tests of grammatical reasoning, spatial working memory, verbal working memory and episodic memory. Regression analyses suggested that frequency of engaging in Sudoku or similar puzzles was significantly positively associated with grammatical reasoning, spatial working memory and episodic memory scores. Furthermore, for participants aged under 65 years, frequency of playing non-cognitive training computer games was also positively associated with performance in the same cognitive domains. The results also suggest that grammatical reasoning and episodic memory are particularly vulnerable to age-related decline. Further investigation to determine the potential benefits of participating in Sudoku puzzles and non-cognitive computer games is indicated, particularly as they are associated with grammatical reasoning and episodic memory, cognitive domains found to be strongly associated with age-related cognitive decline. Results of this study have implications for developing improved guidance for the public regarding the potential value of cognitively stimulating leisure activities. The results also suggest that grammatical reasoning and episodic memory should be targeted in developing appropriate outcome measures to assess efficacy of future interventions, and in developing cognitive training programmes to prevent or delay cognitive decline. Copyright © 2014 John Wiley & Sons, Ltd.

Understanding the gender gap: Social cognitive changes during an introductory stem course.

PubMed

Hardin, Erin E; Longhurst, Melanie O

2016-03-01

Despite robust support for the basic theoretical model of social cognitive career theory (Lent, Brown, & Hackett, 1994) and predictions that, for example, increases (or declines) in self-efficacy would lead to subsequent increases (or declines) in interest, there has been surprisingly little longitudinal research that has directly examined the extent to which members of different groups (e.g., women and men) actually do experience changes in critical social-cognitive variables over time early in their curricula in the fields of science, technology, engineering, and mathematics (STEM). Knowing the extent to which such changes occur in typical introductory undergraduate courses is important for targeting interventions to increase persistence of underrepresented groups in STEM. We measured social-cognitive-career-theory-relevant variables near the middle and at the end of the 1st semester of a gateway introductory chemistry course and found that women had lower STEM self-efficacy, coping self-efficacy, and STEM interest than did men, even after controlling for actual course performance. Although there were no detrimental changes across the semester for women or men, men experienced a small but significant increase in their perceived support for pursuing a STEM degree, whereas women did not. (c) 2016 APA, all rights reserved).

Functional magnetic resonance imaging of semantic memory as a presymptomatic biomarker of Alzheimer's disease risk.

PubMed

Sugarman, Michael A; Woodard, John L; Nielson, Kristy A; Seidenberg, Michael; Smith, J Carson; Durgerian, Sally; Rao, Stephen M

2012-03-01

Extensive research efforts have been directed toward strategies for predicting risk of developing Alzheimer's disease (AD) prior to the appearance of observable symptoms. Existing approaches for early detection of AD vary in terms of their efficacy, invasiveness, and ease of implementation. Several non-invasive magnetic resonance imaging strategies have been developed for predicting decline in cognitively healthy older adults. This review will survey a number of studies, beginning with the development of a famous name discrimination task used to identify neural regions that participate in semantic memory retrieval and to test predictions of several key theories of the role of the hippocampus in memory. This task has revealed medial temporal and neocortical contributions to recent and remote memory retrieval, and it has been used to demonstrate compensatory neural recruitment in older adults, apolipoprotein E ε4 carriers, and amnestic mild cognitive impairment patients. Recently, we have also found that the famous name discrimination task provides predictive value for forecasting episodic memory decline among asymptomatic older adults. Other studies investigating the predictive value of semantic memory tasks will also be presented. We suggest several advantages associated with the use of semantic processing tasks, particularly those based on person identification, in comparison to episodic memory tasks to study AD risk. Future directions for research and potential clinical uses of semantic memory paradigms are also discussed. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease. Copyright © 2011 Elsevier B.V. All rights reserved.

Cognitive decline and dementia in the oldest-old.

PubMed

Kravitz, Efrat; Schmeidler, James; Beeri, Michal Schnaider

2012-10-01

The oldest-old are the fastest growing segment of the Western population. Over half of the oldest-old will have dementia, but the etiology is yet unknown. Age is the only risk factor consistently associated with dementia in the oldest-old. Many of the risk and protective factors for dementia in the young elderly, such as ApoE genotype, physical activity, and healthy lifestyle, are not relevant for the oldest-old. Neuropathology is abundant in the oldest-old brains, but specific pathologies of Alzheimer's disease (AD) or vascular dementia are not necessarily correlated with cognition, as in younger persons. It has been suggested that accumulation of both AD-like and vascular pathologies, loss of synaptic proteins, and neuronal loss contribute to the cognitive decline observed in the oldest-old. Several characteristics of the oldest-old may confound the diagnosis of dementia in this age group. A gradual age-related cognitive decline, particularly in executive function and mental speed, is evident even in non-demented oldest-old. Hearing and vision losses, which are also prevalent in the oldest-old and found in some cases to precede/predict cognitive decline, may mechanically interfere in neuropsychological evaluations. Difficulties in carrying out everyday activities, observed in the majority of the oldest-old, may be the result of motor or physical dysfunction and of neurodegenerative processes. The oldest-old appear to be a select population, who escapes major illnesses or delays their onset and duration toward the end of life. Dementia in the oldest-old may be manifested when a substantial amount of pathology is accumulated, or with a composition of a variety of pathologies. Investigating the clinical and pathological features of dementia in the oldest-old is of great importance in order to develop therapeutic strategies and to provide the most elderly of our population with good quality of life.

Cognitive Decline and Dementia in the Oldest-Old

PubMed Central

Kravitz, Efrat; Schmeidler, James; Beeri, Michal Schnaider

2012-01-01

The oldest-old are the fastest growing segment of the Western population. Over half of the oldest-old will have dementia, but the etiology is yet unknown. Age is the only risk factor consistently associated with dementia in the oldest-old. Many of the risk and protective factors for dementia in the young elderly, such as ApoE genotype, physical activity, and healthy lifestyle, are not relevant for the oldest-old. Neuropathology is abundant in the oldest-old brains, but specific pathologies of Alzheimer’s disease (AD) or vascular dementia are not necessarily correlated with cognition, as in younger persons. It has been suggested that accumulation of both AD-like and vascular pathologies, loss of synaptic proteins, and neuronal loss contribute to the cognitive decline observed in the oldest-old. Several characteristics of the oldest-old may confound the diagnosis of dementia in this age group. A gradual age-related cognitive decline, particularly in executive function and mental speed, is evident even in non-demented oldest-old. Hearing and vision losses, which are also prevalent in the oldest-old and found in some cases to precede/predict cognitive decline, may mechanically interfere in neuropsychological evaluations. Difficulties in carrying out everyday activities, observed in the majority of the oldest-old, may be the result of motor or physical dysfunction and of neurodegenerative processes. The oldest-old appear to be a select population, who escapes major illnesses or delays their onset and duration toward the end of life. Dementia in the oldest-old may be manifested when a substantial amount of pathology is accumulated, or with a composition of a variety of pathologies. Investigating the clinical and pathological features of dementia in the oldest-old is of great importance in order to develop therapeutic strategies and to provide the most elderly of our population with good quality of life. PMID:23908850

Can psychosocial work conditions protect against age-related cognitive decline? Results from a systematic review.

PubMed

Nexø, Mette Andersen; Meng, Annette; Borg, Vilhelm

2016-07-01

According to the use it or lose it hypothesis, intellectually stimulating activities postpone age-related cognitive decline. A previous systematic review concluded that a high level of mental work demands and job control protected against cognitive decline. However, it did not distinguish between outcomes that were measured as cognitive function at one point in time or as cognitive decline. Our study aimed to systematically review which psychosocial working conditions were prospectively associated with high levels of cognitive function and/or changes in cognitive function over time. Articles were identified by a systematic literature search (MEDLINE, Web of Science (WOS), PsycNET, Occupational Safety and Health (OSH)). We included only studies with longitudinal designs examining the impact of psychosocial work conditions on outcomes defined as cognitive function or changes in cognitive function. Two independent reviewers compared title-abstract screenings, full-text screenings and quality assessment ratings. Eleven studies were included in the final synthesis and showed that high levels of mental work demands, occupational complexity or job control at one point in time were prospectively associated with higher levels of cognitive function in midlife or late life. However, the evidence to clarify whether these psychosocial factors also affected cognitive decline was insufficient, conflicting or weak. It remains speculative whether job control, job demands or occupational complexity can protect against cognitive decline. Future studies using methodological advancements can reveal whether workers gain more cognitive reserve in midlife and late life than the available evidence currently suggests. The public health implications of a previous review should thereby be redefined accordingly. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The effects of soy milk and isoflavone supplements on cognitive performance in healthy, postmenopausal women.

PubMed

Fournier, L R; Ryan Borchers, T A; Robison, L M; Wiediger, M; Park, J S; Chew, B P; McGuire, M K; Sclar, D A; Skaer, T L; Beerman, K A

2007-01-01

The decline in estrogen concentrations in women after menopause can contribute to health related changes including impairments in cognition, especially memory. Because of the health concerns related to hormone replacement therapy (HRT), alternative approaches to treat menopausal symptoms, such as nutritional supplements and/or diet containing isoflavones, are of interest. This study investigated whether soy isoflavones (soy milk and supplement) could improve cognitive functioning in healthy, postmenopausal women. PARTICIPANTS, INTERVENTION AND DESIGN: A total of 79 postmenopausal women, 48-65 years of age, completed a double-blind, placebo-controlled trial in which they were randomly assigned to one of three experimental groups: cow's milk and a placebo supplement (control); soy milk and placebo supplement (soy milk, 72 mg isoflavones/day); or cow's milk and isoflavone supplement (isoflavone supplement, 70 mg isoflavones/day). Cognitive functioning was assessed using various cognitive tasks before the intervention (baseline) and after the intervention (test). In contrast to predictions, soy isoflavones did not improve selective attention (Stroop task), visual long-term memory (pattern recognition), short-term visuospatial memory (Benton Visual Retention Test), or visuo-spatial working memory (color match task). Also, the soy milk group showed a decline in verbal working memory (Digit Ordering Task) compared to the soy supplement and control groups. Soy isoflavones consumed as a food or supplement over a 16-week period did not improve or appreciably affect cognitive functioning in healthy, postmenopausal women.

Alzheimer Disease Cerebrospinal Fluid Biomarkers Moderate Baseline Differences and Predict Longitudinal Change in Attentional Control and Episodic Memory Composites in the Adult Children Study

PubMed Central

Aschenbrenner, Andrew J.; Balota, David A.; Fagan, Anne M.; Duchek, Janet M.; Benzinger, Tammie L.S.; Morris, John C.

2015-01-01

Objective Cognitive measures that are sensitive to biological markers of Alzheimer disease (AD) pathology are needed in order to (a) facilitate preclinical staging, (b) identify individuals who are at the highest risk for developing clinical symptoms and (c) serve as endpoints for evaluating the efficacy of interventions. The present study assesses the utility of two cognitive composite scores of attentional control and episodic memory as markers for preclinical AD pathology in a group of cognitively normal older adults (N = 238), as part of the Adult Children Study. Method All participants were given a baseline cognitive assessment and follow-up assessments every 3 years over an 8-year period, as well as a lumbar puncture within two years of the initial assessment to collect cerebrospinal fluid (CSF) and a PET-PIB scan for amyloid imaging. Results Results indicated that attentional control was correlated with levels of Aβ42 at the initial assessment whereas episodic memory was not. Longitudinally, individuals with high CSF tau exhibited a decline in both attention and episodic memory over the course of the study. Conclusion These results indicate that measures of attentional control and episodic memory can be utilized to evaluate cognitive decline in preclinical AD and provide support that CSF tau may be a key mechanism driving longitudinal cognitive change. PMID:26416094

Alzheimer Disease Cerebrospinal Fluid Biomarkers Moderate Baseline Differences and Predict Longitudinal Change in Attentional Control and Episodic Memory Composites in the Adult Children Study.

PubMed

Aschenbrenner, Andrew J; Balota, David A; Fagan, Anne M; Duchek, Janet M; Benzinger, Tammie L S; Morris, John C

2015-09-01

Cognitive measures that are sensitive to biological markers of Alzheimer disease (AD) pathology are needed to (a) facilitate preclinical staging, (b) identify individuals who are at the highest risk for developing clinical symptoms, and (c) serve as endpoints for evaluating the efficacy of interventions. The present study assesses the utility of two cognitive composite scores of attentional control and episodic memory as markers for preclinical AD pathology in a group of cognitively normal older adults (N = 238), as part of the Adult Children Study. All participants were given a baseline cognitive assessment and follow-up assessments every 3 years over an 8-year period, as well as a lumbar puncture within 2 years of the initial assessment to collect cerebrospinal fluid (CSF) and amyloid tracer Pittsburgh compound-B scan for amyloid imaging. Results indicated that attentional control was correlated with levels of Aβ42 at the initial assessment whereas episodic memory was not. Longitudinally, individuals with high CSF tau exhibited a decline in both attention and episodic memory over the course of the study. These results indicate that measures of attentional control and episodic memory can be used to evaluate cognitive decline in preclinical AD and provide support that CSF tau may be a key mechanism driving longitudinal cognitive change.

Personality stability is associated with better cognitive performance in adulthood: are the stable more able?

PubMed

Graham, Eileen K; Lachman, Margie E

2012-09-01

Although personality is relatively stable over time, there are individual differences in the patterns and magnitude of change. There is some evidence that personality change in adulthood is related to physical health and longevity. The present study expanded this work to consider whether personality stability or change would be associated with better cognitive functioning, especially in later adulthood. A total of 4,974 individuals participated in two waves of The Midlife in the United States Study (MIDUS) in 1994-1995 and 2004-2005. Participants completed the MIDUS personality inventory at both times and the Brief Test of Adult Cognition by Telephone cognitive battery at Time 2. Multiple regression and analysis of covariance analyses showed that, consistent with predictions, individuals remaining stable in openness to experience and neuroticism had faster reaction times and better inductive reasoning than those who changed. Among older adults, those who remained stable or decreased in neuroticism had significantly faster reaction times than those who increased. As predicted, personality stability on some traits was associated with more adaptive cognitive performance on reasoning and reaction time. Personality is discussed as a possible resource for protecting against or minimizing age-related declines in cognition.

Perioperative Embolization Load and S-100β Do Not Predict Cognitive Outcome after Carotid Revascularization.

PubMed

Plessers, Maarten; Van Herzeele, Isabelle; Hemelsoet, Dimitri; Vingerhoets, Guy; Vermassen, Frank

2016-10-01

Cognitive changes after carotid revascularization have been reported in 10-20% of patients. The etiology of cognitive impairments remains largely unknown. This study evaluates the predictive value of S-100β serum values and perioperative microembolization on cognition after carotid revascularization. Forty-six patients with significant carotid stenosis underwent carotid endarterectomy (CEA, n = 26), transfemoral carotid artery stenting with distal protection (CASdp, n = 10), or transcervical carotid stenting with dynamic flow reversal (CASfr, n = 10). Twenty-six matched vascular patients without carotid stenosis were recruited as controls. All patients underwent comprehensive cognitive testing on the day before and 1 month after carotid revascularization. S-100β analysis was performed in 31 cases pre-, peri-, and 2, 6, and 24 hr after carotid surgery, and in 25 patients transcranial Doppler monitoring was done during surgery. In the 3 treatment groups similar transient increases in S-100β values were observed. CASdp was associated with a higher embolic load than CEA and CASfr, while CEA was also associated with less microembolization than CASfr. Cognitive improvement or deterioration could not be predicted by S-100β or perioperative embolic load for any of the investigated cognitive domains. Cognitive deterioration could not be predicted using perioperative embolic load and S-100β changes. A similar inverted u-curve of the S-100β levels was observed in the 3 groups and may be caused by impairment in the blood-brain barrier during intervention, and not due to cerebral infarction. Distal protection CAS is associated with a higher embolic load than transcervical CAS using dynamic flow reversal and CEA, but the long-term impact of this higher embolic load is yet unknown. Perfusion-related measures seem promising in their ability to predict cognitive decline. Copyright © 2016 Elsevier Inc. All rights reserved.

Dietary Sodium/Potassium Intake Does Not Affect Cognitive Function or Brain Imaging Indices.

PubMed

Nowak, Kristen L; Fried, Linda; Jovanovich, Anna; Ix, Joachim; Yaffe, Kristine; You, Zhiying; Chonchol, Michel

2018-01-01

Dietary sodium may influence cognitive function through its effects on cerebrovascular function and cerebral blood flow. The aim of this study was to evaluate the association of dietary sodium intake with cognitive decline in community-dwelling older adults. We also evaluated the associations of dietary potassium and sodium:potassium intake with cognitive decline, and associations of these nutrients with micro- and macro-structural brain magnetic resonance imaging (MRI) indices. In all, 1,194 participants in the Health Aging and Body Composition study with measurements of dietary sodium intake (food frequency questionnaire [FFQ]) and change in the modified Mini Mental State Exam (3MS) were included. The age of participants was 74 ± 3 years with a mean dietary sodium intake of 2,677 ± 1,060 mg/day. During follow-up (6.9 ± 0.1 years), 340 (28%) had a clinically significant decline in 3MS score (≥1.5 SD of mean decline). After adjustment, dietary sodium intake was not associated with odds of cognitive decline (OR 0.96, 95% CI 0.50-1.84 per doubling of sodium). Similarly, potassium was not associated with cognitive decline; however, higher sodium:potassium intake was associated with increased odds of cognitive decline (OR 2.02 [95% CI 1.01-4.03] per unit increase). Neither sodium or potassium alone nor sodium:potassium were associated with micro- or macro-structural brain MRI indices. These results are limited by the use of FFQ. In community-dwelling older adults, higher sodium:potassium, but not sodium or potassium intake alone, was associated with decline in cognitive function, with no associations observed with micro- and macro-structural brain MRI indices. These findings do not support reduction dietary sodium/increased potassium intake to prevent cognitive decline with aging. © 2018 S. Karger AG, Basel.

Predictors and Outcomes of Revisits in Older Adults Discharged from the Emergency Department.

PubMed

de Gelder, Jelle; Lucke, Jacinta A; de Groot, Bas; Fogteloo, Anne J; Anten, Sander; Heringhaus, Christian; Dekkers, Olaf M; Blauw, Gerard J; Mooijaart, Simon P

2018-04-01

To study predictors of emergency department (ED) revisits and the association between ED revisits and 90-day functional decline or mortality. Multicenter cohort study. One academic and two regional Dutch hospitals. Older adults discharged from the ED (N=1,093). At baseline, data on demographic characteristics, illness severity, and geriatric parameters (cognition, functional capacity) were collected. All participants were prospectively followed for an unplanned revisit within 30 days and for functional decline and mortality 90 days after the initial visit. The median age was 79 (interquartile range 74-84), and 114 participants (10.4%) had an ED revisit within 30 days of discharge. Age (hazard ratio (HR)=0.96, 95% confidence interval (CI)=0.92-0.99), male sex (HR=1.61, 95% CI=1.05-2.45), polypharmacy (HR=2.06, 95% CI=1.34-3.16), and cognitive impairment (HR=1.71, 95% CI=1.02-2.88) were independent predictors of a 30-day ED revisit. The area under the receiver operating characteristic curve to predict an ED revisit was 0.65 (95% CI=0.60-0.70). In a propensity score-matched analysis, individuals with an ED revisit were at higher risk (odds ratio=1.99 95% CI=1.06-3.71) of functional decline or mortality. Age, male sex, polypharmacy, and cognitive impairment were independent predictors of a 30-day ED revisit, but no useful clinical prediction model could be developed. However, an early ED revisit is a strong new predictor of adverse outcomes in older adults. © 2018 The Authors. The Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.

Kidney function and cognitive decline in an oldest-old Chinese population.

PubMed

Bai, Kunhao; Pan, Yujing; Lu, Fanghong; Zhao, Yingxin; Wang, Jinwei; Zhang, Luxia

2017-01-01

Early-stage chronic kidney disease has been suggested to be correlated with cognitive decline, but the association has rarely been explored in the oldest old. This prospective study included 284 Chinese participants aged 80 years or older with serum creatinine levels <150 µmol/L. The median follow-up time was 3.3 years, and 247 (87.0%) participants provided valid data at their last visit. Kidney function was evaluated by measuring the estimated glomerular filtration rate (eGFR) at baseline, and cognitive function was evaluated using the Mini-Mental State Examination (MMSE) at both baseline and annual visits. A reliable decrease in the MMSE score over the follow-up period was observed based on a Reliable Change Index of 1.645 (equivalent to a 90% confidence interval [CI]), which was used to define cognitive decline. Poisson regression models were built to analyze the association between baseline kidney function and cognitive decline. A total of 18 (7.3%) cases of incident cognitive decline were observed during the follow-up period. After adjusting for potential confounders, the relative risk of developing cognitive decline was 4.03 (95% CI 1.09-13.81) among participants with an eGFR of 30-59 mL/min/1.73 m 2 compared to participants with an eGFR of ≥60 mL/min/1.73 m 2 . Early-stage chronic kidney disease was correlated with cognitive decline in an oldest-old Chinese population.

Age identity, gender, and perceptions of decline: does feeling older lead to pessimistic dispositions about cognitive aging?

PubMed

Schafer, Markus H; Shippee, Tetyana P

2010-01-01

Drawing on past studies of age identity, this article examined whether feeling older was associated with more pessimistic views about cognitive aging. Using respondents aged 55 years and older in the Midlife Development in the United States study, we estimated a series of linear regression models to predict people's dispositions toward their cognitive aging. The main comparison is whether the effects of age identity on cognitive aging differ for men and women. Beyond the effects of chronological age, older age identities were associated with more pessimistic dispositions about cognitive aging. This relationship, however, was found only among women. Age identity shapes cognitive aging dispositions, though the gendered nature of this relationship remains somewhat unclear. The findings give further evidence about the far-reaching implications of age identity for successful aging and suggest that future work can explicate how subjective aging processes may differ by gender.

Effect of retirement on cognitive function: the Whitehall II cohort study.

PubMed

Xue, Baowen; Cadar, Dorina; Fleischmann, Maria; Stansfeld, Stephen; Carr, Ewan; Kivimäki, Mika; McMunn, Anne; Head, Jenny

2017-12-26

According to the 'use it or lose it' hypothesis, a lack of mentally challenging activities might exacerbate the loss of cognitive function. On this basis, retirement has been suggested to increase the risk of cognitive decline, but evidence from studies with long follow-up is lacking. We tested this hypothesis in a cohort of 3433 civil servants who participated in the Whitehall II Study, including repeated measurements of cognitive functioning up to 14 years before and 14 years after retirement. Piecewise models, centred at the year of retirement, were used to compare trajectories of verbal memory, abstract reasoning, phonemic verbal fluency, and semantic verbal fluency before and after retirement. We found that all domains of cognition declined over time. Declines in verbal memory were 38% faster after retirement compared to before, after taking account of age-related decline. In analyses stratified by employment grade, higher employment grade was protective against verbal memory decline while people were still working, but this 'protective effect' was lost when individuals retired, resulting in a similar rate of decline post-retirement across employment grades. We did not find a significant impact of retirement on the other cognitive domains. In conclusion, these findings are consistent with the hypothesis that retirement accelerates the decline in verbal memory function. This study points to the benefits of cognitively stimulating activities associated with employment that could benefit older people's memory.

Association Between Cognitive Decline in Older Adults and Utilization of Primary Care Physician Services in Pennsylvania

PubMed Central

Fowler, Nicole R.; Morrow, Lisa A.; Tu, Li-Chuan; Landsittel, Douglas P.; Snitz, Beth E.; Rodriquez, Eric G.; Saxton, Judith A.

2012-01-01

OBJECTIVE To assess the relationship between cognitive decline of older patients (≥65 years) and utilization of primary care physician (PCP) services over 24-months. DESIGN Retrospective analysis of prospectively collected data from a cluster randomized trial that took place from 2006 to 2010 and investigated the relationship between formal neuropsychological evaluation and patient outcomes in primary care. SETTING Twenty-four PCPs in 11 practices in southwestern Pennsylvania. Most practices were suburban and included more than 5 PCPs. PARTICIPANTS A sample of 423 primary care patients 65 years or older. MEASUREMENTS The association between the number of PCP visits and a decline in cognitive status, as determined by multivariable analyses that controlled for patient-level, physician-level, and practice-level factors (e.g., patient age, comorbidities, and symptoms of depression; practice location and size; PCP age and sex) and used a linear mixed model with a random intercept to adjust for clustering. RESULTS Over a two year follow-up, 199 patients (47.0%) experienced a decline in cognitive status. Patients with a cognitive decline had a mean of 0.69 more PCP visits than did patients without a cognitive decline (P<0.05). CONCLUSIONS Early signs of cognitive decline may be an indicator of greater utilization of primary care. Given the demographic trends, more PCPs are likely to be needed to meet the increasing needs of the older population. PMID:22798988

Diagnostic and Prognostic Utility of the Synaptic Marker Neurogranin in Alzheimer Disease

PubMed Central

Tarawneh, Rawan; D’Angelo, Gina; Crimmins, Dan; Herries, Elizabeth; Griest, Terry; Fagan, Anne M.; Zipfel, Gregory J.; Ladenson, Jack H.; Morris, John C.; Holtzman, David M.

2016-01-01

IMPORTANCE Synaptic loss is an early pathologic substrate of Alzheimer disease (AD). Neurogranin is a postsynaptic neuronal protein that has demonstrated utility as a cerebrospinal fluid (CSF) marker of synaptic loss in AD. OBJECTIVE To investigate the diagnostic and prognostic utility of CSF neurogranin levels in a large, well-characterized cohort of individuals with symptomatic AD and cognitively normal controls. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional and longitudinal observational study of cognitive decline in patients with symptomatic AD and cognitively normal controls was performed. Participants were individuals with a clinical diagnosis of early symptomatic AD and cognitively normal controls who were enrolled in longitudinal studies of aging and dementia at the Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, from January 21, 2000, through March 21, 2011. Data analysis was performed from November 1, 2013, to March 31, 2015. MAIN OUTCOMES AND MEASURES Correlations between baseline CSF biomarker levels and future cognitive decline in patients with symptomatic AD and cognitively normal controls overtime. RESULTS A total of 302 individuals (mean [SE] age, 73.1 [0.4] years) were included in this study (95 patients [52 women and 43 men] with AD and 207 controls [125 women and 82 men]). The CSF neurogranin levels differentiated patients with early symptomatic AD from controls with comparable diagnostic utility (mean [SE] area under the receiver operating characteristic curve, 0.71 [0.03]; 95% CI, 0.64–0.77) to the other CSF biomarkers. The CSF neurogranin levels correlated with brain atrophy (normalized whole-brain volumes: adjusted r = −0.38, P = .02; hippocampal volumes: adjusted r = −0.36, P = .03; entorhinal volumes: adjusted r = −0.46, P = .006; and parahippocampal volumes: adjusted r = −0.47, P = .005, n = 38) in AD and with amyloid load (r = 0.39, P = .02, n = 36) in preclinical AD. The CSF neurogranin levels predicted future cognitive impairment (adjusted hazard ratio, 1.89; 95% CI, 1.29–2.78; P = .001 as a continuous measure, and adjusted hazard ratio, 2.78; 95% CI, 1.13–5.99; P = .02 as a categorical measure using the 85th percentile cutoff value) in controls and rates of cognitive decline (Clinical Dementia Rating sum of boxes score: β estimate, 0.29; P = .001; global composite scores: β estimate, −0.11; P = .001; episodic memory scores: β estimate, −0.18; P < .001; and semantic memory scores: β estimate, −0.06; P = .04, n = 57) in patients with symptomatic AD over time, similarly to the CSF proteins VILIP-1, tau, and p-tau181. CONCLUSIONS AND RELEVANCE The CSF levels of the synaptic marker neurogranin offer diagnostic and prognostic utility for early symptomatic AD that is comparable to other CSF markers of AD. Importantly, CSF neurogranin complements the collective ability of these markers to predict future cognitive decline in cognitively normal individuals and, therefore, will be a useful addition to the current panel of AD biomarkers. PMID:27018940

Cognitive deficit in methamphetamine users relative to childhood academic performance: link to cortical thickness.

PubMed

Dean, Andy C; Morales, Angelica M; Hellemann, Gerhard; London, Edythe D

2018-04-20

Individuals with cognitive problems may be predisposed to develop substance use disorders; therefore, differences in cognitive function between methamphetamine users and control participants may be attributable to premorbid factors rather than methamphetamine use. The goal of this study was to clarify the extent to which this is the case. Childhood academic transcripts were obtained for 37 methamphetamine-dependent adults and 41 control participants of similar educational level and premorbid IQ. Each participant completed a comprehensive cognitive battery and received a structural magnetic resonance imaging scan. Data from control participants and linear regression were used to develop a normative model to describe the relationship between childhood academic performance and scores on the cognitive battery. Using this model, cognitive performance of methamphetamine users was predicted from their premorbid academic scores. Results indicated that methamphetamine users' childhood grade point average was significantly lower than that of the control group (p < 0.05). Further, methamphetamine users' overall cognitive performance was lower than was predicted from their grade point average prior to methamphetamine use (p = 0.001), with specific deficits in attention/concentration and memory (ps < 0.01). Memory deficits were associated with lower whole-brain cortical thickness (p < 0.05). Thus, in addition to having an apparent premorbid weakness in cognition, methamphetamine users exhibit subsequent cognitive function that is significantly lower than premorbid estimates would predict. The results support the view that chronic methamphetamine use causes a decline in cognition and/or a failure to develop normative cognitive abilities, although aside from methamphetamine use per se, other drug use and unidentified factors likely contribute to the observed effects.

Identification of multiple sclerosis patients at highest risk of cognitive impairment using an integrated brain magnetic resonance imaging assessment approach.

PubMed

Uher, T; Vaneckova, M; Sormani, M P; Krasensky, J; Sobisek, L; Dusankova, J Blahova; Seidl, Z; Havrdova, E; Kalincik, T; Benedict, R H B; Horakova, D

2017-02-01

While impaired cognitive performance is common in multiple sclerosis (MS), it has been largely underdiagnosed. Here a magnetic resonance imaging (MRI) screening algorithm is proposed to identify patients at highest risk of cognitive impairment. The objective was to examine whether assessment of lesion burden together with whole brain atrophy on MRI improves our ability to identify cognitively impaired MS patients. Of the 1253 patients enrolled in the study, 1052 patients with all cognitive, volumetric MRI and clinical data available were included in the analysis. Brain MRI and neuropsychological assessment with the Brief International Cognitive Assessment for Multiple Sclerosis were performed. Multivariable logistic regression and individual prediction analysis were used to investigate the associations between MRI markers and cognitive impairment. The results of the primary analysis were validated at two subsequent time points (months 12 and 24). The prevalence of cognitive impairment was greater in patients with low brain parenchymal fraction (BPF) (<0.85) and high T2 lesion volume (T2-LV) (>3.5 ml) than in patients with high BPF (>0.85) and low T2-LV (<3.5 ml), with an odds ratio (OR) of 6.5 (95% CI 4.4-9.5). Low BPF together with high T2-LV identified in 270 (25.7%) patients predicted cognitive impairment with 83% specificity, 82% negative predictive value, 51% sensitivity and 75% overall accuracy. The risk of confirmed cognitive decline over the follow-up was greater in patients with high T2-LV (OR 2.1; 95% CI 1.1-3.8) and low BPF (OR 2.6; 95% CI 1.4-4.7). The integrated MRI assessment of lesion burden and brain atrophy may improve the stratification of MS patients who may benefit from cognitive assessment. © 2016 EAN.

Aβ-related memory decline in APOE ε4 noncarriers: Implications for Alzheimer disease.

PubMed

Lim, Yen Ying; Laws, Simon M; Villemagne, Victor L; Pietrzak, Robert H; Porter, Tenielle; Ames, David; Fowler, Christopher; Rainey-Smith, Stephanie; Snyder, Peter J; Martins, Ralph N; Salvado, Olivier; Bourgeat, Pierrick; Rowe, Christopher C; Masters, Colin L; Maruff, Paul

2016-04-26

As the absence of Aβ-related memory decline in APOE ε4 noncarriers may be due to the relative brevity of previous studies, we aimed to characterize Aβ-related cognitive decline over 72 months in APOE ε4 carriers and noncarriers who were cognitively normal (CN). CN older adults (n = 423) underwent Aβ imaging and APOE genotyping. Participants completed comprehensive neuropsychological testing at baseline 18-, 36-, 54-, and 72-month assessments. Relative to Aβ- CN ε4 noncarriers, both Aβ+ CN ε4 carriers and noncarriers showed significantly increased decline in measures of memory, language, and executive function as well as higher rates of progression to a clinical classification of mild cognitive impairment. Memory decline was greater in Aβ+ CN ε4 carriers than in Aβ+ CN ε4 noncarriers. No cognitive decline was evident in Aβ- CN ε4 carriers. In CN older adults, Aβ+ is associated with memory decline in ε4 noncarriers; however, the rate of this decline is much slower than that observed in ε4 carriers. These data indicate that the processes by which ε4 carriage increases the rate of Aβ-related cognitive decline occur in the preclinical stage of Alzheimer disease. © 2016 American Academy of Neurology.

The emerging role of dietary fructose in obesity and cognitive decline

PubMed Central

2013-01-01

The incidence of obesity has increased dramatically over the past several years, and in parallel, so has the prevalence of type 2 diabetes (T2D). Numerous studies have demonstrated that both obesity and T2D are associated with lower cognitive performance, cognitive decline, and dementia. Intake of dietary fructose has also increased. In fact, high-fructose corn syrup (HFCS) accounts for as much as 40% of caloric sweeteners used in the United States. Given the increase in the incidence of Alzheimer’s disease (AD), characterized by an age-related decline in memory and cognitive functioning, in this report we review the effects of obesity on cognitive performance and the impact of high fructose intake in promoting cognitive decline. The paper then considers the effects of omega-3 fatty acids (FAs), which have been linked to promising results in cognitive function including ameliorating the impact of a high-fructose diet. PMID:23924506

The emerging role of dietary fructose in obesity and cognitive decline.

PubMed

Lakhan, Shaheen E; Kirchgessner, Annette

2013-08-08

The incidence of obesity has increased dramatically over the past several years, and in parallel, so has the prevalence of type 2 diabetes (T2D). Numerous studies have demonstrated that both obesity and T2D are associated with lower cognitive performance, cognitive decline, and dementia. Intake of dietary fructose has also increased. In fact, high-fructose corn syrup (HFCS) accounts for as much as 40% of caloric sweeteners used in the United States. Given the increase in the incidence of Alzheimer's disease (AD), characterized by an age-related decline in memory and cognitive functioning, in this report we review the effects of obesity on cognitive performance and the impact of high fructose intake in promoting cognitive decline. The paper then considers the effects of omega-3 fatty acids (FAs), which have been linked to promising results in cognitive function including ameliorating the impact of a high-fructose diet.

Telmisartan prevented cognitive decline partly due to PPAR-{gamma} activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mogi, Masaki; Li Jianmei; Tsukuda, Kana

Telmisartan is a unique angiotensin receptor blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor (PPAR)-{gamma}. Here, we investigated the preventive effect of telmisartan on cognitive decline in Alzheimer disease. In ddY mice, intracerebroventricular injection of A{beta} 1-40 significantly attenuated their cognitive function evaluated by shuttle avoidance test. Pretreatment with a non-hypotensive dose of telmisartan significantly inhibited such cognitive decline. Interestingly, co-treatment with GW9662, a PPAR-{gamma} antagonist, partially inhibited this improvement of cognitive decline. Another ARB, losartan, which has less PPAR-{gamma} agonistic effect, also inhibited A{beta}-injection-induced cognitive decline; however the effect was smaller than that of telmisartan and was notmore » affected by GW9662. Immunohistochemical staining for A{beta} showed the reduced A{beta} deposition in telmisartan-treated mice. However, this reduction was not observed in mice co-administered GW9662. These findings suggest that ARB has a preventive effect on cognitive impairment in Alzheimer disease, and telmisartan, with PPAR-{gamma} activation, could exert a stronger effect.« less

Memory Decline in Peri- and Post-menopausal Women: The Potential of Mind–Body Medicine to Improve Cognitive Performance

PubMed Central

Sliwinski, Jim R; Johnson, Aimee K; Elkins, Gary R

2014-01-01

Cognitive decline is a frequent complaint during the menopause transition and among post-menopausal women. Changes in memory correspond with diminished estrogen production. Further, many peri- and post-menopausal women report sleep concerns, depression, and hot flashes, and these factors may contribute to cognitive decline. Hormone therapy can increase estrogen but is contraindicated for many women. Mind–body medicine has been shown to have beneficial effects on sleep, mood, and hot flashes, among post-menopausal women. Further, mind–body medicine holds potential in addressing symptoms of cognitive decline post-menopause. This study proposes an initial framework for how mind–body interventions may improve cognitive performance and inform future research seeking to identify the common and specific factors associated with mind–body medicine for addressing memory decline in peri- and post-menopausal women. It is our hope that this article will eventually lead to a more holistic and integrative approach to the treatment of cognitive deficits in peri- and post-menopausal women. PMID:25125972

The effect of telemedicine on cognitive decline in patients with dementia.

PubMed

Kim, Heeseok; Jhoo, Jin Hyeong; Jang, Jae-Won

2017-01-01

Introduction Telemedicine has the advantage of providing medical resources in rural areas, but few studies have been conducted to investigate its efficacy in dementia care, compared to face-to-face care. This study evaluated the effectiveness of telemedicine in relation to cognitive changes in patients with dementia. Methods We evaluated cognitive changes over time, according to care modality, in 188 patients with dementia who were registered at our university-based dementia clinic. We followed 98 patients using telemedicine services and 90 patients who attended the dementia clinic in person. Patients in the telemedicine group also visited a public health center located in a rural area about 50 km from the dementia clinic. Results Changes in the mean annualized Mini-Mental State Examination (MMSE) score were not significantly different between the telemedicine group and the face-to-face dementia clinic group ( p = 0.291), with changes of 0.60 and 1.03 points, respectively. However, cognitive decline was significantly lower in the telemedicine group for the less severe initial cognitive performance subgroup than more severe cognitive performance subgroup ( p = 0.049), with changes of 0.62 and 1.59 points, respectively. Higher initial Clinical Dementia Rating (CDR) scores, MMSE scores, and age were found to be independent predictive factors of subsequent cognitive changes, as indicated by mean annualized MMSE scores. Discussion These findings suggest that telemedicine may be a useful alternative to face-to-face clinical visits for management of dementia in patients who are located in rural areas.

Test Accuracy of Informant-Based Cognitive Screening Tests for Diagnosis of Dementia and Multidomain Cognitive Impairment in Stroke.

PubMed

McGovern, Aine; Pendlebury, Sarah T; Mishra, Nishant K; Fan, Yuhua; Quinn, Terence J

2016-02-01

Poststroke cognitive assessment can be performed using standardized questionnaires designed for family or care givers. We sought to describe the test accuracy of such informant-based assessments for diagnosis of dementia/multidomain cognitive impairment in stroke. We performed a systematic review using a sensitive search strategy across multidisciplinary electronic databases. We created summary test accuracy metrics and described reporting and quality using STARDdem and Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tools, respectively. From 1432 titles, we included 11 studies. Ten papers used the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Four studies described IQCODE for diagnosis of poststroke dementia (n=1197); summary sensitivity: 0.81 (95% confidence interval, 0.60-0.93); summary specificty: 0.83 (95% confidence interval, 0.64-0.93). Five studies described IQCODE as tool for predicting future dementia (n=837); summary sensitivity: 0.60 (95% confidence interval, 0.32-0.83); summary specificity: 0.97 (95% confidence interval, 0.70-1.00). All papers had issues with at least 1 aspect of study reporting or quality. There is a limited literature on informant cognitive assessments in stroke. IQCODE as a diagnostic tool has test properties similar to other screening tools, IQCODE as a prognostic tool is specific but insensitive. We found no papers describing test accuracy of informant tests for diagnosis of prestroke cognitive decline, few papers on poststroke dementia and all included papers had issues with potential bias. © 2015 American Heart Association, Inc.

Hippocampal dose volume histogram predicts Hopkins Verbal Learning Test scores after brain irradiation.

PubMed

Okoukoni, Catherine; McTyre, Emory R; Ayala Peacock, Diandra N; Peiffer, Ann M; Strowd, Roy; Cramer, Christina; Hinson, William H; Rapp, Steve; Metheny-Barlow, Linda; Shaw, Edward G; Chan, Michael D

2017-01-01

Radiation-induced cognitive decline is relatively common after treatment for primary and metastatic brain tumors; however, identifying dosimetric parameters that are predictive of radiation-induced cognitive decline is difficult due to the heterogeneity of patient characteristics. The memory function is especially susceptible to radiation effects after treatment. The objective of this study is to correlate volumetric radiation doses received by critical neuroanatomic structures to post-radiation therapy (RT) memory impairment. Between 2008 and 2011, 53 patients with primary brain malignancies were treated with conventionally fractionated RT in prospectively accrued clinical trials performed at our institution. Dose-volume histogram analysis was performed for the hippocampus, parahippocampus, amygdala, and fusiform gyrus. Hopkins Verbal Learning Test-Revised scores were obtained at least 6 months after RT. Impairment was defined as an immediate recall score ≤15. For each anatomic region, serial regression was performed to correlate volume receiving a given dose (V D(Gy) ) with memory impairment. Hippocampal V 53.4Gy to V 60.9Gy significantly predicted post-RT memory impairment ( P  < .05). Within this range, the hippocampal V 55Gy was the most significant predictor ( P  = .004). Hippocampal V 55Gy of 0%, 25%, and 50% was associated with tumor-induced impairment rates of 14.9% (95% confidence interval [CI], 7.2%-28.7%), 45.9% (95% CI, 24.7%-68.6%), and 80.6% (95% CI, 39.2%-96.4%), respectively. The hippocampal V 55Gy is a significant predictor for impairment, and a limiting dose below 55 Gy may minimize radiation-induced cognitive impairment.

Disparities in Age-Associated Cognitive Decline Between African-American and Caucasian Populations: The Roles of Health Literacy and Education.

PubMed

Gupta, Vishal K; Winter, Michael; Cabral, Howard; Henault, Lori; Waite, Katherine; Hanchate, Amresh; Bickmore, Timothy W; Wolf, Michael S; Paasche-Orlow, Michael K

2016-08-01

To examine health literacy as a mediator of racial disparities in cognitive decline as measured by executive function in elderly adults. Prospective cohort study. Secondary analysis of ElderWalk trial in Boston, Massachusetts. English-speaking African-American and Caucasian individuals in a walking intervention for community-dwelling adults aged 65 and older without dementia at baseline who completed baseline and 12-month evaluations (N = 198). Health literacy was measured using the Short Test of Functional Health Literacy in Adults. Fluid and crystallized cognitive functions were measured at baseline and 12 months using the Trail-Making Test Part B minus Part B (TMT B-A) and the Controlled Oral Word Association Test (COWAT). Associations between health literacy and 12-month cognitive decline were modeled using multivariate linear regression. Participants with higher health literacy and education experienced less cognitive decline than those with limited health literacy according to the TMT B-A (P = .01). After adjusting for covariates, Caucasian participants (n = 63) experienced less decline than African-American participants (n = 135) on TMT B-A (P = .001) and COWAT (P = .001). Adjusting for health literacy led to a 25.3% decrease in the point estimate for racial difference in TMT B-A and a 19.5% decrease in COWAT. Although independently related to cognitive decline, educational attainment did not mediate racial differences. Health literacy is a partial mediator of racial disparities in cognitive decline. These results indicate the need to develop interventions to mitigate cognitive decline that individuals with low heath literacy can use and to modify the healthcare environment to better accommodate this population. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Cognitive Changes After Adjuvant Treatment in Older Adults with Early-Stage Breast Cancer.

PubMed

Lange, Marie; Heutte, Natacha; Noal, Sabine; Rigal, Olivier; Kurtz, Jean-Emmanuel; Lévy, Christelle; Allouache, Djelila; Rieux, Chantal; Lefel, Johan; Clarisse, Bénédicte; Leconte, Alexandra; Veyret, Corinne; Barthélémy, Philippe; Longato, Nadine; Tron, Laure; Castel, Hélène; Eustache, Francis; Giffard, Bénédicte; Joly, Florence

2018-06-22

Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls. Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status. The sample consisted of women newly diagnosed with EBC ( n  = 118) and healthy controls ( n  = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant ( p  = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline. This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC. The Oncologist IMPLICATIONS FOR PRACTICE: After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced accelerated cognitive decline. Initial cognitive functioning should be included in the balance of benefits and harms of systemic therapy for patients who are likely to be at highest risk for cognitive decline after cancer treatments. Regular cognitive follow-up of patients who had cognitive impairment before cancer treatment should monitor symptoms suggestive of neurodegenerative disease and avert the effect of cognitive disorders on patients' autonomy. © AlphaMed Press 2018.

"Brain-muscle loop" in the fragility of older persons: from pathophysiology to new organizing models.

PubMed

Lauretani, Fulvio; Meschi, Tiziana; Ticinesi, Andrea; Maggio, Marcello

2017-12-01

The imperative action of the geriatric medicine is to prevent disability in older persons. Many epidemiological studies have been conducted in the last decades for improving knowledge of the aging process and their interactions with age-related diseases, especially for the identification of the relationship between sarcopenia and loss of mobility. Factors influencing muscle integrity can be classified into six main physiologic subsystems, but the central nervous system certainly plays a crucial role for maintaining muscle integrity in older persons. Recent data show that the reduced muscle strength and not muscle mass could be considered the core of the fragility in predicting changes of gait velocity and mobility and conferring a higher risk of mortality in older persons. Sarcopenia and cognitive decline could, therefore, produce slow gait velocity in older persons, with devastating effect and consequences. Perhaps the most notorious corollary is falling, which is often caused by an underlying gait problem. Injuries caused by accidental falls range from relatively innocent bruises to major fractures or head trauma. Another important consequence is reduced mobility, which leads to loss of independence. This immobility is often compounded by a fear of falling, which further immobilises patients and affects their quality of life and physical performance. When we search the association between brain pathology and muscle function in older persons, we amazingly find that established composite measure of physical frailty is associated with brain pathology. Sarcopenia, which produces muscle dysfunction, slow gait velocity and cognitive decline, could share a strong bidirectional relationship, and this suggests the coexistence of both cognitive and motor dysfunctions in older persons to characterize a new syndrome characterized by slow gait and cognitive complaints, the motoric-cognitive risk syndrome (MRC). In this review, we want to emphasize the relationship between memory complaints with muscle function integrating cognitive and physical evaluation, even with amyloid PET study, to identify older patients at high risk of cognitive and physical decline.

Adverse Childhood and Recent Negative Life Events: Contrasting Associations With Cognitive Decline in Older Persons.

PubMed

Korten, Nicole C M; Penninx, Brenda W J H; Pot, Anne Margriet; Deeg, Dorly J H; Comijs, Hannie C

2014-06-01

To examine whether persons who experienced adverse childhood events or recent negative life events have a worse cognitive performance and faster cognitive decline and the role of depression and apolipoprotein E-∊4 in this relationship. The community-based sample consisted of 10-year follow-up data of 1312 persons participating in the Longitudinal Aging Study Amsterdam (age range 65-85 years). Persons who experienced adverse childhood events showed a faster 10-year decline in processing speed but only when depressive symptoms were experienced. Persons with more recent negative life events showed slower processing speed at baseline but no faster decline. Childhood adversity may cause biological or psychological vulnerability, which is associated with both depressive symptoms and cognitive decline in later life. The accumulation of recent negative life events did not affect cognitive functioning over a longer time period. © The Author(s) 2014.

Higher Blood Vitamin C Levels are Associated with Reduction of Apolipoprotein E E4-related Risks of Cognitive Decline in Women: The Nakajima Study.

PubMed

Noguchi-Shinohara, Moeko; Abe, Chiemi; Yuki-Nozaki, Sohshi; Dohmoto, Chiaki; Mori, Ayaka; Hayashi, Koji; Shibata, Syutaro; Ikeda, Yoshihisa; Sakai, Kenji; Iwasa, Kazuo; Yokogawa, Masami; Ishimiya, Mai; Nakamura, Hiroyuki; Yokoji, Hidehiro; Komai, Kiyonobu; Nakamura, Hiroyuki; Yamada, Masahito

2018-05-11

Antioxidants like vitamins C and E may minimize the risk for Alzheimer's disease. We examined whether vitamins C and E modify the apolipoprotein E (APOE) E4-related risks for developing cognitive decline. We conducted a population-based prospective study including Japanese residents aged 65 years from Nakajima, Japan. The participants received an evaluation of cognitive function and underwent blood tests including tests for vitamins C and E levels and APOE phenotypes. The APOE E4-by-gender-by-vitamin C or E interactions on developing cognitive decline were analyzed. Of 606 participants with normal cognitive function determined using a baseline survey (2007-2008), 349 completed the follow up survey between 2014 and 2016. In women with APOE E4, significantly reduced risk for cognitive decline was observed for the highest blood vitamin C concentration tertile [multivariate OR 0.10 (95% CI 0.01-0.93)] compared with the lowest tertile. In men without APOE E4, significantly reduced risk for cognitive decline was observed for the highest blood vitamin E concentration tertile [multivariate OR 0.19 (0.05-0.74)] as compared with the lowest tertile. Our results demonstrate significant beneficial effects of vitamins C and E in reducing the risk of cognitive decline in women with APOE E4 and men without APOE E4, respectively.

Left Ventricular Hypertrophy and Cognitive Decline in Old Age.

PubMed

Mahinrad, Simin; Vriend, Annelotte E; Jukema, J Wouter; van Heemst, Diana; Sattar, Naveed; Blauw, Gerard Jan; Macfarlane, Peter W; Clark, Elaine N; de Craen, Anton J M; Sabayan, Behnam

2017-01-01

Patients with advanced heart failure run a greater risk of dementia. Whether early cardiac structural changes also associate with cognitive decline is yet to be determined. We tested whether left ventricular hypertrophy (LVH) derived from electrocardiogram associates with cognitive decline in older subjects at risk of cardiovascular disease. We included 4,233 participants (mean age 75.2 years, 47.8% male) from PROSPER (PROspective Study of Pravastatin in the Elderly at Risk). LVH was assessed from baseline electrocardiograms by measuring the Sokolow-Lyon index. Higher levels of Sokolow-Lyon index indicate higher degrees of LVH. Cognitive domains involving selective attention, processing speed, and immediate and delayed memory were measured at baseline and repeated during a mean follow-up of 3.2 years. At baseline, LVH was not associated with worse cognitive function. During follow-up, participants with higher levels of LVH had a steeper decline in cognitive function including in selective attention (p = 0.009), processing speed (p = 0.010), immediate memory (p < 0.001), and delayed memory (p = 0.002). These associations were independent of cardiovascular risk factors, co-morbidities, and medications. LVH assessed by electrocardiogram associates with steeper decline in cognitive function of older subjects independent of cardiovascular risk factors and co-morbidities. This study provides further evidence on the link between subclinical cardiac structural changes and cognitive decline in older subjects.

Responder analysis of a randomized comparison of the 13.3 mg/24 h and 9.5 mg/24 h rivastigmine patch.

PubMed

Molinuevo, José L; Frölich, Lutz; Grossberg, George T; Galvin, James E; Cummings, Jeffrey L; Krahnke, Tillmann; Strohmaier, Christine

2015-01-01

OPtimizing Transdermal Exelon In Mild-to-moderate Alzheimer's disease (OPTIMA) was a randomized, double-blind comparison of 13.3 mg/24 h versus 9.5 mg/24 h rivastigmine patch in patients with mild-to-moderate Alzheimer's disease who declined despite open-label treatment with 9.5 mg/24 h patch. Over 48 weeks of double-blind treatment, high-dose patch produced greater functional and cognitive benefits compared with 9.5 mg/24 h patch. Using OPTIMA data, a post-hoc responder analysis was performed to firstly, compare the proportion of patients demonstrating improvement or absence of decline with 13.3 mg/24 h versus 9.5 mg/24 h patch; and secondly, identify predictors of improvement or absence of decline. 'Improvers' were patients who improved on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) by ≥4 points from baseline, and did not decline on the instrumental domain of the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-IADL). 'Non-decliners' were patients who did not decline on either scale. Overall, 265 patients randomized to 13.3 mg/24 h and 271 to 9.5 mg/24 h patch met the criteria for inclusion in the intention-to-treat population and were included in the analyses. Significantly more patients were 'improvers' with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Weeks 24 (44 (16.6%) versus 19 (7.0%); P < 0.001) and 48 (21 (7.9%) versus 10 (3.7%); P = 0.023). A significantly greater proportion of patients were 'non-decliners' with 13.3 mg/24 h compared with 9.5 mg/24 h patch at Week 24 (71 (26.8%) versus 44 (16.2%); P = 0.002). At Week 48, there was a trend in favor of 13.3 mg/24 h patch. Functional and cognitive assessment scores at double-blind baseline did not consistently predict effects at Weeks 24 or 48. More patients with mild-to-moderate Alzheimer's disease who are titrated to 13.3 mg/24 h rivastigmine patch at time of decline are 'improvers' or 'non-decliners' i.e. show responses on cognition and activities of daily living compared with patients remaining on 9.5 mg/24 h patch. Clinicaltrials.gov identifier: NCT00506415; registered July 20, 2007.

Midlife C-reactive protein and risk of cognitive decline: a 31-year follow-up.

PubMed

Laurin, Danielle; David Curb, J; Masaki, Kamal H; White, Lon R; Launer, Lenore J

2009-11-01

There is evidence for a relationship between raised inflammatory markers, including high sensitivity C-reactive protein (hs-CRP), measured late in life, and an increased risk of cognitive decline and dementia. This study evaluates the association of midlife hs-CRP concentrations with late-life longitudinal trends in cognitive function. Data are from the Honolulu-Asia Aging Study (HAAS), a longitudinal community-based study of Japanese American men. hs-CRP levels were measured on average 25 years before cognitive testing began in 1991. Subjects were followed from up to three follow-up examinations (mean of 6.1 years). At each exam, cognitive function was measured with the Cognitive Abilities Screening Instrument (CASI). This analysis includes a sub-sample of 691 subjects dementia-free in 1991. With incident dementia cases included, those with the highest quartile of hs-CRP had significantly more cognitive decline than those in the lowest quartile, after adjustment for baseline CASI score, demographic and cardiovascular risk factors. When cases were removed, there was no difference in cognitive decline by CRP quartile. This relationship was not modified by the presence of apolipoprotein E varepsilon4. These findings suggest that inflammatory mechanisms during midlife may reflect underlying processes contributing to dementia-related cognitive decline late in life.

Decline in Weight and Incident Mild Cognitive Impairment: Mayo Clinic Study of Aging

PubMed Central

Alhurani, Rabe E.; Vassilaki, Maria; Aakre, Jeremiah; Mielke, Michelle M.; Kremers, Walter K.; Machulda, Mary M.; Geda, Yonas E.; Knopman, David S.; Peterson, Ronald C.; Roberts, Rosebud O.

2016-01-01

IMPORTANCE Unintentional weight loss has been associated with risk of dementia. Since mild cognitive impairment (MCI) is a prodromal stage for dementia, we sought to evaluate whether changes in weight and body mass index (BMI) may predict incident MCI. OBJECTIVE To investigate the association of change in weight and BMI with risk of MCI. DESIGN, SETTING, AND PARTICIPANTS A population-based, prospective study of participants aged 70 years and older from the Mayo Clinic Study of Aging. Maximum weight and height in midlife (aged 40 to 65 years old) were retrospectively ascertained from the medical records of participants using a medical records linkage system. MAIN OUTCOMES MEASURES Participants were evaluated for cognitive outcomes of normal cognition, MCI, or dementia at baseline and prospectively assessed for incident events at each 15-month evaluation. The association of rate of change in weight and body mass index with risk of MCI was investigated using proportional hazards models. RESULTS Over a mean follow-up of 4.4 years, 524 of 1895 cognitively normal participants developed incident MCI. The mean (standard deviation) rate of weight change per decade from midlife to study entry was greater for individuals who developed incident MCI vs. those who remained cognitively normal (−2.0 (5.1) vs. −1.2 (4.9) kg; p = 0.006). A greater decline in weight per decade was associated with an increased risk of incident MCI (hazard ratio [HR] 95% confidence interval [CI], 1.04 [1.02, 1.06], p < 0.001) after adjusting for sex, education and apolipoprotein E (APOE) ε4 allele. A weight loss of 5 kg/decade corresponds to a 24% increase in risk of MCI (HR=1.24). Higher decline in BMI per decade was also associated with incident MCI (HR, 1.08, 95% CI = [1.03, 1.13], p = 0.003). CONCLUSIONS AND RELEVANCE These findings suggest that declining weight from midlife to late-life is a marker for MCI and may help identify persons at increased risk for MCI. PMID:26831542

An Application of Pavlovian Principles to the Problems of Obesity and Cognitive Decline

PubMed Central

Davidson, T. L.; Sample, C. H.; Swithers, S. E.

2013-01-01

An enormous amount of research has been aimed at identifying biological and environmental factors that are contributing to the current global obesity pandemic. The present paper reviews recent findings which suggest that obesity is attributable, at least in part, to a disruption of the Pavlovian control of energy regulation. Within our framework, this disruption occurs when (a) consumption of sweet-tasting, but low calorie or noncaloric, foods and beverages reduces the ability of sweet tastes to predict the postingestive caloric consequences of intake and (b) consuming diets high in saturated fat and sugar (a.k.a., Western diet) impairs hippocampal-dependent learning and memory processes that are involved with the use of interoceptive “satiety” signals to anticipate when food and eating are not followed by appetitive postingestive outcomes. The paper concludes with discussion of a “vicious-cycle’ model which links obesity to cognitive decline. PMID:23887140

Differing effects of education on cognitive decline in diverse elders with low versus high educational attainment.

PubMed

Zahodne, Laura B; Stern, Yaakov; Manly, Jennifer J

2015-07-01

In light of growing debate over whether and how early life educational experiences alter late-life cognitive trajectories, this study sought to more thoroughly investigate the relationship between educational attainment and rates of late-life cognitive decline in a racially, ethnically, and educationally diverse population. Older adults (N = 3,435) in the community-based Washington Heights-Inwood Columbia Aging Project were administered neuropsychological tests of memory, language, visuospatial function, and processing speed at approximate 24-month intervals for up to 18 years. Second-order latent growth curves estimated direct and indirect (through income) effects of educational attainment on rates of global cognitive decline separately in individuals with low (0-8 years) and high (9-20 years) educational attainment. More years of education were associated with higher cognitive level and slower cognitive decline in individuals with low or high educational attainment. The association between having more than 9 years of education and exhibiting slower cognitive decline was fully mediated by income. Although having additional years of education up to 8 years was also associated with higher income, this did not explain associations between education and cognitive change in the low-education group. Early education (i.e., up to 8 years) may promote aspects of development during a sensitive period of childhood that protect against late-life cognitive decline independent of income. In contrast, later education (i.e., 9 years and beyond) is associated with higher income, which may influence late-life cognitive health through multiple, nonmutually exclusive pathways. (c) 2015 APA, all rights reserved).

Differing effects of education on cognitive decline in diverse elders with low versus high educational attainment

PubMed Central

Zahodne, Laura B.; Stern, Yaakov; Manly, Jennifer J.

2014-01-01

Objective In light of growing debate over whether and how early-life educational experiences alter late-life cognitive trajectories, this study sought to more thoroughly investigate the relationship between educational attainment and rates of late-life cognitive decline in a racially, ethnically, and educationally diverse population. Method 3,435 older adults in the community-based Washington Heights-Inwood Columbia Aging Project were administered neuropsychological tests of memory, language, visuospatial function, and processing speed at approximate 24-month intervals for up to 18 years. Second-order latent growth curves estimated direct and indirect (through income) effects of educational attainment on rates of global cognitive decline separately in individuals with low (0-8 years) and high (9-20 years) educational attainment. Results More years of education was associated with higher cognitive level and slower cognitive decline in individuals with low or high educational attainment. The association between having more than 9 years of education and exhibiting slower cognitive decline was fully mediated by income. While additional years of education up to 8 years was also associated with higher income, this did not explain associations between education and cognitive change in the low-education group. Conclusions Early education (i.e., up to 8 years) may promote aspects of development during a sensitive period of childhood that protect against late-life cognitive decline independent of income. In contrast, later education (i.e., beyond 9 years) is associated with higher income, which may influence late-life cognitive health through multiple, non-mutually exclusive pathways. PMID:25222199

Premeditation and Sensation Seeking Moderate the Reasoned Action and Social Reaction Pathways in the Prototype/Willingness Model of Alcohol Use.

PubMed

Vaughn, Matthew Gregory; King, Kevin M

2016-05-11

Drinking can occur because of expectations to drink (reasoned pathway) or because of willingness to drink under certain circumstances (reactive pathway). These pathways are thought to be influenced by different cognitions such as alcohol-related attitudes, norms, or drinking prototypes (Gerrard et al., 2008). Impulsive traits reflect individual differences in the influence of reasoned or reactive factors, however little research has investigated whether impulsivity moderates the effects of cognitive factors predicting alcohol use. We tested whether differences in three impulsivity traits (premeditation, sensation seeking and negative urgency) moderated associations of reasoned (risk/disapproval attitudes and social norms) and reactive (prototype) pathway variables on expectation/willingness to drink and recent alcohol use. We collected data from n = 409 college students; the sample was 67% female, 43% Asian American, with Mdnage = 19. Hypotheses were tested using multiple regression. Premeditation and sensation seeking moderated reasoned variable effects on expectation and drinking. Among those low on premeditation, risk attitudes were most associated with drinking expectation, with alcohol prototypes most related to recent drinking. These effects declined at higher premeditation levels. Among those high on sensation seeking, risk attitudes were most associated with expectation and drinking, declining at lower sensation seeking levels. There was little evidence of moderation predicting drinking willingness. Findings imply personality differences may explain association strength between reasoned but not reactive risk behavior pathways with alcohol outcomes. They have ramifications for personalized prevention programs to reduce drinking through cognition change, as alcohol-related cognition influence may differ depending on personality characteristics.

Risk factors associated with cognitive decline in the elderly with type 2 diabetes: pooled logistic analysis of a 6-year observation in the Japanese Elderly Diabetes Intervention Trial.

PubMed

Umegaki, Hiroyuki; Iimuro, Satoshi; Shinozaki, Tomohiro; Araki, Atsushi; Sakurai, Takashi; Iijima, Katsuya; Ohashi, Yasuo; Ito, Hideki

2012-04-01

Considerable attention has been paid to the association between type 2 diabetes mellitus (T2DM) and cognitive dysfunction in the elderly. T2DM is often comorbid with several other metabolic disturbances, including hypertension and dyslipidemia. These comorbid diseases might be associated with cognitive impairment. Many clinical indices should be included as variables for the association with cognitive decline. In the current study, we tried to identify the associated factors with cognitive decline during a 6-year period in elderly T2DM considering the changes in the clinical indices during the follow-up period. The subjects in the present study were 63 Japanese Elderly Interventional Trial participants who were administered the Mini-Mental State Examination at baseline, at the third year, and at the end of the 6-year follow-up period. We applied the pooled logistic analysis method to consider the changes in clinical indices during the observation period and tried to identify the factors associated with cognitive decline during the 6 years in elderly type 2 diabetics using repeated measured data for glycated hemoglobin A1c, blood pressure and serum lipids. In the current study, low high-density lipoprotein-cholesterol and higher diastolic blood pressure were significantly associated with cognitive decline by pooled logistic analysis in the 6-year observation of older diabetic subjects. Higher glycated hemoglobin A1c had a tendency toward association with cognitive decline. The results suggest that comprehensive management of diabetes, including dyslipidemia and hypertension, might contribute to the prevention of declines in cognitive function in older diabetic patients. © 2012 Japan Geriatrics Society.

Demographic and clinical characteristics related to cognitive decline in Alzheimer disease in China: A multicenter survey from 2011 to 2014.

PubMed

Peng, Dantao; Shi, Zhihong; Xu, Jun; Shen, Lu; Xiao, Shifu; Zhang, Nan; Li, Yi; Jiao, Jinsong; Wang, Yan-Jiang; Liu, Shuai; Zhang, Meilin; Wang, Meng; Liu, Shuling; Zhou, Yuying; Zhang, Xiao; Gu, Xiao-Hua; Yang, Ce-Ce; Wang, Yu; Jiao, Bin; Tang, Beisha; Wang, Jinhuan; Yu, Tao; Ji, Yong

2016-06-01

Alzheimer disease (AD) is the most frequent cause of dementia. AD diagnosis, progression, and treatment have not been analyzed nationwide in China. The primary aim of this study was to analyze demographic and clinical characteristics related to cognitive decline in AD patients treated at outpatient clinics in China.We performed a retrospective study of 1993 AD patients at 10 cognitive centers across 8 cities in China from March 2011 to October 2014. Of these, 891 patients were followed for more than 1 year.The mean age at diagnosis was 72.0 ± 10.0 years (range 38-96 years), and the mean age at onset of AD was 69.8 ± 9.5 years. Most patients (65.1%) had moderate to severe symptoms at the time of diagnosis, and mean Mini-Mental State Examination at diagnosis was 15.7 ± 7.7. AD patients showed significant cognitive decline at 12 months after diagnosis. Having more than 9 years of formal education was an independent risk factor related to rapid cognitive decline [odds ratio (OR) = 1.80; 95% confidence interval (95% CI): 1.11-2.91]. Early-onset AD patients experienced more rapid cognitive decline than late-onset patients (OR = 1.83; 95% CI: 1.09-3.06).Most AD patients in China had moderate to severe symptoms at the time of diagnosis and experienced significant cognitive decline within 1 year. Rapid cognitive decline in AD was related to having a higher educational level and younger age of onset.

Effects of education and race on cognitive decline: An integrative analysis of generalizability versus study-specific results

PubMed Central

Gross, Alden L.; Mungas, Dan M.; Crane, Paul K.; Gibbons, Laura E.; MacKay-Brandt, Anna; Manly, Jennifer J.; Mukherjee, Shubhabrata; Romero, Heather; Sachs, Bonnie; Thomas, Michael; Potter, Guy G.; Jones, Richard N.

2015-01-01

Objective To examine variability across multiple prospective cohort studies in level and rate of cognitive decline by race/ethnicity and years of education. Method To compare data across studies, we harmonized estimates of common latent factors representing overall or general cognitive performance, memory, and executive function derived from the: 1) Washington Heights, Hamilton Heights, Inwood Columbia Aging Project (N=4,115), 2) Spanish and English Neuropsychological Assessment Scales (N=525), 3) Duke Memory, Health, and Aging study (N=578), and 4) Neurocognitive Outcomes of Depression in the Elderly (N=585). We modeled cognitive change over age for cognitive outcomes by race, education, and study. We adjusted models for sex, dementia status, and study-specific characteristics. Results For baseline levels of overall cognitive performance, memory, and executive function, differences in race and education tended to be larger than between-study differences and consistent across studies. This pattern did not hold for rate of cognitive decline: effects of education and race/ethnicity on cognitive change were not consistently observed across studies, and when present were small, with racial/ethnic minorities and those with lower education declining at faster rates. Discussion In this diverse set of datasets, non-Hispanic whites and those with higher education had substantially higher baseline cognitive test scores. However, differences in the rate of cognitive decline by race/ethnicity and education did not follow this pattern. This study suggests that baseline test scores and longitudinal change have different determinants, and future studies to examine similarities and differences of causes of cognitive decline in racially/ethnically and educationally diverse older groups is needed. PMID:26523693

Effects of education and race on cognitive decline: An integrative study of generalizability versus study-specific results.

PubMed

Gross, Alden L; Mungas, Dan M; Crane, Paul K; Gibbons, Laura E; MacKay-Brandt, Anna; Manly, Jennifer J; Mukherjee, Shubhabrata; Romero, Heather; Sachs, Bonnie; Thomas, Michael; Potter, Guy G; Jones, Richard N

2015-12-01

The objective of the study was to examine variability across multiple prospective cohort studies in level and rate of cognitive decline by race/ethnicity and years of education. We compare data across studies, we harmonized estimates of common latent factors representing overall or general cognitive performance, memory, and executive function derived from the: (a) Washington Heights, Hamilton Heights, Inwood Columbia Aging Project (N = 4,115), (b) Spanish and English Neuropsychological Assessment Scales (N = 525), (c) Duke Memory, Health, and Aging study (N = 578), and (d) Neurocognitive Outcomes of Depression in the Elderly (N = 585). We modeled cognitive change over age for cognitive outcomes by race, education, and study. We adjusted models for sex, dementia status, and study-specific characteristics. The results found that for baseline levels of overall cognitive performance, memory, and executive function, differences in race and education tended to be larger than between-study differences and consistent across studies. This pattern did not hold for rate of cognitive decline: effects of education and race/ethnicity on cognitive change were not consistently observed across studies, and when present were small, with racial/ethnic minorities and those with lower education declining at faster rates. In this diverse set of datasets, non-Hispanic Whites and those with higher education had substantially higher baseline cognitive test scores. However, differences in the rate of cognitive decline by race/ethnicity and education did not follow this pattern. This study suggests that baseline test scores and longitudinal change have different determinants, and future studies to examine similarities and differences of causes of cognitive decline in racially/ethnically and educationally diverse older groups is needed. (c) 2015 APA, all rights reserved).

Trajectories of cognitive function in dementia-free subjects: Radiation Effects Research Foundation Adult Health Study.

PubMed

Yamada, Michiko; Landes, Reid D; Mimori, Yasuyo; Nagano, Yoshito; Sasaki, Hideo

2015-04-15

To investigate associations between age, sex, education, and birth cohort and global cognitive decline among a population that would most likely not progress to dementia. A total of 1538 dementia-free subjects aged 60 to 80years in 1992 were followed up through 2011 without dementia occurrence. We assessed cognitive function using the Cognitive Ability Screening Instrument (CASI). Using stepwise-like model selection procedure, we built mixed-effects models for initial cognition and longitudinal cognition. Initial CASI scores for younger age and more years of formal education were higher than those for older and less education. Sex did not show a significant effect. In the longitudinal analysis, cognitive decline became more rapid with increasing age. Sex and education did not modify the degree of deterioration with age. CASI scores were higher for younger cohorts and men due to differences in education levels. Among dementia-free subjects, age is an important predictor of cognitive function level and cognitive decline. Education level affects cognitive function level, but did not affect cognitive decline. The results have implications not only for elucidation of the aging process, but also for reference in dementia screening. Copyright © 2015 Elsevier B.V. All rights reserved.

Identifying cognitive impairment in type 2 diabetes with functional connectivity: a multivariate pattern analysis of resting state fMRI data

NASA Astrophysics Data System (ADS)

Liu, Zhenyu; Cui, Xingwei; Tang, Zhenchao; Dong, Di; Zang, Yali; Tian, Jie

2017-03-01

Previous researches have shown that type 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive impairment. Early detection of brain abnormalities at the preclinical stage can be useful for developing preventive interventions to abate cognitive decline. We aimed to investigate the whole-brain resting-state functional connectivity (RSFC) patterns of T2DM patients between 90 regions of interest (ROIs) based on the RS-fMRI data, which can be used to test the feasibility of identifying T2DM patients with cognitive impairment from other T2DM patients. 74 patients were recruited in this study and multivariate pattern analysis was utilized to assess the prediction performance. Elastic net was firstly used to select the key features for prediction, and then a linear discrimination model was constructed. 23 RSFCs were selected and it achieved the performance with classification accuracy of 90.54% and areas under the receiver operating characteristic curve (AUC) of 0.944 using ten-fold cross-validation. The results provide strong evidence that functional interactions of brain regions undergo notable alterations between T2DM patients with cognitive impairment or not. By analyzing the RSFCs that were selected as key features, we found that most of them involved the frontal or temporal. We speculated that cognitive impairment in T2DM patients mainly impacted these two lobes. Overall, the present study indicated that RSFCs undergo notable alterations associated with the cognitive impairment in T2DM patients, and it is possible to predicted cognitive impairment early with RSFCs.

Paradoxical effect of dopamine medication on cognition in Parkinson's disease: relationship to side of motor onset.

PubMed

Hanna-Pladdy, Brenda; Pahwa, Rajesh; Lyons, Kelly E

2015-04-01

Parkinson's disease (PD) is characterized by asymmetric motor symptom onset attributed to greater degeneration of dopamine neurons contralateral to the affected side. However, whether motor asymmetries predict cognitive profiles in PD, and to what extent dopamine influences cognition remains controversial. This study evaluated cognitive variability in PD by measuring differential response to dopamine replacement therapy (DRT) based on hemispheric asymmetries. The influence of DRT on cognition was evaluated in mild PD patients (n = 36) with left or right motor onset symptoms. All subjects were evaluated on neuropsychological measures on and off DRT and compared to controls (n = 42). PD patients were impaired in executive, memory and motor domains irrespective of side of motor onset, although patients with left hemisphere deficit displayed greater cognitive impairment. Patients with right hemisphere deficit responded to DRT with significant improvement in sensorimotor deficits, and with corresponding improvement in attention and verbal memory functions. Conversely, patients with greater left hemisphere dopamine deficiency did not improve in attentional functions and declined in verbal memory recall following DRT. These findings support the presence of extensive mild cognitive deficits in early PD not fully explained by dopamine depletion alone. The paradoxical effects of levodopa on verbal memory were predicted by extent of fine motor impairment and sensorimotor response to levodopa, which reflects extent of dopamine depletion. The findings are discussed with respect to factors influencing variable cognitive profiles in early PD, including hemispheric asymmetries and differential response to levodopa based on dopamine levels predicting amelioration or overdosing.

Obstructive Sleep Apnea and 15-Year Cognitive Decline: The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Lutsey, Pamela L.; Bengtson, Lindsay G.S.; Punjabi, Naresh M.; Shahar, Eyal; Mosley, Thomas H.; Gottesman, Rebecca F.; Wruck, Lisa M.; MacLehose, Richard F.; Alonso, Alvaro

2016-01-01

Study Objectives: Prospective data evaluating abnormal sleep quality and quantity with cognitive decline are limited because most studies used subjective data and/or had short follow-up. We hypothesized that, over 15 y of follow-up, participants with objectively measured obstructive sleep apnea (OSA) and other indices of poor sleep quantity and quality would experience greater decline in cognitive functioning than participants with normal sleep patterns. Methods: ARIC participants (n = 966; mean age 61 y, 55% women) with in-home polysomnography (1996–1998) and repeated cognitive testing were followed for 15 y. Three cognitive tests (Delayed Word Recall, Word Fluency, and Digit Symbol Substitution) were administered at two time points (1996–1998 and 2011–2013). Ten additional cognitive tests were administered at the 2011–2013 neurocognitive examination. OSA was modeled using established clinical OSA severity categories. Multivariable linear regression was used to explore associations of OSA and other sleep indices with change in cognitive tests between the two assessments. Results: A median of 14.9 y (max: 17.3) passed between the two cognitive assessments. OSA category and additional indices of sleep (other measures of hypoxemia and disordered breathing, sleep fragmentation, sleep duration) were not associated with change in any cognitive test. Analyses of OSA severity categories and 10 cognitive tests administered only in 2011–2013 also showed little evidence of an association. Conclusions: Overall, abnormal sleep quality and quantity at midlife was not related to cognitive decline and later-life cognition. The effect of adverse sleep quality and quantity on cognitive decline among the elderly remains to be determined. Citation: Lutsey PL, Bengtson LG, Punjabi NM, Shahar E, Mosley TH, Gottesman RF, Wruck LM, MacLehose RF, Alonso A. Obstructive sleep apnea and 15-year cognitive decline: the Atherosclerosis Risk in Communities (ARIC) study. SLEEP 2016;39(2):309–316. PMID:26446113

High-sensitivity C-reactive protein and cognitive decline: the English Longitudinal Study of Ageing.

PubMed

Zheng, Fanfan; Xie, Wuxiang

2018-06-01

High-sensitivity C-reactive protein (hs-CRP) has been suggested to be involved in the process of cognitive decline. However, the results from previous studies exploring the relationship between hs-CRP concentration and cognitive decline are inconsistent. We employed data from wave 2 (2004-2005) to wave 7 (2014-2015) of the English Longitudinal Study of Ageing. Cognitive function was assessed at baseline (wave 2) and reassessed biennially at waves 3-7. A total of 5257 participants (54.9% women, mean age 65.4 ± 9.4 years) with baseline hs-CRP levels ranged from 0.2 to 210.0 mg/L (median: 2.0 mg/L, interquartile range: 0.9-4.1 mg/L) were studied. The mean follow-up duration was 8.1 ± 2.8 years, and the mean number of cognitive assessment was 4.9 ± 1.5. Linear mixed models show that a one-unit increment in natural log-transformed hs-CRP was associated with faster declines in global cognitive scores [-0.048 points/year, 95% confidence interval (CI) -0.072 to -0.023], memory scores (-0.022 points/year, 95% CI -0.031 to -0.013), and executive function scores (-0.025 points/year, 95% CI -0.043 to -0.006), after multivariable adjustment. Compared with the lowest quartile of hs-CRP, the multivariable-adjusted rate of global cognitive decline associated with the second, third, and highest quartile was faster by -0.043 points/year (95% CI -0.116 to 0.029), -0.090 points/year (95% CI -0.166 to -0.015), -0.145 (95% CI -0.221 to -0.069), respectively (p for trend <0.001). Similarly, memory and executive function also declined faster with increasing quartiles of hs-CRP. A significant association between hs-CRP concentration and long-term cognitive decline was observed in this study. Hs-CRP might serve as a biomarker for cognitive decline.

Pilot age and expertise predict flight simulator performance: a 3-year longitudinal study.

PubMed

Taylor, Joy L; Kennedy, Quinn; Noda, Art; Yesavage, Jerome A

2007-02-27

Expert knowledge may compensate for age-related declines in basic cognitive and sensory-motor abilities in some skill domains. We investigated the influence of age and aviation expertise (indexed by Federal Aviation Administration pilot ratings) on longitudinal flight simulator performance. Over a 3-year period, 118 general aviation pilots aged 40 to 69 years were tested annually, in which their flight performance was scored in terms of 1) executing air-traffic controller communications; 2) traffic avoidance; 3) scanning cockpit instruments; 4) executing an approach to landing; and 5) a flight summary score. More expert pilots had better flight summary scores at baseline and showed less decline over time. Secondary analyses revealed that expertise effects were most evident in the accuracy of executing aviation communications, the measure on which performance declined most sharply over time. Regarding age, even though older pilots initially performed worse than younger pilots, over time older pilots showed less decline in flight summary scores than younger pilots. Secondary analyses revealed that the oldest pilots did well over time because their traffic avoidance performance improved more vs younger pilots. These longitudinal findings support previous cross-sectional studies in aviation as well as non-aviation domains, which demonstrated the advantageous effect of prior experience and specialized expertise on older adults' skilled cognitive performances.

Age-related Effects on Word Recognition: Reliance on Cognitive Control Systems with Structural Declines in Speech-responsive Cortex

PubMed Central

Walczak, Adam; Ahlstrom, Jayne; Denslow, Stewart; Horwitz, Amy; Dubno, Judy R.

2008-01-01

Speech recognition can be difficult and effortful for older adults, even for those with normal hearing. Declining frontal lobe cognitive control has been hypothesized to cause age-related speech recognition problems. This study examined age-related changes in frontal lobe function for 15 clinically normal hearing adults (21–75 years) when they performed a word recognition task that was made challenging by decreasing word intelligibility. Although there were no age-related changes in word recognition, there were age-related changes in the degree of activity within left middle frontal gyrus (MFG) and anterior cingulate (ACC) regions during word recognition. Older adults engaged left MFG and ACC regions when words were most intelligible compared to younger adults who engaged these regions when words were least intelligible. Declining gray matter volume within temporal lobe regions responsive to word intelligibility significantly predicted left MFG activity, even after controlling for total gray matter volume, suggesting that declining structural integrity of brain regions responsive to speech leads to the recruitment of frontal regions when words are easily understood. Electronic supplementary material The online version of this article (doi:10.1007/s10162-008-0113-3) contains supplementary material, which is available to authorized users. PMID:18274825

Enriched childhood experiences moderate age-related motor and cognitive decline

PubMed Central

Metzler, Megan J.; Saucier, Deborah M.; Metz, Gerlinde A.

2012-01-01

Aging is associated with deterioration of skilled manual movement. Specifically, aging corresponds with increased reaction time, greater movement duration, segmentation of movement, increased movement variability, and reduced ability to adapt to external forces and inhibit previously learned sequences. Moreover, it is thought that decreased lateralization of neural function in older adults may point to increased neural recruitment as a compensatory response to deterioration of key frontal and intra-hemispheric networks, particularly of callosal structures. However, factors that mediate age-related motor decline are not well understood. Here we show that music training in childhood is associated with reduced age-related decline of bimanual and unimanual motor skills in a MIDI keyboard motor learning task. Compared to older adults without music training, older adults with more than a year of music training demonstrated proficient bimanual and unimanual movement, evidenced by enhanced speed and decreased movement errors. Further, this group demonstrated significantly better implicit learning in the weather prediction task, a non-motor task. The performance of older adults with music training in those tasks was comparable to young adults. Older adults, however, displayed greater verbal ability compared to young adults irrespective of a past history of music training. Our results indicate that music training early in life may reduce age-associated decline of neural motor and cognitive networks. PMID:23423702

Pilot age and expertise predict flight simulator performance

PubMed Central

Kennedy, Quinn; Noda, Art; Yesavage, Jerome A.

2010-01-01

Background Expert knowledge may compensate for age-related declines in basic cognitive and sensory-motor abilities in some skill domains. We investigated the influence of age and aviation expertise (indexed by Federal Aviation Administration pilot ratings) on longitudinal flight simulator performance. Methods Over a 3-year period, 118 general aviation pilots aged 40 to 69 years were tested annually, in which their flight performance was scored in terms of 1) executing air-traffic controller communications; 2) traffic avoidance; 3) scanning cockpit instruments; 4) executing an approach to landing; and 5) a flight summary score. Results More expert pilots had better flight summary scores at baseline and showed less decline over time. Secondary analyses revealed that expertise effects were most evident in the accuracy of executing aviation communications, the measure on which performance declined most sharply over time. Regarding age, even though older pilots initially performed worse than younger pilots, over time older pilots showed less decline in flight summary scores than younger pilots. Secondary analyses revealed that the oldest pilots did well over time because their traffic avoidance performance improved more vs younger pilots. Conclusions These longitudinal findings support previous cross-sectional studies in aviation as well as non-aviation domains, which demonstrated the advantageous effect of prior experience and specialized expertise on older adults’ skilled cognitive performances. PMID:17325270

Association of Long-Term Adherence to the MIND Diet with Cognitive Function and Cognitive Decline in American Women.

PubMed

Berendsen, A M; Kang, J H; Feskens, E J M; de Groot, C P G M; Grodstein, F; van de Rest, O

2018-01-01

There is increasing attention for dietary patterns as a potential strategy to prevent cognitive decline. We examined the association between adherence to a recently developed Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with cognitive function and cognitive decline, taking into account the interaction between the apolipoprotein E ε4 genotype and the MIND diet. Population-based prospective cohort study. A total of 16,058 older women aged 70 and over from the Nurses' Health Study. Dietary intake was assessed five times between 1984 and 1998 with a 116-item Food Frequency Questionnaire. The MIND score includes ten brain-healthy foods and five unhealthy foods. Cognition was assessed four times by telephone from 1995 to 2001 (baseline) with the Telephone Interview for Cognitive Status (TICS) and by calculating composite scores of verbal memory and global cognition. Linear regression modelling and linear mixed modelling were used to examine the associations of adherence to the MIND diet with average cognitive function and cognitive change over six years, respectively. Greater long-term adherence to the MIND diet was associated with a better verbal memory score (multivariable-adjusted mean differences between extreme MIND quintiles=0.04 (95%CI 0.01-0.07), p-trend=0.006), but not with cognitive decline over 6 years in global cognition, verbal memory or TICS. Long-term adherence to the MIND diet was moderately associated with better verbal memory in later life. Future studies should address this association within populations at greater risk of cognitive decline.

Cognitive resilience to apolipoprotein E ε4: contributing factors in black and white older adults.

PubMed

Kaup, Allison R; Nettiksimmons, Jasmine; Harris, Tamara B; Sink, Kaycee M; Satterfield, Suzanne; Metti, Andrea L; Ayonayon, Hilsa N; Yaffe, Kristine

2015-03-01

Apolipoprotein E (APOE) ε4 is an established risk factor for cognitive decline and the development of dementia, but other factors may help to minimize its effects. Using APOE ε4 as an indicator of high risk, we investigated factors associated with cognitive resilience among black and white older adults who are APOE ε4 carriers. Participants included 2487 community-dwelling older (aged 69-80 years at baseline) black and white adults examined at 2 community clinics in the prospective cohort Health, Aging, and Body Composition (Health ABC) study. The baseline visits occurred from May 1997 through June 1998. Our primary analytic cohort consisted of 670 APOE ε4 carriers (329 black and 341 white participants) who were free of cognitive impairment at baseline and underwent repeated cognitive testing during an 11-year follow-up (through 2008) using the Modified Mini-Mental State Examination. We stratified all analyses by race. Using the Modified Mini-Mental State Examination scores, we assessed normative cognitive change in the entire cohort (n = 2487) and classified the APOE ε4 carriers as being cognitively resilient vs nonresilient by comparing their cognitive trajectories with those of the entire cohort. We then conducted bivariate analyses and multivariable random forest and logistic regression analyses to explore factors predictive of cognitive resilience in APOE ε4 carriers. Among white APOE ε4 carriers, the strongest predictors of cognitive resilience were, in relative order of importance, no recent negative life events, a higher literacy level, advanced age, a higher educational level, and more time spent reading. Among black APOE ε4 carriers, the strongest predictors of cognitive resilience were, in relative order of importance, a higher literacy level, a higher educational level, female sex, and the absence of diabetes mellitus. In follow-up logistic regression models, higher literacy level (adjusted odds ratio [OR], 9.50 [95% CI, 2.67-60.89]), a higher educational level (adjusted OR for college graduate vs less than high school, 3.81 [95% CI, 1.13-17.56]), and age (adjusted OR for 73-76 vs 69-72 years, 2.01 [95% CI, 1.13-3.63]) had significant independent effects in predicting cognitive resilience among white APOE ε4 carriers. Among black APOE ε4 carriers, a higher literacy level (adjusted OR, 2.27 [95% CI, 1.29-4.06]) and a higher educational level (adjusted OR for high school graduate/some college vs less than high school, 2.86 [95% CI, 1.54-5.49]; adjusted OR for college graduate vs less than high school, 2.52 [95% CI, 1.14-5.62]) had significant independent effects in predicting cognitive resilience. Although APOE ε4 carriers are at high risk for cognitive decline, our findings suggest possible intervention targets, including the enhancement of cognitive reserve and improvement of other psychosocial and health factors, to promote cognitive resilience among black and white APOE ε4 carriers.

Disease Progression in Mild Dementia due to Alzheimer Disease in an 18-Month Observational Study (GERAS): The Impact on Costs and Caregiver Outcomes.

PubMed

Jones, Roy W; Lebrec, Jeremie; Kahle-Wrobleski, Kristin; Dell'Agnello, Grazia; Bruno, Giuseppe; Vellas, Bruno; Argimon, Josep M; Dodel, Richard; Haro, Josep Maria; Wimo, Anders; Reed, Catherine

2017-01-01

We assessed whether cognitive and functional decline in community-dwelling patients with mild Alzheimer disease (AD) dementia were associated with increased societal costs and caregiver burden and time outcomes. Cognitive decline was defined as a ≥3-point reduction in the Mini-Mental State Examination and functional decline as a decrease in the ability to perform one or more basic items of the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) or ≥20% of instrumental ADL items. Total societal costs were estimated from resource use and caregiver hours using 2010 costs. Caregiver burden was assessed using the Zarit Burden Interview (ZBI); caregiver supervision and total hours were collected. Of 566 patients with mild AD enrolled in the GERAS study, 494 were suitable for the current analysis. Mean monthly total societal costs were greater for patients showing functional (+61%) or cognitive decline (+27%) compared with those without decline. In relation to a typical mean monthly cost of approximately EUR 1,400 at baseline, this translated into increases over 18 months to EUR 2,254 and 1,778 for patients with functional and cognitive decline, respectively. The number of patients requiring supervision doubled among patients showing functional or cognitive decline compared with those not showing decline, while caregiver total time increased by 70 and 33%, respectively and ZBI total score by 5.3 and 3.4 points, respectively. Cognitive and, more notably, functional decline were associated with increases in costs and caregiver outcomes in patients with mild AD dementia.

Progression from Mild Cognitive Impairment to Alzheimer's disease: effects of gender, butyrylcholinesterase genotype and rivastigmine treatment

PubMed Central

Ferris, Steven; Nordberg, Agneta; Soininen, Hilkka; Darreh-Shori, Taher; Lane, Roger

2014-01-01

Objective Evaluate the influence of gender and butyrylcholinesterase (BuChE) genotype on incidence of progression to AD, rate of cognitive and functional decline, and response to rivastigmine treatment in mild cognitive impairment (MCI) subjects. Methods This retrospective exploratory analysis from a 3–4 year, randomized, placebo-controlled study of rivastigmine in MCI subjects included participants who consented to pharmacogenetic testing. Results Of 1018 total patients, 490 (253 [52%] female) were successfully genotyped for BuChE. In subjects receiving placebo, the BuChE wt/wt genotype was associated with a statistically significantly higher rate of progression to AD and functional decline in women, compared with men with the BuChE wt/wt genotype. In subjects with a BuChE-K allele receiving placebo, incidence of progression to AD and rate of functional decline were not significantly different by gender, however cognitive decline was significantly faster in men. Statistically significant benefits of rivastigmine treatment on progression to AD, functional decline, ventricular volume expansion, whole brain atrophy and white matter loss were evident in female BuChE wt/wt. Conclusion Gender appears to differentially influence the type of decline in MCI subjects according to BuChE genotype, with more rapid progression of cognitive decline in male BuChE-K, and more rapid progression to AD and functional decline in female BuChE wt/wt. Cognitive decline in male BuChE-K and functional decline and progression to AD in female BuChE wt/wt were significantly attenuated by rivastigmine. Rivastigmine treatment also significantly reduced ventricular expansion, whole brain atrophy rate and white matter loss in female BuChE wt/wt, suggesting a possible disease-modifying effect. PMID:19617863

Lipid Profiles and APOE4 Allele Impact Midlife Cognitive Decline in HIV-Infected Men on Antiretroviral Therapy.

PubMed

Mukerji, Shibani S; Locascio, Joseph J; Misra, Vikas; Lorenz, David R; Holman, Alex; Dutta, Anupriya; Penugonda, Sudhir; Wolinsky, Steven M; Gabuzda, Dana

2016-10-15

Dyslipidemia and apolipoprotein E4 (APOE ϵ4) allele are risk factors for age-related cognitive decline, but how these risks are modified by human immunodeficiency virus (HIV) infection is unclear. In a longitudinal nested study from the Multicenter AIDS Cohort Study, 273 HIV type 1-infected (HIV(+)) men aged 50-65 years with baseline HIV RNA <400 copies/mL and on continuous antiretroviral therapy (ART) in ≥95% of follow-up visits were matched by sociodemographic variables to 516 HIV-uninfected (HIV(-)) controls. The association between lipid markers (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides), APOE genotype, and cognitive decline in HIV infection was examined using mixed-effects models. The median baseline age of participants was 51, 81% were white, and 89% had education >12 years. HIV(+) men had similar baseline total cholesterol and LDL-C, but lower HDL-C and higher triglycerides than controls (P < .001). Higher total cholesterol and LDL-C were associated with faster rates of cognitive decline (P < .01), whereas higher HDL-C attenuated decline (P = .02) in HIV(+) men. In HIV(+) men with elevated cholesterol, statin use was associated with a slower estimated rate of decline (P = .02). APOE ϵ4 genotype accelerated cognitive decline in HIV(+) but not HIV(-) men (P = .01), with trajectories diverging from HIV(-) ε4 carriers after age 50. Total cholesterol levels did not modify the association of ϵ4 genotype with decline (P = .9). Elevated cholesterol and APOE ϵ4 genotype are independent risk factors for cognitive decline in ART-adherent HIV(+) men aged >50 years. Treatment of dyslipidemia may be an effective strategy to reduce cognitive decline in older HIV(+) individuals. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Use it or lose it: engaged lifestyle as a buffer of cognitive decline in aging?

PubMed

Hultsch, D F; Hertzog, C; Small, B J; Dixon, R A

1999-06-01

Data from the Victoria Longitudinal Study were used to examine the hypothesis that maintaining intellectual engagement through participation in everyday activities buffers individuals against cognitive decline in later life. The sample consisted of 250 middle-aged and older adults tested 3 times over 6 years. Structural equation modeling techniques were used to examine the relationships among changes in lifestyle variables and an array of cognitive variables. There was a relationship between changes in intellectually related activities and changes in cognitive functioning. These results are consistent with the hypothesis that intellectually engaging activities serve to buffer individuals against decline. However, an alternative model suggested the findings were also consistent with the hypothesis that high-ability individuals lead intellectually active lives until cognitive decline in old age limits their activities.

Subjective cognitive decline: self and informant comparisons.

PubMed

Caselli, Richard J; Chen, Kewei; Locke, Dona E C; Lee, Wendy; Roontiva, Auttawut; Bandy, Dan; Fleisher, Adam S; Reiman, Eric M

2014-01-01

It is unclear whether self- or informant-based subjective cognition better distinguishes emotional factors from early-stage Alzheimer's disease (AD). Healthy members (n = 447) of the Arizona apolipoprotein E (APOE) cohort and their informants completed the self and informant paired Multidimensional Assessment of Neurodegenerative Symptoms questionnaire (MANS). Decline on the MANS was endorsed by 30.6% of members and 26.2% of informants. Self- and informant-based decliners had higher scores of psychological distress and slightly lower cognitive scores than nondecliners. Over the next 6.7 years, 20 developed mild cognitive impairment (MCI). Converters were older at entry than nonconverters (63.8 [7.0] vs 58.8 [7.3] years, P = .003), 85% were APOE ε4 carriers (P < .0001), and they self-endorsed decline earlier than informants (58.9 [39.2] vs 28.0 [40.4] months before MCI; P = .002). Self- and informant-based subjective decline correlated with greater psychological distress and slightly lower cognitive performance. Those with incident MCI generally self-endorsed decline earlier than informants. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Early Recognition of Chronic Traumatic Encephalopathy through FDDNP PET Imaging

DTIC Science & Technology

2014-10-01

Encephalopathy through FDDNP PET Imaging PRINCIPAL INVESTIGATOR: Charles Bernick, MD, MPH...Traumatic Encephalopathy through FDDNP PET Imaging 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0486 5c. PROGRAM ELEMENT NUMBER 6... Encephalopathy . This project will examine whether FDDNP PET imaging correlates with, and/or can predict, decline in cognitive function in those exposed to

Assessing the association between homocysteine and cognition: reflections on Bradford Hill, meta-analyses, and causality.

PubMed

McCaddon, Andrew; Miller, Joshua W

2015-10-01

Hyperhomocysteinemia is a recognized risk factor for cognitive decline and incident dementia in older adults. Two recent reports addressed the cumulative epidemiological evidence for this association but expressed conflicting opinions. Here, the evidence is reviewed in relation to Sir Austin Bradford Hill's criteria for assessing "causality," and the latest meta-analysis of the effects of homocysteine-lowering on cognitive function is critically examined. The meta-analysis included 11 trials, collectively assessing 22,000 individuals, that examined the effects of B vitamin supplements (folic acid, vitamin B12, vitamin B6) on global or domain-specific cognitive decline. It concluded that homocysteine-lowering with B vitamin supplements has no significant effect on cognitive function. However, careful examination of the trials in the meta-analysis indicates that no conclusion can be made regarding the effects of homocysteine-lowering on cognitive decline, since the trials typically did not include individuals who were experiencing such decline. Further definitive trials in older adults experiencing cognitive decline are still urgently needed. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Longitudinal Relationships Between Resources, Motivation, and Functioning

PubMed Central

Emery, Lisa; Neupert, Shevaun D.

2012-01-01

Objectives. We investigated how fluctuations and linear changes in health and cognitive resources influence the motivation to engage in complex cognitive activity and the extent to which motivation mediated the relationship between changing resources and cognitively demanding activities. Method. Longitudinal data from 332 adults aged 20–85 years were examined. Motivation was assessed using a composite of Need for Cognition and Personal Need for Structure and additional measures of health, sensory functioning, cognitive ability, and self-reported activity engagement. Results. Multilevel modeling revealed that age-typical changes in health, sensory functions, and ability were associated with changes in motivation, with the impact of declining health on motivation being particularly strong in older adulthood. Changes in motivation, in turn, predicted involvement in cognitive and social activities as well as changes in cognitive ability. Finally, motivation was observed to partially mediate the relationship between changes in resources and cognitively demanding activities. Discussion. Our results suggest that motivation may play an important role in determining the course of cognitive change and involvement in cognitively demanding everyday activities in adulthood. PMID:21926400

Sensory-Cognitive Interactions in Older Adults

PubMed Central

Humes, Larry E.; Young, Levi A.

2016-01-01

Objectives To review evidence regarding sensory and cognitive interactions in older adults published since 2009, the approximate date of the most recent reviews on this topic. Design Following an electronic database search of articles published in English since 2009 on measures of hearing and cognition or vision and cognition in older adults, a total of 437 articles were identified. Screening by title and abstract for appropriateness of topic and for articles presenting original research in peer-reviewed journals reduced the final number of articles reviewed to 34. These articles were qualitatively evaluated and synthesized with the existing knowledge base. Results Additional evidence has been obtained since 2009 associating declines in vision, hearing, or both with declines in cognition among older adults. The observed sensory-cognitive associations are generally stronger when more than one sensory domain is measured and when the sensory measures involve more than simple threshold sensitivity. Conclusions Evidence continues to accumulate supporting a link between decline in sensory function and cognitive decline in older adults. PMID:27355770

Sensory-Cognitive Interactions in Older Adults.

PubMed

Humes, Larry E; Young, Levi A

2016-01-01

The objective of this study was regarding sensory and cognitive interactions in older adults published since 2009, the approximate date of the most recent reviews on this topic. After an electronic database search of articles published in English since 2009 on measures of hearing and cognition or vision and cognition in older adults, a total of 437 articles were identified. Screening by title and abstract for appropriateness of topic and for articles presenting original research in peer-reviewed journals reduced the final number of articles reviewed to 34. These articles were qualitatively evaluated and synthesized with the existing knowledge base. Additional evidence has been obtained since 2009 associating declines in vision, hearing, or both with declines in cognition among older adults. The observed sensory-cognitive associations are generally stronger when more than one sensory domain is measured and when the sensory measures involve more than simple threshold sensitivity. Evidence continues to accumulate supporting a link between decline in sensory function and cognitive decline in older adults.

Cognitive ability predicts motor learning on a virtual reality game in patients with TBI.

PubMed

O'Neil, Rochelle L; Skeel, Reid L; Ustinova, Ksenia I

2013-01-01

Virtual reality games and simulations have been utilized successfully for motor rehabilitation of individuals with traumatic brain injury (TBI). Little is known, however, how TBI-related cognitive decline affects learning of motor tasks in virtual environments. To fill this gap, we examined learning within a virtual reality game involving various reaching motions in 14 patients with TBI and 15 healthy individuals with different cognitive abilities. All participants practiced ten 90-second gaming trials to assess various aspects of motor learning. Cognitive abilities were assessed with a battery of tests including measures of memory, executive functioning, and visuospatial ability. Overall, participants with TBI showed both reduced performance and a slower learning rate in the virtual reality game compared to healthy individuals. Numerous correlations between overall performance and several of the cognitive ability domains were revealed for both the patient and control groups, with the best predictor being overall cognitive ability. The results may provide a starting point for rehabilitation programs regarding which cognitive domains interact with motor learning.

Age-Related Changes of Adaptive and Neuropsychological Features in Persons with Down Syndrome

PubMed Central

Ghezzo, Alessandro; Salvioli, Stefano; Solimando, Maria Caterina; Palmieri, Alice; Chiostergi, Chiara; Scurti, Maria; Lomartire, Laura; Bedetti, Federica; Cocchi, Guido; Follo, Daniela; Pipitone, Emanuela; Rovatti, Paolo; Zamberletti, Jessica; Gomiero, Tiziano; Castellani, Gastone; Franceschi, Claudio

2014-01-01

Down Syndrome (DS) is characterised by premature aging and an accelerated decline of cognitive functions in the vast majority of cases. As the life expectancy of DS persons is rapidly increasing, this decline is becoming a dramatic health problem. The aim of this study was to thoroughly evaluate a group of 67 non-demented persons with DS of different ages (11 to 66 years), from a neuropsychological, neuropsychiatric and psychomotor point of view in order to evaluate in a cross-sectional study the age-related adaptive and neuropsychological features, and to possibly identify early signs predictive of cognitive decline. The main finding of this study is that both neuropsychological functions and adaptive skills are lower in adult DS persons over 40 years old, compared to younger ones. In particular, language and short memory skills, frontal lobe functions, visuo-spatial abilities and adaptive behaviour appear to be the more affected domains. A growing deficit in verbal comprehension, along with social isolation, loss of interest and greater fatigue in daily tasks, are the main features found in older, non demented DS persons evaluated in our study. It is proposed that these signs can be alarm bells for incipient dementia, and that neuro-cognitive rehabilitation and psycho-pharmacological interventions must start as soon as the fourth decade (or even earlier) in DS persons, i.e. at an age where interventions can have the greatest efficacy. PMID:25419980

Thinner cortex in patients with subjective cognitive decline is associated with steeper decline of memory.

PubMed

Verfaillie, Sander C J; Slot, Rosalinde E; Tijms, Betty M; Bouwman, Femke; Benedictus, Marije R; Overbeek, Jozefien M; Koene, Teddy; Vrenken, Hugo; Scheltens, Philip; Barkhof, Frederik; van der Flier, Wiesje M

2018-01-01

We aimed to investigate associations between regional cortical thickness and rate of decline over time in 4 cognitive domains in patients with subjective cognitive decline (SCD). We included 233 SCD patients with the total number of 654 neuropsychological assessments (median = 3, range = 2-8) and available baseline magnetic resonance imaging from the Amsterdam Dementia Cohort (125 males, age: 63 ± 9, Mini-Mental State Examination score: 28 ± 2). We assessed longitudinal cognitive functioning at baseline and follow-up in 4 cognitive domains (composite Z-scores): memory, attention, executive function, and language. Thickness (millimeter) was estimated using FreeSurfer for frontal, temporal, parietal, cingulate, and occipital cortices. We used linear mixed models to estimate effects of cortical thickness on cognitive performance (dependent variables). There were no associations between cortical thickness and baseline cognition, but a faster subsequent rate of memory loss was associated with thinner cortex of the frontal [β (SE) = 0.20 (0.07)], temporal [β (SE) = 0.18 (0.07)], and occipital [β (SE) = 0.22 (0.09)] cortices (all p < 0.05 FDR ). These findings illustrate that early cortical changes, particularly in the temporal cortex, herald incipient cognitive decline related to neurodegenerative diseases, most prominently Alzheimer's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Cognitive Decline in Older Persons Initiating Anticholinergic Medications

PubMed Central

Shah, Raj C.; Janos, Alicia L.; Kline, Julia E.; Yu, Lei; Leurgans, Sue E.; Wilson, Robert S.; Wei, Peter; Bennett, David A.; Heilman, Kenneth M.; Tsao, Jack W.

2013-01-01

Background This study examines the effect of initiating medications with anticholinergic activity on the cognitive functions of older persons. Methods Participants were 896 older community-dwelling, Catholic clergy without baseline dementia. Medication data was collected annually. The Anticholinergic Cognitive Burden Scale was utilized to identify use of a medication with probable or definite anticholinergic activity. Participants had at least two annual cognitive evaluations. Results Over a mean follow-up of 10 years, the annual rate of global cognitive function decline for never users, prevalent users, and incident users was −0.062 (SE = 0.005), −0.081(SE = 0.011), and −0.096 (SE = 0.007) z-score units/year, respectively. Compared to never users, incident users had a more rapid decline (difference = −0.034 z-score units/year, SE = 0.008, p<0.001) while prevalent users did not have a significantly more rapid decline (p = 0.1). Conclusions Older persons initiating a medication with anticholinergic activity have a steeper annual decline in cognitive functioning than those who are not taking these medications. PMID:23741303

MIND diet slows cognitive decline with aging.

PubMed

Morris, Martha Clare; Tangney, Christy C; Wang, Yamin; Sacks, Frank M; Barnes, Lisa L; Bennett, David A; Aggarwal, Neelum T

2015-09-01

The Mediterranean and dash diets have been shown to slow cognitive decline; however, neither diet is specific to the nutrition literature on dementia prevention. We devised the Mediterranean-Dietary Approach to Systolic Hypertension (DASH) diet intervention for neurodegenerative delay (MIND) diet score that specifically captures dietary components shown to be neuroprotective and related it to change in cognition over an average 4.7 years among 960 participants of the Memory and Aging Project. In adjusted mixed models, the MIND score was positively associated with slower decline in global cognitive score (β = 0.0092; P < .0001) and with each of five cognitive domains. The difference in decline rates for being in the top tertile of MIND diet scores versus the lowest was equivalent to being 7.5 years younger in age. The study findings suggest that the MIND diet substantially slows cognitive decline with age. Replication of these findings in a dietary intervention trial would be required to verify its relevance to brain health. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

APOE, MAPT, and COMT and Parkinson's Disease Susceptibility and Cognitive Symptom Progression.

PubMed

Paul, Kimberly C; Rausch, Rebecca; Creek, Michelle M; Sinsheimer, Janet S; Bronstein, Jeff M; Bordelon, Yvette; Ritz, Beate

2016-04-02

Cognitive decline is well recognized in Parkinson's disease (PD) and a major concern for patients and caregivers. Apolipoprotein E (APOE), catechol-O-methyl transferase (COMT), and microtubule-associated protein tau (MAPT) are of interest related to their contributions to cognitive decline or dementia in PD. Here, we investigate whether APOE, COMT, or MAPT influence the rate of cognitive decline in PD patients. We relied on 634 PD patients and 879 controls to examine gene-PD susceptibility associations, and nested longitudinal cohort of 246 patients from the case-control study, which followed patients on average 5 years and 7.5 years into disease. We repeatedly assessed cognitive symptom progression with the MMSE and conducted a full neuropsychological battery on a subset of 183 cognitively normal patients. We used repeated-measures regression analyses to assess longitudinal associations between genotypes and cognitive progression scores. The MAPT H1 haplotype was associated with PD susceptibility. APOE 4 carriers (ɛ4+) (p = 0.03) and possibly COMT Met/Met (p = 0.06) carriers exhibited faster annual decline on the MMSE. Additionally, APOEɛ4+ carriers showed faster decline in many of the neuropsychological test scores. No such differences in neuropsychological outcomes were seen for the COMT genotypes. This work supports a growing set of research identifying overlapping etiology and pathology between synucleinopathies, such as PD, Alzheimer's disease, and tauopathies, especially in the context of cognitive dysfunction in PD. We provide support for the argument that APOE ɛ4+ and COMT Met/Met genotypes can be used as predictors of faster cognitive decline in PD.

Lagged Associations of Metropolitan Statistical Area- and State-Level Income Inequality with Cognitive Function: The Health and Retirement Study.

PubMed

Kim, Daniel; Griffin, Beth Ann; Kabeto, Mohammed; Escarce, José; Langa, Kenneth M; Shih, Regina A

2016-01-01

Much variation in individual-level cognitive function in late life remains unexplained, with little exploration of area-level/contextual factors to date. Income inequality is a contextual factor that may plausibly influence cognitive function. In a nationally-representative cohort of older Americans from the Health and Retirement Study, we examined state- and metropolitan statistical area (MSA)-level income inequality as predictors of individual-level cognitive function measured by the 27-point Telephone Interview for Cognitive Status (TICS-m) scale. We modeled latency periods of 8-20 years, and controlled for state-/metropolitan statistical area (MSA)-level and individual-level factors. Higher MSA-level income inequality predicted lower cognitive function 16-18 years later. Using a 16-year lag, living in a MSA in the highest income inequality quartile predicted a 0.9-point lower TICS-m score (β = -0.86; 95% CI = -1.41, -0.31), roughly equivalent to the magnitude associated with five years of aging. We observed no associations for state-level income inequality. The findings were robust to sensitivity analyses using propensity score methods. Among older Americans, MSA-level income inequality appears to influence cognitive function nearly two decades later. Policies reducing income inequality levels within cities may help address the growing burden of declining cognitive function among older populations within the United States.

Lagged Associations of Metropolitan Statistical Area- and State-Level Income Inequality with Cognitive Function: The Health and Retirement Study

PubMed Central

Kim, Daniel; Griffin, Beth Ann; Kabeto, Mohammed; Escarce, José; Langa, Kenneth M.; Shih, Regina A.

2016-01-01

Purpose Much variation in individual-level cognitive function in late life remains unexplained, with little exploration of area-level/contextual factors to date. Income inequality is a contextual factor that may plausibly influence cognitive function. Methods In a nationally-representative cohort of older Americans from the Health and Retirement Study, we examined state- and metropolitan statistical area (MSA)-level income inequality as predictors of individual-level cognitive function measured by the 27-point Telephone Interview for Cognitive Status (TICS-m) scale. We modeled latency periods of 8–20 years, and controlled for state-/metropolitan statistical area (MSA)-level and individual-level factors. Results Higher MSA-level income inequality predicted lower cognitive function 16–18 years later. Using a 16-year lag, living in a MSA in the highest income inequality quartile predicted a 0.9-point lower TICS-m score (β = -0.86; 95% CI = -1.41, -0.31), roughly equivalent to the magnitude associated with five years of aging. We observed no associations for state-level income inequality. The findings were robust to sensitivity analyses using propensity score methods. Conclusions Among older Americans, MSA-level income inequality appears to influence cognitive function nearly two decades later. Policies reducing income inequality levels within cities may help address the growing burden of declining cognitive function among older populations within the United States. PMID:27332986

Plasma α-synuclein and cognitive impairment in the Parkinson's Associated Risk Syndrome: A pilot study.

PubMed

Wang, Hua; Atik, Anzari; Stewart, Tessandra; Ginghina, Carmen; Aro, Patrick; Kerr, Kathleen F; Seibyl, John; Jennings, Danna; Jensen, Poul Henning; Marek, Kenneth; Shi, Min; Zhang, Jing

2018-04-27

Plasma total and nervous system derived exosomal (NDE) α-synuclein have been determined as potential biomarkers of Parkinson's disease (PD). To explore the utility of plasma α-synuclein in the prodromal phase of PD, plasma total and NDE α-synuclein were evaluated in baseline and 2-year follow-up samples from 256 individuals recruited as part of the Parkinson's Associated Risk Syndrome (PARS) study. The results demonstrated that baseline and longitudinal increases in total α-synuclein predicted progression of cognitive decline in hyposmic individuals with dopamine transporter (DAT) binding reduction. On the other hand, a longitudinal decrease in NDE α-synuclein predicted worsening cognitive scores in hyposmic individuals with DAT binding reduction. Finally, in individuals with faster DAT progression, decreasing NDE/total α-synuclein ratio was associated with a larger reduction in DAT from baseline to follow-up. These results suggest that, though underlying mechanisms remain to be defined, alterations in plasma total and NDE α-synuclein concentrations are likely associated with PD progression, especially in the aspect of cognitive impairment, at early stages of the disease. Copyright © 2018. Published by Elsevier Inc.

Functional decline in the elderly with MCI: Cultural adaptation of the ADCS-ADL scale.

PubMed

Cintra, Fabiana Carla Matos da Cunha; Cintra, Marco Túlio Gualberto; Nicolato, Rodrigo; Bertola, Laiss; Ávila, Rafaela Teixeira; Malloy-Diniz, Leandro Fernandes; Moraes, Edgar Nunes; Bicalho, Maria Aparecida Camargos

2017-07-01

Translate, transcultural adaptation and application to Brazilian Portuguese of the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale as a cognitive screening instrument. We applied the back translation added with pretest and bilingual methods. The sample was composed by 95 elderly individuals and their caregivers. Thirty-two (32) participants were diagnosed as mild cognitive impairment (MCI) patients, 33 as Alzheimer's disease (AD) patients and 30 were considered as cognitively normal individuals. There were only little changes on the scale. The Cronbach alpha coefficient was 0.89. The scores were 72.9 for control group, followed by MCI (65.1) and by AD (55.9), with a p-value < 0.001. The ROC curve value was 0.89. We considered a cut point of 72 and we observed a sensibility of 86.2%, specificity of 70%, positive predictive value of 86.2%, negative predictive value of 70%, positive likelihood ratio of 2.9 and negative likelihood ratio of 0.2. ADCS-ADL scale presents satisfactory psychometric properties to discriminate between MCI, AD and normal cognition.

Market mechanisms protect the vulnerable brain.

PubMed

Ramchandran, Kanchna; Nayakankuppam, Dhananjay; Berg, Joyce; Tranel, Daniel; Denburg, Natalie L

2011-07-01

Markets are mechanisms of social exchange, intended to facilitate trading. However, the question remains as to whether markets would help or hurt individuals with decision-makings deficits, as is frequently encountered in the case of cognitive aging. Essential for predicting future gains and losses in monetary and social domains, the striatal nuclei in the brain undergo structural, neurochemical, and functional decline with age. We correlated the efficacy of market mechanisms with dorsal striatal decline in an aging population, by using market based trading in the context of the 2008 U.S. Presidential Elections (primary cycle). Impaired decision-makers displayed higher prediction error (difference between their prediction and actual outcome). Lower in vivo caudate volume was also associated with higher prediction error. Importantly, market-based trading protected older adults with lower caudate volume to a greater extent from their own poorly calibrated predictions. Counterintuitive to the traditional public perception of the market as a fickle, risky proposition where vulnerable traders are most surely to be burned, we suggest that market-based mechanisms protect individuals with brain-based decision-making vulnerabilities. Copyright © 2011 Elsevier Ltd. All rights reserved.

Market mechanisms protect the vulnerable brain

PubMed Central

Ramchandran, Kanchna; Nayakankuppam, Dhananjay; Berg, Joyce; Tranel, Daniel

2011-01-01

Markets are mechanisms of social exchange, intended to facilitate trading. However, the question remains as to whether markets would help or hurt individuals with decision-makings deficits, as is frequently encountered in the case of cognitive aging. Essential for predicting future gains and losses in monetary and social domains, the striatal nuclei in the brain undergo structural, neurochemical, and functional decline with age. We correlated the efficacy of market mechanisms with dorsal striatal decline in an aging population, by using market based trading in the context of the 2008 U.S Presidential Elections (primary cycle). Impaired decision-makers displayed higher prediction error (difference between their prediction and actual outcome). Lower in vivo caudate volume was also associated with higher prediction error. Importantly, market-based trading protected older adults with lower caudate volume to a greater extent from their own poorly calibrated predictions. Counterintuitive to the traditional public perception of the market as a fickle, risky proposition where vulnerable traders are most surely to be burned, we suggest that market-based mechanisms protect individuals with brain-based decision-making vulnerabilities. PMID:21600226

Linking the developmental and degenerative theories of schizophrenia: association between infant development and adult cognitive decline.

PubMed

Kobayashi, Hiroyuki; Isohanni, Matti; Jääskeläinen, Erika; Miettunen, Jouko; Veijola, Juha; Haapea, Marianne; Järvelin, Marjo-Riitta; Jones, Peter B; Murray, Graham K

2014-11-01

Neurodevelopmental and neurodegenerative theories may be viewed as incompatible accounts that compete to explain the pathogenesis of schizophrenia. However, it is possible that neurodevelopmental and neurodegenerative processes could both reflect common underlying causal mechanisms. We hypothesized that cognitive dysfunction would gradually deteriorate over time in schizophrenia and the degree of this deterioration in adulthood would be predicted by an infant measure of neurodevelopment. We aimed to examine the association between age of learning to stand in infancy and deterioration of cognitive function in adulthood. Participants were nonpsychotic control subjects (n = 76) and participants with schizophrenia (n = 36) drawn from the Northern Finland 1966 Birth Cohort study. The schizophrenia group showed greater deterioration in abstraction with memory than controls, but there were no differences between schizophrenia and controls in rate of change of other cognitive measures. Age of learning to stand in infancy significantly inversely predicted later deterioration of abstraction with memory in adult schizophrenia (later infant development linked to greater subsequent cognitive deterioration during adulthood), possibly suggesting a link between abnormal neurodevelopmental and neurodegenerative processes in schizophrenia. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Dissociated control as a signature of typological variability in high hypnotic suggestibility.

PubMed

Terhune, Devin Blair; Cardeña, Etzel; Lindgren, Magnus

2011-09-01

This study tested the prediction that dissociative tendencies modulate the impact of a hypnotic induction on cognitive control in different subtypes of highly suggestible individuals. Low suggestible (LS), low dissociative highly suggestible (LDHS), and high dissociative highly suggestible (HDHS) participants completed the Stroop color-naming task in control and hypnosis conditions. The magnitude of conflict adaptation (faster response times on incongruent trials preceded by an incongruent trial than those preceded by a congruent trial) was used as a measure of cognitive control. LS and LDHS participants displayed marginally superior up-regulation of cognitive control following a hypnotic induction, whereas HDHS participants' performance declined. These findings indicate that dissociative tendencies modulate the influence of a hypnotic induction on cognitive control in high hypnotic suggestibility and suggest that HS individuals are comprised of distinct subtypes with dissimilar cognitive profiles. Copyright © 2010 Elsevier Inc. All rights reserved.

Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog): Normative Data for the Portuguese Population.

PubMed

Nogueira, Joana; Freitas, Sandra; Duro, Diana; Tábuas-Pereira, Miguel; Guerreiro, Manuela; Almeida, Jorge; Santana, Isabel

2018-02-28

The Alzheimer's Disease Assessment Scale - Cognitive Subscale is a brief battery developed to assess cognitive functioning in Alzheimer's disease that encompasses the core characteristics of cognitive decline (e.g. memory, language, praxis, constructive ability and orientation). The early detection, as well as the monitoring of cognitive decline along disease progression, is extremely important in clinical care and interventional research. The main goals of the present study were to analyze the psychometric properties of the Portuguese version of the Alzheimer's Disease Assessment Scale - Cognitive Subscale, and to establish normative values for the Portuguese population. The Portuguese version of Alzheimer's Disease Assessment Scale - Cognitive Subscale was administered to 223 cognitively healthy participants according to a standard assessment protocol consisting of the Mini-Mental State Examination, the Montreal Cognitive Assessment and the Adults and Older Adults Functional Assessment Inventory. Normal performance on the assessment protocol was the inclusion criteria for the study. The Alzheimer's Disease Assessment Scale - Cognitive Subscale revealed good psychometric properties when used in the Portuguese population. Age was the main predictor of the Alzheimer's Disease Assessment Scale - Cognitive Subscale total score (R2 = 0.123), whereas the influence of education level was lower (R2 = 0.027). These two variables explained 14.4% of the variance on the Alzheimer's Disease Assessment Scale - Cognitive Subscale scores and were used to stratify the normative values for the Portuguese population presented here. On the total sample, the average total score in the Alzheimer's Disease Assessment Scale - Cognitive Subscale was 6 points. The normative data were determined according to age and educational level as these were the sociodemographic variables that significantly contributed to the prediction of the Alzheimer's Disease Assessment Scale - Cognitive Subscale total scores, explaining 14.4% of their variance. The normative data are of the utmost importance to ensure proper use of this battery in Portugal.

Childhood Cognitive Ability and Age-Related Changes in Physical Capability From Midlife: Findings From a British Birth Cohort Study.

PubMed

Cooper, Rachel; Richards, Marcus; Kuh, Diana

2017-09-01

The aim of the study was to test the hypothesis that higher childhood cognitive ability is associated with reduced risk of decline in physical capability in late midlife. Participants were 1954 men and women from the Medical Research Council National Survey of Health and Development with complete data on cognitive ability at age of 15 years and measures of grip strength and chair rise speed at ages of 53 and 60 to 64 years. Using multinomial logistic regression, associations of childhood cognitive ability with categories of change in grip strength and chair rise speed (i.e., decline, stable high, stable low, reference) were investigated. Adjustments were made for potential confounders from early life and adult mediators including health behaviors, educational level, and cognitive ability at age of 53 years. Higher childhood cognitive scores were associated with reduced risks of decline in grip strength and chair rise speed, for example, the sex-adjusted relative-risk ratio of decline (versus reference) in grip strength per 1SD increase in childhood cognitive score was 0.82 (95% confidence interval = 0.73-0.92). Higher childhood cognitive scores were also associated with reduced risk of stable low and increased likelihood of stable high chair rise speed. These findings suggest that childhood cognitive ability may be related to decline in physical capability in late midlife. A number of life course pathways are implicated, including those linking childhood and adult cognitive ability. Future research aiming to identify new opportunities to prevent or minimize age-related declines in physical capability may benefit from considering the potential role of neurodevelopmental as well as neurodegenerative pathways.

Decline in cognitive function and risk of elder self-neglect: finding from the Chicago Health Aging Project.

PubMed

Dong, XinQi; Simon, Melissa A; Wilson, Robert S; Mendes de Leon, Carlos F; Rajan, K Bharat; Evans, Denis A

2010-12-01

To examine the longitudinal association between decline in cognitive function and risk of elder self-neglect in a community-dwelling population. Prospective population-based study. Geographically defined community in Chicago. Community-dwelling subjects reported to the social services agency from 1993 to 2005 for self-neglect who also participated in the Chicago Health Aging Project (CHAP). Of the 5,519 participants in CHAP, 1,017 were reported to social services agency for suspected elder self-neglect from 1993 to 2005. Social services agency identified reported elder self-neglect. The primary predictor was decline in cognitive function assessed using the Mini-Mental State Examination (MMSE), the Symbol Digit Modalities Test (Executive Function), and immediate and delayed recall of the East Boston Memory Test (Episodic Memory). An index of global cognitive function scores was derived by averaging z-scores of all tests. Outcome of interest was elder self-neglect. Logistic and linear regression models were used to assess these longitudinal associations. After adjusting for potential confounding factors, decline in global cognitive function, MMSE score, and episodic memory were not independently associated with greater risk of reported and confirmed elder self-neglect. Decline in executive function was associated with greater risk of reported and confirmed elder self-neglect. Decline in global cognitive function was associated with greater risk of greater self-neglect severity (parameter estimate=0.76, standard error=0.31, P=.01). Decline in executive function was associated with risk of reported and confirmed elder self-neglect. Decline in global cognitive function was associated with risk of greater self-neglect severity. © 2010, Copyright the Authors. Journal compilation © 2010, The American Geriatrics Society.

Imaging-based biomarkers of cognitive performance in older adults constructed via high-dimensional pattern regression applied to MRI and PET.

PubMed

Wang, Ying; Goh, Joshua O; Resnick, Susan M; Davatzikos, Christos

2013-01-01

In this study, we used high-dimensional pattern regression methods based on structural (gray and white matter; GM and WM) and functional (positron emission tomography of regional cerebral blood flow; PET) brain data to identify cross-sectional imaging biomarkers of cognitive performance in cognitively normal older adults from the Baltimore Longitudinal Study of Aging (BLSA). We focused on specific components of executive and memory domains known to decline with aging, including manipulation, semantic retrieval, long-term memory (LTM), and short-term memory (STM). For each imaging modality, brain regions associated with each cognitive domain were generated by adaptive regional clustering. A relevance vector machine was adopted to model the nonlinear continuous relationship between brain regions and cognitive performance, with cross-validation to select the most informative brain regions (using recursive feature elimination) as imaging biomarkers and optimize model parameters. Predicted cognitive scores using our regression algorithm based on the resulting brain regions correlated well with actual performance. Also, regression models obtained using combined GM, WM, and PET imaging modalities outperformed models based on single modalities. Imaging biomarkers related to memory performance included the orbito-frontal and medial temporal cortical regions with LTM showing stronger correlation with the temporal lobe than STM. Brain regions predicting executive performance included orbito-frontal, and occipito-temporal areas. The PET modality had higher contribution to most cognitive domains except manipulation, which had higher WM contribution from the superior longitudinal fasciculus and the genu of the corpus callosum. These findings based on machine-learning methods demonstrate the importance of combining structural and functional imaging data in understanding complex cognitive mechanisms and also their potential usage as biomarkers that predict cognitive status.

Orthostatic Changes in Blood Pressure and Cognitive Status in the Elderly: The Progetto Veneto Anziani Study.

PubMed

Curreri, Chiara; Giantin, Valter; Veronese, Nicola; Trevisan, Caterina; Sartori, Leonardo; Musacchio, Estella; Zambon, Sabina; Maggi, Stefania; Perissinotto, Egle; Corti, Maria Chiara; Crepaldi, Gaetano; Manzato, Enzo; Sergi, Giuseppe

2016-08-01

We studied a cohort of 1408 older subjects to explore whether postural changes in blood pressure (BP; defined as orthostatic hypo- or hypertension) can predict the onset of cognitive deterioration. Orthostatic hypotension was defined as a drop of 20 mm Hg in systolic or 10 mm Hg in diastolic BP and orthostatic hypertension as a rise of 20 mm Hg in systolic BP. Orthostatic BP values were grouped into quintiles for secondary analyses. Two cognitive assessments were considered: (1) cognitive impairment, that is, Mini-Mental State Examination scores ≤24/30, and (2) cognitive decline (CD), that is, a 3-point decrease in Mini-Mental State Examination score from the baseline to the follow-up. At the baseline, the prevalence of orthostatic hypotension and hypertension was 18.3% and 10.9%, respectively. At the follow-up (4.4±1.2 years), 286 participants were found cognitively impaired and 138 had a CD. Using logistic regression analysis adjusted for potential baseline confounders, participants with orthostatic hypertension were at significantly higher risk of CD (odds ratio =1.50; 95% confidence intervals =1.26-1.78). Neither orthostatic hypotension nor orthostatic hypertension raised the risk of developing a cognitive impairment. Using quintiles of orthostatic BP values, we found that both decreases and increases in systolic and diastolic BP raised the risk of CD, but not of cognitive impairment. In conclusion, we found that orthostatic hypertension predicts the onset of CD, but not of cognitive impairment in the elderly, whereas orthostatic hypotension predicts neither of these conditions. Further studies are needed to confirm our findings. © 2016 American Heart Association, Inc.

An Evaluation of the Evidence that Methamphetamine Abuse Causes Cognitive Decline in Humans

PubMed Central

Dean, Andy C; Groman, Stephanie M; Morales, Angelica M; London, Edythe D

2013-01-01

Methamphetamine (MA) is one of the most commonly abused illicit substances worldwide. Among other problems, abuse of the drug has been associated with reduced cognitive function across several domains. However, much of the literature has not attempted to differentiate cognitive difficulties caused by MA abuse from preexisting cognitive difficulties that are likely caused by other factors. Here, we address this question, evaluating evidence for a priori hypotheses pertaining to six lines of research: (a) animal studies; (b) cross-sectional human studies; (c) a twin study; (d) studies of changes in cognition with abstinence from MA; (e) studies of changes in brain structure and function with abstinence from MA; and (f) studies of the relationship between the severity of MA abuse and the extent of cognitive deficits observed. Overall the findings were mixed, with some support for a causal relationship between MA abuse and cognitive decline, and other findings suggesting that there is no relationship. The preponderance of the data, however, does support the possibility that MA abuse causes cognitive decline, of unknown duration, in at least some users of the drug. When averaged across individuals, this decline is likely to be mild in early-to-middle adulthood. However, moderator variables are likely to contribute to the presence and/or severity of cognitive decline exhibited by a given individual. PMID:22948978

No association between dietary patterns and risk for cognitive decline in older women with nine-year follow-up: data from the Women’s Health Initiative Memory Study

PubMed Central

Haring, Bernhard; Wu, Chunyuan; Mossavar-Rahmani, Yasmin; Snetselaar, Linda; Brunner, Robert; Wallace, Robert B.; Neuhouser, Marian L.; Wassertheil-Smoller, Sylvia

2015-01-01

Background Data on the association between dietary patterns and age-related cognitive decline are inconsistent. Objective To determine whether dietary patterns assessed by the alternate Mediterranean diet score (aMED), the Healthy Eating Index (HEI) 2010, the Alternate Healthy Eating Index (AHEI) 2010 or the Dietary Approach to Stop Hypertension (DASH) diet score are associated with cognitive decline in older women. To examine if dietary patterns modify the risk for cognitive decline in hypertensive women. Design Prospective, longitudinal cohort study. Food frequency questionnaires (FFQs) were used to derive dietary patterns at baseline. Hypertension was defined as self-report of current drug therapy for hypertension or clinic measurement of SBP ≥ 140mmHg or DBP ≥ 90mmHg. Participants/setting Postmenopausal women (N=6,425) aged 65 to 79 years who participated in the Women’s Health Initiative Memory Study (WHIMS) and were cognitively intact at baseline. Main Outcome Measures Cognitive decline was defined as cases of mild cognitive impairment (MCI) or probable dementia (PD). Cases were identified through rigorous screening and expert adjudication. Statistical Analyses performed Cox proportional hazards models with multivariable adjustment were used to estimate the relative risk for developing MCI or PD. Results During a median follow-up of 9.11 years, we documented 499 cases of MCI and 390 of PD. In multivariable analyses we did not detect any statistically significant relationships across quintiles of aMED, HEI-2010, DASH and AHEI-2010 scores and MCI or PD (ptrend=0.30, 0.44, 0.23 and 0.45). In hypertensive women we found no significant association between dietary patterns and cognitive decline (ptrend=0.19, 0.08, 0.07 and 0.60). Conclusions Dietary patterns characterized by the aMED, HEI-2010, AHEI-2010 or DASH dietary score were not associated with cognitive decline in older women. Adherence to a healthy dietary pattern did not modify the risk for cognitive decline in hypertensive women. PMID:27050728

Cognitive Decline and Its Risk Factors in Prevalent Hemodialysis Patients.

PubMed

Drew, David A; Weiner, Daniel E; Tighiouart, Hocine; Duncan, Sarah; Gupta, Aditi; Scott, Tammy; Sarnak, Mark J

2017-06-01

Cognitive impairment is common in patients treated with hemodialysis. The trajectory of cognitive function and risk factors for cognitive decline remain uncertain in this population. Longitudinal cohort. 314 prevalent hemodialysis patients. Age, sex, race, education level, hemodialysis vintage, cause of end-stage renal disease, and baseline history of cardiovascular disease. Cognitive function as determined by a comprehensive neurocognitive battery, administered at baseline and yearly when possible. Individual cognitive test results were reduced into 2 domain scores using principal components analysis, representing memory and executive function, which were used as our coprimary outcomes and by definition have a mean of zero and SD of 1. Mean age was 63 years; 54% were men, 22% were black, and 90% had at least a high school education. During a median follow-up of 2.1 (IQR, 0.9-4.2) years, 196 had at least 1 follow-up test, 156 died, and 43 received a kidney transplant. Linear mixed models and joint models, which accounted for competing risks from death, dropout, or kidney transplantation, showed nearly identical results. The joint model demonstrated a decline in executive function (-0.09 [95% CI, -0.13 to -0.05] SD per year), whereas memory improved slightly (0.05 [95% CI, 0.02 to 0.08] SD per year). A significant yearly decline was also seen in the Mini-Mental State Examination score (median change, -0.41; 95% CI, -0.57 to -0.25). Older age was the only significant risk factor for steeper executive function decline (-0.04 [95% CI, -0.06 to -0.02] SD steeper annual decline for each 10 years of age). Prevalent hemodialysis patients only, limited follow-up testing due to high mortality rate, and exclusion of participants with severe cognitive deficits or dementia. Prevalent hemodialysis patients demonstrate significant cognitive decline, particularly within tests of executive function. Older age was the only statistically significant risk factor for steeper cognitive decline, which may have important clinical consequences for patient management and education. Future studies should evaluate strategies to maintain or improve cognitive function. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Vitamin D Insufficiency and Cognitive Function Trajectories in Older Adults: The Rancho Bernardo Study.

PubMed

Laughlin, Gail A; Kritz-Silverstein, Donna; Bergstrom, Jaclyn; Reas, Emilie T; Jassal, Simerjot K; Barrett-Connor, Elizabeth; McEvoy, Linda K

2017-01-01

Evidence of a role for vitamin D (VitD) in cognitive aging is mixed and based primarily on extreme VitD deficiency. We evaluated the association of VitD insufficiency with cognitive function in older, community-dwelling adults living in a temperate climate with year-round sunshine. A population-based longitudinal study of 1,058 adults (median age 75; 62% women) who had cognitive function assessed and serum levels of 25-hydroxyvitaminD (25OHD) measured in 1997-99 and were followed for up to three additional cognitive function assessments over a 12-year period. Overall, 14% (n = 145) of participants had VitD insufficiency defined as 25OHD <30 ng/ml. Adjusting for age, sex, education, and season, VitD insufficiency was associated with poorer baseline performance on the Mini-Mental Status Exam (MMSE) (p = 0.013), Trails Making Test B (Trails B) (p = 0.015), Category Fluency (p = 0.006), and Long Term Retrieval (p = 0.019); differences were equivalent to 5 years of age. For those with VitD insufficiency, the odds of mildly impaired performance at baseline were 38% higher for MMSE (p = 0.08), 78% higher for Trails B (p = 0.017), and 2-fold higher for Category Fluency and Long Term Retrieval (both p = 0.001). VitD insufficiency was not related to the rate of cognitive decline on any test or the risk of developing impaired performance during follow-up. In this population with little VitD deficiency, even moderately low VitD was associated with poorer performance on multiple domains of cognitive function. Low VitD did not predict 12-year cognitive decline. Clinical trials are essential to establish a causal link between VitD and cognitive well-being.

Interleukin-6 and Depressive Mood Symptoms: Mediators of the Association Between Childhood Abuse and Cognitive Performance in Middle-Aged Adults.

PubMed

Davis, Mary C; Lemery-Chalfant, Kathryn; Yeung, Ellen WanHeung; Luecken, Linda J; Zautra, Alex J; Irwin, Michael R

2018-03-19

Childhood abuse is a risk factor for the development of cognitive deficits in adulthood, a relation that is likely mediated by stress-sensitive psychological and physiological indicators. To evaluate whether the link between exposure to childhood abuse and cognitive function in middle adulthood is mediated by interleukin-6 (IL-6), metabolic risk, and depressive mood symptoms. Participants were 770 adults aged 40-65 recruited from the community, who completed the following: (i) a questionnaire assessing exposure to abuse prior to age 18, (ii) a phone interview assessing current depressive mood symptoms, and (iii) a home visit that included blood sampling for evaluation of IL-6 and assessment of metabolic risk indices. A follow-up telephone assessment evaluating cognitive function was completed by 555 of the participants. Structural equation modeling was used to test study hypotheses. Childhood abuse predicted higher levels of IL-6, depressive mood symptoms, and metabolic risk scores (p < .05). The relation between childhood abuse and poorer cognitive performance was mediated by IL-6 (p = .046) and depressive mood symptoms (p = .023), but not metabolic risk. IL-6 and depressive mood symptoms significantly mediated the relation between childhood abuse and adult cognitive function. Exposure to early abuse conveys enduring physiological and psychological effects, which may contribute to cognitive deficits that are evident by middle adulthood. Increased vulnerability for cognitive decline among adults with a history of early trauma and the mediating roles of IL-6 and depressive mood symptoms point to the potential value of interventions that address inflammation or depression, singly or together, to prevent cognitive decline in this at-risk population.

Cardiorespiratory Fitness and Cognitive Function are Positively Related Among Participants with Mild and Subjective Cognitive Impairment.

PubMed

Stuckenschneider, Tim; Askew, Christopher David; Rüdiger, Stefanie; Cristina Polidori, Maria; Abeln, Vera; Vogt, Tobias; Krome, Andreas; Olde Rikkert, Marcel; Lawlor, Brian; Schneider, Stefan

2018-01-01

By 2030, about 74 million people will be diagnosed with dementia, and many more will experience subjective (SCI) or mild cognitive impairment (MCI). As physical inactivity has been identified to be a strong modifiable risk factor for dementia, exercise and physical activity (PA) may be important parameters to predict the progression from MCI to dementia, but might also represent disease trajectory modifying strategies for SCI and MCI. A better understanding of the relationship between activity, fitness, and cognitive function across the spectrum of MCI and SCI would provide an insight into the potential utility of PA and fitness as early markers, and treatment targets to prevent cognitive decline. 121 participants were stratified into three groups, late MCI (LMCI), early MCI (EMCI), and SCI based on the Montreal Cognitive Assessment (MoCA). Cognitive function assessments also included the Trail Making Test A+B, and a verbal fluency test. PA levels were evaluated with an interviewer-administered questionnaire (LAPAQ) and an activity monitor. An incremental exercise test was performed to estimate cardiorespiratory fitness and to determine exercise capacity relative to population normative data. ANCOVA revealed that LMCI subjects had the lowest PA levels (LAPAQ, p = 0.018; activity monitor, p = 0.041), and the lowest exercise capacity in relation to normative values (p = 0.041). Moreover, a modest correlation between MoCA and cardiorespiratory fitness (r = 0.25; p < 0.05) was found. These findings suggest that during the earliest stages of cognitive impairment PA and exercise capacity might present a marker for the risk of further cognitive decline. This finding warrants further investigation using longitudinal cohort studies.

Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future “Non-Cognitive” Outcomes of Alzheimer’s Disease

PubMed Central

Ingber, Adam P.; Hassenstab, Jason; Fagan, Anne M.; Benzinger, Tammie L.S.; Grant, Elizabeth A.; Holtzman, David M.; Morris, John C.; Roe, Catherine M.

2016-01-01

Background The influence of reserve variables and Alzheimer’s disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on “non-cognitive” outcomes, including functional abilities and mood. Objective We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior. Methods Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants. Results Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers. Conclusions The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD. PMID:27104893

Sleep-disordered breathing and the risk of cognitive decline: a meta-analysis of 19,940 participants.

PubMed

Zhu, Xiaoxia; Zhao, Yanli

2018-03-01

Sleep-disordered breathing (SDB) is related to the incidence of cognitive decline. However, results of cohort studies were inconsistent. We performed a meta-analysis of cohort studies to evaluate the sequential association between SDB and cognitive decline. Cohort studies were identified by the searching of PubMed and Embase databases. A random effect model was applied to combine the results. Nineteen thousand nine hundred forty participants from six cohort studies were included. Participants with SDB at baseline had significantly higher risk of cognitive decline, as indicated by a combined outcome of mild cognitive impairment (MCI) or dementia (RR = 1.69, p < 0.001; I 2  = 60%). The association between SDB and the subsequent risk of cognitive decline remains in older people (RR = 1.70, p < 0.001; I 2  = 66%). Results of subgroup analyses indicated consistent results regardless of whether SDB was confirmed by PSG or whether the apolipoprotein E4 allele was adjusted. However, participants with SDB at baseline were with higher risk for developing MCI (RR = 2.44, p < 0.001) than dementia (RR = 1.61, p < 0.001; p for subgroup difference = 0.04). Moreover, SDB was associated with a significantly higher risk of cognitive decline in female participants (RR = 2.06, p < 0.001), but not in the males (RR = 1.18, p = 0.19; p for subgroup difference = 0.03). SDB may be an independent risk factor for the developing of cognitive decline, and gender difference may exist regarding this association.

Age-related decline in cognitive control: the role of fluid intelligence and processing speed

PubMed Central

2014-01-01

Background Research on cognitive control suggests an age-related decline in proactive control abilities whereas reactive control seems to remain intact. However, the reason of the differential age effect on cognitive control efficiency is still unclear. This study investigated the potential influence of fluid intelligence and processing speed on the selective age-related decline in proactive control. Eighty young and 80 healthy older adults were included in this study. The participants were submitted to a working memory recognition paradigm, assessing proactive and reactive cognitive control by manipulating the interference level across items. Results Repeated measures ANOVAs and hierarchical linear regressions indicated that the ability to appropriately use cognitive control processes during aging seems to be at least partially affected by the amount of available cognitive resources (assessed by fluid intelligence and processing speed abilities). Conclusions This study highlights the potential role of cognitive resources on the selective age-related decline in proactive control, suggesting the importance of a more exhaustive approach considering the confounding variables during cognitive control assessment. PMID:24401034

Linking Cognitive and Visual Perceptual Decline in Healthy Aging: The Information Degradation Hypothesis

PubMed Central

Monge, Zachary A.; Madden, David J.

2016-01-01

Several hypotheses attempt to explain the relation between cognitive and perceptual decline in aging (e.g., common-cause, sensory deprivation, cognitive load on perception, information degradation). Unfortunately, the majority of past studies examining this association have used correlational analyses, not allowing for these hypotheses to be tested sufficiently. This correlational issue is especially relevant for the information degradation hypothesis, which states that degraded perceptual signal inputs, resulting from either age-related neurobiological processes (e.g., retinal degeneration) or experimental manipulations (e.g., reduced visual contrast), lead to errors in perceptual processing, which in turn may affect non-perceptual, higher-order cognitive processes. Even though the majority of studies examining the relation between age-related cognitive and perceptual decline have been correlational, we reviewed several studies demonstrating that visual manipulations affect both younger and older adults’ cognitive performance, supporting the information degradation hypothesis and contradicting implications of other hypotheses (e.g., common-cause, sensory deprivation, cognitive load on perception). The reviewed evidence indicates the necessity to further examine the information degradation hypothesis in order to identify mechanisms underlying age-related cognitive decline. PMID:27484869

Executive Function and Personality Predict Instrumental Activities of Daily Living in Alzheimer Disease.

PubMed

Roy, Shumita; Ficarro, Stephanie; Duberstein, Paul; Chapman, Benjamin P; Dubovsky, Steven; Paroski, Margaret; Szigeti, Kinga; Benedict, Ralph H B

2016-11-01

Previous research shows that executive function (EF) and personality independently predict functional decline. Our objective was to determine whether personality traits predict independence with instrumental activities of daily living (IADLs), after accounting for executive dysfunction, in a mixed sample of patients with amnestic mild cognitive impairment (MCI) and Alzheimer disease (AD). In a cross-sectional analysis at a university medical center, 63 healthy older adults (median age: 67.6 years; 71% women) and 119 patients (median age: 75.0 years; 58% women) with varying degrees of AD (probable AD: 85; possible AD: 3; amnestic MCI: 31) were studied. Standardized neuropsychological measures, NEO Five-Factor Inventory (NEO-FFI), and informant-report Lawton and Brody IADL scales were used. All participants underwent neuropsychological evaluation, including administration of self- and informant-report NEO-FFI. Patients additionally underwent neurologic examination, and their informants completed the Lawton and Brody IADL scale. When testing the association between EF and personality on IADLs in the patient sample, conceptual card sorting, informant-report Openness, and informant-report Conscientiousness all significantly predicted IADLs, after accounting for age, education, and depression. In addition, a significant interaction showed that low Conscientiousness and executive dysfunction, in combination, can predict impairment of IADLs. Personality has a unique association with IADLs in patients with AD pathology that is not explained by EF. The findings confirm prior speculation that personality, in addition to cognitive dysfunction, is a risk factor for functional decline. Early identification of vulnerable individuals may allow for intervention to prolong functional independence. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

High blood pressure and cognitive decline in mild cognitive impairment.

PubMed

Goldstein, Felicia C; Levey, Allan I; Steenland, N Kyle

2013-01-01

To determine whether high blood pressure (BP) levels are associated with faster decline in specific cognitive domains. Prospective longitudinal cohort. Uniform Data Set of the National Institutes of Health, National Institute on Aging Alzheimer's Disease Centers. One thousand three hundred eighty-five participants with a diagnosis of mild cognitive impairment (MCI) and measured BP values at baseline and two annual follow-up visits. Neuropsychological test scores and Clinical Dementia Rating Sum of Boxes (CDR Sum) score. Participants with MCI with two or three annual occasions of high BP values (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg) had significantly faster decline on neuropsychological measures of visuomotor sequencing, set shifting, and naming than those who were normotensive on all three occasions. High systolic BP values were associated as well with faster decline on the CDR Sum score. Hypertension is associated with faster cognitive decline in persons at risk for dementia. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

High Blood Pressure and Cognitive Decline in Mild Cognitive Impairment

PubMed Central

Goldstein, Felicia C.; Levey, Allan I.; Steenland, N. Kyle

2013-01-01

Objectives To determine whether high blood pressure (BP) levels are associated with faster decline in specific cognitive domains. Design Prospective longitudinal cohort. Setting Uniform Data Set of the National Institutes of Health, National Institute on Aging Alzheimer's Disease Centers. Participants One thousand three hundred eighty-five participants with a diagnosis of mild cognitive impairment (MCI) and measured BP values at baseline and two annual follow-up visits. Measurements Neuropsychological test scores and Clinical Dementia Rating Sum of Boxes (CDR Sum) score. Results Participants with MCI with two or three annual occasions of high BP values (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) had significantly faster decline on neuropsychological measures of visuomotor sequencing, set shifting, and naming than those who were normotensive on all three occasions. High systolic BP values were associated as well with faster decline on the CDR Sum score. Conclusion Hypertension is associated with faster cognitive decline in persons at risk for dementia. PMID:23301925

Efficacy of Cognitive Training in Older Adults with and without Subjective Cognitive Decline Is Associated with Inhibition Efficiency and Working Memory Span, Not with Cognitive Reserve.

PubMed

López-Higes, Ramón; Martín-Aragoneses, María T; Rubio-Valdehita, Susana; Delgado-Losada, María L; Montejo, Pedro; Montenegro, Mercedes; Prados, José M; de Frutos-Lucas, Jaisalmer; López-Sanz, David

2018-01-01

The present study explores the role of cognitive reserve, executive functions, and working memory (WM) span, as factors that might explain training outcomes in cognitive status. Eighty-one older adults voluntarily participated in the study, classified either as older adults with subjective cognitive decline or cognitively intact. Each participant underwent a neuropsychological assessment that was conducted both at baseline (entailing cognitive reserve, executive functions, WM span and depressive symptomatology measures, as well as the Mini-Mental State Exam regarding initial cognitive status), and then 6 months later, once each participant had completed the training program (Mini-Mental State Exam at the endpoint). With respect to cognitive status the training program was most beneficial for subjective cognitive decline participants with low efficiency in inhibition at baseline (explaining a 33% of Mini-Mental State Exam total variance), whereas for cognitively intact participants training gains were observed for those who presented lower WM span.

Handgrip Strength Predicts Functional Decline at Discharge in Hospitalized Male Elderly: A Hospital Cohort Study

PubMed Central

García-Peña, Carmen; García-Fabela, Luis C.; Gutiérrez-Robledo, Luis M.; García-González, Jose J.; Arango-Lopera, Victoria E.; Pérez-Zepeda, Mario U.

2013-01-01

Functional decline after hospitalization is a common adverse outcome in elderly. An easy to use, reproducible and accurate tool to identify those at risk would aid focusing interventions in those at higher risk. Handgrip strength has been shown to predict adverse outcomes in other settings. The aim of this study was to determine if handgrip strength measured upon admission to an acute care facility would predict functional decline (either incident or worsening of preexisting) at discharge among older Mexican, stratified by gender. In addition, cutoff points as a function of specificity would be determined. A cohort study was conducted in two hospitals in Mexico City. The primary endpoint was functional decline on discharge, defined as a 30-point reduction in the Barthel Index score from that of the baseline score. Handgrip strength along with other variables was measured at initial assessment, including: instrumental activities of daily living, cognition, depressive symptoms, delirium, hospitalization length and quality of life. All analyses were stratified by gender. Logistic regression to test independent association between handgrip strength and functional decline was performed, along with estimation of handgrip strength test values (specificity, sensitivity, area under the curve, etc.). A total of 223 patients admitted to an acute care facility between 2007 and 2009 were recruited. A total of 55 patients (24.7%) had functional decline, 23.46% in male and 25.6% in women. Multivariate analysis showed that only males with low handgrip strength had an increased risk of functional decline at discharge (OR 0.88, 95% CI 0.79–0.98, p = 0.01), with a specificity of 91.3% and a cutoff point of 20.65 kg for handgrip strength. Females had not a significant association between handgrip strength and functional decline. Measurement of handgrip strength on admission to acute care facilities may identify male elderly patients at risk of having functional decline, and intervene consequently. PMID:23936113

Age-Related Decline in Anticipatory Motor Planning and Its Relation to Cognitive and Motor Skill Proficiency.

PubMed

Stöckel, Tino; Wunsch, Kathrin; Hughes, Charmayne M L

2017-01-01

Anticipatory motor planning abilities mature as children grow older, develop throughout childhood and are likely to be stable till the late sixties. In the seventh decade of life, motor planning performance dramatically declines, with anticipatory motor planning abilities falling to levels of those exhibited by children. At present, the processes enabling successful anticipatory motor planning in general, as do the cognitive processes mediating these age-related changes, remain elusive. Thus, the aim of the present study was (a) to identify cognitive and motor functions that are most affected by normal aging and (b) to elucidate key (cognitive and motor) factors that are critical for successful motor planning performance in young ( n = 40, mean age = 23.1 ± 2.6 years) and older adults ( n = 37, mean age = 73.5 ± 7.1 years). Results indicate that normal aging is associated with a marked decline in all aspects of cognitive and motor functioning tested. However, age-related declines were more apparent for fine motor dexterity, processing speed and cognitive flexibility. Furthermore, up to 64% of the variance in motor planning performance across age groups could be explained by the cognitive functions processing speed, response planning and cognitive flexibility. It can be postulated that anticipatory motor planning abilities are strongly influenced by cognitive control processes, which seem to be key mechanisms to compensate for age-related decline. These findings support the general therapeutic and preventive value of cognitive-motor training programs to reduce adverse effects associated with high age.

Education mitigates age-related decline in N-Acetylaspartate levels.

PubMed

Erickson, Kirk I; Leckie, Regina L; Weinstein, Andrea M; Radchenkova, Polina; Sutton, Bradley P; Prakash, Ruchika Shaurya; Voss, Michelle W; Chaddock-Heyman, Laura; McAuley, Edward; Kramer, Arthur F

2015-03-01

Greater educational attainment is associated with better neurocognitive health in older adults and is thought to reflect a measure of cognitive reserve. In vivo neuroimaging tools have begun to identify the brain systems and networks potentially responsible for reserve. We examined the relationship between education, a commonly used proxy for cognitive reserve, and N-acetylaspartate (NAA) in neurologically healthy older adults (N=135; mean age=66 years). Using single voxel MR spectroscopy, we predicted that higher levels of education would moderate an age-related decline in NAA in the frontal cortex. After controlling for the variance associated with cardiorespiratory fitness, sex, annual income, and creatine levels, there were no significant main effects of education (B=0.016, P=0.787) or age (B=-0.058, P=0.204) on NAA levels. However, consistent with our predictions, there was a significant education X age interaction such that more years of education offset an age-related decline in NAA (B=0.025, P=0.031). When examining working memory via the backwards digit span task, longer span length was associated with greater education (P<0.01) and showed a trend with greater NAA concentrations (P<0.06); however, there was no age X education interaction on digit span performance nor a significant moderated mediation effect between age, education, and NAA on digit span performance. Taken together, these results suggest that higher levels of education may attenuate an age-related reduction in neuronal viability in the frontal cortex.

Education mitigates age-related decline in N-Acetylaspartate levels

PubMed Central

Erickson, Kirk I; Leckie, Regina L; Weinstein, Andrea M; Radchenkova, Polina; Sutton, Bradley P; Prakash, Ruchika Shaurya; Voss, Michelle W; Chaddock-Heyman, Laura; McAuley, Edward; Kramer, Arthur F

2015-01-01

Background Greater educational attainment is associated with better neurocognitive health in older adults and is thought to reflect a measure of cognitive reserve. In vivo neuroimaging tools have begun to identify the brain systems and networks potentially responsible for reserve. Methods We examined the relationship between education, a commonly used proxy for cognitive reserve, and N-acetylaspartate (NAA) in neurologically healthy older adults (N = 135; mean age = 66 years). Using single voxel MR spectroscopy, we predicted that higher levels of education would moderate an age-related decline in NAA in the frontal cortex. Results After controlling for the variance associated with cardiorespiratory fitness, sex, annual income, and creatine levels, there were no significant main effects of education (B = 0.016, P = 0.787) or age (B = −0.058, P = 0.204) on NAA levels. However, consistent with our predictions, there was a significant education X age interaction such that more years of education offset an age-related decline in NAA (B = 0.025, P = 0.031). When examining working memory via the backwards digit span task, longer span length was associated with greater education (P < 0.01) and showed a trend with greater NAA concentrations (P < 0.06); however, there was no age X education interaction on digit span performance nor a significant moderated mediation effect between age, education, and NAA on digit span performance. Conclusions Taken together, these results suggest that higher levels of education may attenuate an age-related reduction in neuronal viability in the frontal cortex. PMID:25798329

AIDS-related dementia: a case report of rapid cognitive decline.

PubMed

Morgan, M K; Clark, M E; Hartman, W L

1988-11-01

Little is known psychometrically about the pattern of cognitive decline associated with acquired immunodeficiency syndrome (AIDS)-related dementia. Pre- and posttest results are presented to illustrate a case example of rapid cognitive decline. Increased psychometric assessment is recommended with additional examination of inconsistent results, which may be dismissed mistakenly as related to psychiatric symptoms. Implications for clinical practice and the role of the psychologist are discussed.

A Pilot Study: The Beneficial Effects of Combined Statin-exercise Therapy on Cognitive Function in Patients with Coronary Artery Disease and Mild Cognitive Decline.

PubMed

Toyama, Kensuke; Sugiyama, Seigo; Oka, Hideki; Hamada, Mari; Iwasaki, Yuri; Horio, Eiji; Rokutanda, Taku; Nakamura, Shinichi; Spin, Joshua M; Tsao, Philip S; Ogawa, Hisao

2017-01-01

Objective Hypercholesterolemia, a risk factor in cognitive impairment, can be treated with statins. However, cognitive decline associated with "statins" (HMG-CoA reductase inhibitors) is a clinical concern. This pilot study investigated the effects of combining statins and regular exercise on cognitive function in coronary artery disease (CAD) patients with prior mild cognitive decline. Methods We recruited 43 consecutive CAD patients with mild cognitive decline. These patients were treated with a statin and weekly in-hospital aerobic exercise for 5 months. We measured serum lipids, exercise capacity, and cognitive function using the mini mental state examination (MMSE). Results Low-density lipoprotein cholesterol levels were significantly decreased, and maximum exercise capacity (workload) was significantly increased in patients with CAD and mild cognitive decline after treatment compared with before. Combined statin-exercise therapy significantly increased the median (range) MMSE score from 24 (22-25) to 25 (23-27) across the cohort (p<0.01). Changes in body mass index (BMI) were significantly and negatively correlated with changes in the MMSE. After treatment, MMSE scores in the subgroup of patients that showed a decrease in BMI were significantly improved, but not in the BMI-increased subgroup. Furthermore, the patients already on a statin at the beginning of the trial displayed a more significant improvement in MMSE score than statin-naïve patients, implying that exercise might be the beneficial aspect of this intervention as regards cognition. In a multivariate logistic regression analysis adjusted for age >65 years, sex, and presence of diabetes mellitus, a decrease in BMI during statin-exercise therapy was significantly correlated with an increase in the MMSE score (odds ratio: 4.57, 95% confidence interval: 1.05-20.0; p<0.05). Conclusion Statin-exercise therapy may help improve cognitive dysfunction in patients with CAD and pre-existing mild cognitive decline.

White matter hyperintensities associated with small vessel disease impair social cognition beside attention and memory.

PubMed

Kynast, Jana; Lampe, Leonie; Luck, Tobias; Frisch, Stefan; Arelin, Katrin; Hoffmann, Karl-Titus; Loeffler, Markus; Riedel-Heller, Steffi G; Villringer, Arno; Schroeter, Matthias L

2018-06-01

Age-related white matter hyperintensities (WMH) are a manifestation of white matter damage seen on magnetic resonance imaging (MRI). They are related to vascular risk factors and cognitive impairment. This study investigated the cognitive profile at different stages of WMH in a large community-dwelling sample; 849 subjects aged 21 to 79 years were classified on the 4-stage Fazekas scale according to hyperintense lesions seen on individual T2-weighted fluid-attenuated inversion recovery MRI scans. The evaluation of cognitive functioning included seven domains of cognitive performance and five domains of subjective impairment, as proposed by the DSM-5. For the first time, the impact of age-related WMH on Theory of Mind was investigated. Differences between Fazekas groups were analyzed non-parametrically and effect sizes were computed. Effect sizes revealed a slight overall cognitive decline in Fazekas groups 1 and 2 relative to healthy subjects. Fazekas group 3 presented substantial decline in social cognition, attention and memory, although characterized by a high inter-individual variability. WMH groups reported subjective cognitive decline. We demonstrate that extensive WMH are associated with specific impairment in attention, memory, social cognition, and subjective cognitive performance. The detailed neuropsychological characterization of WMH offers new therapeutic possibilities for those affected by vascular cognitive decline.

Validation analysis of informant's ratings of cognitive function in African Americans and Nigerians

PubMed Central

Shen, Jianzhao; Gao, Sujuan; Unverzagt, Frederick W.; Ogunniyi, Adesola; Baiyewu, Olusegun; Gureje, Oye; Hendrie, Hugh C.; Hall, Kathleen S.

2011-01-01

SUMMARY Objectives To examine informant validity using the Community Screening Interview for Dementia (CSI ‘D’) both cross-sectionally and longitudinally in two very different cultures and to explore the effects of informants and study participants’ characteristics on the validity of informants’ reports. Methods Elderly African Americans age 65 years and older residing in Indianapolis, USA and elderly Yoruba Nigerians age 65 years and older residing in Ibadan, Nigeria were assessed on cognitive functioning using the CSI ‘D’ at baseline (1992–1993) and five-year follow-up (1997–1998). At baseline, the informant validity in both samples was evaluated against participants’ cognitive tests using Pearson correlation and regular regression models. At follow-up, informants ratings on cognitive decline were assessed against participants’ cognitive decline scores from baseline to follow-up using biserial correlation and logistic regressions. Results At baseline, informants’ reports on cognitive functioning significantly correlated with cognitive scores in both samples (Indianapolis:r = –0.43, p < 0.001; Ibadan:r = –0.47, p < 0.001). The participant–informant relationships significantly affected the informants’ reports in the two samples with different patterns (p = 0.005 for Indianapolis and p < 0.001 for Ibadan) at a given level of cognitive functioning. African Americans spouses reported more cognitive problems, while siblings reported more problems for the Yoruba Nigerians. At follow-up, informants’ ratings on cognitive decline significantly correlated with the cognitive decline scores (Indianapolis r = 0.38, p < 0.001; Ibadan r = 0.32, p < 0.001). The characteristics of study participants and informants had little impact on the informants’ ratings on cognitive decline. Conclusions Informant reports are valid in assessing the cognitive functioning of study participants both cross-sectionally and longitudinally in two very different cultures, languages and environments. PMID:16802282

Disease Progression in Mild Dementia due to Alzheimer Disease in an 18-Month Observational Study (GERAS): The Impact on Costs and Caregiver Outcomes

PubMed Central

Jones, Roy W.; Lebrec, Jeremie; Kahle-Wrobleski, Kristin; Dell'Agnello, Grazia; Bruno, Giuseppe; Vellas, Bruno; Argimon, Josep M.; Dodel, Richard; Haro, Josep Maria; Wimo, Anders; Reed, Catherine

2017-01-01

Background/Aims We assessed whether cognitive and functional decline in community-dwelling patients with mild Alzheimer disease (AD) dementia were associated with increased societal costs and caregiver burden and time outcomes. Methods Cognitive decline was defined as a ≥3-point reduction in the Mini-Mental State Examination and functional decline as a decrease in the ability to perform one or more basic items of the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) or ≥20% of instrumental ADL items. Total societal costs were estimated from resource use and caregiver hours using 2010 costs. Caregiver burden was assessed using the Zarit Burden Interview (ZBI); caregiver supervision and total hours were collected. Results Of 566 patients with mild AD enrolled in the GERAS study, 494 were suitable for the current analysis. Mean monthly total societal costs were greater for patients showing functional (+61%) or cognitive decline (+27%) compared with those without decline. In relation to a typical mean monthly cost of approximately EUR 1,400 at baseline, this translated into increases over 18 months to EUR 2,254 and 1,778 for patients with functional and cognitive decline, respectively. The number of patients requiring supervision doubled among patients showing functional or cognitive decline compared with those not showing decline, while caregiver total time increased by 70 and 33%, respectively and ZBI total score by 5.3 and 3.4 points, respectively. Conclusion Cognitive and, more notably, functional decline were associated with increases in costs and caregiver outcomes in patients with mild AD dementia. PMID:28611822

Intraindividual variability in reaction time predicts cognitive outcomes 5 years later.

PubMed

Bielak, Allison A M; Hultsch, David F; Strauss, Esther; Macdonald, Stuart W S; Hunter, Michael A

2010-11-01

Building on results suggesting that intraindividual variability in reaction time (inconsistency) is highly sensitive to even subtle changes in cognitive ability, this study addressed the capacity of inconsistency to predict change in cognitive status (i.e., cognitive impairment, no dementia [CIND] classification) and attrition 5 years later. Two hundred twelve community-dwelling older adults, initially aged 64-92 years, remained in the study after 5 years. Inconsistency was calculated from baseline reaction time performance. Participants were assigned to groups on the basis of their fluctuations in CIND classification over time. Logistic and Cox regressions were used. Baseline inconsistency significantly distinguished among those who remained or transitioned into CIND over the 5 years and those who were consistently intact (e.g., stable intact vs. stable CIND, Wald (1) = 7.91, p < .01, Exp(β) = 1.49). Average level of inconsistency over time was also predictive of study attrition, for example, Wald (1) = 11.31, p < .01, Exp(β) = 1.24. For both outcomes, greater inconsistency was associated with a greater likelihood of being in a maladaptive group 5 years later. Variability based on moderately cognitively challenging tasks appeared to be particularly sensitive to longitudinal changes in cognitive ability. Mean rate of responding was a comparable predictor of change in most instances, but individuals were at greater relative risk of being in a maladaptive outcome group if they were more inconsistent rather than if they were slower in responding. Implications for the potential utility of intraindividual variability in reaction time as an early marker of cognitive decline are discussed. (c) 2010 APA, all rights reserved

Atrial fibrillation and cognitive decline-the role of subclinical cerebral infarcts: the atherosclerosis risk in communities study.

PubMed

Chen, Lin Y; Lopez, Faye L; Gottesman, Rebecca F; Huxley, Rachel R; Agarwal, Sunil K; Loehr, Laura; Mosley, Thomas; Alonso, Alvaro

2014-09-01

The mechanism underlying the association of atrial fibrillation (AF) with cognitive decline in stroke-free individuals is unclear. We examined the association of incident AF with cognitive decline in stroke-free individuals, stratified by subclinical cerebral infarcts (SCIs) on brain MRI scans. We analyzed data from 935 stroke-free participants (mean age±SD, 61.5±4.3 years; 62% women; and 51% black) from 1993 to 1995 through 2004 to 2006 in the Atherosclerosis Risk in Communities Study, a biracial community-based prospective cohort study. Cognitive testing (including the digit symbol substitution and the word fluency tests) was performed in 1993 to 1995, 1996 to 1998, and 2004 to 2006 and brain MRI scans in 1993 to 1995 and 2004 to 2006. During follow-up, there were 48 incident AF events. Incident AF was associated with greater annual average rate of decline in digit symbol substitution (-0.77; 95% confidence interval, -1.55 to 0.01; P=0.054) and word fluency (-0.80; 95% confidence interval, -1.60 to -0.01; P=0.048). Among participants without SCIs on brain MRI scans, incident AF was not associated with cognitive decline. In contrast, incident AF was associated with greater annual average rate of decline in word fluency (-2.65; 95% confidence interval, -4.26 to -1.03; P=0.002) among participants with prevalent SCIs in 1993 to 1995. Among participants who developed SCIs during follow-up, incident AF was associated with a greater annual average rate of decline in digit symbol substitution (-1.51; 95% confidence interval, -3.02 to -0.01; P=0.049). The association of incident AF with cognitive decline in stroke-free individuals can be explained by the presence or development of SCIs, raising the possibility of anticoagulation as a strategy to prevent cognitive decline in AF. © 2014 American Heart Association, Inc.

Cognitive decline impairs financial and health literacy among community-based older persons without dementia

PubMed Central

Boyle, Patricia A.; Yu, Lei; Wilson, Robert S.; Segawa, Eisuke; Buchman, Aron S.; Bennett, David A.

2013-01-01

Literacy is an important determinant of health and well-being across the lifespan but is critical in aging, when many influential health and financial decisions are made. Prior studies suggest that older persons exhibit lower literacy than younger persons, particularly in the domains of financial and health literacy, but the reasons why remain unknown. The objectives of this study were to: a) examine pathways linking diverse resources (i.e., education, word knowledge, cognitive function, and decision making style) to health and financial literacy among older persons and determine the extent to which the relation of age with literacy represents a direct effect versus an indirect effect due to decrements in specific cognitive functions (i.e., executive functions and episodic memory), and b) test the hypothesis that declines in executive function and episodic memory are associated with lower literacy among older persons without dementia. 645 community-based older persons without dementia underwent detailed assessments of diverse resources, including education, word knowledge, cognitive function (i.e., executive function, episodic memory) and decision making style (i.e., risk aversion), and completed a measure of literacy that included items similar to those assessed in the Health and Retirement Study, such as numeracy, financial concepts such as compound inflation and knowledge of stocks and bonds, and important health concepts such as understanding of drug risk and Medicare Part D. Path analysis revealed a strong effect of age on literacy, with about half of the effect of age on literacy due to decrements in executive functions and episodic memory. In addition, executive function had an indirect effect on literacy via decision making style (i.e., risk aversion), and education and word knowledge had independent effects on literacy. Finally, among (n=447) persons with repeated cognitive assessments available for up to 14 years, regression analysis supported the association of multiple resources with literacy; moreover, more rapid declines in executive function and episodic memory over an average of 6.4 years prior to the literacy assessment predicted lower literacy scores (p’s<0.02), but rate of decline in word knowledge did not. These findings suggest that diverse individual resources contribute to financial and health literacy and lower literacy in old age is partially due to declines in executive function and episodic memory. PMID:23957225

Cognitive decline impairs financial and health literacy among community-based older persons without dementia.

PubMed

Boyle, Patricia A; Yu, Lei; Wilson, Robert S; Segawa, Eisuke; Buchman, Aron S; Bennett, David A

2013-09-01

Literacy is an important determinant of health and well-being across the life span but is critical in aging, when many influential health and financial decisions are made. Prior studies suggest that older persons exhibit lower literacy than younger persons, particularly in the domains of financial and health literacy, but the reasons why remain unknown. The objectives of this study were to: (a) examine pathways linking diverse resources (i.e., education, word knowledge, cognitive function, and decision making style) to health and financial literacy among older persons and determine the extent to which the relation of age with literacy represents a direct effect versus an indirect effect due to decrements in specific cognitive functions (i.e., executive functions and episodic memory); and (b) test the hypothesis that declines in executive function and episodic memory are associated with lower literacy among older persons without dementia. Six-hundred and forty-five community-based older persons without dementia underwent detailed assessments of diverse resources, including education, word knowledge, cognitive function (i.e., executive function, episodic memory) and decision making style (i.e., risk aversion), and completed a measure of literacy that included items similar to those used in the Health and Retirement Study, such as numeracy, financial concepts such as compound inflation and knowledge of stocks and bonds, and important health concepts such as understanding of drug risk and Medicare Part D. Path analysis revealed a strong effect of age on literacy, with about half of the effect of age on literacy due to decrements in executive functions and episodic memory. In addition, executive function had an indirect effect on literacy via decision making style (i.e., risk aversion), and education and word knowledge had independent effects on literacy. Finally, among (n = 447) persons with repeated cognitive assessments available for up to 14 years, regression analysis supported the association of multiple resources with literacy; moreover, more rapid declines in executive function and episodic memory over an average of 6.4 years prior to the literacy assessment predicted lower literacy scores (ps < 0.02), but rate of decline in word knowledge did not. These findings suggest that diverse individual resources contribute to financial and health literacy and lower literacy in old age is partially due to declines in executive function and episodic memory.

Physical Exercise-Induced Adult Neurogenesis: A Good Strategy to Prevent Cognitive Decline in Neurodegenerative Diseases?

PubMed Central

Yau, Suk-yu; Christie, Brian R.; So, Kwok-fai

2014-01-01

Cumulative evidence has indicated that there is an important role for adult hippocampal neurogenesis in cognitive function. With the increasing prevalence of cognitive decline associated with neurodegenerative diseases among the ageing population, physical exercise, a potent enhancer of adult hippocampal neurogenesis, has emerged as a potential preventative strategy/treatment to reduce cognitive decline. Here we review the functional role of adult hippocampal neurogenesis in learning and memory, and how this form of structural plasticity is altered in neurodegenerative diseases known to involve cognitive impairment. We further discuss how physical exercise may contribute to cognitive improvement in the ageing brain by preserving adult neurogenesis, and review the recent approaches for measuring changes in neurogenesis in the live human brain. PMID:24818140

A more randomly organized grey matter network is associated with deteriorating language and global cognition in individuals with subjective cognitive decline.

PubMed

Verfaillie, Sander C J; Slot, Rosalinde E R; Dicks, Ellen; Prins, Niels D; Overbeek, Jozefien M; Teunissen, Charlotte E; Scheltens, Philip; Barkhof, Frederik; van der Flier, Wiesje M; Tijms, Betty M

2018-03-30

Grey matter network disruptions in Alzheimer's disease (AD) are associated with worse cognitive impairment cross-sectionally. Our aim was to investigate whether indications of a more random network organization are associated with longitudinal decline in specific cognitive functions in individuals with subjective cognitive decline (SCD). We included 231 individuals with SCD who had annually repeated neuropsychological assessment (3 ± 1 years; n = 646 neuropsychological investigations) available from the Amsterdam Dementia Cohort (54% male, age: 63 ± 9, MMSE: 28 ± 2). Single-subject grey matter networks were extracted from baseline 3D-T1 MRI scans and we computed basic network (size, degree, connectivity density) and higher-order (path length, clustering, betweenness centrality, normalized path length [lambda] and normalized clustering [gamma]) parameters at whole brain and/or regional levels. We tested associations of network parameters with baseline and annual cognition (memory, attention, executive functioning, language composite scores, and global cognition [all domains with MMSE]) using linear mixed models, adjusted for age, sex, education, scanner and total gray matter volume. Lower network size was associated with steeper decline in language (β ± SE = 0.12 ± 0.05, p < 0.05FDR). Higher-order network parameters showed no cross-sectional associations. Lower gamma and lambda values were associated with steeper decline in global cognition (gamma: β ± SE = 0.06 ± 0.02); lambda: β ± SE = 0.06 ± 0.02), language (gamma: β ± SE = 0.11 ± 0.04; lambda: β ± SE = 0.12 ± 0.05; all p < 0.05FDR). Lower path length values in precuneus and fronto-temporo-occipital cortices were associated with a steeper decline in global cognition. A more randomly organized grey matter network was associated with a steeper decline of cognitive functioning, possibly indicating the start of cognitive impairment. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Association Between Persistent Pain and Memory Decline and Dementia in a Longitudinal Cohort of Elders.

PubMed

Whitlock, Elizabeth L; Diaz-Ramirez, L Grisell; Glymour, M Maria; Boscardin, W John; Covinsky, Kenneth E; Smith, Alexander K

2017-08-01

Chronic pain is common among the elderly and is associated with cognitive deficits in cross-sectional studies; the population-level association between chronic pain and longitudinal cognition is unknown. To determine the population-level association between persistent pain, which may reflect chronic pain, and subsequent cognitive decline. Cohort study with biennial interviews of 10 065 community-dwelling older adults in the nationally representative Health and Retirement Study who were 62 years or older in 2000 and answered pain and cognition questions in both 1998 and 2000. Data analysis was conducted between June 24 and October 31, 2016. "Persistent pain," defined as a participant reporting that he or she was often troubled with moderate or severe pain in both the 1998 and 2000 interviews. Coprimary outcomes were composite memory score and dementia probability, estimated by combining neuropsychological test results and informant and proxy interviews, which were tracked from 2000 through 2012. Linear mixed-effects models, with random slope and intercept for each participant, were used to estimate the association of persistent pain with slope of the subsequent cognitive trajectory, adjusting for demographic characteristics and comorbidities measures in 2000 and applying sampling weights to represent the 2000 US population. We hypothesized that persistent pain would predict accelerated memory decline and increased probability of dementia. To quantify the impact of persistent pain on functional independence, we combined our primary results with information on the association between memory and ability to manage medications and finances independently. Of the 10 065 eligible HRS sample members, 60% were female, and median baseline age was 73 years (interquartile range, 67-78 years). At baseline, persistent pain affected 10.9% of participants and was associated with worse depressive symptoms and more limitations in activities of daily living. After covariate adjustment, persistent pain was associated with 9.2% (95% CI, 2.8%-15.0%) more rapid memory decline compared with those without persistent pain. After 10 years, this accelerated memory decline implied a 15.9% higher relative risk of inability to manage medications and an 11.8% higher relative risk of inability to manage finances independently. Adjusted dementia probability increased 7.7% faster (95% CI, 0.55%-14.2%); after 10 years, this translates to an absolute 2.2% increase in dementia probability for those with persistent pain. Persistent pain was associated with accelerated memory decline and increased probability of dementia.

Progression of cognitive impairment in stroke/TIA patients over 3 years.

PubMed

Sachdev, Perminder S; Lipnicki, Darren M; Crawford, John D; Wen, Wei; Brodaty, Henry

2014-12-01

To examine how cognitive deficits progress in the years following a stroke or transient ischaemic attack (TIA). A follow-up study, with neuropsychological and MRI assessments undertaken 3 years after baseline assessments made 3-6 months poststroke in 183 stroke/TIA patients and 97 healthy controls participating in the Sydney Stroke Study. Additional measures included cardiovascular risk factors and apolipoprotein E (APOE) genotype. Stroke/TIA patients had poorer cognitive function and more vascular risk factors than controls at baseline, but did not show greater decline in cognitive function over 3 years except for verbal memory. Patients with a subsequent stroke/TIA showed greater decline in global cognitive function and a number of domains. Rates of incident dementia were 5.9% per year in patients and 0.4% in controls. Both groups showed increased atrophy of the hippocampus, amygdala and whole brain, and an increase in white matter hyperintensities over 3 years; whole brain atrophy was greater in patients. Cognitive decline was greater in women and in those with smaller hippocampi at baseline. For patients without a subsequent stroke/TIA, those with smaller hippocampi or the APOE ε4 allele had greater global cognitive and verbal memory decline. In poststroke patients, cognitive decline was not greater than in comparison subjects, except for verbal memory, unless they had another stroke/TIA. However, dementia incidence was higher in patients, as might be expected from their poorer baseline cognitive functioning. Smaller hippocampi were associated with an increased risk of decline in memory, and APOE ε4 was a risk factor in those without a subsequent stroke/TIA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effect of Vitamin Intake on Cognitive Decline in Older Adults: Evaluation of the Evidence.

PubMed

Krause, D; Roupas, P

2015-08-01

The objective of this review was to evaluate the evidence from human studies on the intake of vitamins, either as monotherapies or in combination with other vitamins, as neuroprotective agents that may delay the onset of cognitive decline in older adults. Evidence-based methodologies were used to capture and evaluate the highest levels of evidence. The current evidence available showed no association for cognitive benefits of vitamins B6 or B12 as a monotherapy, and recent systematic reviews provide no clear evidence that supplementation with vitamin B6, B12 and/or folic acid improves dementia outcomes or slows cognitive decline, even though it may normalise homocysteine levels. Meta-analyses from systematic reviews have shown an association between low vitamin D levels and diminished cognitive function, although causality cannot be confirmed from the available evidence. There is no convincing evidence for an association of vitamin A, vitamin C or vitamin E either as a monotherapy or in combination with other antioxidant vitamins such as β-carotene and the prevention of cognitive decline. The appraisal of nineteen systematic reviews and meta-analyses has highlighted the heterogeneity between studies, and the need for better consensus on definitions of cognitive decline, duration of testing and agreement on which specific endpoints are clinically relevant. Evaluation of the totality of the currently available evidence indicates that intake of the above vitamins, either as a monotherapy, or in combination with other vitamins, has no clinically-relevant effect on delaying cognitive decline or delaying the onset of dementia in older adults.

Accelerated cognitive decline in a rodent model for temporal lobe epilepsy.

PubMed

Schipper, Sandra; Aalbers, Marlien W; Rijkers, Kim; Lagiere, Melanie; Bogaarts, Jan G; Blokland, Arjan; Klinkenberg, Sylvia; Hoogland, Govert; Vles, Johan S H

2016-12-01

Cognitive impairment is frequently observed in patients with temporal lobe epilepsy. It is hypothesized that cumulative seizure exposure causes accelerated cognitive decline in patients with epilepsy. We investigated the influence of seizure frequency on cognitive decline in a rodent model for temporal lobe epilepsy. Neurobehavioral assessment was performed before and after surgery, after the induction of self-sustaining limbic status epilepticus (SSLSE), and in the chronic phase in which rats experienced recurrent seizures. Furthermore, we assessed potential confounders of memory performance. Rats showed a deficit in spatial working memory after the induction of the SSLSE, which endured in the chronic phase. A progressive decline in recognition memory developed in SSLSE rats. Confounding factors were absent. Seizure frequency and also the severity of the status epilepticus were not correlated with the severity of cognitive deficits. The effect of the seizure frequency on cognitive comorbidity in epilepsy has long been debated, possibly because of confounders such as antiepileptic medication and the heterogeneity of epileptic etiologies. In an animal model of temporal lobe epilepsy, we showed that a decrease in spatial working memory does not relate to the seizure frequency. This suggests for other mechanisms are responsible for memory decline and potentially a common pathophysiology of cognitive deterioration and the occurrence and development of epileptic seizures. Identifying this common denominator will allow development of more targeted interventions treating cognitive decline in patients with epilepsy. The treatment of interictal symptoms will increase the quality of life of many patients with epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Stressful life events and cognitive decline in late life: moderation by education and age. The Cache County Study.

PubMed

Tschanz, Joann T; Pfister, Roxane; Wanzek, Joseph; Corcoran, Chris; Smith, Ken; Tschanz, Brian T; Steffens, David C; Østbye, Truls; Welsh-Bohmer, Kathleen A; Norton, Maria C

2013-08-01

Stressful life events (SLE) have been associated with increased dementia risk, but their association with cognitive decline has been inconsistent. In a longitudinal population-based study of older individuals, we examined the association between SLE and cognitive decline, and the role of potential effect modifiers. A total of 2665 non-demented participants of the Cache County Memory Study completed an SLE questionnaire at Wave 2 and were revisited 4 and 7 years later. The events were represented via several scores: total number, subjective rating (negative, positive, and unexpected), and a weighted summary based on their impact. Cognition was assessed at each visit with the modified Mini-Mental State Exam. General linear models were used to examine the association between SLE scores and cognition. Effect modification by age, education, and APOE genotype was tested. Years of formal education (p = 0.006) modified the effect of number of SLE, and age (p = 0.009) modified the effect of negative SLE on the rate of cognitive decline. Faster decline was observed among those with fewer years of education experiencing more SLE and also among younger participants experiencing more negative SLE. There was no association between other indicators of SLE and cognitive decline. APOE genotype did not modify any of the aforementioned associations. The effects of SLE on cognition in late life are complex and vary by individual factors such as age and education. These results may explain some of the contradictory findings in the literature. Copyright © 2012 John Wiley & Sons, Ltd.

Does Stroke Contribute to Racial Differences in Cognitive Decline?

PubMed Central

Levine, Deborah A.; Kabeto, Mohammed; Langa, Kenneth M.; Lisabeth, Lynda D.; Rogers, Mary A.M.; Galecki, Andrzej T.

2015-01-01

Background and Purpose It is unknown whether blacks’ elevated risk of dementia is because of racial differences in acute stroke, the impact of stroke on cognitive health, or other factors. We investigated whether racial differences in cognitive decline are explained by differences in the frequency or impact of incident stroke between blacks and whites, controlling for baseline cognition. Methods Among 4908 black and white participants aged ≥65 years free of stroke and cognitive impairment in the nationally representative Health and Retirement Study with linked Medicare data (1998–2010), we examined longitudinal changes in global cognition (modified version of the Telephone Interview for Cognitive Status) by race, before and after adjusting for time-dependent incident stroke followed by a race-by-incident stroke interaction term, using linear mixed-effects models that included fixed effects of participant demographics, clinical factors, and cognition, and random effects for intercept and slope for time. Results We identified 34 of 453 (7.5%) blacks and 300 of 4455 (6.7%) whites with incident stroke over a mean (SD) of 4.1 (1.9) years of follow-up (P=0.53). Blacks had greater cognitive decline than whites (adjusted difference in modified version of the Telephone Interview for Cognitive Status score, 1.47 points; 95% confidence interval, 1.21 to 1.73 points). With further adjustment for cumulative incidence of stroke, the black–white difference in cognitive decline persisted. Incident stroke was associated with a decrease in global cognition (1.21 points; P<0.001) corresponding to ≈7.9 years of cognitive aging. The effect of incident stroke on cognition did not statistically differ by race (P=0.52). Conclusions In this population-based cohort of older adults, incident stroke did not explain black–white differences in cognitive decline or impact cognition differently by race. PMID:25999389

Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging.

PubMed

Voss, Michelle W; Weng, Timothy B; Burzynska, Agnieszka Z; Wong, Chelsea N; Cooke, Gillian E; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P; Olson, Erin A; McAuley, Edward; Kramer, Arthur F

2016-05-01

Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the default mode network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks. Copyright © 2015 Elsevier Inc. All rights reserved.

Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging

PubMed Central

Voss, Michelle W.; Weng, Timothy B.; Burzynska, Agnieszka Z.; Wong, Chelsea N.; Cooke, Gillian E.; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P.; Olson, Erin A.; McAuley, Edward; Kramer, Arthur F.

2015-01-01

Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the Default Mode Network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks. PMID:26493108

Associations of Objectively and Subjectively Measured Sleep Quality with Subsequent Cognitive Decline in Older Community-Dwelling Men: The MrOS Sleep Study

PubMed Central

Blackwell, Terri; Yaffe, Kristine; Laffan, Alison; Ancoli-Israel, Sonia; Redline, Susan; Ensrud, Kristine E.; Song, Yeonsu; Stone, Katie L.

2014-01-01

Study Objectives: To examine associations of objectively and subjectively measured sleep with subsequent cognitive decline. Design: A population-based longitudinal study. Setting: Six centers in the United States. Participants: Participants were 2,822 cognitively intact community-dwelling older men (mean age 76.0 ± 5.3 y) followed over 3.4 ± 0.5 y. Interventions: None. Measurements and Results: Objectively measured sleep predictors from wrist actigraphy: total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), number of long wake episodes (LWEP). Self-reported sleep predictors: sleep quality (Pittsburgh Sleep Quality Index [PSQI]), daytime sleepiness (Epworth Sleepiness Scale [ESS]), TST. Clinically significant cognitive decline: five-point decline on the Modified Mini-Mental State examination (3MS), change score for the Trails B test time in the worse decile. Associations of sleep predictors and cognitive decline were examined with logistic regression and linear mixed models. After multivariable adjustment, higher levels of WASO and LWEP and lower SE were associated with an 1.4 to 1.5-fold increase in odds of clinically significant decline (odds ratio 95% confidence interval) Trails B test: SE < 70% versus SE ≥ 70%: 1.53 (1.07, 2.18); WASO ≥ 90 min versus WASO < 90 min: 1.47 (1.09, 1.98); eight or more LWEP versus fewer than eight: 1.38 (1.02, 1.86). 3MS: eight or more LWEP versus fewer than eight: 1.36 (1.09, 1.71), with modest relationships to linear change in cognition over time. PSQI was related to decline in Trails B performance (3 sec/y per standard deviation increase). Conclusions: Among older community-dwelling men, reduced sleep efficiency, greater nighttime wakefulness, greater number of long wake episodes, and poor self-reported sleep quality were associated with subsequent cognitive decline. Citation: Blackwell T; Yaffe K; Laffan A; Ancoli-Israel S; Redline S; Ensrud KE; Song Y; Stone KL. Associations of objectively and subjectively measured sleep quality with subsequent cognitive decline in older community-dwelling men: the MrOS sleep study. SLEEP 2014;37(4):655-663. PMID:24899757

A systematic review of cognitive decline in dementia with Lewy bodies versus Alzheimer’s disease

PubMed Central

2014-01-01

Introduction The aim of this review was to investigate whether there is a faster cognitive decline in dementia with Lewy bodies (DLB) than in Alzheimer’s disease (AD) over time. Methods PsycINFO and Medline were searched from 1946 to February 2013. A quality rating from 1 to 15 (best) was applied to the included studies. A quantitative meta-analysis was done on studies with mini mental state examination (MMSE) as the outcome measure. Results A total of 18 studies were included. Of these, six (36%) reported significant differences in the rate of cognitive decline. Three studies reported a faster cognitive decline on MMSE in patients with mixed DLB and AD compared to pure forms, whereas two studies reported a faster decline on delayed recall and recognition in AD and one in DLB on verbal fluency. Mean quality scores for studies that did or did not differ were not significantly different. Six studies reported MMSE scores and were included in the meta-analysis, which showed no significant difference in annual decline on MMSE between DLB (mean 3.4) and AD (mean 3.3). Conclusions Our findings do not support the hypothesis of a faster rate of cognitive decline in DLB compared to AD. Future studies should apply recent diagnostic criteria, as well as extensive diagnostic evaluation and ideally autopsy diagnosis. Studies with large enough samples, detailed cognitive tests, at least two years follow up and multivariate statistical analysis are also needed. PMID:25478024

Risk factors associated with cognitive decline in the elderly with type 2 diabetes: baseline data analysis of the Japanese Elderly Diabetes Intervention Trial.

PubMed

Umegaki, Hiroyuki; Iimuro, Satoshi; Shinozaki, Tomohiro; Araki, Atsushi; Sakurai, Takashi; Iijima, Katsuya; Ohashi, Yasuo; Ito, Hideki

2012-04-01

Recent evidence has shown that type 2 diabetes mellitus (T2DM) in the elderly is a risk factor for cognitive dysfunction or dementia. However, the precise mechanisms have not yet been elucidated. In the current study, we attempted to elucidate the association of clinical indices and diabetic complications at baseline with cognitive declines after 6-year follow up in type 2 diabetic elderly. The subjects were 261 participants who were administered the Mini-Mental State Examination (MMSE) at baseline and after 6 years, at the end of the observation period. The cognitive decline was determined as a 5-point or greater decline in MMSE scores during the observation period. Logistic regression analysis to find the factors associated with cognitive decline, adjusted for age and sex, were carried out, and factors with P-values of less than 0.2 were included in four models of multiple logistic regression analysis. We found that the existence of diabetic nephropathy, higher systolic blood pressure and higher serum triglycerides (or lower high-density lipoprotein cholesterol) at baseline were significantly associated with cognitive declines after 6 years in Japanese elderly diabetics in all four models. The comorbidity of diabetic nephropathy, hypertension and hypertriglyceridemia at baseline were associated with more than 5-point declines in MMSE. Elucidation of the underlying mechanisms of this association is warranted. © 2012 Japan Geriatrics Society.

APOE ε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline

PubMed Central

Wang, Yamin; Barnes, Lisa L.; Tangney, Christine; Bennett, David A.; Morris, Martha Clare

2016-01-01

Objective: To examine the association between consumption of seafood and long-chain n-3 fatty acids with change in 5 cognitive domains over an average of 4.9 years. Methods: From an ongoing longitudinal, community-based epidemiologic study of aging and dementia (the Rush Memory and Aging Project), we included 915 participants (age 81.4 ± 7.2 years, 25% men) who had completed at least one follow-up cognitive assessment and dietary data. Diet was assessed by semiquantitative food frequency questionnaire. Scores for global cognitive function and 5 cognitive domains (episodic, semantic, and working memory, perceptual speed, and visuospatial ability) were assessed using 19 cognitive tests. Mixed models adjusted for multiple risk factors of cognitive change were used to assess the associations. Results: Consumption of seafood was associated with slower decline in semantic memory (β = 0.024; p = 0.03) and perceptual speed (β = 0.020; p = 0.05) in separate models adjusted for age, sex, education, participation in cognitive activities, physical activity, alcohol consumption, smoking, and total energy intake. In secondary analyses, APOE ε4 carriers demonstrated slower rates of decline in global cognition and in multiple cognitive domains with weekly seafood consumption and with moderate to high long-chain n-3 fatty acid intake from food. These associations were not present in APOE ε4 noncarriers. Higher intake levels of α-linolenic acid were associated with slower global cognitive decline, but also only in APOE ε4 carriers. Conclusions: These results suggest protective relations of one meal per week of seafood and long-chain n-3 fatty acids against decline in multiple cognitive domains. The role of APOE ε4 in this association needs further study. PMID:27164694

The Cognitive Change Index as a Measure of Self and Informant Perception of Cognitive Decline: Relation to Neuropsychological Tests.

PubMed

Rattanabannakit, Chatchawan; Risacher, Shannon L; Gao, Sujuan; Lane, Kathleen A; Brown, Steven A; McDonald, Brenna C; Unverzagt, Frederick W; Apostolova, Liana G; Saykin, Andrew J; Farlow, Martin R

2016-01-01

The perception of cognitive decline by individuals and those who know them well ("informants") has been inconsistently associated with objective cognitive performance, but strongly associated with depressive symptoms. We investigated associations of self-report, informant-report, and discrepancy between self- and informant-report of cognitive decline obtained from the Cognitive Change Index (CCI) with cognitive test performance and self-reported depressive symptoms. 267 participants with normal cognition, mild cognitive impairment (MCI), or mild dementia were included from a cohort study and memory clinic. Association of test performance and self-rated depression (Geriatric Depression Scale, GDS) with CCI scores obtained from subjects (CCI-S), their informants (CCI-I), and discrepancy scores between subjects and informants (CCI-D; CCI-S minus CCI-I) were analyzed using correlation and analysis of covariance (ANCOVA) models. CCI-S and CCI-I scores showed high internal consistency (Cronbach alpha 0.96 and 0.98, respectively). Higher scores on CCI-S and CCI-I, and lower scores on the CCI-D, were associated with lower performance on various cognitive tests in both univariate and in ANCOVA models adjusted for age, gender, and education. Adjustment for GDS slightly weakened the relationships between CCI and test performance but most remained significant. Self- and informant-report of cognitive decline, as measured by the CCI, show moderately strong relationships with objective test performance independent of age, gender, education, and depressive symptoms. The CCI appears to be a valid cross-sectional measure of self and informant perception of cognitive decline across the continuum of functioning. Studies are needed to address the relationship of CCI scores to longitudinal outcome.

Chocolate Consumption is Associated with a Lower Risk of Cognitive Decline.

PubMed

Moreira, Afonso; Diógenes, Maria José; de Mendonça, Alexandre; Lunet, Nuno; Barros, Henrique

2016-05-06

Cocoa-related products like chocolate have taken an important place in our food habits and culture. In this work, we aim to examine the relationship between chocolate consumption and cognitive decline in an elderly cognitively healthy population. In the present longitudinal prospective study, a cohort of 531 participants aged 65 and over with normal Mini-Mental State Examination (MMSE; median 28) was selected. The median follow-up was 48 months. Dietary habits were evaluated at baseline. The MMSE was used to assess global cognitive function at baseline and at follow-up. Cognitive decline was defined by a decrease ≥ 2 points in the MMSE score between evaluations. Relative risk (RR) and 95% confidence interval (95% CI) estimates were adjusted for age, education, smoking, alcohol drinking, body mass index, hypertension, and diabetes. Chocolate intake was associated with a lower risk of cognitive decline (RR = 0.59, 95% CI 0.38-0.92). This protective effect was observed only among subjects with an average daily consumption of caffeine lower than 75 mg (69% of the participants; RR = 0.50, 95% CI 0.31-0.82). To our knowledge, this is the first prospective cohort study to show an inverse association between regular long-term chocolate consumption and cognitive decline in humans.

Hypothesis testing of a change point during cognitive decline among Alzheimer's disease patients.

PubMed

Ji, Ming; Xiong, Chengjie; Grundman, Michael

2003-10-01

In this paper, we present a statistical hypothesis test for detecting a change point over the course of cognitive decline among Alzheimer's disease patients. The model under the null hypothesis assumes a constant rate of cognitive decline over time and the model under the alternative hypothesis is a general bilinear model with an unknown change point. When the change point is unknown, however, the null distribution of the test statistics is not analytically tractable and has to be simulated by parametric bootstrap. When the alternative hypothesis that a change point exists is accepted, we propose an estimate of its location based on the Akaike's Information Criterion. We applied our method to a data set from the Neuropsychological Database Initiative by implementing our hypothesis testing method to analyze Mini Mental Status Exam scores based on a random-slope and random-intercept model with a bilinear fixed effect. Our result shows that despite large amount of missing data, accelerated decline did occur for MMSE among AD patients. Our finding supports the clinical belief of the existence of a change point during cognitive decline among AD patients and suggests the use of change point models for the longitudinal modeling of cognitive decline in AD research.

Amyloid-β, anxiety, and cognitive decline in preclinical Alzheimer disease: a multicenter, prospective cohort study.

PubMed

Pietrzak, Robert H; Lim, Yen Ying; Neumeister, Alexander; Ames, David; Ellis, Kathryn A; Harrington, Karra; Lautenschlager, Nicola T; Restrepo, Carolina; Martins, Ralph N; Masters, Colin L; Villemagne, Victor L; Rowe, Christopher C; Maruff, Paul

2015-03-01

Alzheimer disease (AD) is now known to have a long preclinical phase in which pathophysiologic processes develop many years, even decades, before the onset of clinical symptoms. Although the presence of abnormal levels of amyloid-β (Aβ) is associated with higher rates of progression to clinically classified mild cognitive impairment or dementia, little research has evaluated potentially modifiable moderators of Aβ-related cognitive decline, such as anxiety and depressive symptoms. To evaluate the association between Aβ status and cognitive changes, and the role of anxiety and depressive symptoms in moderating Aβ-related cognitive changes in the preclinical phase of AD. In this multicenter, prospective cohort study with baseline and 18-, 36-, and 54-month follow-up assessments, we studied 333 healthy, older adults at hospital-based research clinics. Carbon 11-labeled Pittsburgh Compound B (PiB)-, florbetapir F 18-, or flutemetamol F 18-derived measures of Aβ, Hospital Anxiety and Depression Scale scores, and comprehensive neuropsychological evaluation that yielded measures of global cognition, verbal memory, visual memory, attention, language, executive function, and visuospatial ability. A positive Aβ (Aβ+) status at baseline was associated with a significant decline in global cognition, verbal memory, language, and executive function, and elevated anxiety symptoms moderated these associations. Compared with the Aβ+, low-anxiety group, slopes of cognitive decline were significantly more pronounced in the Aβ+, high-anxiety group, with Cohen d values of 0.78 (95% CI, 0.33-1.23) for global cognition, 0.54 (95% CI, 0.10-0.98) for verbal memory, 0.51 (95% CI, 0.07-0.96) for language, and 0.39 (95% CI, 0.05-0.83) for executive function. These effects were independent of age, educational level, IQ, APOE genotype, subjective memory complaints, vascular risk factors, and depressive symptoms; furthermore, depressive symptoms and subjective memory complaints did not moderate the association between Aβ and cognitive decline. These results provide additional support for the deleterious effect of elevated Aβ levels on cognitive function in preclinical AD. They further suggest that elevated anxiety symptoms moderate the effect of Aβ on cognitive decline in preclinical AD, resulting in more rapid decline in several cognitive domains. Given that there is currently no standard antiamyloid therapy and that anxiety symptoms are amenable to treatment, these findings may help inform risk stratification and management of the preclinical phase of AD.

Rationale and design of the CAROLINA® - cognition substudy: a randomised controlled trial on cognitive outcomes of linagliptin versus glimepiride in patients with type 2 diabetes mellitus.

PubMed

Biessels, Geert Jan; Janssen, Jolien; van den Berg, Esther; Zinman, Bernard; Espeland, Mark A; Mattheus, Michaela; Johansen, Odd Erik

2018-01-15

Type 2 diabetes mellitus is associated with cognitive dysfunction and an increased risk of dementia. Linagliptin is a glucose-lowering agent of the dipeptidyl peptidase-IV (DPP-IV) inhibitor class that is of particular interest for the prevention of accelerated cognitive decline, because it may potentially benefit the brain through pleiotropic effects, beyond glucose lowering. This paper presents the design of a study that aims to establish if linagliptin is superior to the sulfonylurea glimepiride in the prevention of accelerated cognitive decline in patients with type 2 diabetes mellitus. The cognition substudy is an integral part of the ongoing event-driven, randomised, double blind CARdiOvascular safety of LINAgliptin (CAROLINA®) trial, which evaluates the effect of treatment with linagliptin versus glimepiride on cardiovascular outcomes. CAROLINA® includes patients with type 2 diabetes mellitus with sub-optimal glycaemic control at elevated cardiovascular risk. The substudy will evaluate patients randomised and treated who have a baseline Mini Mental State Examination (MMSE) score ≥ 24, documented years of formal education with at least one valid cognitive assessment at baseline and during follow-up. The primary cognitive outcome is the occurrence of accelerated cognitive decline at the end of follow-up. The two treatment groups will be compared by using a logistic regression. Accelerated cognitive decline is defined as a rate of cognitive decline that falls at or below the 16th percentile of decline for the whole cohort on either the MMSE or a combined score of the trail making and verbal fluency test. Potential confounders are taken into account at an individual patient level, using a regression based index. Between December 2010 and December 2012, 6042 patients were randomised and treated with either linagliptin (5 mg) or glimepiride (1-4 mg) once daily in CAROLINA®. Cognitive tests were conducted in nearly 4500 participants at baseline and are scheduled for two subsequent assessments, after 160 weeks of follow-up and end of follow-up. This substudy of the ongoing CAROLINA® trial will establish if linagliptin is superior to glimepiride in the prevention of accelerated cognitive decline in patients with type 2 diabetes mellitus. Final results are expected in 2019. ClinicalTrials.gov Identifier: NCT 01243424 .

Patterns of brain atrophy associated with episodic memory and semantic fluency decline in aging.

PubMed

Pelletier, Amandine; Bernard, Charlotte; Dilharreguy, Bixente; Helmer, Catherine; Le Goff, Melanie; Chanraud, Sandra; Dartigues, Jean-François; Allard, Michèle; Amieva, Hélène; Catheline, Gwénaëlle

2017-03-09

The cerebral substratum of age-related cognitive decline was evaluated in an elderly-cohort followed for 12 years (n=306). Participants, free of dementia, received neuropsychological assessments every two years and an MRI exam at baseline and four years later. Cognitive decline was evaluated on two broadly used tests to detect dementia: the Free and Cued Selective Reminding Test (FCSRT), a verbal episodic memory task, and the Isaacs Set Test (IST), a semantic fluency task. Using voxel-based approach, the relationship between cognitive decline with 1/ baseline grey matter volumes and 2/ grey matter volume loss between the two scans was explored. Baseline volumes analysis revealed that FCSRT and IST declines were both associated with lower volumes of the medial temporal region. Volumes loss analysis confirmed that both declines are related to medial temporal lobe atrophy and revealed that FCSRT decline was specifically associated with atrophy of the posterior cingulate cortex whereas IST decline was specifically related to temporal pole atrophy. These results suggest that cognitive decline across aging is firstly related to structural modifications of the medial temporal lobe, followed by an atrophy in the posterior midline structures for episodic memory and an atrophy of the temporal pole for semantic fluency.

Utilizing Structural Equation Modeling and Social Cognitive Career Theory to Identify Factors in Choice of It as a Major

ERIC Educational Resources Information Center

Luse, Andy; Rursch, Julie A.; Jacobson, Doug

2014-01-01

In the United States, the number of students entering into and completing degrees in science, technology, engineering, and mathematics (STEM) areas has declined significantly over the past decade. Although modest increases have been shown in enrollments in computer-related majors in the past 4 years, the prediction is that even in 3 to 4 years…

Education does not slow cognitive decline with aging: 12-year evidence from the victoria longitudinal study.

PubMed

Zahodne, Laura B; Glymour, M Maria; Sparks, Catharine; Bontempo, Daniel; Dixon, Roger A; MacDonald, Stuart W S; Manly, Jennifer J

2011-11-01

Although the relationship between education and cognitive status is well-known, evidence regarding whether education moderates the trajectory of cognitive change in late life is conflicting. Early studies suggested that higher levels of education attenuate cognitive decline. More recent studies using improved longitudinal methods have not found that education moderates decline. Fewer studies have explored whether education exerts different effects on longitudinal changes within different cognitive domains. In the present study, we analyzed data from 1014 participants in the Victoria Longitudinal Study to examine the effects of education on composite scores reflecting verbal processing speed, working memory, verbal fluency, and verbal episodic memory. Using linear growth models adjusted for age at enrollment (range, 54-95 years) and gender, we found that years of education (range, 6-20 years) was strongly related to cognitive level in all domains, particularly verbal fluency. However, education was not related to rates of change over time for any cognitive domain. Results were similar in individuals older or younger than 70 at baseline, and when education was dichotomized to reflect high or low attainment. In this large longitudinal cohort, education was related to cognitive performance but unrelated to cognitive decline, supporting the hypothesis of passive cognitive reserve with aging.

Physical Frailty Is Associated with Longitudinal Decline in Global Cognitive Function in Non-Demented Older Adults: A Prospective Study.

PubMed

Chen, S; Honda, T; Narazaki, K; Chen, T; Kishimoto, H; Haeuchi, Y; Kumagai, S

2018-01-01

To assess the relationship between physical frailty and subsequent decline in global cognitive function in the non-demented elderly. A prospective population-based study in a west Japanese suburban town, with two-year follow-up. Community-dwellers aged 65 and older without placement in long-term care, and not having a history of dementia, Parkinson's disease and depression at baseline, who participated in the cohort of the Sasaguri Genkimon Study and underwent follow-up assessments two years later (N = 1,045). Global cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Physical frailty was identified according to the following five components: weight loss, low grip strength, exhaustion, slow gait speed and low physical activities. Linear regression models were used to examine associations between baseline frailty status and the MoCA scores at follow-up. Logistic regression models were used to estimate the risk of cognitive decline (defined as at least two points decrease of MoCA score) according to baseline frailty status. Seven hundred and eight non-demented older adults were included in the final analyses (mean age: 72.6 ± 5.5 years, male 40.3%); 5.8% were frail, and 40.8% were prefrail at baseline. One hundred and fifty nine (22.5%) participants experienced cognitive decline over two years. After adjustment for baseline MoCA scores and all confounders, being frail at baseline was significantly associated with a decline of 1.48 points (95% confidence interval [CI], -2.37 to -0.59) in MoCA scores, as compared with non-frailty. Frail persons were over two times more likely to experience cognitive decline (adjusted odds ratio 2.28; 95% CI, 1.02 to 5.08), compared to non-frail persons. Physical frailty is associated with longitudinal decline in global cognitive function in the non-demented older adults over a period of two years. Physically frail older community-dwellers should be closely monitored for cognitive decline that can be sensitively captured by using the MoCA.

Does physical activity prevent cognitive decline and dementia?: A systematic review and meta-analysis of longitudinal studies

PubMed Central

2014-01-01

Background By 2050, it has been estimated that approximately one-fifth of the population will be made up of older adults (aged ≥60 years). Old age often comes with cognitive decline and dementia. Physical activity may prevent cognitive decline and dementia. Methods We reviewed and synthesised prospective studies into physical activity and cognitive decline, and physical activity and dementia, published until January 2014. Forty-seven cohorts, derived from two previous systematic reviews and an updated database search, were used in the meta-analyses. Included participants were aged ≥40 years, in good health and/or randomly selected from the community. Studies were assessed for methodological quality. Results Twenty-one cohorts on physical activity and cognitive decline and twenty-six cohorts on physical activity and dementia were included. Meta-analysis, using the quality-effects model, suggests that participants with higher levels of physical activity, when compared to those with lower levels, are at reduced risk of cognitive decline, RR 0.65, 95% CI 0.55-0.76, and dementia, RR 0.86, 95% CI 0.76-0.97. Sensitivity analyses revealed a more conservative estimate of the impact of physical activity on cognitive decline and dementia for high quality studies, studies reporting effect sizes as ORs, greater number of adjustments (≥10), and longer follow-up time (≥10 years). When one heavily weighted study was excluded, physical activity was associated with an 18% reduction in the risk of dementia (RR 0.82; 0.73-0.91). Conclusions Longitudinal observational studies show an association between higher levels of physical activity and a reduced risk of cognitive decline and dementia. A case can be made for a causal interpretation. Future research should use objective measures of physical activity, adjust for the full range of confounders and have adequate follow-up length. Ideally, randomised controlled trials will be conducted. Regardless of any effect on cognition, physical activity should be encouraged, as it has been shown to be beneficial on numerous levels. PMID:24885250

Prefrontal Cortex Structure Predicts Training-Induced Improvements in Multitasking Performance.

PubMed

Verghese, Ashika; Garner, K G; Mattingley, Jason B; Dux, Paul E

2016-03-02

The ability to perform multiple, concurrent tasks efficiently is a much-desired cognitive skill, but one that remains elusive due to the brain's inherent information-processing limitations. Multitasking performance can, however, be greatly improved through cognitive training (Van Selst et al., 1999, Dux et al., 2009). Previous studies have examined how patterns of brain activity change following training (for review, see Kelly and Garavan, 2005). Here, in a large-scale human behavioral and imaging study of 100 healthy adults, we tested whether multitasking training benefits, assessed using a standard dual-task paradigm, are associated with variability in brain structure. We found that the volume of the rostral part of the left dorsolateral prefrontal cortex (DLPFC) predicted an individual's response to training. Critically, this association was observed exclusively in a task-specific training group, and not in an active-training control group. Our findings reveal a link between DLPFC structure and an individual's propensity to gain from training on a task that taps the limits of cognitive control. Cognitive "brain" training is a rapidly growing, multibillion dollar industry (Hayden, 2012) that has been touted as the panacea for a variety of disorders that result in cognitive decline. A key process targeted by such training is "cognitive control." Here, we combined an established cognitive control measure, multitasking ability, with structural brain imaging in a sample of 100 participants. Our goal was to determine whether individual differences in brain structure predict the extent to which people derive measurable benefits from a cognitive training regime. Ours is the first study to identify a structural brain marker-volume of left hemisphere dorsolateral prefrontal cortex-associated with the magnitude of multitasking performance benefits induced by training at an individual level. Copyright © 2016 the authors 0270-6474/16/362638-08$15.00/0.

Cross-sectional and longitudinal relationships between cerebrospinal fluid biomarkers and cognitive function in people without cognitive impairment from across the adult life span.

PubMed

Li, Ge; Millard, Steven P; Peskind, Elaine R; Zhang, Jing; Yu, Chang-En; Leverenz, James B; Mayer, Cynthia; Shofer, Jane S; Raskind, Murray A; Quinn, Joseph F; Galasko, Douglas R; Montine, Thomas J

2014-06-01

Age-related cognitive decline among older individuals with normal cognition is a complex trait that potentially derives from processes of aging, inherited vulnerabilities, environmental factors, and common latent diseases that can progress to cause dementia, such as Alzheimer disease and vascular brain injury. To use cerebrospinal fluid (CSF) biomarkers to gain insight into this complex trait. Secondary analyses of an academic multicenter cross-sectional (n = 315) and longitudinal (n = 158) study of 5 neuropsychological tests (Immediate Recall, Delayed Recall, Trail Making Test Parts A and B, and Category Fluency) in cognitively normal individuals aged 21 to 100 years. To investigate the association of these cognitive function test results with age, sex, educational level, inheritance of the ε4 allele of the apolipoprotein E gene, and CSF concentrations of β-amyloid 42 (Aβ42) and tau (biomarkers of Alzheimer disease) as well as F2-isoprostanes (measures of free radical injury). Age and educational level were broadly predictive of cross-sectional cognitive performance; of the genetic and CSF measures, only greater CSF F2-isoprostane concentration was significantly associated with poorer executive function (adjusted R2 ≤0.31). Longitudinal measures of cognitive abilities, except Category Fluency, also were associated broadly with age; of the genetic and CSF measures, only lower baseline CSF Aβ42 concentration was associated with longitudinal measures of immediate and delayed recall (marginal R2 ≤0.31). Our results suggest that age and educational level accounted for a substantial minority of variance in cross-sectional or longitudinal cognitive test performance in this large group of cognitively normal adults. Latent Alzheimer disease and other diseases that produce free radical injury, such as vascular brain injury, accounted for a small amount of variation in cognitive test performance across the adult human life span. Additional genetic and environmental factors likely contribute substantially to age-related cognitive decline.

The Integrity of the Corpus Callosum Mitigates the Impact of Blood Pressure on the Ventral Attention Network and Information Processing Speed in Healthy Adults

PubMed Central

Wong, Nichol M. L.; Ma, Ernie Po-Wing; Lee, Tatia M. C.

2017-01-01

Hypertension is a risk factor for cognitive impairment in older age. However, evidence of the neural basis of the relationship between the deterioration of cognitive function and elevated blood pressure is sparse. Based on previous research, we speculate that variations in brain connectivity are closely related to elevated blood pressure even before the onset of clinical conditions and apparent cognitive decline in individuals over 60 years of age. Forty cognitively healthy adults were recruited. Each received a blood pressure test before and after the cognitive assessment in various domains. Diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rsfMRI) data were collected. Our findings confirm that elevated blood pressure is associated with brain connectivity variations in cognitively healthy individuals. The integrity of the splenium of the corpus callosum is closely related to individual differences in systolic blood pressure. In particular, elevated systolic blood pressure is related to resting-state ventral attention network (VAN) and information processing speed. Serial mediation analyses have further revealed that lower integrity of the splenium statistically predicts elevated systolic blood pressure, which in turn predicts weakened functional connectivity (FC) within the VAN and eventually poorer processing speed. The current study sheds light on how neural correlates are involved in the impact of elevated blood pressure on cognitive functioning. PMID:28484386

Effects of non-steroidal anti-inflammatory drug treatments on cognitive decline vary by phase of pre-clinical Alzheimer disease: findings from the randomized controlled Alzheimer's Disease Anti-inflammatory Prevention Trial.

PubMed

Leoutsakos, Jeannie-Marie S; Muthen, Bengt O; Breitner, John C S; Lyketsos, Constantine G

2012-04-01

We examined the effects of non-steroidal anti-inflammatory drugs on cognitive decline as a function of phase of pre-clinical Alzheimer disease. Given recent findings that cognitive decline accelerates as clinical diagnosis is approached, we used rate of decline as a proxy for phase of pre-clinical Alzheimer disease. We fit growth mixture models of Modified Mini-Mental State (3MS) Examination trajectories with data from 2388 participants in the Alzheimer's Disease Anti-inflammatory Prevention Trial and included class-specific effects of naproxen and celecoxib. We identified three classes: "no decline", "slow decline", and "fast decline", and examined the effects of celecoxib and naproxen on linear slope and rate of change by class. Inclusion of quadratic terms improved fit of the model (-2 log likelihood difference: 369.23; p < 0.001) but resulted in reversal of effects over time. Over 4 years, participants in the slow-decline class on placebo typically lost 6.6 3MS points, whereas those on naproxen lost 3.1 points (p-value for difference: 0.19). Participants in the fast-decline class on placebo typically lost 11.2 points, but those on celecoxib first declined and then gained points (p-value for difference from placebo: 0.04), whereas those on naproxen showed a typical decline of 24.9 points (p-value for difference from placebo: <0.0001). Our results appeared statistically robust but provided some unexpected contrasts in effects of different treatments at different times. Naproxen may attenuate cognitive decline in slow decliners while accelerating decline in fast decliners. Celecoxib appeared to have similar effects at first but then attenuated change in fast decliners. Copyright © 2011 John Wiley & Sons, Ltd.

Is air pollution associated with increased risk of cognitive decline? A systematic review.

PubMed

Peters, Ruth; Peters, Jean; Booth, Andrew; Mudway, Ian

2015-09-01

exposure to air pollution has been shown to increase risk of inflammatory processes and risk of cardiovascular mortality. Such exposure may therefore also be a risk factor for cognitive impairment/dementia. a systematic review of the literature was conducted with databases searched using keywords for air pollution, cognitive decline and dementia. All identified abstracts and potentially relevant articles were double read. For those papers meeting the inclusion criteria, summary tables were prepared and papers quality assessed. from 1,551 abstracts identified, 10 articles were retrieved of which two were rejected. Of the eight remaining six reported prevalent cognitive assessment with historical pollution exposure and two incident cognitive decline, also with historical pollution exposure. In general, an association was reported between exposure and poorer prevalent measures of cognitive function. Data were mixed for incident cognitive decline with one study finding an association and the other not. Reports were limited by a lack of detailed reporting, use of proxy measures of pollution exposure and a lack of clarity regarding cognitive testing methodology and analysis. this systematic review highlights that there is some evidence of a potential association between air pollution and subsequent cognitive decline. Further work is clearly required and longitudinal analysis of ongoing cohort studies or new research would add much needed clarity to this area. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cognitive development in childhood and drinking behaviour over two decades in adulthood.

PubMed

Jefferis, B J M H; Manor, O; Power, C

2008-06-01

Childhood cognition predicts adult morbidity and mortality, potentially working through health behaviours. This study investigates if childhood cognition influences life course (i) non-drinking and (ii) binge drinking and pathways through which this might act-namely, childhood behaviour problems, adult social position and educational qualifications. Prospective cohort of British births in March 1958, with information on cognition at 7, 11 and 16 years and alcohol use at 23, 33 and 42 years. Non-drinkers drank "infrequently/on special occasions" or "never". Binge drinkers consumed >or=10 units/occasion (men) and >or=7 units/occasion (women). Lower cognitive ability increased the odds of non-drinking at each adult survey (for example, for men at 42 years OR 1.52 (95% CI 1.34 to 1.72) per SD decrease in 7-year maths). Associations remained after adjustment for pathway factors (i) behaviour problems, (ii) adult social position and (iii) educational qualifications. Decreased ability rank across childhood (7-16 years) also increased odds of non-drinking at 42 years, but the association operated via pathway factors. Lower 7-year ability elevated the odds of 42-year binge drinking, operating via pathway factors. Declining ability rank across childhood also increased the odds of adult binge drinking; associations operated through behavioural problems, adult social position and qualifications. In women, the decline in risk of binge drinking from an age 23-year peak to 42 years was associated with higher 7-year score. Poorer childhood cognition was associated with non-drinking and binge drinking up to the early 40s. Associations between childhood cognition and drinking status may mediate between childhood cognition and adult health.

Age-associated Cognitive Decline: Insights into Molecular Switches and Recovery Avenues.

PubMed

Konar, Arpita; Singh, Padmanabh; Thakur, Mahendra K

2016-03-01

Age-associated cognitive decline is an inevitable phenomenon that predisposes individuals for neurological and psychiatric disorders eventually affecting the quality of life. Scientists have endeavored to identify the key molecular switches that drive cognitive decline with advancing age. These newly identified molecules are then targeted as recovery of cognitive aging and related disorders. Cognitive decline during aging is multi-factorial and amongst several factors influencing this trajectory, gene expression changes are pivotal. Identifying these genes would elucidate the neurobiological underpinnings as well as offer clues that make certain individuals resilient to withstand the inevitable age-related deteriorations. Our laboratory has focused on this aspect and investigated a wide spectrum of genes involved in crucial brain functions that attribute to senescence induced cognitive deficits. We have recently identified master switches in the epigenome regulating gene expression alteration during brain aging. Interestingly, these factors when manipulated by chemical or genetic strategies successfully reverse the age-related cognitive impairments. In the present article, we review findings from our laboratory and others combined with supporting literary evidences on molecular switches of brain aging and their potential as recovery targets.

Aging-Resilient Associations between the Arcuate Fasciculus and Vocabulary Knowledge: Microstructure or Morphology?

PubMed Central

Vaden, Kenneth I.; Cute, Stephanie L.; Yeatman, Jason D.; Dougherty, Robert F.

2016-01-01

Vocabulary knowledge is one of the few cognitive functions that is relatively preserved in older adults, but the reasons for this relative preservation have not been well delineated. We tested the hypothesis that individual differences in vocabulary knowledge are influenced by arcuate fasciculus macrostructure (i.e., shape and volume) properties that remain stable during the aging process, rather than white matter microstructure that demonstrates age-related declines. Vocabulary was not associated with age compared to pronounced age-related declines in cognitive processing speed across 106 healthy adults (19.92–88.29 years) who participated in this neuroimaging experiment. Fractional anisotropy in the left arcuate fasciculus was significantly related to individual variability in vocabulary. This effect was present despite marked age-related differences in a T1-weighted/T2-weighted ratio (T1w/T2w) estimate of myelin that were observed throughout the left arcuate fasciculus and associated with age-related differences in cognitive processing speed. However, atypical patterns of arcuate fasciculus morphology or macrostructure were associated with decreased vocabulary knowledge. These results suggest that deterioration of tissue in the arcuate fasciculus occurs with normal aging, while having limited impact on tract organization that underlies individual differences in the acquisition and retrieval of lexical and semantic information. SIGNIFICANCE STATEMENT Vocabulary knowledge is resilient to widespread age-related declines in brain structure that limit other cognitive functions. We tested the hypothesis that arcuate fasciculus morphology, which supports the development of reading skills that bolster vocabulary, could explain this relative preservation. We disentangled (1) the effects of age-related declines in arcuate microstructure (mean diffusivity; myelin content estimate) that predicted cognitive processing speed but not vocabulary, from (2) relatively stable arcuate macrostructure (shape/volume) that explained significant variance in an age-independent association between fractional anisotropy and vocabulary. This latter result may reflect differences in fiber trajectory and organization that are resilient to aging. We propose that developmental sculpting of the arcuate fasciculus determines acquisition, storage, and access of lexical information across the adult lifespan. PMID:27383595

Improved power for characterizing longitudinal amyloid-β PET changes and evaluating amyloid-modifying treatments with a cerebral white matter reference region.

PubMed

Chen, Kewei; Roontiva, Auttawut; Thiyyagura, Pradeep; Lee, Wendy; Liu, Xiaofen; Ayutyanont, Napatkamon; Protas, Hillary; Luo, Ji Luo; Bauer, Robert; Reschke, Cole; Bandy, Daniel; Koeppe, Robert A; Fleisher, Adam S; Caselli, Richard J; Landau, Susan; Jagust, William J; Weiner, Michael W; Reiman, Eric M

2015-04-01

In this article, we describe an image analysis strategy with improved power for tracking longitudinal amyloid-β (Aβ) PET changes and evaluating Aβ-modifying treatments. Our aims were to compare the power of template-based cerebellar, pontine, and cerebral white matter reference regions to track 24-mo florbetapir standardized uptake value (SUV) ratio (SUVR) changes; to relate those changes to 24-mo clinical declines; and to evaluate Aβ-modifying treatments in Aβ-positive (Aβ+) and Aβ-negative (Aβ-) patients with probable Alzheimer dementia (pAD), in patients with mild cognitive impairment (MCI), in cognitively normal controls (NCs), and in cognitively normal apolipoprotein E4 (APOE4) carriers and noncarriers. We used baseline and follow-up (∼24 mo) florbetapir PET scans from 332 Aβ+ and Aβ- subjects participating in the multicenter Alzheimer's Disease Neuroimaging Initiative. Each of the proposed analyses included 31 pAD patients, 187 MCI patients, and 114 NCs. Cerebral-to-white matter, cerebellar, and pontine SUVRs were characterized in terms of their longitudinal variability; their power to track longitudinal fibrillar Aβ increases in Aβ+ and Aβ- subgroups and cognitively normal APOE4 carriers and noncarriers; the sample sizes needed to detect attenuated accumulation of or clearance of fibrillar Aβ accumulation in randomized clinical trials; and their ability to relate 24-mo fibrillar Aβ increases to clinical declines. As predicted, cerebral-to-white matter SUVR changes were significantly less variable and had significantly greater power to detect 24-mo fibrillar Aβ increases and evaluate Aβ-modifying treatment effects in Aβ+ pAD, MCI, and NC subjects and cognitively normal APOE4 carriers. They were also distinguished by the ability to detect significant associations between 24-mo Aβ increases and clinical declines. A cerebral white matter reference region may improve the power to track longitudinal fibrillar Aβ increases, to characterize their relationship to longitudinal clinical declines, and to evaluate Aβ-modifying treatments in randomized clinical trials. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Age-Related Decline in Anticipatory Motor Planning and Its Relation to Cognitive and Motor Skill Proficiency

PubMed Central

Stöckel, Tino; Wunsch, Kathrin; Hughes, Charmayne M. L.

2017-01-01

Anticipatory motor planning abilities mature as children grow older, develop throughout childhood and are likely to be stable till the late sixties. In the seventh decade of life, motor planning performance dramatically declines, with anticipatory motor planning abilities falling to levels of those exhibited by children. At present, the processes enabling successful anticipatory motor planning in general, as do the cognitive processes mediating these age-related changes, remain elusive. Thus, the aim of the present study was (a) to identify cognitive and motor functions that are most affected by normal aging and (b) to elucidate key (cognitive and motor) factors that are critical for successful motor planning performance in young (n = 40, mean age = 23.1 ± 2.6 years) and older adults (n = 37, mean age = 73.5 ± 7.1 years). Results indicate that normal aging is associated with a marked decline in all aspects of cognitive and motor functioning tested. However, age-related declines were more apparent for fine motor dexterity, processing speed and cognitive flexibility. Furthermore, up to 64% of the variance in motor planning performance across age groups could be explained by the cognitive functions processing speed, response planning and cognitive flexibility. It can be postulated that anticipatory motor planning abilities are strongly influenced by cognitive control processes, which seem to be key mechanisms to compensate for age-related decline. These findings support the general therapeutic and preventive value of cognitive-motor training programs to reduce adverse effects associated with high age. PMID:28928653

Ascorbic Acid and the Brain: Rationale for the Use against Cognitive Decline

PubMed Central

Harrison, Fiona E.; Bowman, Gene L.; Polidori, Maria Cristina

2014-01-01

This review is focused upon the role of ascorbic acid (AA, vitamin C) in the promotion of healthy brain aging. Particular attention is attributed to the biochemistry and neuronal metabolism interface, transport across tissues, animal models that are useful for this area of research, and the human studies that implicate AA in the continuum between normal cognitive aging and age-related cognitive decline up to Alzheimer’s disease. Vascular risk factors and comorbidity relationships with cognitive decline and AA are discussed to facilitate strategies for advancing AA research in the area of brain health and neurodegeneration. PMID:24763117

APOE ε4 and the risk for Alzheimer disease and cognitive decline in African Americans and Yoruba

PubMed Central

Hendrie, Hugh C.; Murrell, Jill; Baiyewu, Olusegun; Lane, Kathleen A.; Purnell, Christianna; Ogunniyi, Adesola; Unverzagt, Frederick W.; Hall, Kathleen; Callahan, Christopher M.; Saykin, Andrew J.; Gureje, Oye; Hake, Ann; Foroud, Tatiana; Gao, Sujuan

2014-01-01

Background There is little information on the association of the APOEe4 allele and AD risk in African populations. In previous analyses from the Indianapolis-Ibadan dementia project, we have reported that APOE ε4 increased the risk for Alzheimer’s disease (AD) in African Americans but not in Yoruba. This study represents a replication of this earlier work using enriched cohorts and extending the analysis to include cognitive decline. Methods In this longitudinal study of two community dwelling cohorts of elderly Yoruba and African Americans, APOE genotyping was conducted from blood samples taken on or before 2001 (1,871 African Americans & 2,200 Yoruba). Mean follow up time was 8.5 years for African Americans and 8.8 years for Yoruba. The effects of heterozygosity or homozygosity of ε4 and of the possession of e4 on time to incident AD and on cognitive decline were determined using Cox’s proportional hazards regression and mixed effects models. Results After adjusting for covariates, one or two copies of the APOE ε4 allele were significant risk factors for incident AD (p < 0.0001) and cognitive decline in the African-American population (p < 0001). In the Yoruba, only homozygosity for APOE ε4 was a significant risk factor for AD (p = 0.0002) but not for cognitive decline (p = 0.2346), however, possession of an e4 allele was significant for both incident AD (p = 0.0489) and cognitive decline (p = 0.0425). Conclusions In this large longitudinal comparative study, APOE ε4 had a significant, but weaker, effect on incident AD and on cognitive decline in Yoruba than in African Americans. The reasons for these differences remain unclear. PMID:24565289

Physical fitness is predictive for a decline in the ability to perform instrumental activities of daily living in older adults with intellectual disabilities: Results of the HA-ID study.

PubMed

Oppewal, Alyt; Hilgenkamp, Thessa I M; van Wijck, Ruud; Schoufour, Josje D; Evenhuis, Heleen M

2015-01-01

The ability to perform instrumental activities of daily living (IADL) is important for one's level of independence. A high incidence of limitations in IADL is seen in older adults with intellectual disabilities (ID), which is an important determinant for the amount of support one needs. The aim of this study was to assess the predictive value of physical fitness for the ability to perform IADL, over a 3-year follow-up period, in 601 older adults with ID. At baseline, an extensive physical fitness assessment was performed. In addition, professional caregivers completed the Lawton IADL scale, both at baseline and at follow-up. The average ability to perform IADL declined significantly over the 3-year follow-up period. A decline in the ability to perform IADL was seen in 44.3% of the participants. The percentage of participants being completely independent in IADL declined from 2.7% to 1.3%. Manual dexterity, balance, comfortable and fast gait speed, muscular endurance, and cardiorespiratory fitness were significant predictors for a decline in IADL after correcting for baseline IADL and personal characteristics (age, gender, level of ID, and Down syndrome). This can be interpreted as representing the predictive validity of the physical tests for a decline in IADL. This study shows that even though older adults with ID experience dependency on others due to cognitive limitations, physical fitness also is an important aspect for IADL, which stresses the importance of using physical fitness tests and physical fitness enhancing programs in the care for older adults with ID. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synergistic effects of aerobic exercise and cognitive training on cognition, physiological markers, daily function, and quality of life in stroke survivors with cognitive decline: study protocol for a randomized controlled trial.

PubMed

Yeh, Ting-Ting; Wu, Ching-Yi; Hsieh, Yu-Wei; Chang, Ku-Chou; Lee, Lin-Chien; Hung, Jen-Wen; Lin, Keh-Chung; Teng, Ching-Hung; Liao, Yi-Han

2017-08-31

Aerobic exercise and cognitive training have been effective in improving cognitive functions; however, whether the combination of these two can further enhance cognition and clinical outcomes in stroke survivors with cognitive decline remains unknown. This study aimed to determine the treatment effects of a sequential combination of aerobic exercise and cognitive training on cognitive function and clinical outcomes. Stroke survivors (n = 75) with cognitive decline will be recruited and randomly assigned to cognitive training, aerobic exercise, and sequential combination of aerobic exercise and cognitive training groups. All participants will receive training for 60 minutes per day, 3 days per week for 12 weeks. The aerobic exercise group will receive stationary bicycle training, the cognitive training group will receive cognitive-based training, and the sequential group will first receive 30 minutes of aerobic exercise, followed by 30 minutes of cognitive training. The outcome measures involve cognitive functions, physiological biomarkers, daily function and quality of life, physical functions, and social participation. Participants will be assessed before and immediately after the interventions, and 6 months after the interventions. Repeated measures of analysis of variance will be used to evaluate the changes in outcome measures at the three assessments. This trial aims to explore the benefits of innovative intervention approaches to improve the cognitive function, physiological markers, daily function, and quality of life in stroke survivors with cognitive decline. The findings will provide evidence to advance post-stroke cognitive rehabilitation. ClinicalTrials.gov, NCT02550990 . Registered on 6 September 2015.

Type 2 Diabetes Mellitus and Impaired Renal Function Are Associated With Brain Alterations and Poststroke Cognitive Decline.

PubMed

Ben Assayag, Einor; Eldor, Roy; Korczyn, Amos D; Kliper, Efrat; Shenhar-Tsarfaty, Shani; Tene, Oren; Molad, Jeremy; Shapira, Itzhak; Berliner, Shlomo; Volfson, Viki; Shopin, Ludmila; Strauss, Yehuda; Hallevi, Hen; Bornstein, Natan M; Auriel, Eitan

2017-09-01

Type 2 diabetes mellitus (T2DM) is associated with diseases of the brain, kidney, and vasculature. However, the relationship between T2DM, chronic kidney disease, brain alterations, and cognitive function after stroke is unknown. We aimed to evaluate the inter-relationship between T2DM, impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. The TABASCO (Tel Aviv brain acute stroke cohort) is a prospective cohort of stroke/transient ischemic attack survivors. The volume and white matter integrity, ischemic lesions, and brain and hippocampal volumes were measured at baseline using 3-T MRI. Cognitive tests were performed on 507 patients, who were diagnosed as having mild cognitive impairment, dementia, or being cognitively intact after 24 months. At baseline, T2DM and impaired renal function (estimated creatinine clearance [eCCl] <60 mL/min) were associated with smaller brain and hippocampal volumes, reduced cortical thickness, and worse white matter microstructural integrity. Two years later, both T2DM and eCCl <60 mL/min were associated with poorer cognitive scores, and 19.7% of the participants developed cognitive decline (mild cognitive impairment or dementia). Multiple analysis, controlling for age, sex, education, and apolipoprotein E4, showed a significant association of both T2DM and eCCl <60 mL/min with cognitive decline. Having both conditions doubled the risk compared with patients with T2DM or eCCl <60 mL/min alone and almost quadrupled the risk compared with patients without either abnormality. T2DM and impaired renal function are independently associated with abnormal brain structure, as well as poorer performance in cognitive tests, 2 years after stroke. The presence of both conditions quadruples the risk for cognitive decline. T2DM and lower eCCl have an independent and additive effect on brain atrophy and the risk of cognitive decline. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01926691. © 2017 American Heart Association, Inc.

Milk Intake at Midlife and Cognitive Decline over 20 Years. The Atherosclerosis Risk in Communities (ARIC) Study.

PubMed

Petruski-Ivleva, Natalia; Kucharska-Newton, Anna; Palta, Priya; Couper, David; Meyer, Katie; Graff, Misa; Haring, Bernhard; Sharrett, Richey; Heiss, Gerardo

2017-10-17

Background : Faster rates of cognitive decline are likely to result in earlier onset of cognitive impairment and dementia. d-galactose, a derivative of lactose, is used in animal studies to induce neurodegeneration. Milk is the primary source of lactose in the human diet, and its effects on cognitive decline have not been fully evaluated. Objective : Assess the association of milk intake with change in cognitive function over 20 years. Methods : A total of 13,751 participants of the Atherosclerosis Risk in Communities (ARIC) cohort completed a food frequency questionnaire and three neurocognitive evaluations from 1990 through 2013. Two single nucleotide polymorphisms (SNPs) were used to determine lactase persistence (LCT-13910 C/T for Whites and LCT-14010 G/C for Blacks). Mixed-effects models were used to study the association of milk intake with cognitive change. Multiple imputations by chained equations were used to account for attrition. Results : Milk intake greater than 1 glass/day was associated with greater decline in the global z-score over a 20-year period. The difference in decline was 0.10 (95% CI: 0.16, 0.03) z-scores, or an additional 10% decline, relative to the group reporting "almost never" consuming milk. Conclusions : Replication of these results is warranted in diverse populations with greater milk intake and higher variability of lactase persistence genotype.

Milk Intake at Midlife and Cognitive Decline over 20 Years. The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Petruski-Ivleva, Natalia; Kucharska-Newton, Anna; Palta, Priya; Meyer, Katie; Graff, Misa; Haring, Bernhard; Sharrett, Richey; Heiss, Gerardo

2017-01-01

Background: Faster rates of cognitive decline are likely to result in earlier onset of cognitive impairment and dementia. d-galactose, a derivative of lactose, is used in animal studies to induce neurodegeneration. Milk is the primary source of lactose in the human diet, and its effects on cognitive decline have not been fully evaluated. Objective: Assess the association of milk intake with change in cognitive function over 20 years. Methods: A total of 13,751 participants of the Atherosclerosis Risk in Communities (ARIC) cohort completed a food frequency questionnaire and three neurocognitive evaluations from 1990 through 2013. Two single nucleotide polymorphisms (SNPs) were used to determine lactase persistence (LCT-13910 C/T for Whites and LCT-14010 G/C for Blacks). Mixed-effects models were used to study the association of milk intake with cognitive change. Multiple imputations by chained equations were used to account for attrition. Results: Milk intake greater than 1 glass/day was associated with greater decline in the global z-score over a 20-year period. The difference in decline was 0.10 (95% CI: 0.16, 0.03) z-scores, or an additional 10% decline, relative to the group reporting “almost never” consuming milk. Conclusions: Replication of these results is warranted in diverse populations with greater milk intake and higher variability of lactase persistence genotype. PMID:29039795

Cognitive performance and age-related changes in the hippocampal proteome.

PubMed

Freeman, W M; VanGuilder, H D; Bennett, C; Sonntag, W E

2009-03-03

Declining cognitive performance is associated with increasing age, even in the absence of overt pathological processes. We and others have reported that declining cognitive performance is associated with age-related changes in brain glucose utilization, long-term potentiation and paired-pulse facilitation, protein expression, neurotransmitter levels, and trophic factors. However, it is unclear whether these changes are causes or symptoms of the underlying alterations in dendritic and synaptic morphology that occur with age. In this study, we examined the hippocampal proteome for age- and cognition-associated changes in behaviorally stratified young and old rats, using two-dimensional in-gel electrophoresis and MS/MS. Comparison of old cognitively intact with old cognitively impaired animals revealed additional changes that would not have been detected otherwise. Interestingly, not all age-related changes in protein expression were associated with cognitive decline, and distinct differences in protein expression were found when comparing old cognitively intact with old cognitively impaired rats. A large number of protein changes with age were related to the glycolysis/gluconeogenesis pathway. In total, the proteomic changes suggest that age-related alterations act synergistically with other perturbations to result in cognitive decline. This study also demonstrates the importance of examining behaviorally-defined animals in proteomic studies, as comparison of young to old animals regardless of behavioral performance would have failed to detect many cognitive impairment-specific protein expression changes evident when behavioral stratification data were used.