Pharmacologic Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review.

PubMed

Fink, Howard A; Jutkowitz, Eric; McCarten, J Riley; Hemmy, Laura S; Butler, Mary; Davila, Heather; Ratner, Edward; Calvert, Collin; Barclay, Terry R; Brasure, Michelle; Nelson, Victoria A; Kane, Robert L

2018-01-02

Optimal treatment to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia is uncertain. To summarize current evidence on the efficacy and harms of pharmacologic interventions to prevent or delay cognitive decline, MCI, or dementia in adults with normal cognition or MCI. Several electronic databases from January 2009 to July 2017, bibliographies, and expert recommendations. English-language trials of at least 6 months' duration enrolling adults without dementia and comparing pharmacologic interventions with placebo, usual care, or active control on cognitive outcomes. Two reviewers independently rated risk of bias and strength of evidence; 1 extracted data, and a second checked accuracy. Fifty-one unique trials were rated as having low to moderate risk of bias (including 3 that studied dementia medications, 16 antihypertensives, 4 diabetes medications, 2 nonsteroidal anti-inflammatory drugs [NSAIDs] or aspirin, 17 hormones, and 7 lipid-lowering agents). In persons with normal cognition, estrogen and estrogen-progestin increased risk for dementia or a combined outcome of MCI or dementia (1 trial, low strength of evidence); high-dose raloxifene decreased risk for MCI but not for dementia (1 trial, low strength of evidence); and antihypertensives (4 trials), NSAIDs (1 trial), and statins (1 trial) did not alter dementia risk (low to insufficient strength of evidence). In persons with MCI, cholinesterase inhibitors did not reduce dementia risk (1 trial, low strength of evidence). In persons with normal cognition and those with MCI, these pharmacologic treatments neither improved nor slowed decline in cognitive test performance (low to insufficient strength of evidence). Adverse events were inconsistently reported but were increased for estrogen (stroke), estrogen-progestin (stroke, coronary heart disease, invasive breast cancer, and pulmonary embolism), and raloxifene (venous thromboembolism). High attrition, short follow-up, inconsistent cognitive outcomes, and possible selective reporting and publication. Evidence does not support use of the studied pharmacologic treatments for cognitive protection in persons with normal cognition or MCI. Agency for Healthcare Research and Quality.

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.

Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review.

PubMed

Butler, Mary; Nelson, Victoria A; Davila, Heather; Ratner, Edward; Fink, Howard A; Hemmy, Laura S; McCarten, J Riley; Barclay, Terry R; Brasure, Michelle; Kane, Robert L

2018-01-02

Optimal interventions to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia are uncertain. To summarize the evidence on efficacy and harms of over-the-counter (OTC) supplements to prevent or delay cognitive decline, MCI, or clinical Alzheimer-type dementia in adults with normal cognition or MCI but no dementia diagnosis. Multiple electronic databases from 2009 to July 2017 and bibliographies of systematic reviews. English-language trials of at least 6 months' duration that enrolled adults without dementia and compared cognitive outcomes with an OTC supplement versus placebo or active controls. Extraction performed by a single reviewer and confirmed by a second reviewer; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence. Thirty-eight trials with low to medium risk of bias compared ω-3 fatty acids, soy, ginkgo biloba, B vitamins, vitamin D plus calcium, vitamin C or β-carotene, multi-ingredient supplements, or other OTC interventions with placebo or other supplements. Few studies examined effects on clinical Alzheimer-type dementia or MCI, and those that did suggested no benefit. Daily folic acid plus vitamin B12 was associated with improvements in performance on some objectively measured memory tests that were statistically significant but of questionable clinical significance. Moderate-strength evidence showed that vitamin E had no benefit on cognition. Evidence about effects of ω-3 fatty acids, soy, ginkgo biloba, folic acid alone or with other B vitamins, β-carotene, vitamin C, vitamin D plus calcium, and multivitamins or multi-ingredient supplements was either insufficient or low-strength, suggesting that these supplements did not reduce risk for cognitive decline. Adverse events were rarely reported. Studies had high attrition and short follow-up and used a highly variable set of cognitive outcome measures. Evidence is insufficient to recommend any OTC supplement for cognitive protection in adults with normal cognition or MCI. Agency for Healthcare Research and Quality.

A Longitudinal Item Response Theory Model to Characterize Cognition Over Time in Elderly Subjects

PubMed Central

Bornkamp, Björn; Krahnke, Tillmann; Mielke, Johanna; Monsch, Andreas; Quarg, Peter

2017-01-01

For drug development in neurodegenerative diseases such as Alzheimer's disease, it is important to understand which cognitive domains carry the most information on the earliest signs of cognitive decline, and which subject characteristics are associated with a faster decline. A longitudinal Item Response Theory (IRT) model was developed for the Basel Study on the Elderly, in which the Consortium to Establish a Registry for Alzheimer's Disease – Neuropsychological Assessment Battery (with additions) and the California Verbal Learning Test were measured on 1,750 elderly subjects for up to 13.9 years. The model jointly captured the multifaceted nature of cognition and its longitudinal trajectory. The word list learning and delayed recall tasks carried the most information. Greater age at baseline, fewer years of education, and positive APOEɛ4 carrier status were associated with a faster cognitive decline. Longitudinal IRT modeling is a powerful approach for progressive diseases with multifaceted endpoints. PMID:28643388

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

Feasibility and first results of a group program to increase the frequency of cognitively stimulating leisure activities in people with mild cognitive impairment (AKTIVA-MCI)

PubMed Central

Tesky, Valentina A; Köbe, Theresa; Witte, A Veronica; Flöel, Agnes; Schuchardt, Jan Philipp; Hahn, Andreas; Pantel, Johannes

2017-01-01

AKTIVA-MCI is a program for patients with mild cognitive impairment (MCI) that aims to enhance participation in cognitively stimulating leisure activities. Participation in cognitively stimulating activities seems to be a potential strategy for people with MCI delaying cognitive decline for a while. In total, 35 MCI patients were enrolled in the pilot study of whom 29 completed the whole program (16 female, 71.1±7.5 years; Mini Mental Status Examination score: 28±2.2). Daily activity protocols were used to measure the frequency of participation in cognitively stimulating activities during the program (12 sessions). Additional standardized psychometric tests and questionnaires were used to assess cognition, mood, and subjective memory decline. Analyses of the daily activity protocols showed that during the intervention participants increased the frequency of several cognitively stimulating leisure activities. Comparison of pre-post data indicates no changes in cognitive status, mood, and subjective memory decline. These findings indicate that the program is suitable for patients with MCI. PMID:28979108

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.

Mental and physical activities delay cognitive decline in older persons with dementia.

PubMed

Cheng, Sheung-Tak; Chow, Pizza K; Song, You-Qiang; Yu, Edwin C S; Chan, Alfred C M; Lee, Tatia M C; Lam, John H M

2014-01-01

To examine the effects of cognitive stimulation (mahjong) and physical exercise (tai chi [TC]) on cognitive performance in persons with dementia. Cluster-randomized open-label controlled design. Nursing homes. One hundred ten residents, most of whom were cholinesterase-inhibitor naive. Inclusion criteria were Mini-Mental State Examination (MMSE) = 10-24 and suffering from at least very mild dementia (Clinical Dementia Rating ≥ 0.5). Exclusion criteria were being bedbound, audio/visual impairment, regular activity participation before study, or contraindications for physical or group activities. Homes were randomized into three conditions (mahjong, TC, and simple handicrafts [control]). Activities were conducted three times weekly for 12 weeks. Primary outcome was MMSE. Secondary outcomes were immediate/delayed recall, categorical fluency, and digit span. Various biological risk factors, including apolipoprotein E ε4 allele, were included as covariates. Measures were collected at 0 (baseline), 3 (posttreatment), 6, and 9 months. Intent-to-treat analyses were performed using mixed-effects regression. Mahjong's effect varied by time for MMSE, delayed recall, and forward digit span. TC had similar effects but not for delayed recall. The typical pattern was that control participants deteriorated while mahjong and TC participants maintained their abilities over time, leading to enlarged treatment effects as time progressed. By 9 months, mahjong and TC differed from control by 4.5 points (95% confidence interval: 2.0-6.9; d = 0.48) and 3.7 points (95% confidence interval: 1.4-6.0; d = 0.40), respectively, on MMSE. No treatment effects were observed for immediate recall and backward digit span. Mahjong and TC can preserve functioning or delay decline in certain cognitive domains, even in those with significant cognitive impairment. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

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.

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

Hydrocephalus

MedlinePlus

... lethargy Nausea or vomiting Unstable balance Poor coordination Poor appetite Seizures Urinary incontinence Behavioral and cognitive changes Irritability Change in personality Decline in school performance Delays or problems with previously acquired skills, such ...

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.

Associations of cumulative Pb exposure and longitudinal changes in Mini-Mental Status Exam scores, global cognition and domains of cognition: The VA Normative Aging Study.

PubMed

Farooqui, Zishaan; Bakulski, Kelly M; Power, Melinda C; Weisskopf, Marc G; Sparrow, David; Spiro, Avron; Vokonas, Pantel S; Nie, Linda H; Hu, Howard; Park, Sung Kyun

2017-01-01

Lead (Pb) exposure has been associated with poorer cognitive function cross-sectionally in aging adults, however the association between cumulative Pb exposure and longitudinal changes in cognition is little characterized. In a 1993-2007 subcohort of the VA Normative Aging Study (Mini-mental status exam (MMSE) n=741; global cognition summary score n=715), we used linear mixed effects models to test associations between cumulative Pb exposure (patella or tibia bone Pb) and repeated measures of cognition (MMSE, individual cognitive tests, and global cognition summary). Cox proportional hazard modeling assessed the risk of an MMSE score falling below 25. Among men 51-98 at baseline, higher patella Pb concentration (IQR: 21μg/g) was associated with -0.13 lower baseline MMSE (95% CI: -0.25, -0.004) and faster longitudinal MMSE decline (-0.016 units/year, 95% CI: -0.032, -0.0004) over 15 years. Each IQR increase in patella Pb was associated with increased risk of a MMSE score below 25 (HR=1.21, 95% CI: 0.99, 1.49; p=0.07). There were no significant associations between Pb and global cognition (both baseline and longitudinal change). Patella Pb was associated with faster longitudinal decline in Word List Total Recall in the language domain (0.014 units/year, 95% CI: -0.026, -0.001) and Word List Delayed Recall in the memory domain (0.014 units/year, 95% CI: -0.027, -0.002). We found weaker associations with tibia Pb. Cumulative Pb exposure is associated with faster declines in MMSE and Word List Total and Delayed Recall tests. These findings support the hypothesis that Pb exposure accelerates cognitive aging. Copyright © 2016 Elsevier Inc. All rights reserved.

P3 amplitude attenuation secondary to increases in target-to-target interval (TTI) during spatial serial order recall: Implications for EEG models of working memory function.

PubMed

Hochberger, William C; Axelrod, Jenna L; Sarapas, Casey; Shankman, Stewart A; Hill, S Kristian

2018-06-08

Research suggests that increasing delays in stimulus read-out can trigger declines in serial order recall accuracy due to increases in cognitive demand imposed by the delay; however, the exact neural mechanisms associated with this decline are unclear. Changes in neural resource allocation present as the ideal target and can easily be monitored by examining changes in the amplitude of an ERP component known as the P3. Changes in P3 amplitude secondary to exogenous pacing of stimulus read-out via increased target-to-target intervals (TTI) during recall could reflect decreased neural resource allocation due to increased cognitive demand. This shift in resource allocation could result in working memory storage decay and the declines in serial order accuracy described by prior research. In order to examine this potential effect, participants were administered a spatial serial order processing task, with the recall series consisting of a series of correct ("match") or incorrect ("non-match" or "oddball") stimuli. Moreover, the recall series included either a brief (500ms) or extended (2000ms) delay between stimuli. Results were significant for the presence of a P3 response to non-match stimuli for both experimental conditions, and attenuation of P3 amplitude secondary to the increase in target-to-target interval (TTI). These findings suggest that extending the delay between target recognition could increase cognitive demand and trigger a decrease in neural resource allocation that results in a decay of working memory stores.

Natural history of Sanfilippo syndrome type A.

PubMed

Buhrman, Dakota; Thakkar, Kavita; Poe, Michele; Escolar, Maria L

2014-05-01

To describe the natural history of Sanfilippo syndrome type A. We performed a retrospective review of 46 children (21 boys, 25 girls) with Sanfilippo syndrome type A evaluated between January 2000 and April 2013. Assessments included neurodevelopmental evaluations, audiologic testing, and assessment of growth, adaptive behavior, cognitive behavior, motor function, and speech/language skills. Only the baseline evaluation was included for patients who received hematopoietic stem cell transplantation. Median age at diagnosis was 35 months, with a median delay between initial symptoms to diagnosis of 24 months. The most common initial symptoms were speech/language delay (48%), dysmorphology (22%), and hearing loss (20%). Early behavioral problems included perseverative chewing and difficulty with toilet training. All children developed sleep difficulties and behavioral changes (e.g., hyperactivity, aggression). More than 93% of the children experienced somatic symptoms such as hepatomegaly (67%), abnormal dentition (39%), enlarged tongue (37%), coarse facial features (76%), and protuberant abdomen (43%). Kaplan-Meier analysis showed a 60% probability of surviving past 17 years of age. Sanfilippo type A is characterized by severe hearing loss and speech delay, followed by a rapid decline in cognitive skills by 3 years of age. Significant somatic disease occurs in more than half of patients. Behavioral difficulties presented between 2 and 4 years of age during a rapid period of cognitive decline. Gross motor abilities are maintained during this period, which results in an active child with impaired cognition. Sleep difficulties are concurrent with the period of cognitive degeneration. There is currently an unacceptable delay in diagnosis, highlighting the need to increase awareness of this disease among clinicians.

Dietary supplementation with a combination of alpha-lipoic acid, acetyl-L-carnitine, glycerophosphocoline, docosahexaenoic acid, and phosphatidylserine reduces oxidative damage to murine brain and improves cognitive performance.

PubMed

Suchy, James; Chan, Amy; Shea, Thomas B

2009-01-01

Alzheimer disease has a complex etiology composed of nutritional and genetic risk factors and predispositions. Moreover, genetic risk factors for cognitive decline may remain latent pending age-related decline in nutrition, suggesting the potential importance of early nutritional intervention, including preventative approaches. We hypothesized that a combination of multiple nutritional additives may be able to provide neuroprotection. We demonstrate herein that dietary supplementation with a mixture of ALA, ALCAR, GPC, DHA, and PS reduced reactive oxygen species in normal mice by 57% and prevented the increase in reactive oxygen species normally observed in mice lacking murine ApoE when maintained on a vitamin-free, iron-enriched, oxidative-challenge diet. We further demonstrate that supplementation with these agents prevented the marked cognitive decline otherwise observed in normal mice maintained on this challenge diet. These findings add to the growing body of research indicating that key dietary supplementation may delay the progression of age-related cognitive decline.

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.

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.

Psychometric characteristics of the Rivermead Behavioural Memory Test (RBMT) as an early detection instrument for dementia and mild cognitive impairment in Brazil.

PubMed

Yassuda, Mônica Sanches; Flaks, Mariana Kneese; Viola, Luciane Fátima; Pereira, Fernanda Speggiorin; Memória, Claudia Maia; Nunes, Paula Villela; Forlenza, Orestes Vicente

2010-09-01

The Rivermead Behavioural Memory Test (RBMT) assesses everyday memory by means of tasks which mimic daily challenges. The objective was to examine the validity of the Brazilian version of the RBMT to detect cognitive decline. 195 older adults were diagnosed as normal controls (NC) or with mild cognitive impairment (MCI) or Alzheimer's disease (AD) by a multidisciplinary team, after participants completed clinical and neuropsychological protocols. Cronbach's alpha was high for the total sample for the RBMT profile (PS) and screening scores (SS) (PS = 0.91, SS = 0.87) and for the AD group (PS = 0.84, SS = 0.85), and moderate for the MCI (PS = 0.62, SS = 0.55) and NC (PS = 0.62, SS = 0.60) groups. RBMT total scores, Appointment, Pictures, Immediate and Delayed Story, Immediate and Delayed Route, Delayed Message and Date contributed to differentiate NC from MCI. ROC curve analyses indicated high accuracy to differentiate NC from AD patients, and, moderate accuracy to differentiate NC from MCI. The Brazilian version of the RBMT seems to be an appropriate instrument to identify memory decline in Brazilian older adults.

NIH state-of-the-science conference statement: Preventing Alzheimer's disease and cognitive decline.

PubMed

Daviglus, Martha L; Bell, Carl C; Berrettini, Wade; Bowen, Phyllis E; Connolly, E Sander; Cox, Nancy Jean; Dunbar-Jacob, Jacqueline M; Granieri, Evelyn C; Hunt, Gail; McGarry, Kathleen; Patel, Dinesh; Potosky, Arnold L; Sanders-Bush, Elaine; Silberberg, Donald; Trevisan, Maurizio

2010-04-28

To provide health care providers, patients, and the general public with a responsible assessment of currently available data on prevention of Alzheimer's disease and cognitive decline. A non-Department of Health and Human Services, nonadvocate 15-member panel representing the fields of preventive medicine, geriatrics, internal medicine, neurology, neurological surgery, psychiatry, mental health, human nutrition, pharmacology, genetic medicine, nursing, health economics, health services research, family caregiving, and a public representative. In addition, 20 experts from pertinent fields presented data to the panel and conference audience. Presentations by experts and a systematic review of the literature prepared by the Duke University Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. Cognitive decline and Alzheimer’s disease are major causes of morbidity and mortality worldwide and are substantially burdensome to the affected persons, their caregivers, and society in general. Extensive research over the past 20 years has provided important insights on the nature of Alzheimer’s disease and cognitive decline and the magnitude of the problem. Nevertheless, there remain important and formidable challenges in conducting research on these diseases, particularly in the area of prevention. Currently, firm conclusions cannot be drawn about the association of any modifiable risk factor with cognitive decline or Alzheimer’s disease. Highly reliable consensus-based diagnostic criteria for cognitive decline, mild cognitive impairment, and Alzheimer’s disease are lacking, and available criteria have not been uniformly applied. Evidence is insufficient to support the use of pharmaceutical agents or dietary supplements to prevent cognitive decline or Alzheimer’s disease. We recognize that a large amount of promising research is under way; these efforts need to be increased and added to by new understandings and innovations (as noted in our recommendations for future research). For example, ongoing studies including (but not limited to) studies on antihypertensive medications, omega-3 fatty acids, physical activity, and cognitive engagement may provide new insights into the prevention or delay of cognitive decline or Alzheimer’s disease. This important research needs to be supplemented by further studies. Large-scale population-based studies and randomized controlled trials (RCTs) are critically needed to investigate strategies to maintain cognitive function in individuals at risk for decline, to identify factors that may delay the onset of Alzheimer’s disease among persons at risk, and to identify factors that may slow the progression of Alzheimer’s disease among persons in whom the condition is already diagnosed.

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

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.

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.

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

Contribution of N-methyl-D-aspartate receptors to attention and episodic spatial memory during senescence

PubMed Central

Guidi, Michael; Rani, Asha; Karic, Semir; Severance, Barrett; Kumar, Ashok; Foster, Thomas C.

2015-01-01

A decrease in N-methyl-D-aspartate receptor (NMDAR) function is associated with age-related cognitive impairments. However, NMDAR antagonists are prescribed for cognitive decline associated with age-related neurodegenerative disease, raising questions as to the role of NMDAR activity in cognitive function during aging. The current studies examined effects of NMDAR blockade on cognitive task that are sensitive to aging. Young and middle-age rats were trained on the five-choice serial reaction time task (5-CSRTT) and challenged with MK-801 (0.025, 0.05, and 0.1 mg/kg or vehicle). Attention deficits were apparent in middle-age and performance of young and middle-age rats was enhanced for low doses of MK-801 (0.025 and 0.05). The beneficial effects on attention were reversed by the highest dose of MK-801. Older animals exhibited a delay-dependent impairment of episodic spatial memory examined on a delayed-matching to place water maze task. Similarly, a low dose of MK-801 (0.05 mg/kg) impaired performance with increasing delay and aged animals were more susceptible to disruption by NMDAR blockade. Despite MK-801 impairment of episodic spatial memory, MK-801 had minimal effects on spatial reference memory. Our results confirm that NMDARs contribute to rapidly acquired and flexible spatial memory and support the idea that a decline in NMDAR function contributes to the age-related impairments in cognition. PMID:26234588

Contribution of N-methyl-D-aspartate receptors to attention and episodic spatial memory during senescence.

PubMed

Guidi, Michael; Rani, Asha; Karic, Semir; Severance, Barrett; Kumar, Ashok; Foster, Thomas C

2015-11-01

A decrease in N-methyl-D-aspartate receptor (NMDAR) function is associated with age-related cognitive impairments. However, NMDAR antagonists are prescribed for cognitive decline associated with age-related neurodegenerative disease, raising questions as to the role of NMDAR activity in cognitive function during aging. The current studies examined effects of NMDAR blockade on cognitive task that are sensitive to aging. Young and middle-age rats were trained on the five-choice serial reaction time task (5-CSRTT) and challenged with MK-801 (0.025, 0.05, and 0.1mg/kg or vehicle). Attention deficits were apparent in middle-age and performance of young and middle-age rats was enhanced for low doses of MK-801 (0.025 and 0.05). The beneficial effects on attention were reversed by the highest dose of MK-801. Older animals exhibited a delay-dependent impairment of episodic spatial memory examined on a delayed-matching to place water maze task. Similarly, a low dose of MK-801 (0.05mg/kg) impaired performance with increasing delay and aged animals were more susceptible to disruption by NMDAR blockade. Despite MK-801 impairment of episodic spatial memory, MK-801 had minimal effects on spatial reference memory. Our results confirm that NMDARs contribute to rapidly acquired and flexible spatial memory and support the idea that a decline in NMDAR function contributes to the age-related impairments in cognition. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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

Bilingualism and Cognitive Decline: A Story of Pride and Prejudice.

PubMed

Woumans, Evy; Versijpt, Jan; Sieben, Anne; Santens, Patrick; Duyck, Wouter

2017-01-01

In a recent review, Mukadam, Sommerlad, and Livingston (2017) argue that bilingualism offers no protection against cognitive decline. The authors examined the results of 13 studies (five prospective, eight retrospective) in which monolinguals and bilinguals were compared for cognitive decline and onset of dementia symptoms. Analysis of four of the five prospective studies resulted in the conclusion that there was no difference between monolinguals and bilinguals, whereas seven of the eight retrospective studies actually showed bilingualism to result in a four-to-five year delay of symptom onset. The authors decided to ignore the results from the retrospective studies in favor of those from the prospective studies, reasoning that the former may be confounded by participants' cultural background and education levels. In this commentary, we argue that most of these studies actually controlled for these two variables and still found a positive effect of bilingualism. Furthermore, we argue that the meta-analysis of the prospective studies is not complete, lacking the results of two crucial reports. We conclude that the literature offers substantial evidence for a bilingual effect on the development of cognitive decline and dementia.

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.

Associations of cumulative Pb exposure and longitudinal changes in Mini-Mental Status Exam scores, global cognition and domains of cognition: The VA Normative Aging Study

PubMed Central

Farooqui, Zishaan; Bakulski, Kelly M.; Power, Melinda C.; Weisskopf, Marc G.; Sparrow, David; Spiro, Avron; Vokonas, Pantel S.; Nie, Huiling; Hu, Howard; Park, Sung Kyun

2016-01-01

Background Lead (Pb) exposure has been associated with poorer cognitive function cross-sectionally in aging adults, however the association between cumulative Pb exposure and longitudinal changes in cognition is little characterized. Methods In a 1993–2007 subcohort of the VA Normative Aging Study (Mini-mental status exam (MMSE) n=741; global cognition summary score n=715), we used linear mixed effects models to test associations between cumulative Pb exposure (patella or tibia bone Pb) and repeated measures of cognition (MMSE, individual cognitive tests, and global cognition summary). Cox proportional hazard modeling assessed the risk of an MMSE score falling below 25. Results Among men 51–98 at baseline, higher patella Pb concentration (IQR: 21 µg/g) was associated with −0.13 lower baseline MMSE (95% CI: −0.25, −0.004) and faster longitudinal MMSE decline (−0.016 units/year, 95% CI: −0.032, −0.0004) over 15 years. Each IQR increase in patella Pb was associated with increased risk of a MMSE score below 25 (HR=1.21, 95% CI: 0.99, 1.49; p=0.07). There were no significant associations between Pb and global cognition (both baseline and longitudinal change). Patella Pb was associated with faster longitudinal decline in Word List Total Recall in the language domain (0.014 units/year, 95% CI: −0.026, −0.001) and Word List Delayed Recall in the memory domain (0.014 units/year, 95% CI: −0.027, −0.002). We found weaker associations with tibia Pb. Conclusions Cumulative Pb exposure is associated with faster declines in MMSE and Word List Total and Delayed Recall tests. These findings support the hypothesis that Pb exposure accelerates cognitive aging. PMID:27770710

A population-based study of the association between coronary artery bypass graft surgery (CABG) and cognitive decline: the Cache County study.

PubMed

Lyketsos, Constantine G; Toone, Leslie; Tschanz, Joann; Corcoran, Christopher; Norton, Maria; Zandi, Peter; Munger, Ron; Breitner, John C S; Welsh-Bohmer, Kathleen

2006-06-01

The relationship between coronary artery bypass graft (CABG) surgery and cognitive decline remains uncertain, in particular with regard to whether there is delayed cognitive decline associated with this procedure. This was a population-based cohort study involving participants in the Cache County Study of Memory Health and Aging. At baseline the study enrolled 5,092 persons age 65 and older and followed them up three years later and again four years after that. Individuals who reported having undergone CABG surgery at study baseline or had this surgery in between follow-up waves were compared to individuals who never reported having the surgery. The main outcome measure was the Modified Mini Mental State (3MS). Multilevel models were used to examine the relationship between CABG surgery and cognitive decline over time. Study participants who had CABG surgery evidenced 0.95 points of greater decline relative to baseline on the 3MS at the first follow-up interview after CABG, and an average of 1.9 points of greater decline at the second follow-up interview, than those without CABG (t = -2.51, df = 2,316, p = 0.0121), after adjusting for several covariates, including number of vascular conditions. This decline was restricted to individuals who were more than five years past the procedure and was not evident in the early years after the surgery. CABG surgery is associated with accelerated cognitive decline more than five years after the procedure in a long-lived population. This decline is small and its clinical significance is uncertain. We could not find an association between CABG and decline in the first five post-operative years.

An Autistic Endophenotype and Testosterone Are Involved in an Atypical Decline in Selective Attention and Visuospatial Processing in Middle-Aged Women.

PubMed

Ángel, Romero-Martínez; Luis, Moya-Albiol

2015-12-15

Mothers of offspring with autism spectrum disorders (ASD) could present mild forms of their children's cognitive characteristics, resulting from prenatal brain exposure and sensitivity to testosterone (T). Indeed, their cognition is frequently characterized by hyper-systemizing, outperforming in tests that assess cognitive domains such as selective attention, and fine motor and visuospatial skills. In the general population, all these start to decline around the mid-forties. This study aimed to characterize whether middle-aged women who are biological mothers of individuals with ASD had better performance in the aforementioned cognitive skills than mothers of normative children (in both groups n = 22; mean age = 45), using the standardized Stroop and mirror-drawing tests. We also examined the role of T in their performance in the aforementioned tests. ASD mothers outperformed controls in both tests, giving more correct answers and making fewer mistakes. In addition, they presented higher T levels, which have been associated with better cognitive performance. Cognitive decline in specific skills with aging could be delayed in these middle-aged women, corresponding to a cognitive endophenotype, T playing an important role in this process.

An Autistic Endophenotype and Testosterone Are Involved in an Atypical Decline in Selective Attention and Visuospatial Processing in Middle-Aged Women

PubMed Central

Ángel, Romero-Martínez; Luis, Moya-Albiol

2015-01-01

Mothers of offspring with autism spectrum disorders (ASD) could present mild forms of their children’s cognitive characteristics, resulting from prenatal brain exposure and sensitivity to testosterone (T). Indeed, their cognition is frequently characterized by hyper-systemizing, outperforming in tests that assess cognitive domains such as selective attention, and fine motor and visuospatial skills. In the general population, all these start to decline around the mid-forties. This study aimed to characterize whether middle-aged women who are biological mothers of individuals with ASD had better performance in the aforementioned cognitive skills than mothers of normative children (in both groups n = 22; mean age = 45), using the standardized Stroop and mirror-drawing tests. We also examined the role of T in their performance in the aforementioned tests. ASD mothers outperformed controls in both tests, giving more correct answers and making fewer mistakes. In addition, they presented higher T levels, which have been associated with better cognitive performance. Cognitive decline in specific skills with aging could be delayed in these middle-aged women, corresponding to a cognitive endophenotype, T playing an important role in this process. PMID:26694433

Cognitive reserve and long-term change in cognition in aging and preclinical Alzheimer's disease.

PubMed

Soldan, Anja; Pettigrew, Corinne; Cai, Qing; Wang, Jiangxia; Wang, Mei-Cheng; Moghekar, Abhay; Miller, Michael I; Albert, Marilyn

2017-12-01

We examined if baseline levels of cognitive reserve (CR) and of Alzheimer's disease (AD) biomarkers modify the rate of change in cognition among individuals with normal cognition at baseline (n = 303, mean baseline age = 57 years, mean follow-up = 12 years); 66 participants subsequently developed mild cognitive impairment (MCI) or dementia due to AD. CR was indexed by years of education, reading, and vocabulary measures. AD biomarkers were measured with a composite score composed of measures of amyloid, phosphorylated tau, and neurodegeneration. Higher CR scores were associated with better cognitive performance but did not modify the rate of change in cognition among those who remained cognitively normal, nor among those who progressed to MCI before symptom onset, independent of baseline biomarker levels. However, higher CR scores were associated with faster cognitive decline after symptom onset of MCI. These results suggest that the mechanism by which CR mediates the relationship between pathology and cognitive function is by delaying the onset of symptoms rather than reducing the rate of cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

The effects of computer-assisted cognitive rehabilitation on Alzheimer's dementia patients memories.

PubMed

Hwang, Jung-Ha; Cha, Hyun-Gyu; Cho, Young-Seok; Kim, Tae-Sue; Cho, Hyuk-Shin

2015-09-01

[Purpose] The purpose of the present study was to conduct Computer-Assisted Cognitive Rehabilitation (COMCOG) to examine the effects of COMCOG on Alzheimer's dementia patients' memories. [Subjects] Thirty-five patients diagnosed with Alzheimer's dementia received COMCOG for 30 minutes per day, five days per week for four weeks. [Methods] Before and after the COMCOG intervention, subjects' cognitive functions were evaluated using the Cognitive Assessment Reference Diagnosis System (CARDS) and Mini-Mental State Examination-Korea (MMSE-K) test. [Results] According to the results of the evaluation, among the CARDS scores of the subjects who received COMCOG, the scores of the delayed 10-word list, delayed 10-object list, recognition 10-object, and recent memory significantly increased while the scores of recognition 10-word significantly decreased after intervention compared to before intervention. In addition, among the MMSE-K items, the orientation, registration, and recall showed significant increases. [Conclusion] Based on these results, delay in the progress of memory deterioration can be expected when COMCOG is conducted for Alzheimer's dementia patients who show declines in cognitive functions.

Integrity of white matter structure is related to episodic memory performance in the low-educated elderly.

PubMed

Resende, Elisa de Paula França; Tovar-Moll, Fernanda Freire; Ferreira, Fernanda Meireles; Bramati, Ivanei; de Souza, Leonardo Cruz; Carmona, Karoline Carvalho; Guimarães, Henrique Cerqueira; Carvalho, Viviane Amaral; Barbosa, Maira Tonidandel; Caramelli, Paulo

2017-11-01

The low-educated elderly are a vulnerable population in whom studying the role of white matter integrity on memory may provide insights for understanding how memory declines with aging and disease. Thirty-one participants (22 women), 23 cognitively healthy and eight with cognitive impairment-no dementia, aged 80.4 ± 3.8 years, with 2.2 ± 1.9 years of education, underwent an MRI scan with diffusion tensor imaging (DTI) acquisition. We verified if there were correlations between the performance on the Brief Cognitive Screening Battery (BCSB) and the Rey Auditory Verbal Learning Test (RAVLT) with DTI parameters. The BCSB delayed recall task correlated with frontotemporoparietal connection bundles, with the hippocampal part of the cingulum bilaterally and with the right superior longitudinal fasciculus. The RAVLT learning and delayed recall scores also correlated with the hippocampal part of the cingulum bilaterally. Although preliminary, our study suggests that the integrity of white matter frontotemporoparietal fasciculi seems to play a role in episodic memory performance in the low-educated elderly. This finding opens opportunities to study potential targets for memory decline prevention in vulnerable populations.

Impact of Education on Memory Deficits in Subclinical Depression

PubMed Central

McLaren, Molly E.; Szymkowicz, Sarah M.; Kirton, Joshua W.; Dotson, Vonetta M.

2015-01-01

Elevated depressive symptoms are associated with cognitive deficits, while higher education protects against cognitive decline. This study was conducted to test if education level moderates the relationship between depressive symptoms and cognitive function. Seventy-three healthy, dementia-free adults aged 18–81 completed neuropsychological tests, as well as depression and anxiety questionnaires. Controlling for age, sex, and state anxiety, we found a significant interaction of depressive symptoms and education for immediate and delayed verbal memory, such that those with a higher education level performed well regardless of depressive symptomatology, whereas those with lower education and high depressive symptoms had worse performance. No effects were found for executive functioning or processing speed. Results suggest that education protects against verbal memory deficits in individuals with elevated depressive symptoms. Further research on cognitive reserve in depression-related cognitive deficits and decline is needed to understand the mechanisms behind this phenomenon. PMID:26109434

Aging related cognitive changes associated with Alzheimer's disease in Down syndrome.

PubMed

Firth, Nicholas C; Startin, Carla M; Hithersay, Rosalyn; Hamburg, Sarah; Wijeratne, Peter A; Mok, Kin Y; Hardy, John; Alexander, Daniel C; Strydom, André

2018-06-01

Individuals with Down syndrome (DS) have an extremely high genetic risk for Alzheimer's disease (AD), however, the course of cognitive decline associated with progression to dementia is ill-defined. Data-driven methods can estimate long-term trends from cross-sectional data while adjusting for variability in baseline ability, which complicates dementia assessment in those with DS. We applied an event-based model to cognitive test data and informant-rated questionnaire data from 283 adults with DS (the largest study of cognitive functioning in DS to date) to estimate the sequence of cognitive decline and individuals' disease stage. Decline in tests of memory, sustained attention/motor coordination, and verbal fluency occurred early, demonstrating that AD in DS follows a similar pattern of change to other forms of AD. Later decline was found for informant measures. Using the resulting staging model, we showed that adults with a clinical diagnosis of dementia and those with APOE 3:4 or 4:4 genotype were significantly more likely to be staged later, suggesting that the model is valid. Our results identify tests of memory and sustained attention may be particularly useful measures to track decline in the preclinical/prodromal stages of AD in DS whereas informant-measures may be useful in later stages (i.e. during conversion into dementia, or postdiagnosis). These results have implications for the selection of outcome measures of treatment trials to delay or prevent cognitive decline due to AD in DS. As clinical diagnoses are generally made late into AD progression, early assessment is essential.

Dietary Patterns, Cognitive Decline, and Dementia: A Systematic Review12

PubMed Central

van de Rest, Ondine; Berendsen, Agnes AM; Haveman-Nies, Annemien; de Groot, Lisette CPGM

2015-01-01

Nutrition is an important modifiable risk factor that plays a role in the strategy to prevent or delay the onset of dementia. Research on nutritional effects has until now mainly focused on the role of individual nutrients and bioactive components. However, the evidence for combined effects, such as multinutrient approaches, or a healthy dietary pattern, such as the Mediterranean diet, is growing. These approaches incorporate the complexity of the diet and possible interaction and synergy between nutrients. Over the past few years, dietary patterns have increasingly been investigated to better understand the link between diet, cognitive decline, and dementia. In this systematic review we provide an overview of the literature on human studies up to May 2014 that examined the role of dietary patterns (derived both a priori as well as a posteriori) in relation to cognitive decline or dementia. The results suggest that better adherence to a Mediterranean diet is associated with less cognitive decline, dementia, or Alzheimer disease, as shown by 4 of 6 cross-sectional studies, 6 of 12 longitudinal studies, 1 trial, and 3 meta-analyses. Other healthy dietary patterns, derived both a priori (e.g., Healthy Diet Indicator, Healthy Eating Index, and Program National Nutrition Santé guideline score) and a posteriori (e.g., factor analysis, cluster analysis, and reduced rank regression), were shown to be associated with reduced cognitive decline and/or a reduced risk of dementia as shown by all 6 cross-sectional studies and 6 of 8 longitudinal studies. More conclusive evidence is needed to reach more targeted and detailed guidelines to prevent or postpone cognitive decline. PMID:25770254

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

Augmented reality cube game for cognitive training: an interaction study.

PubMed

Boletsis, Costas; Mccallum, Simon

2014-01-01

There is the potential that cognitive activity may delay cognitive decline in people with mild cognitive impairment. Games provide both cognitive challenge and motivation for repeated use, a prerequisite for long lasting effect. Recent advances in technology introduce several new interaction methods, potentially leading to more efficient, personalized cognitive gaming experiences. In this paper, we present an Augmented Reality (AR) cognitive training game, utilizing cubes as input tools, and we test the cube interaction with a pilot study. The results of the study revealed the marker occlusion problem, and that novice AR users can adjust to the developed AR environment after a small number of sessions.

Cognitively Stimulating Leisure Activity and Subsequent Cognitive Function: A SHARE-based Analysis.

PubMed

Litwin, Howard; Schwartz, Ella; Damri, Noam

2017-10-01

The aim of the inquiry was to examine whether cognitively stimulating leisure activity (CSLA) can delay or reduce cognitive decline in late life and whether its effect is moderated by education, age, or activity pattern. Employing secondary analysis of data on respondents aged 65 and older from the 4th and 5th waves of the Survey of Health, Ageing and Retirement in Europe (N = 16,572), the inquiry regressed cognitive function (memory, numeracy, and fluency) at Time 2 on frequency of engagement in CSLA at baseline, controlling for cognitive function scores at baseline and a range of confounders. The study also considered education by CSLA and age by CSLA interactions, as well as the effect of CSLA patterns. CSLA frequency was found to be positively related to subsequent cognitive functioning on all measures, 2 years later. The effect of CSLA on memory and fluency was stronger among those with lower education, whereas the age by CSLA interaction was not significant. Respondents who started CSLA after baseline showed better cognitive functioning at Time 2 than those who did not engage in CSLA at all and those who had engaged in such activity at baseline but stopped. The study documents that CSLAs constitute a potential source for the delay or reduction of cognitive decline, regardless of one's age. As such, practitioners should recognize the value of this medium and encourage its greater use in appropriate settings. © 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.

Fish Intake, Genetic Predisposition to Alzheimer Disease, and Decline in Global Cognition and Memory in 5 Cohorts of Older Persons.

PubMed

Samieri, Cécilia; Morris, Martha-Clare; Bennett, David A; Berr, Claudine; Amouyel, Philippe; Dartigues, Jean-François; Tzourio, Christophe; Chasman, Daniel I; Grodstein, Francine

2018-05-01

Fish are a primary source of long-chain omega-3 fatty acids, which may help delay cognitive aging. We pooled participants from the French Three-City study and 4 US cohorts (Nurses' Health Study, Women's Health Study, Chicago Health and Aging Project, and Rush Memory and Aging Project) for whom diet and cognitive data were available (n = 23,688 white persons, aged ≥65 years, 88% female, baseline year range of 1992-1999, and median follow-up range of 3.9-9.1 years) to investigate the relationship of fish intake to cognitive decline and examine interactions with genes related to Alzheimer disease. We estimated cohort-specific associations between fish and change in composite scores of global cognition and episodic memory using linear mixed models, and we pooled results using inverse-variance weighted meta-analysis. In multivariate analyses, higher fish intake was associated with slower decline in both global cognition and memory (P for trend ≤ 0.031). Consuming ≥4 servings/week versus <1 serving/week of fish was associated with a lower rate of memory decline: 0.018 (95% confidence interval: 0.004, 0.032) standard units, an effect estimate equivalent to that found for 4 years of age. For global cognition, no comparisons of higher versus low fish intake reached statistical significance. In this meta-analysis, higher fish intake was associated with a lower rate of memory decline. We found no evidence of effect modification by genes associated with Alzheimer disease.

Influence of Educational Attainment on Cognition-Based Intervention Programs for Persons with Mild Alzheimer's Disease.

PubMed

Contador, Israel; Fernández-Calvo, Bernardino; Ramos, Francisco; Olazarán, Javier

2016-05-01

This research retrospectively analyzed the effect of education on cognitive interventions carried out in patients with mild Alzheimer's disease (AD). The total sample consisted of 75 patients with mild AD receiving treatment with cholinesterase inhibitors. The participants were divided into two groups: cognitive intervention (IG; n=45) and waiting list (WLG; n=30). Patients in the IG received either the Big Brain Academy (n=15) or the Integrated Psychostimulation Program (n=30) during 12 weeks. The influence of education on intervention effect was analyzed comparing mean change scores of the two study groups in the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), stratified by educational level. The potential effect of age, sex, cognitive status, and type of intervention was examined using post hoc stratification analyses. Higher education was associated with faster cognitive decline in the WLG (effect size=0.51; p<.01). However, cognitive evolution was not influenced by education in the IG (effect size=0.12; p=.42). Our results suggest that cognitive intervention might delay accelerated cognitive decline in higher educated individuals with mild AD.

Real-Time fMRI in Neuroscience Research and Its Use in Studying the Aging Brain

PubMed Central

Rana, Mohit; Varan, Andrew Q.; Davoudi, Anis; Cohen, Ronald A.; Sitaram, Ranganatha; Ebner, Natalie C.

2016-01-01

Cognitive decline is a major concern in the aging population. It is normative to experience some deterioration in cognitive abilities with advanced age such as related to memory performance, attention distraction to interference, task switching, and processing speed. However, intact cognitive functioning in old age is important for leading an independent day-to-day life. Thus, studying ways to counteract or delay the onset of cognitive decline in aging is crucial. The literature offers various explanations for the decline in cognitive performance in aging; among those are age-related gray and white matter atrophy, synaptic degeneration, blood flow reduction, neurochemical alterations, and change in connectivity patterns with advanced age. An emerging literature on neurofeedback and Brain Computer Interface (BCI) reports exciting results supporting the benefits of volitional modulation of brain activity on cognition and behavior. Neurofeedback studies based on real-time functional magnetic resonance imaging (rtfMRI) have shown behavioral changes in schizophrenia and behavioral benefits in nicotine addiction. This article integrates research on cognitive and brain aging with evidence of brain and behavioral modification due to rtfMRI neurofeedback. We offer a state-of-the-art description of the rtfMRI technique with an eye towards its application in aging. We present preliminary results of a feasibility study exploring the possibility of using rtfMRI to train older adults to volitionally control brain activity. Based on these first findings, we discuss possible implementations of rtfMRI neurofeedback as a novel technique to study and alleviate cognitive decline in healthy and pathological aging. PMID:27803662

Relationships of Dietary Patterns, Foods, and Micro- and Macronutrients with Alzheimer's Disease and Late-Life Cognitive Disorders: A Systematic Review.

PubMed

Solfrizzi, Vincenzo; Custodero, Carlo; Lozupone, Madia; Imbimbo, Bruno P; Valiani, Vincenzo; Agosti, Pasquale; Schilardi, Andrea; D'Introno, Alessia; La Montagna, Maddalena; Calvani, Mariapaola; Guerra, Vito; Sardone, Rodolfo; Abbrescia, Daniela I; Bellomo, Antonello; Greco, Antonio; Daniele, Antonio; Seripa, Davide; Logroscino, Giancarlo; Sabbá, Carlo; Panza, Francesco

2017-01-01

In the last decade, the association between diet and cognitive function or dementia has been largely investigated. In the present article, we systematically reviewed observational studies published in the last three years (2014-2016) on the relationship among dietary factors and late-life cognitive disorders at different levels of investigation (i.e., dietary patterns, foods and food-groups, and dietary micro- and macronutrients), and possible underlying mechanisms of the proposed associations. From the reviewed evidence, the National Institute on Aging-Alzheimer's Association guidelines for Alzheimer's disease (AD) and cognitive decline due to AD pathology introduced some evidence suggesting a direct relation between diet and changes in the brain structure and activity. There was also accumulating evidence that combinations of foods and nutrients into certain patterns may act synergistically to provide stronger health effects than those conferred by their individual dietary components. In particular, higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline. Moreover, also other emerging healthy dietary patterns such as the Dietary Approach to Stop Hypertension (DASH) and the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) diets were associated with slower rates of cognitive decline and significant reduction of AD rate. Furthermore, some foods or food groups traditionally considered harmful such as eggs and red meat have been partially rehabilitated, while there is still a negative correlation of cognitive functions with saturated fatty acids and a protective effect against cognitive decline of elevated fish consumption, high intake of monounsaturated fatty acids and polyunsaturated fatty acids (PUFA), particularly n-3 PUFA.

Impact of Education on Memory Deficits in Subclinical Depression.

PubMed

McLaren, Molly E; Szymkowicz, Sarah M; Kirton, Joshua W; Dotson, Vonetta M

2015-08-01

Elevated depressive symptoms are associated with cognitive deficits, while higher education protects against cognitive decline. This study was conducted to test if education level moderates the relationship between depressive symptoms and cognitive function. Seventy-three healthy, dementia-free adults aged 18-81 completed neuropsychological tests, as well as depression and anxiety questionnaires. Controlling for age, sex, and state anxiety, we found a significant interaction of depressive symptoms and education for immediate and delayed verbal memory, such that those with a higher education level performed well regardless of depressive symptomatology, whereas those with lower education and high depressive symptoms had worse performance. No effects were found for executive functioning or processing speed. Results suggest that education protects against verbal memory deficits in individuals with elevated depressive symptoms. Further research on cognitive reserve in depression-related cognitive deficits and decline is needed to understand the mechanisms behind this phenomenon. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

Cognitive Training Program to Improve Working Memory in Older Adults with MCI.

PubMed

Hyer, Lee; Scott, Ciera; Atkinson, Mary Michael; Mullen, Christine M; Lee, Anna; Johnson, Aaron; Mckenzie, Laura C

2016-01-01

Deficits in working memory (WM) are associated with age-related decline. We report findings from a clinical trial that examined the effectiveness of Cogmed, a computerized program that trains WM. We compare this program to a Sham condition in older adults with Mild Cognitive Impairment (MCI). Older adults (N = 68) living in the community were assessed. Participants reported memory impairment and met criteria for MCI, either by poor delayed memory or poor performance in other cognitive areas. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, Delayed Memory Index) and the Clinical Dementia Rating scale (CDR) were utilized. All presented with normal Mini Mental State Exams (MMSE) and activities of daily living (ADLs). Participants were randomized to Cogmed or a Sham computer program. Twenty-five sessions were completed over five to seven weeks. Pre, post, and follow-up measures included a battery of cognitive measures (three WM tests), a subjective memory scale, and a functional measure. Both intervention groups improved over time. Cogmed significantly outperformed Sham on Span Board and exceeded in subjective memory reports at follow-up as assessed by the Cognitive Failures Questionnaire (CFQ). The Cogmed group demonstrated better performance on the Functional Activities Questionnaire (FAQ), a measure of adjustment and far transfer, at follow-up. Both groups, especially Cogmed, enjoyed the intervention. Results suggest that WM was enhanced in both groups of older adults with MCI. Cogmed was better on one core WM measure and had higher ratings of satisfaction. The Sham condition declined on adjustment.

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.

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).

Mild cognitive impairment: an opportunity to identify patients at high risk for progression to Alzheimer's disease.

PubMed

Levey, Allan; Lah, James; Goldstein, Felicia; Steenland, Kyle; Bliwise, Donald

2006-07-01

There is increasing evidence that subtle losses in cognitive function may be symptomatic of a transition to early Alzheimer's disease (AD). Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to AD. Of the MCI subtypes, patients with amnestic MCI (a-MCI) are at greatest risk. The objectives of this article were to review the relationship between MCI, normal aging, and AD, and to summarize recent research on the diagnosis and potential treatment of MCI. Relevant articles were identified through searches of MEDLINE and EMBASE using the terms mild cognitive impairment; cognitive impairment, no dementia; and dementia prodrome, with no restrictions as to year. Additional papers of interest were identified from the reference lists of the identified articles. The search was current as of February 2006. Guidelines and recommendations are being developed to assist physicians in diagnosing MCI, identifying its subtype and etiology, understanding the risks for conversion to AD, and managing disease progression. Given the existence of a subset of individuals with a-MCI, who are at greatest risk for progression to AD but still have high levels of cognition and function, the ability to improve symptoms and delay progression to AD would be particularly beneficial. In a 3-year, randomized, double-blind, placebo-controlled study in 769 patients with a-MCI, treatment with the cholinesterase inhibitor donepezil was associated with a significantly lower rate of progression to AD compared with placebo during the first 12 months of treatment (hazard ratio=0.42; 95% CI, 0.24-0.76; P=0.004) but not at later time points. Of other types of agents that have been investigated (antioxidants, estrogen replacement therapy, cyclooxygenase-2-selective inhibitors), none have shown significant beneficial effects in delaying cognitive decline or progression to AD. New drugs such as secretase inhibitors, small molecules that disrupt amyloid aggregation, and immunotherapies are in preclinical development. MCI involves more substantial cognitive and memory decline than normal aging and represents a significant risk factor for the development of dementia. Further research is needed into treatments to delay the conversion from MCI to AD.

Role of social support in cognitive function among elders.

PubMed

Zhu, Shuzhen; Hu, Jie; Efird, Jimmy T

2012-08-01

To examine cognitive function and its relationships to demographic characteristics and social support among elders in central China. Cognitive decline is prevalent among elders. Few studies have explored the relationship between social support and cognitive function among elders. A cross-sectional, descriptive correlational study. A quasi-random, point of reference sample of 120 elders residing in central China was recruited for study. Instruments used included a: Socio-demographic Questionnaire, the Multidimensional Scale on Perceived Social Support and the Mini-Mental State Examination. Hierarchical multiple regression was performed to examine the relationships among demographic variables, social support and cognitive function. Age, education and social support accounted for 45·2% of the variance in cognitive function. Family support was the strongest predictor of cognitive function. Elders who had higher educational levels and more family support had better cognitive function. Relevance to clinical practice.  Community healthcare providers should consolidate social support among elders in China and use family support interventions to reduce or delay cognitive decline, especially among those of increased age who are illiterate. Elders who had higher educational level and more family support had better cognitive function levels. Interventions that include family support are needed to improve cognitive function among elders in China. © 2012 Blackwell Publishing Ltd.

Antioxidant intake and cognitive function of elderly men and women: the Cache County Study.

PubMed

Wengreen, H J; Munger, R G; Corcoran, C D; Zandi, P; Hayden, K M; Fotuhi, M; Skoog, I; Norton, M C; Tschanz, J; Breitner, J C S; Welsh-Bohmer, K A

2007-01-01

We prospectively examined associations between intakes of antioxidants (vitamins C, vitamin E, and carotene) and cognitive function and decline among elderly men and women of the Cache County Study on Memory and Aging in Utah. In 1995, 3831 residents 65 years of age or older completed a baseline survey that included a food frequency questionnaire and cognitive assessment. Cognitive function was assessed using an adapted version of the Modified Mini-Mental State examination (3MS) at baseline and at three subsequent follow-up interviews spanning approximately 7 years. Multivariable-mixed models were used to estimate antioxidant nutrient effects on average 3MS score over time. Increasing quartiles of vitamin C intake alone and combined with vitamin E were associated with higher baseline average 3MS scores (p-trend = 0.013 and 0.02 respectively); this association appeared stronger for food sources compared to supplement or food and supplement sources combined. Study participants with lower levels of intake of vitamin C, vitamin E and carotene had a greater acceleration of the rate of 3MS decline over time compared to those with higher levels of intake. High antioxidant intake from food and supplement sources of vitamin C, vitamin E, and carotene may delay cognitive decline in the elderly.

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.

Bilingualism: consequences for mind and brain.

PubMed

Bialystok, Ellen; Craik, Fergus I M; Luk, Gigi

2012-04-01

Building on earlier evidence showing a beneficial effect of bilingualism on children's cognitive development, we review recent studies using both behavioral and neuroimaging methods to examine the effects of bilingualism on cognition in adulthood and explore possible mechanisms for these effects. This research shows that bilingualism has a somewhat muted effect in adulthood but a larger role in older age, protecting against cognitive decline, a concept known as 'cognitive reserve'. We discuss recent evidence that bilingualism is associated with a delay in the onset of symptoms of dementia. Cognitive reserve is a crucial research area in the context of an aging population; the possibility that bilingualism contributes to cognitive reserve is therefore of growing importance as populations become increasingly diverse. Copyright © 2012 Elsevier Ltd. All rights reserved.

Bilingualism: Consequences for Mind and Brain

PubMed Central

Bialystok, Ellen; Craik, Fergus I.M.; Luk, Gigi

2012-01-01

Building on earlier evidence showing a beneficial effect of bilingualism on children’s cognitive development, we review recent studies using both behavioral and neuroimaging methods to examine the effects of bilingualism on cognition in adulthood and explore possible mechanisms for these effects. This research shows that bilingualism has a somewhat muted effect in adulthood but a larger role in older age, protecting against cognitive decline, a concept known as “cognitive reserve”. We discuss recent evidence that bilingualism is associated with a delay in the onset of symptoms of dementia. Cognitive reserve is a crucial research area in the context of an aging population; the possibility that bilingualism contributes to cognitive reserve is therefore of growing importance as populations become increasingly diverse. PMID:22464592

Comparable Rest-related Promotion of Spatial Memory Consolidation in Younger and Older Adults

PubMed Central

Craig, Michael; Wolbers, Thomas; Harris, Mathew A.; Hauff, Patrick; Della Sala, Sergio; Dewar, Michaela

2017-01-01

Flexible spatial navigation depends on cognitive mapping, a function that declines with increasing age. In young adults, a brief period of post-navigation rest promotes the consolidation/integration of spatial memories into accurate cognitive maps. We examined (1) whether rest promotes spatial memory consolidation/integration in older adults and (2) whether the magnitude of the rest benefit changes with increasing age. Young and older adults learned a route through a virtual environment, followed by a 10min delay comprising either wakeful rest or a perceptual task, and a subsequent cognitive mapping task, requiring the pointing to landmarks from different locations. Pointing accuracy was lower in the older than younger adults. However, there was a comparable rest-related enhancement in pointing accuracy in the two age groups. Together our findings suggest that (i) the age-related decline in cognitive mapping cannot be explained by increased consolidation interference in older adults, and (ii) as we grow older rest continues to support the consolidation/integration of spatial memories. PMID:27689512

Impairments of spatial working memory and attention following acute psychosocial stress.

PubMed

Olver, James S; Pinney, Myra; Maruff, Paul; Norman, Trevor R

2015-04-01

Few studies have investigated the effect of an acute psychosocial stress paradigm on impaired attention and working memory in humans. Further, the duration of any stress-related cognitive impairment remains unclear. The aim of this study was to examine the effect of an acute psychosocial stress paradigm, the Trier Social Stress, on cognitive function in healthy volunteers. Twenty-three healthy male and female subjects were exposed to an acute psychosocial stress task. Physiological measures (salivary cortisol, heart rate and blood pressure) and subjective stress ratings were measured at baseline, in anticipation of stress, immediately post-stress and after a period of rest. A neuropsychological test battery including spatial working memory and verbal memory was administered at each time point. Acute psychosocial stress produced significant increases in cardiovascular and subjective measures in the anticipatory and post-stress period, which recovered to baseline after rest. Salivary cortisol steadily declined over the testing period. Acute psychosocial stress impaired delayed verbal recall, attention and spatial working memory. Attention remained impaired, and delayed verbal recall continued to decline after rest. Acute psychosocial stress is associated with an impairment of a broad range of cognitive functions in humans and with prolonged abnormalities in attention and memory. Copyright © 2014 John Wiley & Sons, Ltd.

AMPK Agonist AICAR Improves Cognition and Motor Coordination in Young and Aged Mice

ERIC Educational Resources Information Center

Kobilo, Tali; Guerrieri, Davide; Zhang, Yongqing; Collica, Sarah C.; Becker, Kevin G.; van Praag, Henriette

2014-01-01

Normal aging can result in a decline of memory and muscle function. Exercise may prevent or delay these changes. However, aging-associated frailty can preclude physical activity. In young sedentary animals, pharmacological activation of AMP-activated protein kinase (AMPK), a transcriptional regulator important for muscle physiology, enhanced…

A longitudinal examination of the relationship between cannabis use and cognitive function in mid-life adults.

PubMed

McKetin, Rebecca; Parasu, Praneeth; Cherbuin, Nicolas; Eramudugolla, Ranmalee; Anstey, Kaarin J

2016-12-01

The relationship between cannabis use and cognitive function in mid-life has rarely been examined despite verbal learning deficits in young adults. A longitudinal cohort study of 1,897 Australians recruited at 40-46 years of age and followed up 4 years (94%) and 8 years (87%) later. Random effects regression was used to assess within- and between-person associations between cannabis use and cognitive function across waves of data, and examine whether age-related changes in cognitive performance were modified by cannabis use. The first list of the California Verbal Learning Test (immediate and delayed recall), Symbol Digit Modality Test, Digit Backwards, simple and choice reaction time tasks, were administered at each wave. The Spot-the-Word test was used to assess premorbid verbal ability. Self-reported cannabis use in the past year (no use, < weekly use,≥weekly use) was assessed at each wave. Participants who used cannabis≥weekly had worse immediate recall (b=-0.68, p=0.014) and showed a trend toward worse delayed recall (b=-0.55, p=0.062) compared to non-users after adjusting for correlates of cannabis use and premorbid verbal ability. These effects were due to between-person differences. There were no significant within-person associations between cannabis use and recall, nor was there evidence of greater cognitive decline in cannabis users with age. Mid-life cannabis users had poorer verbal recall than non-users, but this was not related to their current level of cannabis use, and cannabis use was not associated with accelerated cognitive decline. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Does multilingualism affect the incidence of Alzheimer's disease?: A worldwide analysis by country.

PubMed

Klein, Raymond M; Christie, John; Parkvall, Mikael

2016-12-01

It has been suggested that the cognitive requirements associated with bi- and multilingual processing provide a form of mental exercise that, through increases in cognitive reserve and brain fitness, may delay the symptoms of cognitive failure associated with Alzheimer's disease and other forms of dementia. We collected data on a country-by-country basis that might shed light on this suggestion. Using the best available evidence we could find, the somewhat mixed results we obtained provide tentative support for the protective benefits of multilingualism against cognitive decline. But more importantly, this study exposes a critical issue, which is the need for more comprehensive and more appropriate data on the subject.

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.

Cross-sectional study of the association of cognitive function and hippocampal volume among healthy elderly adults

PubMed Central

Jiang, Lijuan; CHENG, Yan; LI, Qingwei; TANG, Yingying; SHEN, Yuan; LI, Ting; FENG, Wei; CAO, Xinyi; WU, Wenyuan; WANG, Jijun; LI, Chunbo

2014-01-01

Background Cognitive impairment and dementia among elderly adults is a pressing public health issue in China but research on biomarkers of cognitive decline has been limited. Aim Explore the relationship between multiple domains of cognitive functioning and the volume of the left and right hippocampus in healthy elderly adults. Methods Structural MRI scanning was performed on 65 community-dwelling healthy participants 65 to 75 years of age using the Siemens 3.0 T Trio Tim with the MPRAGE sequence. The volumes of the left and right hippocampus were determined using Freesurfer software. Cognitive functioning was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Both unadjusted and adjusted associations between the hippocampal volumes and cognitive functioning were estimated. Results Within this relatively narrow age range, age was significantly associated with most of the cognitive measures assessed in women but was not significantly associated with any of the cognitive measures in men. In both men and women right hippocampal volume was positively associated with delayed memory and left hippocampal volume was positively associated with both immediate memory and delayed memory (though the relationship with delayed memory in women was only at a trend level). After adjustment for age, gender, and years of formal education (the variable that was most strongly associated with all of the cognitive measures), both left hippocampal volume and right hippocampal volume were positively associated with delayed memory, but not with immediate memory. Interestingly, the difference in the volumes of the left and right hippocampi was negatively associated with the score of the RBANS attention subscale, a relationship that was stronger in women than in men. Conclusions This study confirms previous work about the relationship of hippocampal volume and memory, identifies a possible relationship between attention and the difference in size of the two hippocampi, and suggests that there may be some differences in these relationships by gender. PMID:25477721

The effects of an extensive exercise programme on the progression of Mild Cognitive Impairment (MCI): study protocol for a randomised controlled trial.

PubMed

Devenney, Kate E; Sanders, Marit L; Lawlor, Brian; Olde Rikkert, Marcel G M; Schneider, Stefan

2017-03-22

Exercise interventions to prevent dementia and delay cognitive decline have gained considerable attention in recent years. Human and animal studies have demonstrated that regular physical activity targets brain function by increasing cognitive reserve. There is also evidence of structural changes caused by exercise in preventing or delaying the genesis of neurodegeneration. Although initial studies indicate enhanced cognitive performance in patients with mild cognitive impairment (MCI) following an exercise intervention, little is known about the effect of an extensive, controlled and regular exercise regimen on the neuropathology of patients with MCI. This study aims to determine the effects of an extensive exercise programme on the progression of MCI. This randomised controlled clinical intervention study will take place across three European sites. Seventy-five previously sedentary patients with a clinical diagnosis of MCI will be recruited at each site. Participants will be randomised to one of three groups. One group will receive a standardised 1-year extensive aerobic exercise intervention (3 units of 45 min/week). The second group will complete stretching and toning (non-aerobic) exercise (3 units of 45 min/week) and the third group will act as the control group. Change in all outcomes will be measured at baseline (T0), after six months (T1) and after 12 months (T2). The primary outcome, cognitive performance, will be determined by a neuropsychological test battery (CogState battery, Trail Making Test and Verbal fluency). Secondary outcomes include Montreal Cognitive Assessment (MoCA), cardiovascular fitness, physical activity, structural changes of the brain, quality of life measures and measures of frailty. Furthermore, outcome variables will be related to genetic variations on genes related to neurogenesis and epigenetic changes in these genes caused by the exercise intervention programme. The results will add new insights into the prevailing notion that exercise may slow the rate of cognitive decline in MCI. ClinicalTrials.gov NCT02913053.

Cognitive intervention through a training program for picture book reading in community-dwelling older adults: a randomized controlled trial.

PubMed

Suzuki, Hiroyuki; Kuraoka, Masataka; Yasunaga, Masashi; Nonaka, Kumiko; Sakurai, Ryota; Takeuchi, Rumi; Murayama, Yoh; Ohba, Hiromi; Fujiwara, Yoshinori

2014-11-21

Non-pharmacological interventions are expected to be important strategies for reducing the age-adjusted prevalence of senile dementia, considering that complete medical treatment for cognitive decline has not yet been developed. From the viewpoint of long-term continuity of activity, it is necessary to develop various cognitive stimulating programs. The aim of this study is to examine the effectiveness of a cognitive intervention through a training program for picture book reading for community-dwelling older adults. Fifty-eight Japanese older participants were divided into the intervention and control groups using simple randomization (n =29 vs 29). In the intervention group, participants took part in a program aimed at learning and mastering methods of picture book reading as a form of cognitive training intervention. The control group listened to lectures about elderly health maintenance. Cognitive tests were conducted individually before and after the programs. The rate of memory retention, computed by dividing Logical Memory delayed recall by immediate recall, showed a significant interaction (p < .05) in analysis of covariance. Simple main effects showed that the rate of memory retention of the intervention group improved after the program completion (p < .05). In the participants with mild cognitive impairment (MCI) examined by Japanese version of the Montreal Cognitive Assessment (MoCA-J) (n =14 vs 15), significant interactions were seen in Trail Making Test-A (p < .01), Trail Making Test-B (p < .05), Kana pick-out test (p < .05) and the Mini-Mental State Examination (p < .05). The intervention effect was found in delayed verbal memory. This program is also effective for improving attention and executive function in those with MCI. The short-term interventional findings suggest that this program might contribute to preventing a decline in memory and executive function. UMIN000014712 (Date of ICMJE and WHO compliant trial information disclosure: 30 July 2014).

A 24-Week Multi-Modality Exercise Program Improves Executive Control in Older Adults with a Self-Reported Cognitive Complaint: Evidence from the Antisaccade Task.

PubMed

Heath, Matthew; Shellington, Erin; Titheridge, Sam; Gill, Dawn P; Petrella, Robert J

2017-01-01

Exercise programs involving aerobic and resistance training (i.e., multiple-modality) have shown promise in improving cognition and executive control in older adults at risk, or experiencing, cognitive decline. It is, however, unclear whether cognitive training within a multiple-modality program elicits an additive benefit to executive/cognitive processes. This is an important question to resolve in order to identify optimal training programs that delay, or ameliorate, executive deficits in persons at risk for further cognitive decline. In the present study, individuals with a self-reported cognitive complaint (SCC) participated in a 24-week multiple-modality (i.e., the M2 group) exercise intervention program. In addition, a separate group of individuals with a SCC completed the same aerobic and resistance training as the M2 group but also completed a cognitive-based stepping task (i.e., multiple-modality, mind-motor intervention: M4 group). Notably, pre- and post-intervention executive control was examined via the antisaccade task (i.e., eye movement mirror-symmetrical to a target). Antisaccades are an ideal tool for the study of individuals with subtle executive deficits because of its hands- and language-free nature and because the task's neural mechanisms are linked to neuropathology in cognitive decline (i.e., prefrontal cortex). Results showed that M2 and M4 group antisaccade reaction times reliably decreased from pre- to post-intervention and the magnitude of the decrease was consistent across groups. Thus, multi-modality exercise training improved executive performance in persons with a SCC independent of mind-motor training. Accordingly, we propose that multiple-modality training provides a sufficient intervention to improve executive control in persons with a SCC.

Self-Reported History of Chemotherapy and Cognitive Decline in Adults Aged 60 and Older: The PATH Through Life Project.

PubMed

Anstey, Kaarin J; Sargent-Cox, Kerry; Cherbuin, Nicolas; Sachdev, Perminder S

2015-06-01

There is a lack of data from cohort studies assessing cognitive function prior to and after chemotherapy. We evaluated the effect of self-reported cancer chemotherapy on cognitive function in a cohort assessed at baseline, 4 and 8 years. Participants were from the population-based PATH Through Life Study. Of the 2,551 participants aged 60-64 at baseline without cognitive impairment, 1,949 completed wave 3 and had data on cancer and chemotherapy and cognitive function. Linear mixed models were used to analyze the data. At wave 3, participants reporting history of chemotherapy (n = 76) had lower scores on memory, processing speed, and executive function compared with those reporting cancer without chemotherapy (n = 289) and no cancer history (n = 1508). After adjustment for depression and disability, effects remained for processing speed and memory. Chemotherapy prior to the study commencement (n = 24), but not between waves 1 and 3 (n = 81), was associated with greater decline in delayed recall (β = -.21 [95% CI -0.38, -.03], p = .02) and digits backwards β = -.05 [95% CI -0.09, -.01], p = .02) over 8 years compared with those with no cancer history (n = 1562). Women reporting chemotherapy for breast cancer after wave 1 (n = 26) had slower choice reaction time (-0.81 (95% CI -1.28, -0.34), p = .001) but did not decline faster on this measure compared with those reporting no breast cancer history (n = 818). Results suggest chemotherapy prior to old age is associated with faster decline in memory in late life but that it does not affect decline in other domains of cognitive function. © The Author 2013. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved. For permissions, please email: journals.permissions@oup.com.

All about running: synaptic plasticity, growth factors and adult hippocampal neurogenesis.

PubMed

Vivar, Carmen; Potter, Michelle C; van Praag, Henriette

2013-01-01

Accumulating evidence from animal and human research shows exercise benefits learning and memory, which may reduce the risk of neurodegenerative diseases, and could delay age-related cognitive decline. Exercise-induced improvements in learning and memory are correlated with enhanced adult hippocampal neurogenesis and increased activity-dependent synaptic plasticity. In this present chapter we will highlight the effects of physical activity on cognition in rodents, as well as on dentate gyrus (DG) neurogenesis, synaptic plasticity, spine density, neurotransmission and growth factors, in particular brain-derived nerve growth factor (BDNF).

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.

Environmental enrichment and social interaction improve cognitive function and decrease reactive oxidative species in normal adult mice.

PubMed

Doulames, Vanessa; Lee, Sangmook; Shea, Thomas B

2014-05-01

Environmental stimulation and increased social interactions stimulate cognitive performance, while decrease in these parameters can exacerbate cognitive decline as a function of illness, injury, or age. We examined the impact of environmental stimulation and social interactions on cognitive performance in healthy adult C57B1/6J mice. Mice were housed for 1 month individually or in groups of three (to prevent or allow social interaction) in either a standard environment (SE) or an enlarged cage containing nesting material and items classically utilized to stimulate exploration and activity ("enriched environment"; EE). Cognitive performance was tested by Y maze navigation and Novel Object Recognition (NOR; which compares the relative amount of time mice spent investigating a novel vs. a familiar object). Mice maintained for 1 month under isolated conditions in the SE statistically declined in performance versus baseline in the Y maze (p < 0.02; ANOVA). Performance under all other conditions did not change from baseline. Maintenance in groups in the SE statistically improved NOR (p < 0.01), whereas maintenance in isolation in the SE did not alter performance from baseline. Maintenance in the EE statistically improved performance in NOR for mice housed in groups and individually (p < 0.01). Maintenance under isolated conditions slightly increased reactive oxygen/nitrogen species (ROS/RNS) in brain. Environmental enrichment did not influence ROS/RNS. These findings indicate that environmental and social enrichment can positively influence cognitive performance in healthy adult mice, and support the notion that proactive approaches may delay age-related cognitive decline.

Maintaining older brain functionality: A targeted review.

PubMed

Ballesteros, Soledad; Kraft, Eduard; Santana, Silvina; Tziraki, Chariklia

2015-08-01

The unprecedented growth in the number of older adults in our society is accompanied by the exponential increase in the number of elderly people who will suffer cognitive decline and dementia in the next decades. This will create an enormous cost for governments, families and individuals. Brain plasticity and its role in brain adaptation to the process of aging is influenced by other changes as a result of co-morbidities, environmental factors, personality traits (psychosocial variables) and genetic and epigenetic factors. This review summarizes recent findings obtained mostly from interventional studies that aim to prevent and/or delay age-related cognitive decline in healthy adults. There are a multitude of such studies. In this paper, we focused our review on physical activity, computerized cognitive training and social enhancement interventions on improving cognition, physical health, independent living and wellbeing of older adults. The methodological limitations of some of these studies, and the need for new multi-domain synergistic interventions, based on current advances in neuroscience and social-brain theories, are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Decline in Tested and Self-Reported Cognitive Functioning After Prophylactic Cranial Irradiation for Lung Cancer: Pooled Secondary Analysis of Radiation Therapy Oncology Group Randomized Trials 0212 and 0214

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

Gondi, Vinai, E-mail: vgondi@chicagocancer.org; University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin; Paulus, Rebecca

Purpose: To assess the impact of prophylactic cranial irradiation (PCI) on self-reported cognitive functioning (SRCF), a functional scale on the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 0214 randomized patients with locally advanced non-small cell lung cancer to PCI or observation; RTOG 0212 randomized patients with limited-disease small cell lung cancer to high- or standard-dose PCI. In both trials, Hopkins Verbal Learning Test (HVLT)-Recall and -Delayed Recall and SRCF were assessed at baseline (after locoregional therapy but before PCI or observation) and atmore » 6 and 12 months. Patients developing brain relapse before follow-up evaluation were excluded. Decline was defined using the reliable change index method and correlated with receipt of PCI versus observation using logistic regression modeling. Fisher's exact test correlated decline in SRCF with HVLT decline. Results: Of the eligible patients pooled from RTOG 0212 and RTOG 0214, 410 (93%) receiving PCI and 173 (96%) undergoing observation completed baseline HVLT or EORTC QLQ-C30 testing and were included in this analysis. Prophylactic cranial irradiation was associated with a higher risk of decline in SRCF at 6 months (odds ratio 3.60, 95% confidence interval 2.34-6.37, P<.0001) and 12 months (odds ratio 3.44, 95% confidence interval 1.84-6.44, P<.0001). Decline on HVLT-Recall at 6 and 12 months was also associated with PCI (P=.002 and P=.002, respectively) but was not closely correlated with decline in SRCF at the same time points (P=.05 and P=.86, respectively). Conclusions: In lung cancer patients who do not develop brain relapse, PCI is associated with decline in HVLT-tested and self-reported cognitive functioning. Decline in HVLT and decline in SRCF are not closely correlated, suggesting that they may represent distinct elements of the cognitive spectrum.« less

Cognitive stimulation intervention for elders with mild cognitive impairment compared with normal aged subjects: preliminary results.

PubMed

Wenisch, Emilie; Cantegreil-Kallen, Inge; De Rotrou, Jocelyne; Garrigue, Pia; Moulin, Florence; Batouche, Fériel; Richard, Aurore; De Sant'Anna, Martha; Rigaud, Anne Sophie

2007-08-01

Cognitive training programs have been developed for Alzheimer's disease patients and the healthy elderly population. Collective cognitive stimulation programs have been shown to be efficient for subjects with memory complaint. The aim of this study was to evaluate the benefit of such cognitive programs in populations with Mild Cognitive Impairment (MCI). Twelve patients with MCI and twelve cognitively normal elders were administered a cognitive stimulation program. Cognitive performance (Logical Memory, Word paired associative learning task, Trail Making Test, verbal fluency test) were collected before and after the intervention. A gain score [(post-score - pre-score)/ pre-score] was calculated for each variable and compared between groups. The analysis revealed a larger intervention size effect in MCI than in normal elders' performances on the associative learning task (immediate recall: p<0.05, delayed recall: p<0.01). The intervention was more beneficial in improving associative memory abilities in MCI than in normal subjects. At the end of the intervention, the MCI group had lower results than the normal group only for the delayed recall of Logical Memory. Although further studies are needed for more details on the impact of cognitive stimulation programs on MCI patients, this intervention is effective in compensating associative memory difficulties of these patients. Among non-pharmacological interventions, cognitive stimulation therapy is a repeatable and inexpensive collective method that can easily be provided to various populations with the aim of slowing down the rate of decline in elderly persons with cognitive impairment.

Cognitive side-effects of electroconvulsive therapy in elderly depressed patients.

PubMed

Dybedal, Gro Strømnes; Tanum, Lars; Sundet, Kjetil; Gaarden, Torfinn Lødøen; Bjølseth, Tor Magne

2014-01-01

Knowledge about cognitive side-effects induced by electroconvulsive therapy (ECT) in depressed elderly patients is sparse. In this study we investigated changes in the cognitive functioning of non-demented elderly depressed patients receiving ECT (n = 62) compared with healthy elderly people (n = 17). Neuropsychological tests were administered at the start of treatment and again within 1 week after treatment. We computed reliable change indices (RCIs) using simple regression methods. RCIs are statistical methods for analyzing change in individuals that have not yet been used in studies of the acute cognitive side-effects of ECT. At the group level, only letter fluency performance was found to be significantly reduced in the ECT group compared with the controls, whereas both groups demonstrated stable or improved performance on all other measures. At the individual level, however, 11% of patients showed retrograde amnesia for public facts post-ECT and 40% of the patients showed a significant decline in neuropsychological functioning. Decline on a measure of delayed verbal anterograde memory was most common. Our findings indicate that there are mild neurocognitive impairments in the acute phase for a substantial minority of elderly patients receiving ECT. Analysis of reliable change facilitated the illumination of cognitive side-effects in our sample.

Multiple effects of physical activity on molecular and cognitive signs of brain aging: can exercise slow neurodegeneration and delay Alzheimer's disease?

PubMed

Brown, B M; Peiffer, J J; Martins, R N

2013-08-01

Western countries are experiencing aging populations and increased longevity; thus, the incidence of dementia and Alzheimer's disease (AD) in these countries is projected to soar. In the absence of a therapeutic drug, non-pharmacological preventative approaches are being investigated. One of these approaches is regular participation in physical activity or exercise. This paper reviews studies that have explored the relationship between physical activity and cognitive function, cognitive decline, AD/dementia risk and AD-associated biomarkers and processes. There is now strong evidence that links regular physical activity or exercise to higher cognitive function, decreased cognitive decline and reduced risk of AD or dementia. Nevertheless, these associations require further investigation, more specifically with interventional studies that include long follow-up periods. In particular, relatively little is known about the underlying mechanism(s) of the associations between physical activity and AD neuropathology; clearly this is an area in need of further research, particularly in human populations. Although benefits of physical activity or exercise are clearly recognised, there is a need to clarify how much physical activity provides the greatest benefit and also whether people of different genotypes require tailored exercise regimes.

An empirically derived composite cognitive test score with improved power to track and evaluate treatments for preclinical Alzheimer's disease.

PubMed

Langbaum, Jessica B; Hendrix, Suzanne B; Ayutyanont, Napatkamon; Chen, Kewei; Fleisher, Adam S; Shah, Raj C; Barnes, Lisa L; Bennett, David A; Tariot, Pierre N; Reiman, Eric M

2014-11-01

There is growing interest in the evaluation of preclinical Alzheimer's disease (AD) treatments. As a result, there is a need to identify a cognitive composite that is sensitive to track preclinical AD decline to be used as a primary endpoint in treatment trials. Longitudinal data from initially cognitively normal, 70- to 85-year-old participants in three cohort studies of aging and dementia from the Rush Alzheimer's Disease Center were examined to empirically define a composite cognitive endpoint that is sensitive to detect and track cognitive decline before the onset of cognitive impairment. The mean-to-standard deviation ratios (MSDRs) of change over time were calculated in a search for the optimal combination of cognitive tests/subtests drawn from the neuropsychological battery in cognitively normal participants who subsequently progressed to clinical stages of AD during 2- and 5-year periods, using data from those who remained unimpaired during the same period to correct for aging and practice effects. Combinations that performed well were then evaluated for representation of relevant cognitive domains, robustness across individual years before diagnosis, and occurrence of selected items within top performing combinations. The optimal composite cognitive test score comprised seven cognitive tests/subtests with an MSDR = 0.964. By comparison, the most sensitive individual test score was Logical Memory Delayed Recall with an MSDR = 0.64. We have identified a composite cognitive test score representing multiple cognitive domains that has improved power compared with the most sensitive single test item to track preclinical AD decline and evaluate preclinical AD treatments. We are confirming the power of the composite in independent cohorts and with other analytical approaches, which may result in refinements, have designated it as the primary endpoint in the Alzheimer's Prevention Initiative's preclinical treatment trials for individuals at high imminent risk for developing symptoms due to late-onset AD. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Omega-3 Supplementation and Loneliness-Related Memory Problems: Secondary Analyses Of A Randomized Controlled Trial

PubMed Central

Jaremka, Lisa M.; Derry, Heather M.; Bornstein, Robert; Prakash, Ruchika Shaurya; Peng, Juan; Belury, Martha A.; Andridge, Rebecca R.; Malarkey, William B.; Kiecolt-Glaser, Janice K.

2014-01-01

Objective Loneliness enhances risk for episodic memory declines over time. Omega-3 supplementation can improve cognitive function for people experiencing mild cognitive difficulties. Accordingly, we explored whether omega-3 supplementation would attenuate loneliness-related episodic memory problems. Methods Participants (N=138) from a parent randomized controlled trial (RCT) were randomized to the placebo, 1.25 grams/day of omega-3, or 2.50 grams/day of omega-3 conditions for a 4-month period. They completed a baseline loneliness questionnaire and a battery of cognitive tests both at baseline and at the end of the RCT. Results Controlling for baseline verbal episodic memory scores, lonelier people within the placebo condition had poorer verbal episodic memory post-supplementation, as measured by immediate (b = −0.28, t(117) = −2.62, p = .010) and long-delay (b = −.06, t(116) = −2.07, p = .040) free recall, than their less lonely counterparts. This effect was not observed in the 1.25 grams/day and 2.50 grams/day supplementation groups, all p values > .10. The plasma omega-6:omega-3 ratio data mirrored these results. There were no loneliness-related effects of omega-3 supplementation on short-delay recall or the other cognitive tests, all p values > .32. Conclusion These results suggest that omega-3 supplementation attenuates loneliness-related verbal episodic memory declines over time and support the utility of exploring novel interventions for treating episodic memory problems among lonely people. ClinicalTrials.gov identifier: NCT00385723 PMID:25264972

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.

Can older "at risk" adults benefit from psychoeducation targeting healthy brain aging?

PubMed

Norrie, Louisa M; Diamond, Keri; Hickie, Ian B; Rogers, Naomi L; Fearns, Samantha; Naismith, Sharon L

2011-04-01

Multifactorial strategies that prevent or delay the onset or progress of cognitive decline and dementia are needed, and should include education regarding recognized risk factors. The current study sought to investigate whether older adults "at risk" of cognitive decline benefit from psychoeducation targeting healthy brain aging. 65 participants (mean age 64.8 years, SD 9.6) with a lifetime history of major depression; vascular risk as evidenced by at least one vascular risk factor; and/or subjective or objective memory impairment were allocated to weekly psychoeducation sessions or a waitlist control group. The small group sessions were conducted over ten weeks by a team of medical and allied health professionals with expertise in late-life depression and cognition. Sessions focused on modifiable risk factors for cognitive decline including vascular risk, diet, exercise, depression, anxiety and sleep disturbance, as well as providing practical strategies for memory and cognition. Both the psychoeducation and waitlist group completed a 20-item knowledge test at baseline and follow-up. Participants in the psychoeducation group were asked to complete follow-up self-report satisfaction questionnaires. Repeated measures ANOVA showed a significant interaction effect depicting improvements in knowledge associated with psychoeducation, corresponding to an improvement of 15% from baseline. Satisfaction data additionally showed that 92.3% of participants rated the program as "good" to "excellent", and over 90% suggested they would recommend it to others. A group-based psychoeducation program targeting healthy brain aging is effective in improving knowledge. Additionally, it is acceptable and rated highly by participants.

Influence of patient-related and surgery-related risk factors on cognitive performance, emotional state, and convalescence after cardiac surgery.

PubMed

Ille, Rottraut; Lahousen, Theresa; Schweiger, Stefan; Hofmann, Peter; Kapfhammer, Hans-Peter

2007-01-01

Cardiac surgery may account for complications such as cognitive impairment, depression, and delay of convalescence. This study investigated the influence of different risk factors on cognitive performance, emotional state, and convalescence. We included 83 patients undergoing cardiac surgery who had no indication of postoperative delirium. Psychometric testing was performed 1 day before and 7 days after surgery. Neuron-specific enolase (NSE) levels were measured 1 day before and 36 h after surgery. Depression score increased after surgery, but patients showed no clinically significant depression. Postoperative cognitive performance correlated with postoperative depression level and preoperative cognitive performance. Forty-three percent of patients showed postoperative decline. Older patients exhibited a higher postoperative increase in NSE concentrations. Patients undergoing coronary artery bypass grafts or combined procedures exhibited more medical risk factors than those undergoing valve surgery alone. The number of bypass grafts was associated with time of hospitalization, and the number of patient-related risk factors correlated with stay in intensive care unit. For elderly patients undergoing cardiac surgery, older age, total preexisting medical risk factors, and surgery duration seem to be the most important factors influencing cognitive outcome and convalescence. Results show that, also for patients without postoperative delirium, medical risk factors and intraoperative parameters can result in delay of convalescence.

Cognitive changes in people with temporal lobe epilepsy over a 13-year period.

PubMed

Mameniškienė, Rūta; Rimšienė, Justė; Puronaitė, Roma

2016-10-01

The aims of our study were to evaluate cognitive decline in people with temporal lobe epilepsy over a period of 13years and to determine what clinical and treatment characteristics may have been associated with these. Thirty-three individuals with temporal lobe epilepsy underwent the same neuropsychological assessment of verbal and nonverbal memory, attention, and executive functions using the same cognitive test battery as one used 13years ago. Long-term verbal and nonverbal memory was tested four weeks later. Results were compared with those carried out 13years earlier. There was no significant change in verbal and verbal-logical memory tests; however, nonverbal memory worsened significantly. Long-term verbal memory declined for 21.9% of participants, long-term verbal-logical memory for 34.4%, and long-term nonverbal memory for 56.3%. Worsening of working verbal and verbal-logical memory was associated with longer epilepsy duration and lower levels of patients' education; worsening of verbal delayed recall and long-term verbal-logical memory was associated with higher seizure frequency. Decline in long-term nonverbal memory had significant association with a longer duration of epilepsy. The worsening of reaction and attention inversely correlated with the symptoms of depression. Over a 13-year period, cognitive functions did not change significantly. Good seizure control and reduced symptoms of depression in this sample of people with temporal lobe epilepsy were associated with better cognitive functioning. The predictors of change of cognitive functions could be complex and require further study. Copyright © 2016 Elsevier Inc. All rights reserved.

The Effect of Vascular Neuropathology on Late-life Cognition: Results from the SMART Project.

PubMed

Kryscio, R J; Abner, E L; Nelson, P T; Bennett, D; Schneider, J; Yu, L; Hemmy, L S; Lim, K O; Masaki, K; Cairns, N; Xiong, C; Woltjer, R; Dodge, H H; Tyas, S; Fardo, D W; Lou, W; Wan, L; Schmitt, F A

2016-06-01

Cerebral vascular pathology may contribute to cognitive decline experienced by some elderly near death. Given evidence for mixed neuropathologies in advanced age, preventing or reducing cerebrovascular burden in late life may be beneficial. To correlate measures of cerebral vascular pathology with cognitive trajectories. Observational study. A cohort of 2,274 individuals who came to autopsy at a mean age of 89.3 years and 82 percent of whom had at least two cognitive assessments within the last six years of life was compiled from six centers conducting longitudinal studies. For each cognitive domain: immediate and delayed memory, language, and naming, three trajectories were examined: good, intermediate, and poor cognition. The probability of a participant belonging to each trajectory was associated with measures of cerebral vascular pathology after adjustment for demographics, APOE, and Alzheimer neuropathology. A large proportion of the cohort (72-94%) experienced good or intermediate cognition in the four domains examined. The presence of arteriolosclerosis and the presence of lacunar infarcts doubled the odds of belonging to the poor cognitive trajectory for language when compared to the good trajectory. The presence of lacunar infarcts increased the odds of an intermediate or poor trajectory for immediate and delayed recall while the presence of large artery infarcts increased the odds of poor trajectories for all four cognitive domains examined. Microinfarcts and cerebral amyloid angiopathy had little effect on the trajectories. Indicators of cerebral vascular pathology act differently on late life cognition.

The Effect of Vascular Neuropathology on Late-life Cognition: Results from the SMART Project

PubMed Central

Kryscio, R.J.; Abner, E.L.; Nelson, P.T.; Bennett, D.; Schneider, J.; Yu, L.; Hemmy, L.S.; Lim, K.O.; Masaki, K.; Cairns, N.; Xiong, C.; Woltjer, R.; Dodge, H.H.; Tyas, S.; Fardo, D.W.; Lou, W.; Wan, L.; Schmitt, F.A.

2016-01-01

Background Cerebral vascular pathology may contribute to cognitive decline experienced by some elderly near death. Given evidence for mixed neuropathologies in advanced age, preventing or reducing cerebrovascular burden in late life may be beneficial. Objective To correlate measures of cerebral vascular pathology with cognitive trajectories. Setting Observational study. Participants A cohort of 2,274 individuals who came to autopsy at a mean age of 89.3 years and 82 percent of whom had at least two cognitive assessments within the last six years of life was compiled from six centers conducting longitudinal studies. Measurements For each cognitive domain: immediate and delayed memory, language, and naming, three trajectories were examined: good, intermediate, and poor cognition. The probability of a participant belonging to each trajectory was associated with measures of cerebral vascular pathology after adjustment for demographics, APOE, and Alzheimer neuropathology. Results A large proportion of the cohort (72-94%) experienced good or intermediate cognition in the four domains examined. The presence of arteriolosclerosis and the presence of lacunar infarcts doubled the odds of belonging to the poor cognitive trajectory for language when compared to the good trajectory. The presence of lacunar infarcts increased the odds of an intermediate or poor trajectory for immediate and delayed recall while the presence of large artery infarcts increased the odds of poor trajectories for all four cognitive domains examined. Microinfarcts and cerebral amyloid angiopathy had little effect on the trajectories. Conclusion Indicators of cerebral vascular pathology act differently on late life cognition. PMID:27709107

Cholinesterase Inhibitors Improve Both Memory and Complex Learning in Aged Beagle Dogs

PubMed Central

Araujo, Joseph A.; Greig, Nigel H.; Ingram, Donald K.; Sandin, Johan; de Rivera, Christina; Milgram, Norton W.

2016-01-01

Similar to patients with Alzheimer’s disease (AD), dogs exhibit age-dependent cognitive decline, amyloid-β (Aβ) pathology, and evidence of cholinergic hypofunction. The present study sought to further investigate the role of cholinergic hypofunction in the canine model by examining the effect of the cholinesterase inhibitors phenserine and donepezil on performance of two tasks, a delayed non-matching-to-position task (DNMP) designed to assess working memory, and an oddity discrimination learning task designed to assess complex learning, in aged dogs. Phenserine (0.5 mg/kg; PO) significantly improved performance on the DNMP at the longest delay compared to wash-out and partially attenuated scopolamine-induced deficits (15 μg/kg; SC). Phenserine also improved learning on a difficult version of an oddity discrimination task compared to placebo, but had no effect on an easier version. We also examined the effects of three doses of donepezil (0.75, 1.5, and 6 mg/kg; PO) on performance of the DNMP. Similar to the results with phenserine, 1.5 mg/kg of donepezil improved performance at the longest delay compared to baseline and wash-out, indicative of memory enhancement. These results further extend the findings of cholinergic hypofunction in aged dogs and provide pharmacological validation of the canine model with a cholinesterase inhibitor approved for use in AD. Collectively, these studies support utilizing the aged dog in future screening of therapeutics for AD, as well as for investigating the links among cholinergic function, Aβ pathology, and cognitive decline. PMID:21593569

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

Age-related decline in verbal learning is moderated by demographic factors, working memory capacity, and presence of amnestic mild cognitive impairment.

PubMed

Constantinidou, Fofi; Zaganas, Ioannis; Papastefanakis, Emmanouil; Kasselimis, Dimitrios; Nidos, Andreas; Simos, Panagiotis G

2014-09-01

Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17-86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity.

Personality and Cognitive Decline in the Baltimore Epidemiologic Catchment Area Follow-up Study

PubMed Central

Hock, Rebecca S.; Lee, Hochang Benjamin; Bienvenu, O. Joseph; Nestadt, Gerald; Samuels, Jack F.; Parisi, Jeanine M.; Costa, Paul T.; Spira, Adam P.

2013-01-01

Objective To determine the association between personality domains and 11-year cognitive decline in a sample from a population-based study. Method Data from Waves 3 (1993–1996) and 4 (2003–2004) of the Baltimore cohort of the Epidemiologic Catchment Area (ECA) study were used for analyses. The sample included 561 adults (mean age ±SD = 45.2 ±10.78 years) who completed the NEO Personality Inventory-Revised (NEO PI-R) prior to Wave 4. Participants also completed the Mini-Mental State Examination (MMSE) and immediate and delayed word recall tests at Wave 3, and at Wave 4 10.9 ±0.6 years later. Results In models adjusted for baseline cognitive performance, demographic characteristics, medical conditions, depressive symptoms, and psychotropic medication use, each 10-point increase in Neuroticism T-scores was associated with a 0.15-point decrease in MMSE scores (B = −0.15 95% confidence interval (CI) −0.30, −0.01), whereas each 10-point increase in Conscientiousness T-scores was associated with a 0.18-point increase on the MMSE (B = 0.18, 95% CI 0.04, 0.32) and a 0.21-point increase in immediate recall (B = 0.21, 95% CI 0.003, 0.41) between baseline and follow-up. Conclusion Findings suggest that greater Neuroticism is associated with decline, and greater Conscientiousness is associated with improvement in performance on measures of general cognitive function, and memory in adults. Further studies are needed to determine the extent to which personality traits in midlife are associated with clinically significant cognitive outcomes in older adults, such as mild cognitive impairment and dementia, and to identify potential mediators of the association between personality and cognitive trajectories. PMID:23759291

Personality and cognitive decline in the Baltimore Epidemiologic Catchment Area follow-up study.

PubMed

Hock, Rebecca S; Lee, Hochang Benjamin; Bienvenu, O Joseph; Nestadt, Gerald; Samuels, Jack F; Parisi, Jeanine M; Costa, Paul T; Spira, Adam P

2014-09-01

To determine the association between personality domains and 11-year cognitive decline in a sample from a population-based study. Data from Waves 3 (1993-1996) and 4 (2003-2004) of the Baltimore cohort of the Epidemiologic Catchment Area (ECA) study were used for analyses. The sample included 561 adults (mean age ± SD: 45.2 ± 10.78 years) who completed the NEO Personality Inventory-Revised prior to Wave 4. Participants also completed the Mini-Mental State Examination (MMSE) and immediate and delayed word recall tests at Wave 3, and at Wave 4, 10.9 ± 0.6 years later. In models adjusted for baseline cognitive performance, demographic characteristics, medical conditions, depressive symptoms, and psychotropic medication use, each 10-point increase in Neuroticism T-scores was associated with a 0.15-point decrease in MMSE scores (B = -0.15, 95% confidence interval [CI]: -0.30, -0.01), whereas each 10-point increase in Conscientiousness T-scores was associated with a 0.18-point increase on the MMSE (B = 0.18, 95% CI: 0.04, 0.32) and a 0.21-point increase in immediate recall (B = 0.21, 95% CI: 0.003, 0.41) between baseline and follow-up. Findings suggest that greater Neuroticism is associated with decline, and greater Conscientiousness is associated with improvement in performance on measures of general cognitive function and memory in adults. Further studies are needed to determine the extent to which personality traits in midlife are associated with clinically significant cognitive outcomes in older adults, such as mild cognitive impairment and dementia, and to identify potential mediators of the association between personality and cognitive trajectories. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

An International Evaluation of Cognitive Reserve and Memory Changes in Early Old Age in 10 European Countries.

PubMed

Cadar, Dorina; Robitaille, Annie; Clouston, Sean; Hofer, Scott M; Piccinin, Andrea M; Muniz-Terrera, Graciela

2017-01-01

Cognitive reserve was postulated to explain individual differences in susceptibility to ageing, offering apparent protection to those with higher education. We investigated the association between education and change in memory in early old age. Immediate and delayed memory scores from over 10,000 individuals aged 65 years and older, from 10 countries of the Survey of Health, Ageing and Retirement in Europe, were modeled as a function of time in the study over an 8-year period, fitting independent latent growth models. Education was used as a marker of cognitive reserve and evaluated in association with memory performance and rate of change, while accounting for income, general health, smoking, body mass index, gender, and baseline age. In most countries, more educated individuals performed better on both memory tests at baseline, compared to those less educated. However, education was not protective against faster decline, except for in Spain for both immediate and delayed recall (0.007 [SE = 0.003] and 0.006 [SE = 0.002]), and Switzerland for immediate recall (0.006 [SE = 0.003]). Interestingly, highly educated Italian respondents had slightly faster declines in immediate recall (-0.006 [SE = 0.003]). We found weak evidence of a protective effect of education on memory change in most European samples, although there was a positive association with memory performance at individuals' baseline assessment. © 2017 The Author(s) Published by S. Karger AG, Basel.

Vision-Enhancing Interventions in Nursing Home Residents and Their Short-Term Impact on Physical and Cognitive Function

PubMed Central

Elliott, Amanda F.; McGwin, Gerald; Owsley, Cynthia

2009-01-01

OBJECTIVE To evaluate the effect of vision-enhancing interventions (i.e., cataract surgery or refractive error correction) on physical function and cognitive status in nursing home residents. DESIGN Longitudinal cohort study. SETTING Seventeen nursing homes in Birmingham, AL. PARTICIPANTS A total of 187 English-speaking older adults (>55 years of age). INTERVENTION Participants took part in one of two vision-enhancing interventions: cataract surgery or refractive error correction. Each group was compared against a control group (persons eligible for but who declined cataract surgery, or who received delayed correction of refractive error). MEASUREMENTS Physical function (i.e., ability to perform activities of daily living and mobility) was assessed with a series of self-report and certified nursing assistant ratings at baseline and at 2 months for the refractive error correction group, and at 4 months for the cataract surgery group. The Mini Mental State Exam was also administered. RESULTS No significant differences existed within or between groups from baseline to follow-up on any of the measures of physical function. Mental status scores significantly declined from baseline to follow-up for both the immediate (p= 0.05) and delayed (p< 0.02) refractive error correction groups and for the cataract surgery control group (p= 0.05). CONCLUSION Vision-enhancing interventions did not lead to short-term improvements in physical functioning or cognitive status in this sample of elderly nursing home residents. PMID:19170783

Pericortical Enhancement on Delayed Postgadolinium Fluid-Attenuated Inversion Recovery Images in Normal Aging, Mild Cognitive Impairment, and Alzheimer Disease.

PubMed

Freeze, W M; Schnerr, R S; Palm, W M; Jansen, J F; Jacobs, H I; Hoff, E I; Verhey, F R; Backes, W H

2017-09-01

Breakdown of BBB integrity occurs in dementia and may lead to neurodegeneration and cognitive decline. We assessed whether extravasation of gadolinium chelate could be visualized on delayed postcontrast FLAIR images in older individuals with and without cognitive impairment. Seventy-four individuals participated in this study (15 with Alzheimer disease, 33 with mild cognitive impairment, and 26 with normal cognition). We assessed the appearance of pericortical enhancement after contrast administration, MR imaging markers of cerebrovascular damage, and medial temporal lobe atrophy. Three participants who were positive for pericortical enhancement (1 with normal cognition and 2 with mild cognitive impairment) were followed up for approximately 2 years. In vitro experiments with a range of gadolinium concentrations served to elucidate the mechanisms underlying the postcontrast FLAIR signals. Postcontrast pericortical enhancement was observed in 21 participants (28%), including 6 individuals with Alzheimer disease (40%), 10 with mild cognitive impairment (30%), and 5 with normal cognition (19%). Pericortical enhancement was positively associated with age ( P < .02) and ischemic stroke ( P < .05), but not with cognitive status ( P = .3). Foci with enhanced signal remained stable across time in all follow-up cases. The in vitro measurements confirmed that FLAIR imaging is highly sensitive for the detection of low gadolinium concentrations in CSF, but not in cerebral tissue. Postcontrast pericortical enhancement on FLAIR images occurs in older individuals with normal cognition, mild cognitive impairment, and dementia. It may represent chronic focal superficial BBB leakage. Future longitudinal studies are needed to determine its clinical significance. © 2017 by American Journal of Neuroradiology.

Trajectories of change in cognitive function in people with chronic obstructive pulmonary disease.

PubMed

Park, Soo Kyung

2018-04-01

To describe changes in cognitive function, as measured by the trail making test; to identify distinct patterns of change in cognitive function; and to examine predictors of change in cognitive function in people with severe chronic obstructive pulmonary disease. How cognitive function changes in people with chronic obstructive pulmonary disease and what factors influence those changes over time is not well known, despite the fact that it declines rapidly in this population and significantly impacts functional decline in healthy older adults. A secondary analysis and longitudinal study with a follow-up period of 3 years. A data set from the National Emphysema Treatment Trial provided participant data. Patients with severe chronic obstructive pulmonary disease (n = 307) were recruited at a clinical site. Several demographic and clinical measures were assessed at baseline. Trail making test scores were measured at baseline, 1, 2 and 3 years. Cognitive function was stable for 3 years in people with chronic obstructive pulmonary disease. However, four distinct patterns of change in cognitive function were identified. Age, education, 6-min walk distance and cognitive impairment scores at baseline on the trail making test Part B were significant predictors of worsening cognitive function and below-average cognitive function over 3 years. These findings suggest that increasing exercise capacity improves cognitive function and delays deterioration of cognitive function in people with COPD. Understanding the trajectories of change in cognitive function and predictors of change in cognitive function over 3 years may enable health care providers to identify patients at greatest risk of developing mental deterioration and those who might benefit from interventions to improve cognitive function. Health care providers should periodically assess and frequently screen people with COPD for cognitive function. © 2018 John Wiley & Sons Ltd.

Comparative Effects of Education and Bilingualism on the Onset of Mild Cognitive Impairment.

PubMed

Ramakrishnan, Subasree; Mekala, Shailaja; Mamidipudi, Annapurna; Yareeda, Sireesha; Mridula, Rukmini; Bak, Thomas H; Alladi, Suvarna; Kaul, Subhash

2017-01-01

Increasing evidence suggests that life course factors such as education and bilingualism may have a protective role against dementia due to Alzheimer disease. This study aimed to compare the effects of education and bilingualism on the onset of cognitive decline at the stage of mild cognitive impairment (MCI). A total of 115 patients with MCI evaluated in a specialty memory clinic in Hyderabad, India, formed the cohort. MCI was diagnosed according to Petersen's criteria following clinical evaluation and brain imaging. Age at onset of MCI was compared between bilinguals and monolinguals, and across subjects with high and low levels of education, adjusting for possible confounding variables. The bilingual MCI patients were found to have a clinical onset of cognitive complaints 7.4 years later than monolinguals (65.2 vs. 58.1 years; p = 0.004), while years of education was not associated with delayed onset (1-10 years of education, 59.1 years; 11-15 years of education, 62.6 years; >15 years of education, 62.2 years; p = 0.426). The effect of bilingualism is protective against cognitive decline, and lies along a continuum from normal to pathological states. In comparison, the role of years of education is less robust. © 2017 S. Karger AG, Basel.

Longitudinal Relationship Between Hearing Aid Use and Cognitive Function in Older Americans.

PubMed

Maharani, Asri; Dawes, Piers; Nazroo, James; Tampubolon, Gindo; Pendleton, Neil

2018-04-10

To test whether hearing aid use alters cognitive trajectories in older adults. US population-based longitudinal cohort study SETTING: Data were drawn from the Health and Retirement Study (HRS), which measured cognitive performance repeatedly every 2 years over 18 years (1996-2014). Adults aged 50 and older who who took part in a minimum of 3 waves of the HRS and used hearing aids for the first time between Waves 4 and 11 (N=2,040). Cognitive outcomes were based on episodic memory scores determined according to the sum of immediate and delayed recall of 10 words. Hearing aid use was positively associated with episodic memory scores (β=1.53, p<.001). Decline in episodic memory scores was slower after (β=-0.02, p<.001) than before using hearing aids (β=-0.1, p<.001). These results were robust to adjustment for multiple confounders and to attrition, as accounted for using a joint model. Hearing aids may have a mitigating effect on trajectories of cognitive decline in later life. Providing hearing aids or other rehabilitative services for hearing impairment much earlier in the course of hearing impairment may stem the worldwide rise of dementia. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

Correlation between cognitive functions and syndromes of traditional Chinese medicine in amnestic mild cognitive impairment.

PubMed

Miao, Ying-chun; Tian, Jin-zhou; Shi, Jing; Mao, Min; Zhao, Xiao-dong; Fang, Li-yan; Zeng, Chui-you; Liu, Jian-ping; Wang, Zhi-liang; Li, Xiao-bin

2009-03-01

To explore the correlation between the cognitive functions and syndromes of traditional Chinese medicine (TCM) in amnestic mild cognitive impairment (aMCI), and to provide evidence for clinical syndrome differentiation treatment. Six hundred subjects from Dongzhimen Hospital and seven communities in Beijing, aged between 40 and 85 years, accepted neuropsychological assessments, imaging and biochemical examinations, and syndrome differentiation, from whom 159 aMCI patients, 213 normal control (NC) subjects and 171 Alzheimer's dementia (AD) patients were screened out. Correlation between the cognitive functions and TCM syndromes in aMCI patients was analyzed. Mini-Mental State Examination (MMSE) score in aMCI patients was closely correlated with kidney essence vacuity and deficiency of blood and qi (r = -0.11, r = -0.11; P = 0.003, P = 0.015). Delayed Word Recall (DWR) score was correlated with kidney essence vacuity (r = -0.20, P = 0.020). Instant Story Recall (ISR) and Delayed Story Recall (DSR) scores were respectively correlated with turbid phlegm blocking upper orifices (r = -0.11, r = -0.27; P = 0.021, P = 0.000). Language function was correlated with kidney essence vacuity and deficiency of blood and qi (r = -0.11, r = -0.13; P = 0.042, P = 0.007). Attention/calculation was also closely correlated with kidney essence vacuity and deficiency of blood and qi (r = -0.10, r = -0.21; P = 0.039, P = 0.010). Attention score of aMCI patients was correlated with excess of heat toxin syndrome (r = -0.29, P = 0.026). The memory decline of aMCI is correlated with kidney essence vacuity and turbid phlegm blocking upper orifices. Furthermore, turbid phlegm blocking upper orifices is correlated with episodic memory decline, which is closely related to AD. The aMCI patients with phlegm have the risk to progress into AD. Although other cognitive functions of aMCI remain relatively intact, the patients' language function, attention/calculation and the whole cognitive function may be worsen as the aggravation of kidney essence vacuity, deficiency of blood and qi, phlegm and heat toxin, and may eventually lead to multiple cognitive domains impairment, even dementia.

Assessment and management of nutrition in older people and its importance to health.

PubMed

Ahmed, Tanvir; Haboubi, Nadim

2010-08-09

Nutrition is an important element of health in the older population and affects the aging process. The prevalence of malnutrition is increasing in this population and is associated with a decline in: functional status, impaired muscle function, decreased bone mass, immune dysfunction, anemia, reduced cognitive function, poor wound healing, delayed recovery from surgery, higher hospital readmission rates, and mortality. Older people often have reduced appetite and energy expenditure, which, coupled with a decline in biological and physiological functions such as reduced lean body mass, changes in cytokine and hormonal level, and changes in fluid electrolyte regulation, delay gastric emptying and diminish senses of smell and taste. In addition pathologic changes of aging such as chronic diseases and psychological illness all play a role in the complex etiology of malnutrition in older people. Nutritional assessment is important to identify and treat patients at risk, the Malnutrition Universal Screening Tool being commonly used in clinical practice. Management requires a holistic approach, and underlying causes such as chronic illness, depression, medication and social isolation must be treated. Patients with physical or cognitive impairment require special care and attention. Oral supplements or enteral feeding should be considered in patients at high risk or in patients unable to meet daily requirements.

Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline.

PubMed

Yurko-Mauro, Karin; McCarthy, Deanna; Rom, Dror; Nelson, Edward B; Ryan, Alan S; Blackwell, Andrew; Salem, Norman; Stedman, Mary

2010-11-01

Docosahexaenoic acid (DHA) plays an important role in neural function. Decreases in plasma DHA are associated with cognitive decline in healthy elderly adults and in patients with Alzheimer's disease. Higher DHA intake is inversely correlated with relative risk of Alzheimer's disease. The potential benefits of DHA supplementation in age-related cognitive decline (ARCD) have not been fully examined. Determine effects of DHA administration on improving cognitive functions in healthy older adults with ARCD. Randomized, double-blind, placebo-controlled, clinical study was conducted at 19 U.S. clinical sites. A total of 485 healthy subjects, aged ≥55 with Mini-Mental State Examination >26 and a Logical Memory (Wechsler Memory Scale III) baseline score ≥1 standard deviation below younger adults, were randomly assigned to 900 mg/d of DHA orally or matching placebo for 24 weeks. The primary outcome was the CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test. Intention-to-treat analysis demonstrated significantly fewer PAL six pattern errors with DHA versus placebo at 24 weeks (difference score, -1.63 ± 0.76 [-3.1, -0.14, 95% CI], P = .03). DHA supplementation was also associated with improved immediate and delayed Verbal Recognition Memory scores (P < .02), but not working memory or executive function tests. Plasma DHA levels doubled and correlated with improved PAL scores (P < .02) in the DHA group. DHA was well tolerated with no reported treatment-related serious adverse events. Twenty-four week supplementation with 900 mg/d DHA improved learning and memory function in ARCD and is a beneficial supplement that supports cognitive health with aging. Clinicaltrials.gov, Identifier: NCT0027813. Copyright © 2010 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

The Benefits of Exercise and Metabolic Interventions for the Prevention and Early Treatment of Alzheimer's Disease.

PubMed

Maliszewska-Cyna, Ewelina; Lynch, Madelaine; Oore, Jonathan Jordan; Nagy, Paul Michael; Aubert, Isabelle

2017-01-01

Alzheimer's disease (AD) is characterized by neuronal degeneration, vascular pathology and cognitive decline. Furthermore, deficits in cerebral glucose metabolism and insulin resistance are being increasingly recognized in AD. Many lifestyle-modifying approaches, including diet and exercise, have yielded promising results in modulating brain morphology and function for the prevention and early treatment of AD. This review focuses on the effects of physical exercise on rescuing cognition and limiting the progression of AD pathology. Specifically, the impact of exercise, in human and animal models of AD, on the stimulation and preservation of cognition, neurotransmission, neurogenesis, vasculature, glucose metabolism and insulin signaling is discussed. Studies have highlighted the potential of physical activity to improve overall brain health, which could delay or lessen AD-related cognitive deficits and pathology. Physical activity influences cognitive function, vascular health and brain metabolism, which taken together offers benefits for the aging population, including AD patients.

Neighborhood Environment and Cognition in Older Adults: A Systematic Review.

PubMed

Besser, Lilah M; McDonald, Noreen C; Song, Yan; Kukull, Walter A; Rodriguez, Daniel A

2017-08-01

Some evidence suggests that treating vascular risk factors and performing mentally stimulating activities may delay cognitive impairment onset in older adults. Exposure to a complex neighborhood environment may be one mechanism to help delay cognitive decline. PubMed, Web of Science, and ProQuest Dissertation and Theses Global database were systematically reviewed, identifying 25 studies published from February 1, 1989 to March 5, 2016 (data synthesized, May 3, 2015 to October 7, 2016). The review was restricted to quantitative studies focused on: (1) neighborhood social and built environment and cognition; and (2) community-dwelling adults aged ≥45 years. The majority of studies were cross-sectional, U.S.-based, and found at least one significant association. The diversity of measures and neighborhood definitions limited the synthesis of findings in many instances. Evidence was moderately strong for an association between neighborhood SES and cognition, and modest for associations between neighborhood demographics, design, and destination accessibility and cognition. Most studies examining effect modification found significant associations, with some evidence for effect modification of the neighborhood SES-cognition association by individual-level SES. No studies had low risk of bias and many tested multiple associations that increased the chance of a statistically significant finding. Considering the studies to date, the evidence for an association between neighborhood characteristics and cognition is modest. Future studies should include longitudinal measures of neighborhood characteristics and cognition; examine potential effect modifiers, such as sex and disability; and study mediators that may help elucidate the biological mechanisms linking neighborhood environment and cognition. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Exploring anterograde memory: a volumetric MRI study in patients with mild cognitive impairment.

PubMed

Philippi, N; Noblet, V; Duron, E; Cretin, B; Boully, C; Wisniewski, I; Seux, M L; Martin-Hunyadi, C; Chaussade, E; Demuynck, C; Kremer, S; Lehéricy, S; Gounot, D; Armspach, J P; Hanon, O; Blanc, F

2016-07-30

The aim of this volumetric study was to explore the neuroanatomical correlates of the Free and Cued Selective Reminding Test (FCSRT) and the Delayed Matching-to-Sample-48 items (DMS-48), two tests widely used in France to assess verbal and visual anterograde memory. We wanted to determine to what extent the two tests rely on the medial temporal lobe, and could therefore be predictive of Alzheimer's disease, in which pathological changes typically start in this region. We analysed data from a cohort of 138 patients with mild cognitive impairment participating in a longitudinal multicentre clinical research study. Verbal memory was assessed using the FCSRT and visual recognition memory was evaluated using the DMS-48. Performances on these two tests were correlated to local grey matter atrophy via structural MRI using voxel-based morphometry. Our results confirm the existence of a positive correlation between the volume of the medial temporal lobe and the performance on the FCSRT, prominently on the left, and the performance on the DMS-48, on the right, for the whole group of patients (family-wise error, P < 0.05). Interestingly, this region remained implicated only in the subgroup of patients who had deficient scores on the cued recall of the FCSRT, whereas the free recall was associated with prefrontal aspects. For the DMS-48, it was only implicated for the group of patients whose performances declined between the immediate and delayed trial. Conversely, temporo-parietal cortices were implicated when no decline was observed. Within the medial temporal lobe, the parahippocampal gyrus was prominently involved for the FCSRT and the immediate trial of the DMS-48, whereas the hippocampus was solely involved for the delayed trial of the DMS-48. The two tests are able to detect an amnestic profile of the medial temporal type, under the condition that the scores remain deficient after the cued recall of the FCSRT or decline on the delayed recognition trial of the DMS-48. Strategic retrieval as well as perceptual/attentional processes, supported by prefrontal and temporo-parietal cortices, were also found to have an impact on the performances. Finally, the implication of the hippocampus appears time dependent, triggered by a longer delay than the parahippocampus, rather than determined by the sense of recollection or the encoding strength associated with the memory trace.

Delay Discounting: I'm a "K", You're a "K"

ERIC Educational Resources Information Center

Odum, Amy L.

2011-01-01

Delay discounting is the decline in the present value of a reward with delay to its receipt. Across a variety of species, populations, and reward types, value declines hyperbolically with delay. Value declines steeply with shorter delays, but more shallowly with longer delays. Quantitative modeling provides precise measures to characterize the…

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.

Aging and Strategic Learning: The Impact of Spousal Incentives on Financial Literacy

PubMed Central

Hsu, Joanne W.

2017-01-01

Women tend to be less financially literate than men, consistent with a division of labor where husbands manage finances. However, women tend to outlive their husbands. I find that older women acquire financial literacy as they approach widowhood — 80 percent would catch up with their husbands by the expected onset of widowhood. These gains are not attributable to husbands’ cognitive decline, as captured by cognition tests. The results are consistent with a model in which the division of labor collapses when a spouse dies: women have incentives to delay acquiring financial human capital, but also to begin learning before widowhood. PMID:28148971

Aging and Strategic Learning: The Impact of Spousal Incentives on Financial Literacy.

PubMed

Hsu, Joanne W

2016-01-01

Women tend to be less financially literate than men, consistent with a division of labor where husbands manage finances. However, women tend to outlive their husbands. I find that older women acquire financial literacy as they approach widowhood - 80 percent would catch up with their husbands by the expected onset of widowhood. These gains are not attributable to husbands' cognitive decline, as captured by cognition tests. The results are consistent with a model in which the division of labor collapses when a spouse dies: women have incentives to delay acquiring financial human capital, but also to begin learning before widowhood.

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.

Brain training with non-action video games enhances aspects of cognition in older adults: a randomized controlled trial.

PubMed

Ballesteros, Soledad; Prieto, Antonio; Mayas, Julia; Toril, Pilar; Pita, Carmen; Ponce de León, Laura; Reales, José M; Waterworth, John

2014-01-01

Age-related cognitive and brain declines can result in functional deterioration in many cognitive domains, dependency, and dementia. A major goal of aging research is to investigate methods that help to maintain brain health, cognition, independent living and wellbeing in older adults. This randomized controlled study investigated the effects of 20 1-h non-action video game training sessions with games selected from a commercially available package (Lumosity) on a series of age-declined cognitive functions and subjective wellbeing. Two groups of healthy older adults participated in the study, the experimental group who received the training and the control group who attended three meetings with the research team along the study. Groups were similar at baseline on demographics, vocabulary, global cognition, and depression status. All participants were assessed individually before and after the intervention, or a similar period of time, using neuropsychological tests and laboratory tasks to investigate possible transfer effects. The results showed significant improvements in the trained group, and no variation in the control group, in processing speed (choice reaction time), attention (reduction of distraction and increase of alertness), immediate and delayed visual recognition memory, as well as a trend to improve in Affection and Assertivity, two dimensions of the Wellbeing Scale. Visuospatial working memory (WM) and executive control (shifting strategy) did not improve. Overall, the current results support the idea that training healthy older adults with non-action video games will enhance some cognitive abilities but not others.

Brain training with non-action video games enhances aspects of cognition in older adults: a randomized controlled trial

PubMed Central

Ballesteros, Soledad; Prieto, Antonio; Mayas, Julia; Toril, Pilar; Pita, Carmen; Ponce de León, Laura; Reales, José M.; Waterworth, John

2014-01-01

Age-related cognitive and brain declines can result in functional deterioration in many cognitive domains, dependency, and dementia. A major goal of aging research is to investigate methods that help to maintain brain health, cognition, independent living and wellbeing in older adults. This randomized controlled study investigated the effects of 20 1-h non-action video game training sessions with games selected from a commercially available package (Lumosity) on a series of age-declined cognitive functions and subjective wellbeing. Two groups of healthy older adults participated in the study, the experimental group who received the training and the control group who attended three meetings with the research team along the study. Groups were similar at baseline on demographics, vocabulary, global cognition, and depression status. All participants were assessed individually before and after the intervention, or a similar period of time, using neuropsychological tests and laboratory tasks to investigate possible transfer effects. The results showed significant improvements in the trained group, and no variation in the control group, in processing speed (choice reaction time), attention (reduction of distraction and increase of alertness), immediate and delayed visual recognition memory, as well as a trend to improve in Affection and Assertivity, two dimensions of the Wellbeing Scale. Visuospatial working memory (WM) and executive control (shifting strategy) did not improve. Overall, the current results support the idea that training healthy older adults with non-action video games will enhance some cognitive abilities but not others. PMID:25352805

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

Physical Exercise and Brain Mitochondrial Fitness: The Possible Role Against Alzheimer's Disease.

PubMed

Bernardo, T C; Marques-Aleixo, I; Beleza, J; Oliveira, P J; Ascensão, A; Magalhães, J

2016-09-01

Exercise is one of the most effective strategies to maintain a healthy body and mind, with particular beneficial effects of exercise on promoting brain plasticity, increasing cognition and reducing the risk of cognitive decline and dementia in later life. Moreover, the beneficial effects resulting from increased physical activity occur at different levels of cellular organization, mitochondria being preferential target organelles. The relevance of this review article relies on the need to integrate the current knowledge of proposed mechanisms, focus mitochondria, to explain the protective effects of exercise that might underlie neuroplasticity and seeks to synthesize these data in the context of exploring exercise as a feasible intervention to delay cognitive impairment associated with neurodegenerative conditions, particularly Alzheimer disease. © 2016 International Society of Neuropathology.

Reversible dementia: two nursing home patients with voltage-gated potassium channel antibody-associated limbic encephalitis.

PubMed

Reintjes, Wesley; Romijn, Marloes D M; Hollander, Daan; Ter Bruggen, Jan P; van Marum, Rob J

2015-09-01

Voltage-gated potassium channel antibody-associated limbic encephalitis (VGKC-LE) is a rare disease that is a diagnostic and therapeutic challenge for medical practitioners. Two patients with VGKC-LE, both developing dementia are presented. Following treatment, both patients showed remarkable cognitive and functional improvement enabling them to leave the psychogeriatric nursing homes they both were admitted to. Patients with VGKC-LE can have a major cognitive and functional improvement even after a diagnostic delay of more than 1 year. Medical practitioners who treat patients with unexplained cognitive decline, epileptic seizures, or psychiatric symptoms should be aware of LE as an underlying rare cause. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Adherence to a Mediterranean-Style Diet and Effects on Cognition in Adults: A Qualitative Evaluation and Systematic Review of Longitudinal and Prospective Trials.

PubMed

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

2016-01-01

The Mediterranean-style diet (MedDiet) involves substantial intake of fruits, vegetables, and fish, and a lower consumption of dairy, red meat, and sugars. Over the past 15 years, much empirical evidence supports the suggestion that a MedDiet may be beneficial with respect to reducing the incidence of cardiovascular disease, cancer, metabolic syndrome, and dementia. A number of cross-sectional studies that have examined the impact of MedDiet on cognition have yielded largely positive results. The objective of this review is to evaluate longitudinal and prospective trials to gain an understanding of how a MedDiet may impact cognitive processes over time. The included studies were aimed at improving cognition or minimizing of cognitive decline. Studies reviewed included assessments of dietary status using either a food frequency questionnaire or a food diary assessment. Eighteen articles meeting our inclusion criteria were subjected to systematic review. These revealed that higher adherence to a MedDiet is associated with slower rates of cognitive decline, reduced conversion to Alzheimer's disease, and improvements in cognitive function. The specific cognitive domains that were found to benefit with improved Mediterranean Diet Score were memory (delayed recognition, long-term, and working memory), executive function, and visual constructs. The current review has also considered a number of methodological issues in making recommendations for future research. The utilization of a dietary pattern, such as the MedDiet, will be essential as part of the armamentarium to maintain quality of life and reduce the potential social and economic burden of dementia.

Adherence to a Mediterranean-Style Diet and Effects on Cognition in Adults: A Qualitative Evaluation and Systematic Review of Longitudinal and Prospective Trials

PubMed Central

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

2016-01-01

The Mediterranean-style diet (MedDiet) involves substantial intake of fruits, vegetables, and fish, and a lower consumption of dairy, red meat, and sugars. Over the past 15 years, much empirical evidence supports the suggestion that a MedDiet may be beneficial with respect to reducing the incidence of cardiovascular disease, cancer, metabolic syndrome, and dementia. A number of cross-sectional studies that have examined the impact of MedDiet on cognition have yielded largely positive results. The objective of this review is to evaluate longitudinal and prospective trials to gain an understanding of how a MedDiet may impact cognitive processes over time. The included studies were aimed at improving cognition or minimizing of cognitive decline. Studies reviewed included assessments of dietary status using either a food frequency questionnaire or a food diary assessment. Eighteen articles meeting our inclusion criteria were subjected to systematic review. These revealed that higher adherence to a MedDiet is associated with slower rates of cognitive decline, reduced conversion to Alzheimer’s disease, and improvements in cognitive function. The specific cognitive domains that were found to benefit with improved Mediterranean Diet Score were memory (delayed recognition, long-term, and working memory), executive function, and visual constructs. The current review has also considered a number of methodological issues in making recommendations for future research. The utilization of a dietary pattern, such as the MedDiet, will be essential as part of the armamentarium to maintain quality of life and reduce the potential social and economic burden of dementia. PMID:27500135

Perceived stress and cognitive function in older adults: which aspect of perceived stress is important?

PubMed

Korten, Nicole C M; Comijs, Hannie C; Penninx, Brenda W J H; Deeg, Dorly J H

2017-04-01

Few studies examined the association between perceived stress and cognitive function in older adults. This study will examine which aspects of perceived stress especially impact cognitive function. Cross-sectional data of 1099 older adults between 64 and 100 years from the Longitudinal Aging Study Amsterdam were used. Perceived stress and its subscales perceived helplessness and perceived self-efficacy were measured with the Perceived Stress Scale. Cognitive function was assessed regarding memory, processing speed and executive function. Univariate and multivariate linear regression analyses were performed between the stress measures and the domains of cognitive function. Perceived stress was associated with worse processing speed, direct and delayed recall, semantic fluency and digit span backwards (range β = -0.10; -0.11; p < 0.01). The subscale perceived helplessness showed negative associations only with processing speed (β = -0.06, p < 0.05) and delayed recall (β = -0.06, p < 0.05), which became nonsignificant after the adjustment for depressive symptoms or sense of mastery. The subscale perceived self-efficacy was significantly associated with better cognitive function, also after adjustment for depressive symptoms or sense of mastery (range β = 0.10; 0.18; p < 0.01). In older adults, especially perceived self-efficacy showed independent associations with a broad range of cognitive functions. Perceived self-efficacy might be an important factor in reducing stress and the prevention of cognitive decline. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Subgroup of ADNI Normal Controls Characterized by Atrophy and Cognitive Decline Associated With Vascular Damage

PubMed Central

Nettiksimmons, Jasmine; Beckett, Laurel; Schwarz, Christopher; Carmichael, Owen; Fletcher, Evan; DeCarli, Charles

2013-01-01

Previous work examining Alzheimer’s Disease Neuroimaging Initiative (ADNI) normal controls using cluster analysis identified a subgroup characterized by substantial brain atrophy and white matter hyperintensities (WMH). We hypothesized that these effects could be related to vascular damage. Fifty-three individuals in the suspected vascular cluster (Normal 2) were compared with 31 individuals from the cluster characterized as healthy/typical (Normal 1) on a variety of outcomes, including magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers, vascular risk factors and outcomes, cognitive trajectory, and medications for vascular conditions. Normal 2 was significantly older but did not differ on ApoE4+ prevalence. Normal 2 differed significantly from Normal 1 on all MRI measures but not on Amyloid-Beta1-42 or total tau protein. Normal 2 had significantly higher body mass index (BMI), Hachinksi score, and creatinine levels, and took significantly more medications for vascular conditions. Normal 2 had marginally significantly higher triglycerides and blood glucose. Normal 2 had a worse cognitive trajectory on the Rey’s Auditory Verbal Learning Test (RAVLT) 30-min delay test and the Functional Activity Questionnaire (FAQ). Cerebral atrophy associated with multiple vascular risks is common among cognitively normal individuals, forming a distinct subgroup with significantly increased cognitive decline. Further studies are needed to determine the clinical impact of these findings. PMID:23527743

Turning down the noise: the benefit of musical training on the aging auditory brain.

PubMed

Alain, Claude; Zendel, Benjamin Rich; Hutka, Stefanie; Bidelman, Gavin M

2014-02-01

Age-related decline in hearing abilities is a ubiquitous part of aging, and commonly impacts speech understanding, especially when there are competing sound sources. While such age effects are partially due to changes within the cochlea, difficulties typically exist beyond measurable hearing loss, suggesting that central brain processes, as opposed to simple peripheral mechanisms (e.g., hearing sensitivity), play a critical role in governing hearing abilities late into life. Current training regimens aimed to improve central auditory processing abilities have experienced limited success in promoting listening benefits. Interestingly, recent studies suggest that in young adults, musical training positively modifies neural mechanisms, providing robust, long-lasting improvements to hearing abilities as well as to non-auditory tasks that engage cognitive control. These results offer the encouraging possibility that musical training might be used to counteract age-related changes in auditory cognition commonly observed in older adults. Here, we reviewed studies that have examined the effects of age and musical experience on auditory cognition with an emphasis on auditory scene analysis. We infer that musical training may offer potential benefits to complex listening and might be utilized as a means to delay or even attenuate declines in auditory perception and cognition that often emerge later in life. Copyright © 2013 Elsevier B.V. All rights reserved.

Exercise-induced neuroprotective effects on neurodegenerative diseases: the key role of trophic factors.

PubMed

Campos, Carlos; Rocha, Nuno Barbosa F; Lattari, Eduardo; Paes, Flávia; Nardi, António E; Machado, Sérgio

2016-06-01

Age-related neurodegenerative disorders, like Alzheimer's or Parkinson's disease, are becoming a major issue to public health care. Currently, there is no effective pharmacological treatment to address cognitive impairment in these patients. Here, we aim to explore the role of exercise-induced trophic factor enhancement in the prevention or delay of cognitive decline in patients with neurodegenerative diseases. There is a significant amount of evidence from animal and human studies that links neurodegenerative related cognitive deficits with changes on brain and peripheral trophic factor levels. Several trials with elderly individuals and patients with neurodegenerative diseases report exercise induced cognitive improvements and changes on trophic factor levels including BDNF, IGF-I, among others. Further studies with healthy aging and clinical populations are needed to understand how diverse exercise interventions produce different variations in trophic factor signaling. Genetic profiles and potential confounders regarding trophic factors should also be addressed in future trials.

The continuing benefits of education: adult education and midlife cognitive ability in the British 1946 birth cohort.

PubMed

Hatch, Stephani L; Feinstein, Leon; Link, Bruce G; Wadsworth, Michael E J; Richards, Marcus

2007-11-01

Evidence shows education positively impacts cognitive ability. However, researchers have given little attention to the potential impact of adult education on cognitive ability, still malleable in midlife. The primary study aim was to examine whether there were continuing effects of education over the life course on midlife cognitive ability. This study used data from the Medical Research Council National Survey of Health and Development, also known as the British 1946 birth cohort, and multivariate regression to estimate the continuing effects of adult education on multiple measures of midlife cognitive ability. Educational attainment completed by early adulthood was associated with all measures of cognitive ability in late midlife. The continued effect of education was apparent in the associations between adult education and higher verbal ability, verbal memory, and verbal fluency in late midlife. We found no association between adult education and mental speed and concentration. Associations between adult education and midlife cognitive ability indicate wider benefits of education to health that may be important for social integration, well-being, and the delay of cognitive decline in later life.

Uncovering the Mechanisms Responsible for Why Language Learning May Promote Healthy Cognitive Aging

PubMed Central

Antoniou, Mark; Wright, Sarah M.

2017-01-01

One of the great challenges facing humankind in the 21st century is preserving healthy brain function in our aging population. Individuals over 60 are the fastest growing age group in the world, and by 2050, it is estimated that the number of people over the age of 60 will triple. The typical aging process involves cognitive decline related to brain atrophy, especially in frontal brain areas and regions that subserve declarative memory, loss of synaptic connections, and the emergence of neuropathological symptoms associated with dementia. The disease-state of this age-related cognitive decline is Alzheimer’s disease and other dementias, which may cause older adults to lose their independence and rely on others to live safely, burdening family members and health care systems in the process. However, there are two lines of research that offer hope to those seeking to promote healthy cognitive aging. First, it has been observed that lifestyle variables such as cognitive leisure activities can moderate the risk of Alzheimer’s disease, which has led to the development of plasticity-based interventions for older adults designed to protect against the adverse effects of cognitive decline. Second, there is evidence that lifelong bilingualism acts as a safeguard in preserving healthy brain function, possibly delaying the incidence of dementia by several years. In previous work, we have suggested that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. Here, we will outline potential future lines of research that may uncover the mechanism responsible for the emergence of language learning related brain advantages, such as language typology, bi- vs. multi-lingualism, age of acquisition, and the elements that are likely to result in the largest gains. PMID:29326636

Uncovering the Mechanisms Responsible for Why Language Learning May Promote Healthy Cognitive Aging.

PubMed

Antoniou, Mark; Wright, Sarah M

2017-01-01

One of the great challenges facing humankind in the 21st century is preserving healthy brain function in our aging population. Individuals over 60 are the fastest growing age group in the world, and by 2050, it is estimated that the number of people over the age of 60 will triple. The typical aging process involves cognitive decline related to brain atrophy, especially in frontal brain areas and regions that subserve declarative memory, loss of synaptic connections, and the emergence of neuropathological symptoms associated with dementia. The disease-state of this age-related cognitive decline is Alzheimer's disease and other dementias, which may cause older adults to lose their independence and rely on others to live safely, burdening family members and health care systems in the process. However, there are two lines of research that offer hope to those seeking to promote healthy cognitive aging. First, it has been observed that lifestyle variables such as cognitive leisure activities can moderate the risk of Alzheimer's disease, which has led to the development of plasticity-based interventions for older adults designed to protect against the adverse effects of cognitive decline. Second, there is evidence that lifelong bilingualism acts as a safeguard in preserving healthy brain function, possibly delaying the incidence of dementia by several years. In previous work, we have suggested that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. Here, we will outline potential future lines of research that may uncover the mechanism responsible for the emergence of language learning related brain advantages, such as language typology, bi- vs. multi-lingualism, age of acquisition, and the elements that are likely to result in the largest gains.

Benefits of game-based leisure activities in normal aging and dementia.

PubMed

Narme, Pauline

2016-12-01

Given the increasing prevalence of dementia and the limited efficacy of pharmacological treatments, it is crucial to improve the knowledge of the factors that might delay the onset of dementia for developing non-pharmacological interventions. Recent studies have provided evidence that game-based interventions, especially the practice of video games, could improve the cognitive functioning (e.g. executive functions) in older adults and in demented patients. The positive effects of these games have also been demonstrated on physical health (e.g. improvement of balance and gait). Video gamed-based interventions may also alleviate mood or behavioral disorders, and increase interactions with friends, family, caregivers or other patients. The positive impact of games on these domains (cognitive and physical decline, social isolation) suggests that game-based interventions might contribute to delay the onset of dementia. Thus, playing games might be considered as a protective factor in dementia and even more as a potential non-pharmacological strategy in dementia rather than leisure activity.

Alzheimer disease: diagnosis, costs, and dimensions of treatment.

PubMed

DeKosky, S T; Orgogozo, J M

2001-08-01

Alzheimer disease (AD) is the most frequent cause of dementia in developed Western countries. Over time, affected patients invariably develop cognitive and functional decline, and most develop early or later behavioral disturbances. Declining cognitive and functional abilities contribute to loss of independent living and feelings of denial, confusion, fear and guilt until, finally, the patient loses most abilities to think, move, speak, or perceive. As patients' dependency on assistance increases, the level of caregiver strain rises. The caregiver may develop feelings of anger, grief, loneliness and resentment, and the health and well-being of most caregivers are often affected. Approximately 3-4 million people currently have AD in the USA, at an annual cost of up to US$100 billion, and the disease is expected to reach epidemic proportions by 2020. To achieve a clinically relevant, long-term outcome, pharmacotherapy must have sustained favorable effects on cognitive, functional and behavioral symptoms of AD. Slowing the development of these features of the disease will mean a long-term improvement in quality of life for patients and caregivers. Postponing the emergence of behavioral symptoms would bring about direct beneficial effects on patients with AD and their families, help delay long-term care placement and lower costs.

White matter damage and glymphatic dysfunction in a model of vascular dementia in rats with no prior vascular pathologies

PubMed Central

Venkat, Poornima; Chopp, Michael; Zacharek, Alex; Cui, Chengcheng; Zhang, Li; Li, Qingjiang; Lu, Mei; Zhang, Talan; Liu, Amy; Chen, Jieli

2016-01-01

We investigated cognitive function, axonal/white matter (WM) changes and glymphatic function of vascular dementia (VaD) using a multiple microinfarction (MMI) model in retired breeder (RB) rats. The MMI model induces significant (p<0.05) cognitive decline that worsens with age starting at 2 weeks, which persists until at least 6 weeks after MMI. RB rats subjected to MMI exhibit significant axonal/WM damage identified by decreased myelin thickness, oligodendrocyte progenitor cell numbers, axon density, synaptic protein expression in the cortex and striatum, cortical neuronal branching, and dendritic spine density in the cortex and hippocampus compared with age matched controls. MMI evokes significant dilation of perivascular spaces as well as water channel dysfunction indicated by decreased Aquaporin-4 (AQP-4) expression around blood vessels. MMI induced glymphatic dysfunction with delayed cerebrospinal fluid (CSF) penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. The MMI model in RB rats decreases AQP-4 and induces glymphatic dysfunction which may play an important role in MMI induced axonal/WM damage and cognitive deficits. PMID:27940353

White matter damage and glymphatic dysfunction in a model of vascular dementia in rats with no prior vascular pathologies.

PubMed

Venkat, Poornima; Chopp, Michael; Zacharek, Alex; Cui, Chengcheng; Zhang, Li; Li, Qingjiang; Lu, Mei; Zhang, Talan; Liu, Amy; Chen, Jieli

2017-02-01

We investigated cognitive function, axonal/white matter (WM) changes and glymphatic function of vascular dementia using a multiple microinfarction (MMI) model in retired breeder (RB) rats. The MMI model induces significant (p < 0.05) cognitive decline that worsens with age starting at 2 weeks, which persists until at least 6 weeks after MMI. RB rats subjected to MMI exhibit significant axonal/WM damage identified by decreased myelin thickness, oligodendrocyte progenitor cell numbers, axon density, synaptic protein expression in the cortex and striatum, cortical neuronal branching, and dendritic spine density in the cortex and hippocampus compared with age-matched controls. MMI evokes significant dilation of perivascular spaces as well as water channel dysfunction indicated by decreased Aquaporin-4 expression around blood vessels. MMI-induced glymphatic dysfunction with delayed cerebrospinal fluid penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. The MMI model in RB rats decreases Aquaporin-4 and induces glymphatic dysfunction which may play an important role in MMI-induced axonal/WM damage and cognitive deficits. Copyright © 2016 Elsevier Inc. All rights reserved.

The effects of age, glucose ingestion and gluco-regulatory control on episodic memory.

PubMed

Riby, Leigh Martin; Meikle, Andrew; Glover, Cheryl

2004-09-01

Previous research has been inconclusive regarding the impact of glucose ingestion and gluco-regulatory control on cognitive performance in healthy older adults. The aim of this research was to determine whether glucose specifically enhanced episodic memory in an older population. In addition, the link between individual differences in glucose regulation and the magnitude of the enhancement effect was examined. A within subjects, counterbalanced, crossover design was used with 20 participants (60-80 year olds), each serving as his/her control. Episodic memory was tested by presenting unrelated paired associates followed by immediate and delayed cued recall, and delayed recognition, under single and dual task conditions. In addition, a battery of cognitive tests was administered, including tests of semantic memory, working memory and speed of processing. Glucose ingestion was found to largely facilitate performance of episodic memory. Furthermore, subsidiary analyses found that gluco-regulatory efficiency predicted episodic memory performance in both control and glucose conditions. A boost in performance after glucose ingestion was particularly seen in the episodic memory domain. Notably, strong evidence was provided for the utility of gluco-regulatory control measures as indicators of cognitive decline in the elderly.

Grey matter damage and overall cognitive impairment in primary progressive multiple sclerosis.

PubMed

Tur, C; Penny, S; Khaleeli, Z; Altmann, D R; Cipolotti, L; Ron, M; Thompson, A J; Ciccarelli, O

2011-11-01

To identify associations between cognitive impairment and imaging measures in a cross-sectional study of patients with primary progressive multiple sclerosis (PPMS). Neuropsychological tests were administered to 27 patients with PPMS and 31 controls. Patients underwent brain conventional magnetic resonance imaging (MRI) sequences, volumetric scans and magnetization transfer (MT) imaging; MT ratio (MTR) parameters, grey matter (GM) and normal-appearing white matter (NAWM) volumes, and WM T2 lesion load (T2LL) were obtained. In patients, multiple linear regression models identified the imaging measure associated with the abnormal cognitive tests independently from the other imaging variables. Partial correlation coefficients (PCC) were reported. Patients performed worse on tests of attention/speed of visual information processing, delayed verbal memory, and executive function, and had a worse overall cognitive performance index, when compared with controls. In patients, a lower GM peak location MTR was associated with worse overall cognitive performance (p < 0.001, PCC = 0.77). GM mean and peak height MTR showed the strongest association with the estimated verbal intelligence quotient (IQ) decline (p < 0.001, PCC = -0.62), and executive function (p < 0.001, PCC = 0.79). NAWM volume was associated with attention/speed of visual information processing (p < 0.001, PCC = 0.74), while T2LL was associated with delayed verbal memory (p = 0.007, PCC = -0.55). The finding of strong associations between GM MTR, NAWM volume and T2LL and specific cognitive impairments suggests that models that predict cognitive impairment in PPMS should include comprehensive MRI assessments of both GM and WM. However, GM MTR appears to be the main correlate of overall cognitive dysfunction, underlining the role of abnormal GM integrity in determining cognitive impairment in PPMS.

Longitudinal evaluation of criteria for subjective cognitive decline and preclinical Alzheimer's disease in a memory clinic sample.

PubMed

Eckerström, Marie; Göthlin, Mattias; Rolstad, Sindre; Hessen, Erik; Eckerström, Carl; Nordlund, Arto; Johansson, Boo; Svensson, Johan; Jonsson, Michael; Sacuiu, Simona; Wallin, Anders

2017-01-01

Subjective cognitive decline (SCD) and biomarker-based "at-risk" concepts such as "preclinical" Alzheimer's disease (AD) have been developed to predict AD dementia before objective cognitive impairment is detectable. We longitudinally evaluated cognitive outcome when using these classifications. Memory clinic patients ( n  = 235) were classified as SCD ( n  = 122): subtle cognitive decline ( n  = 36) and mild cognitive impairment ( n  = 77) and subsequently subclassified into SCDplus and National Institute on Aging-Alzheimer's Association (NIA-AA) stages 0 to 3. Mean (standard deviation) follow-up time was 48 (35) months. Proportion declining cognitively and prognostic accuracy for cognitive decline was calculated for all classifications. Among SCDplus patients, 43% to 48% declined cognitively. Among NIA-AA stage 1 to 3 patients, 50% to 100% declined cognitively. The highest positive likelihood ratios (+LRs) for subsequent cognitive decline (+LR 6.3), dementia (+LR 3.4), and AD dementia (+LR 6.5) were found for NIA-AA stage 2. In a memory clinic setting, NIA-AA stage 2 seems to be the most successful classification in predicting objective cognitive decline, dementia, and AD dementia.

Spatial discrimination deficits as a function of mnemonic interference in aged adults with and without memory impairment.

PubMed

Reagh, Zachariah M; Roberts, Jared M; Ly, Maria; DiProspero, Natalie; Murray, Elizabeth; Yassa, Michael A

2014-03-01

It is well established that aging is associated with declines in episodic memory. In recent years, an emphasis has emerged on the development of behavioral tasks and the identification of biomarkers that are predictive of cognitive decline in healthy as well as pathological aging. Here, we describe a memory task designed to assess the accuracy of discrimination ability for the locations of objects. Object locations were initially encoded incidentally, and appeared in a single space against a 5 × 7 grid. During retrieval, subjects viewed repeated object-location pairings, displacements of 1, 2, 3, or 4 grid spaces, and maximal corner-to-opposite-corner displacements. Subjects were tasked with judging objects in this second viewing as having retained their original location, or having moved. Performance on a task such as this is thought to rely on the capacity of the individual to perform hippocampus-mediated pattern separation. We report a performance deficit associated with a physically healthy aged group compared to young adults specific to trials with low mnemonic interference. Additionally, for aged adults, performance on the task was correlated with performance on the delayed recall portion of the Rey Auditory Verbal Learning Test (RAVLT), a neuropsychological test sensitive to hippocampal dysfunction. In line with prior work, dividing the aged group into unimpaired and impaired subgroups based on RAVLT Delayed Recall scores yielded clearly distinguishable patterns of performance, with the former subgroup performing comparably to young adults, and the latter subgroup showing generally impaired memory performance even with minimal interference. This study builds on existing tasks used in the field, and contributes a novel paradigm for differentiation of healthy from possible pathological aging, and may thus provide an avenue for early detection of age-related cognitive decline. Copyright © 2013 Wiley Periodicals, Inc.

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

Exercise, cognitive function, and aging

PubMed Central

2015-01-01

Increasing the lifespan of a population is often a marker of a country's success. With the percentage of the population over 65 yr of age expanding, managing the health and independence of this population is an ongoing concern. Advancing age is associated with a decrease in cognitive function that ultimately affects quality of life. Understanding potential adverse effects of aging on brain blood flow and cognition may help to determine effective strategies to mitigate these effects on the population. Exercise may be one strategy to prevent or delay cognitive decline. This review describes how aging is associated with cardiovascular disease risks, vascular dysfunction, and increasing Alzheimer's disease pathology. It will also discuss the possible effects of aging on cerebral vascular physiology, cerebral perfusion, and brain atrophy rates. Clinically, these changes will present as reduced cognitive function, neurodegeneration, and the onset of dementia. Regular exercise has been shown to improve cognitive function, and we hypothesize that this occurs through beneficial adaptations in vascular physiology and improved neurovascular coupling. This review highlights the potential interactions and ideas of how the age-associated variables may affect cognition and may be moderated by regular exercise. PMID:26031719

Exercise improves cognitive function in aging patients

PubMed Central

Hu, Jian-Ping; Guo, Yan-Hua; Wang, Feng; Zhao, Xin-Ping; Zhang, Quan-Hai; Song, Qing-Hua

2014-01-01

A decline in cognitive ability commonly occurs among older individuals. This study sought to explore the restorative effects of exercise in older patients with existing cognitive disabilities. Ninety-six patients with mild cognitive impairment were placed in an exercise program for six months. Following completion of the program, participants were assessed via the Chinese Mini Mental Status Examination (MMSE), Activity of Daily Living (ADL) assessment, and body movement testing and compared to a control group of patients with mild cognitive impairment who did not participate in the exercise program (N = 102). Statistical analyses were performed using the Student’s t-test and chi-square test to compare results between groups. Compared with control group, patients who exercised showed improved cognitive function in immediate memory (p < 0.001) and delayed recall (p = 0.004) function. In addition, activities associated with daily living showed improvement (p < 0.001), as did body movement (p < 0.05), arm stability (p < 0.001), and the appearance of rotation (p < 0.05). Based on these results, we conclude that participation in an exercise program can improve patients’ cognitive function, physical abilities, and body movement capacity. PMID:25419345

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.

Delayed-onset dementia after stroke or transient ischemic attack.

PubMed

Mok, Vincent C T; Lam, Bonnie Y K; Wang, Zhaolu; Liu, Wenyan; Au, Lisa; Leung, Eric Y L; Chen, Sirong; Yang, Jie; Chu, Winnie C W; Lau, Alexander Y L; Chan, Anne Y Y; Shi, Lin; Fan, Florence; Ma, Sze H; Ip, Vincent; Soo, Yannie O Y; Leung, Thomas W H; Kwok, Timothy C Y; Ho, Chi L; Wong, Lawrence K S; Wong, Adrian

2016-11-01

Patients surviving stroke without immediate dementia are at high risk of delayed-onset dementia. Mechanisms underlying delayed-onset dementia are complex and may involve vascular and/or neurodegenerative diseases. Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA. Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of ≥3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD. Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group. Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Cognitive and Adaptive Functioning after Liver Transplantation for Maple Syrup Urine Disease: A Case Series

PubMed Central

Shellmer, D. A.; Dabbs, A. DeVito; Dew, M. A.; Noll, R. B.; Feldman, H.; Strauss, K.; Morton, D. H.; Vockley, G.; Mazariegos, G. V.

2011-01-01

MSUD is a complex metabolic disorder that has been associated with central nervous system damage, developmental delays, and neurocognitive deficits. Although liver transplantation provides a metabolic cure for MSUD, changes in cognitive and adaptive functioning following transplantation have not been investigated. In this report we present data from 14 patients who completed cognitive and adaptive functioning testing pre- and one year and/or three years post-liver transplantation. Findings show either no significant change or improvement in IQ scores pre- to post-liver transplantation. Greater variability was observed in adaptive functioning scores, but the majority of patients evidenced either no significant change or improvement in adaptive scores. In general, findings may indicate that liver transplantation curtails additional central nervous system damage and neurocognitive decline providing an opportunity for stabilization or improvement in functioning. PMID:20946191

Short-term testosterone manipulations do not affect cognition or motor function but differentially modulate emotions in young and older male rhesus monkeys.

PubMed

Kelly, Brian; Maguire-Herring, Vanessa; Rose, Christian M; Gore, Heather E; Ferrigno, Stephen; Novak, Melinda A; Lacreuse, Agnès

2014-11-01

Human aging is characterized by declines in cognition and fine motor function as well as improved emotional regulation. In men, declining levels of testosterone (T) with age have been implicated in the development of these age-related changes. However, studies examining the effects of T replacement on cognition, emotion and fine motor function in older men have not provided consistent results. Rhesus monkeys (Macaca mulatta) are excellent models for human cognitive aging and may provide novel insights on this issue. We tested 10 aged intact male rhesus monkeys (mean age=19, range 15-25) on a battery of cognitive, motor and emotional tasks at baseline and under low or high T experimental conditions. Their performance was compared to that of 6 young males previously tested in the same paradigm (Lacreuse et al., 2009; Lacreuse et al., 2010). Following a 4-week baseline testing period, monkeys were treated with a gonadotropin releasing hormone agonist (Depot Lupron, 200 μg/kg) to suppress endogenous T and were tested on the task battery under a 4-week high T condition (injection of Lupron+T enanthate, 20 mg/kg, n=8) or 4-week low T condition (injection of Lupron+oil vehicle, n=8) before crossing over to the opposite treatment. The cognitive tasks consisted of the Delayed Non-Matching-to-Sample (DNMS), the Delayed Response (DR), and the Delayed Recognition Span Test (spatial-DRST). The emotional tasks included an object Approach-Avoidance task and a task in which monkeys were played videos of unfamiliar conspecifics in different emotional context (Social Playbacks). The fine motor task was the Lifesaver task that required monkeys to remove a Lifesaver candy from rods of different complexity. T manipulations did not significantly affect visual recognition memory, working memory, reference memory or fine motor function at any age. In the Approach-Avoidance task, older monkeys, but not younger monkeys, spent more time in proximity of novel objects in the high T condition relative to the low T condition. In both age groups, high T increased watching time of threatening social stimuli in the Social Playbacks. These results suggest that T affects some aspects of emotional processing but has no effect on fine motor function or cognition in young or older male macaques. It is possible that the duration of T treatment was not long enough to affect cognition or fine motor function or that T levels were too high to improve these outcomes. An alternative explanation for the discrepancies of our findings with some of the cognitive and emotional effects of T reported in rodents and humans may be the use of a chemical castration, which reduced circulating gonadotropins in addition to T. Further studies will investigate whether the luteinizing hormone LH mediates the effects of T on brain function in male primates. Copyright © 2014 Elsevier Inc. All rights reserved.

Neuroinflammation and brain atrophy in former NFL players: An in vivo multimodal imaging pilot study.

PubMed

Coughlin, Jennifer M; Wang, Yuchuan; Munro, Cynthia A; Ma, Shuangchao; Yue, Chen; Chen, Shaojie; Airan, Raag; Kim, Pearl K; Adams, Ashley V; Garcia, Cinthya; Higgs, Cecilia; Sair, Haris I; Sawa, Akira; Smith, Gwenn; Lyketsos, Constantine G; Caffo, Brian; Kassiou, Michael; Guilarte, Tomas R; Pomper, Martin G

2015-02-01

There are growing concerns about potential delayed, neuropsychiatric consequences (e.g, cognitive decline, mood or anxiety disorders) of sports-related traumatic brain injury (TBI). Autopsy studies of brains from a limited number of former athletes have described characteristic, pathologic changes of chronic traumatic encephalopathy (CTE) leading to questions about the relationship between these pathologic and the neuropsychiatric disturbances seen in former athletes. Research in this area will depend on in vivo methods that characterize molecular changes in the brain, linking CTE and other sports-related pathologies with delayed emergence of neuropsychiatric symptoms. In this pilot project we studied former National Football League (NFL) players using new neuroimaging techniques and clinical measures of cognitive functioning. We hypothesized that former NFL players would show molecular and structural changes in medial temporal and parietal lobe structures as well as specific cognitive deficits, namely those of verbal learning and memory. We observed a significant increase in binding of [(11)C]DPA-713 to the translocator protein (TSPO), a marker of brain injury and repair, in several brain regions, such as the supramarginal gyrus and right amygdala, in 9 former NFL players compared to 9 age-matched, healthy controls. We also observed significant atrophy of the right hippocampus. Finally, we report that these same former players had varied performance on a test of verbal learning and memory, suggesting that these molecular and pathologic changes may play a role in cognitive decline. These results suggest that localized brain injury and repair, indicated by increased [(11)C]DPA-713 binding to TSPO, may be linked to history of NFL play. [(11)C]DPA-713 PET is a promising new tool that can be used in future study design to examine further the relationship between TSPO expression in brain injury and repair, selective regional brain atrophy, and the potential link to deficits in verbal learning and memory after NFL play. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Cognitive and physical training for the elderly: evaluating outcome efficacy by means of neurophysiological synchronization.

PubMed

Frantzidis, Christos A; Ladas, Aristea-Kiriaki I; Vivas, Ana B; Tsolaki, Magda; Bamidis, Panagiotis D

2014-07-01

Recent neuroscientific research has demonstrated that both healthy and pathological aging induces alterations in the co-operative capacity of neuronal populations in the brain. Both compensatory and neurodegenerative mechanisms contribute to neurophysiological synchronization patterns, which provide a valuable marker for age-related cognitive decline. In this study, we propose that neuroplasticity-based training may facilitate coherent interaction of distant brain regions and consequently enhance cognitive performance in elderly people. If this is true, this would make neurophysiological synchronization a valid outcome measure to assess the efficacy of non-pharmacological interventions to prevent or delay age-related cognitive decline. The present study aims at providing an objective, synchronization-based tool to assess cognitive and/or physical interventions, adopting the notion of Relative Wavelet Entropy. This mathematical model employs a robust and parameter-free synchronization metric. By using data mining techniques, a distance value was computed for all participants so as to quantify the proximity of their individual profile to the mean group synchronization increase. In support of our hypothesis, results showed a significant increase in synchronization, for four electrode pairs, in the intervention group as compared to the active control group. It is concluded that the novel introduction of neurophysiological synchronization features could be used as a valid and reliable outcome measure; while the distance-based analysis could provide a reliable means of evaluating individual benefits. Copyright © 2014 Elsevier B.V. All rights reserved.

Activating Developmental Reserve Capacity Via Cognitive Training or Non-invasive Brain Stimulation: Potentials for Promoting Fronto-Parietal and Hippocampal-Striatal Network Functions in Old Age

PubMed Central

Passow, Susanne; Thurm, Franka; Li, Shu-Chen

2017-01-01

Existing neurocomputational and empirical data link deficient neuromodulation of the fronto-parietal and hippocampal-striatal circuitries with aging-related increase in processing noise and declines in various cognitive functions. Specifically, the theory of aging neuronal gain control postulates that aging-related suboptimal neuromodulation may attenuate neuronal gain control, which yields computational consequences on reducing the signal-to-noise-ratio of synaptic signal transmission and hampering information processing within and between cortical networks. Intervention methods such as cognitive training and non-invasive brain stimulation, e.g., transcranial direct current stimulation (tDCS), have been considered as means to buffer cognitive functions or delay cognitive decline in old age. However, to date the reported effect sizes of immediate training gains and maintenance effects of a variety of cognitive trainings are small to moderate at best; moreover, training-related transfer effects to non-trained but closely related (i.e., near-transfer) or other (i.e., far-transfer) cognitive functions are inconsistent or lacking. Similarly, although applying different tDCS protocols to reduce aging-related cognitive impairments by inducing temporary changes in cortical excitability seem somewhat promising, evidence of effects on short- and long-term plasticity is still equivocal. In this article, we will review and critically discuss existing findings of cognitive training- and stimulation-related behavioral and neural plasticity effects in the context of cognitive aging, focusing specifically on working memory and episodic memory functions, which are subserved by the fronto-parietal and hippocampal-striatal networks, respectively. Furthermore, in line with the theory of aging neuronal gain control we will highlight that developing age-specific brain stimulation protocols and the concurrent applications of tDCS during cognitive training may potentially facilitate short- and long-term cognitive and brain plasticity in old age. PMID:28280465

Cognition and Vascular Risk Factors: An Epidemiological Study

PubMed Central

Vicario, Augusto; Del Sueldo, Mildren; Fernández, Ruth A.; Enders, Julio; Zilberman, Judith; Cerezo, Gustavo H.

2012-01-01

We conducted an epidemiological approach to identify the negative impact of the vascular risk factors (such as hypertension, diabetes and hypercholesterolemia) over cognition. The interesting aspect of this study was that the survey was conducted in all age groups through a voluntary call (n = 1365; ≥18 years old, both sexes; age 49 ± 15 y, female 75.7%). Thus, we demonstrated that the use of a Minimum Cognitive Examination (MCE), a brief, simple, and easy managed neuropsychological evaluation, detected a greater number of people with cognitive decline surpassing to the Minimal Mental Statement Examination alone (14.5% of the participants showed MMSE ≤24, 34,6% showed dys-executive function, and 45,8% memory impairment. Out of the 4 studied RF, the only one that was not related to cognitive impairment was dyslipemia. Finally, we noted the importance of cognitive state early detection in all age groups, even in the youngest group. Acting in the middle of the life stages, we can prevent or delay the onset of a disease in adults, nowadays incurable: dementia. PMID:22988488

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.

Practice Effects on Story Memory and List Learning Tests in the Neuropsychological Assessment of Older Adults

PubMed Central

Gurnani, Ashita S.; Saurman, Jessica L.; Chapman, Kimberly R.; Steinberg, Eric G.; Martin, Brett; Chaisson, Christine E.; Mez, Jesse; Tripodis, Yorghos; Stern, Robert A.

2016-01-01

Two of the most commonly used methods to assess memory functioning in studies of cognitive aging and dementia are story memory and list learning tests. We hypothesized that the most commonly used story memory test, Wechsler's Logical Memory, would generate more pronounced practice effects than a well validated but less common list learning test, the Neuropsychological Assessment Battery (NAB) List Learning test. Two hundred eighty-seven older adults, ages 51 to 100 at baseline, completed both tests as part of a larger neuropsychological test battery on an annual basis. Up to five years of recall scores from participants who were diagnosed as cognitively normal (n = 96) or with mild cognitive impairment (MCI; n = 72) or Alzheimer's disease (AD; n = 121) at their most recent visit were analyzed with linear mixed effects regression to examine the interaction between the type of test and the number of times exposed to the test. Other variables, including age at baseline, sex, education, race, time (years) since baseline, and clinical diagnosis were also entered as fixed effects predictor variables. The results indicated that both tests produced significant practice effects in controls and MCI participants; in contrast, participants with AD declined or remained stable. However, for the delayed—but not the immediate—recall condition, Logical Memory generated more pronounced practice effects than NAB List Learning (b = 0.16, p < .01 for controls). These differential practice effects were moderated by clinical diagnosis, such that controls and MCI participants—but not participants with AD—improved more on Logical Memory delayed recall than on delayed NAB List Learning delayed recall over five annual assessments. Because the Logical Memory test is ubiquitous in cognitive aging and neurodegenerative disease research, its tendency to produce marked practice effects—especially on the delayed recall condition—suggests a threat to its validity as a measure of new learning, an essential construct for dementia diagnosis. PMID:27711147

Improved Memory Function 12 Weeks after Bariatric Surgery

PubMed Central

Gunstad, John; Strain, Gladys; Devlin, Michael J.; Wing, Rena; Cohen, Ronald A.; Paul, Robert H.; Crosby, Ross D.; Mitchell, James E.

2010-01-01

Background There is growing evidence that obesity is associated with poor neurocognitive outcome. Bariatric surgery is an effective intervention for morbid obesity and improves many comorbid medical conditions that are associated with cognitive dysfunction. The effects of bariatric surgery on cognition are unknown. Methods Prospective study total of 150 individuals (109 bariatric surgery patients enrolled in the Longitudinal Assessment of Bariatric Surgery (LABS) project and 41 obese controls that did not undergo surgery) completed cognitive evaluation at baseline and 12 week follow-up. Demographic, medical, and psychosocial information was also collected to elucidate possible mechanisms of change. Results Many bariatric surgery patients exhibited impaired performance on cognitive testing at baseline (range from 4.6%–23.9%). However, surgery patients were no more likely to exhibit decline on two or more cognitive tests at 12-week follow-up than obese controls [12.84% vs. 23.26%; χ2 (1) = 2.51, p = .11]. Group comparisons using repeated measures MANOVA showed surgery patients had improved memory performance at 12 week follow-up [λ = .86, F(4, 147) = 5.88, p<.001], whereas obese controls actually declined. Regression analyses showed surgery patients without hypertension had better short delay recall at 12 weeks than those that did [β = 0.31, p = .005], though other demographic and medical variables were largely unrelated to test performance. Conclusion The current results suggest that cognitive impairment is common in bariatric surgery patients, though these deficits may be at least partly reversible. Future studies are needed to clarify underlying mechanisms, particularly longitudinal studies employing neuroimaging and blood markers. PMID:21145295

The Continuing Benefits of Education: Adult Education and Midlife Cognitive Ability in the British 1946 Birth Cohort

PubMed Central

Hatch, Stephani L.; Feinstein, Leon; Link, Bruce G.; Wadsworth, Michael E. J.; Richards, Marcus

2007-01-01

Objectives. Evidence shows education positively impacts cognitive ability. However, researchers have given little attention to the potential impact of adult education on cognitive ability, still malleable in midlife. The primary study aim was to examine whether there were continuing effects of education over the life course on midlife cognitive ability. Methods. This study used data from the Medical Research Council National Survey of Health and Development, also known as the British 1946 birth cohort, and multivariate regression to estimate the continuing effects of adult education on multiple measures of midlife cognitive ability. Results. Educational attainment completed by early adulthood was associated with all measures of cognitive ability in late midlife. The continued effect of education was apparent in the associations between adult education and higher verbal ability, verbal memory, and verbal fluency in late midlife. We found no association between adult education and mental speed and concentration. Discussion. Associations between adult education and midlife cognitive ability indicate wider benefits of education to health that may be important for social integration, well-being, and the delay of cognitive decline in later life. PMID:18079429

Memory consolidation in aging and MCI after 1 week

PubMed Central

Walsh, Christine M; Wilkins, Sarah; Bettcher, Brianne Magouirk; Butler, Christopher R; Miller, Bruce L; Kramer, Joel H

2014-01-01

Objective To assess consolidation in amnestic mild cognitive (aMCI) impairment, controlling for differences in initial learning and using a protracted delay period for recall. Methods Fifteen individuals with MCI were compared to fifteen healthy older adult controls on a story learning task. Subjects were trained to criteria to equalize initial learning across subjects. Recall was tested at both the 30-minute typically used delay and a 1-week delay used to target consolidation. Results Using repeated measures ANOVAs adjusted for age, we found group × time point interactions across the entire task between the final trial and 30-minute delay, and again between the 30-minute and 1-week delay periods, with MCI having greater declines in recall as compared to controls. Significant group main effects were also found, with MCI recalling less than controls. Conclusion Consolidation was impaired in aMCI as compared to controls. Our findings indicate that MCI-related performance typically measured at 30 minutes underestimates MCI-associated memory deficits. This is the first study to isolate consolidation by controlling for initial learning differences and using a protracted delay period to target consolidation in an MCI sample. PMID:24219610

Bilingualism as a protection against the onset of symptoms of dementia.

PubMed

Bialystok, Ellen; Craik, Fergus I M; Freedman, Morris

2007-01-28

This study examined the effect of lifelong bilingualism on maintaining cognitive functioning and delaying the onset of symptoms of dementia in old age. The sample was selected from the records of 228 patients referred to a Memory Clinic with cognitive complaints. The final sample consisted of 184 patients diagnosed with dementia, 51% of whom were bilingual. The bilinguals showed symptoms of dementia 4 years later than monolinguals, all other measures being equivalent. Additionally, the rate of decline in Mini-Mental State Examination (MMSE) scores over the 4 years subsequent to the diagnosis was the same for a subset of patients in the two groups, suggesting a shift in onset age with no change in rate of progression.

Implication of the nutritional and nonnutritional factors in the context of preservation of cognitive performance in patients with dementia/depression and Alzheimer disease.

PubMed

Aliev, Gjumrakch; Ashraf, Ghulam Md; Kaminsky, Yury G; Sheikh, Ishfaq Ahmed; Sudakov, Sergey K; Yakhno, Nikolay N; Benberin, Valery V; Bachurin, Sergey O

2013-11-01

It has been postulated that Alzheimer disease (AD) is a systemic process, which involves multiple pathophysiological factors. A combination of pharmacotherapy and nonpharmacological interventions has been proposed to treat AD and other dementia. The nonpharmacological interventions include but are not limited to increasing sensory input through physical and mental activities, in order to modify cerebral blood flow and implementing nutritional interventions such as diet modification and vitamins and nutraceuticals therapy to vitalize brain functioning. This article highlights the recent research findings regarding novel treatment strategies aimed at modifying natural course of the disease and delaying cognitive decline through simultaneous implementation of pharmacological and nonpharmacological modulators as standardized treatment protocols.

Delayed memory effects after intense stress in Special Forces candidates: exploring path processes between cortisol secretion and memory recall.

PubMed

Taverniers, John; Taylor, Marcus K; Smeets, Tom

2013-05-01

The aim of this paper is twofold. First, it explores delayed effects of high endogenously evoked cortisol concentrations on visuo-spatial declarative memory. Subsequently, it applies multiple mediation (MM) analyses to reveal path processes between stress and cognitive performance in a sample of 24 male Special Forces (SF) candidates (mean age = 27.0 years, SD = 4.1). The SF candidates were randomly assigned to a control (n = 12) or an intense stress group (n = 12), and cortisol secretion for the intense stress condition was triggered by a brusque 60 min prisoner of war exercise. Stress exposure provoked robust increases in cortisol concentrations and a significant decline in immediate recall performance, measured with the Rey-Osterrieth Complex Figure (ROCF). The relative retrieval differences in regard to the ROCF persisted even after a recovery period of 24 h, as both groups showed similar levels of memory decline over 24 h. Next, the study applied a MM design that involved distribution-independent asymptotic and resampling strategies to extend traditional bivariate analyses. MM results showed that ROCF performance was mediated by increases in cortisol concentrations. Considering the studied variables, the current analysis was the first to provide statistical support for the generally accepted thesis that cortisol secretion in itself, rather than subjective strain or the experimental treatment, affects cognitive performance. The revelation of such path processes is important because it establishes process identification and may refine existing paradigms.

An assessment of domain-general metacognitive responding in rhesus monkeys.

PubMed

Brown, Emily Kathryn; Templer, Victoria L; Hampton, Robert R

2017-02-01

Metacognition is the ability to monitor and control one's cognition. Monitoring may involve either public cues or introspection of private cognitive states. We tested rhesus monkeys (Macaca mulatta) in a series of generalization tests to determine which type of cues control metacognition. In Experiment 1, monkeys learned a perceptual discrimination in which a "decline-test" response allowed them to avoid tests and receive a guaranteed small reward. Monkeys declined more difficult than easy tests. In Experiments 2-4, we evaluated whether monkeys generalized this metacognitive responding to new perceptual tests. Monkeys showed a trend toward generalization in Experiments 2 & 3, and reliable generalization in Experiment 4. In Experiments 5 & 6, we presented the decline-test response in a delayed matching-to-sample task. Memory tests differed from perceptual tests in that the appearance of the test display could not control metacognitive responding. In Experiment 6, monkeys made prospective metamemory judgments before seeing the tests. Generalization across perceptual tests with different visual properties and mixed generalization from perceptual to memory tests provide provisional evidence that domain-general, private cues controlled metacognition in some monkeys. We observed individual differences in generalization, suggesting that monkeys differ in use of public and private metacognitive cues. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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.

Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease.

PubMed

Franzmeier, Nicolai; Düzel, Emrah; Jessen, Frank; Buerger, Katharina; Levin, Johannes; Duering, Marco; Dichgans, Martin; Haass, Christian; Suárez-Calvet, Marc; Fagan, Anne M; Paumier, Katrina; Benzinger, Tammie; Masters, Colin L; Morris, John C; Perneczky, Robert; Janowitz, Daniel; Catak, Cihan; Wolfsgruber, Steffen; Wagner, Michael; Teipel, Stefan; Kilimann, Ingo; Ramirez, Alfredo; Rossor, Martin; Jucker, Mathias; Chhatwal, Jasmeer; Spottke, Annika; Boecker, Henning; Brosseron, Frederic; Falkai, Peter; Fliessbach, Klaus; Heneka, Michael T; Laske, Christoph; Nestor, Peter; Peters, Oliver; Fuentes, Manuel; Menne, Felix; Priller, Josef; Spruth, Eike J; Franke, Christiana; Schneider, Anja; Kofler, Barbara; Westerteicher, Christine; Speck, Oliver; Wiltfang, Jens; Bartels, Claudia; Araque Caballero, Miguel Ángel; Metzger, Coraline; Bittner, Daniel; Weiner, Michael; Lee, Jae-Hong; Salloway, Stephen; Danek, Adrian; Goate, Alison; Schofield, Peter R; Bateman, Randall J; Ewers, Michael

2018-04-01

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer's disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer's disease, 55 controls from the Dominantly Inherited Alzheimer's Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer's disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer's disease and cerebrospinal fluid tau levels in sporadic Alzheimer's disease cases. In both autosomal dominant and sporadic Alzheimer's disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer's disease, a significant left frontal cortex connectivity × estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer's disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer's disease is at least partially attributable to higher left frontal cortex-hub connectivity.

Effects of Vitamin E on Cognitive Performance during Ageing and in Alzheimer’s Disease

PubMed Central

La Fata, Giorgio; Weber, Peter; Mohajeri, M. Hasan

2014-01-01

Vitamin E is an important antioxidant that primarily protects cells from damage associated with oxidative stress caused by free radicals. The brain is highly susceptible to oxidative stress, which increases during ageing and is considered a major contributor to neurodegeneration. High plasma vitamin E levels were repeatedly associated with better cognitive performance. Due to its antioxidant properties, the ability of vitamin E to prevent or delay cognitive decline has been tested in clinical trials in both ageing population and Alzheimer’s disease (AD) patients. The difficulty in performing precise and uniform human studies is mostly responsible for the inconsistent outcomes reported in the literature. Therefore, the benefit of vitamin E as a treatment for neurodegenerative disorders is still under debate. In this review, we focus on those studies that mostly have contributed to clarifying the exclusive function of vitamin E in relation to brain ageing and AD. PMID:25460513

Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: a systematic review.

PubMed

Panza, F; Solfrizzi, V; Barulli, M R; Bonfiglio, C; Guerra, V; Osella, A; Seripa, D; Sabbà, C; Pilotto, A; Logroscino, G

2015-03-01

A prolonged preclinical phase of more than two decades before the onset of dementia suggested that initial brain changes of Alzheimer's disease (AD) and the symptoms of advanced AD may represent a unique continuum. Given the very limited therapeutic value of drugs currently used in the treatment of AD and dementia, preventing or postponing the onset of AD and delaying or slowing its progression are becoming mandatory. Among possible reversible risk factors of dementia and AD, vascular, metabolic, and lifestyle-related factors were associated with the development of dementia and late-life cognitive disorders, opening new avenues for the prevention of these diseases. Among diet-associated factors, coffee is regularly consumed by millions of people around the world and owing to its caffeine content, it is the best known psychoactive stimulant resulting in heightened alertness and arousal and improvement of cognitive performance. Besides its short-term effect, some case-control and cross-sectional and longitudinal population-based studies evaluated the long-term effects on brain function and provided some evidence that coffee, tea, and caffeine consumption or higher plasma caffeine levels may be protective against cognitive impairment/decline and dementia. In particular, several cross-sectional and longitudinal population-based studies suggested a protective effect of coffee, tea, and caffeine use against late-life cognitive impairment/decline, although the association was not found in all cognitive domains investigated and there was a lack of a distinct dose-response association, with a stronger effect among women than men. The findings on the association of coffee, tea, and caffeine consumption or plasma caffeine levels with incident mild cognitive impairment and its progression to dementia were too limited to draw any conclusion. Furthermore, for dementia and AD prevention, some studies with baseline examination in midlife pointed to a lack of association, although other case-control and longitudinal population-based studies with briefer follow-up periods supported favourable effects of coffee, tea, and caffeine consumption against AD. Larger studies with longer follow-up periods should be encouraged, addressing other potential bias and confounding sources, so hopefully opening new ways for diet-related prevention of dementia and AD.

Older adults get episodic memory boosting from noninvasive stimulation of prefrontal cortex during learning

PubMed Central

Brambilla, Michela; Cobelli, Chiara; Cohen, Leonardo G.; Cotelli, Maria

2016-01-01

Episodic memory displays the largest degree of age-related decline, a process that is accelerated in pathological conditions such as amnestic mild cognitive impairment and Alzheimer's disease. Previous studies have shown that the left lateral prefrontal cortex (PFC) contributes to the encoding of episodic memories along the life span. The aim of this randomized, double-blind, placebo-controlled study was to test the hypothesis that anodal trascranial direct current stimulation (tDCS) over the left lateral PFC during the learning phase would enhance delayed recall of verbal episodic memories in elderly individuals. Older adults learned a list of words while receiving anodal or placebo (sham) tDCS. Memory recall was tested 48 hours and 1 month later. The results showed that anodal tDCS strengthened episodic memories, an effect indicated by enhanced delayed recall (48 hours) compared to placebo stimulation (Cohen's d effect size = 1.01). The observation that PFC-tDCS during learning can boost verbal episodic memory in the elderly opens up the possibility to design-specific neurorehabilitation protocols targeted to conditions that affect episodic memory such as mild cognitive impairment. PMID:26923418

A Neurophysiological Study of Semantic Processing in Parkinson's Disease.

PubMed

Angwin, Anthony J; Dissanayaka, Nadeeka N W; Moorcroft, Alison; McMahon, Katie L; Silburn, Peter A; Copland, David A

2017-01-01

Cognitive-linguistic impairments in Parkinson's disease (PD) have been well documented; however, few studies have explored the neurophysiological underpinnings of semantic deficits in PD. This study investigated semantic function in PD using event-related potentials. Eighteen people with PD and 18 healthy controls performed a semantic judgement task on written word pairs that were either congruent or incongruent. The mean amplitude of the N400 for new incongruent word pairs was similar for both groups, however the onset latency was delayed in the PD group. Further analysis of the data revealed that both groups demonstrated attenuation of the N400 for repeated incongruent trials, as well as attenuation of the P600 component for repeated congruent trials. The presence of N400 congruity and N400 repetition effects in the PD group suggests that semantic processing is generally intact, but with a slower time course as evidenced by the delayed N400. Additional research will be required to determine whether N400 and P600 repetition effects are sensitive to further cognitive decline in PD. (JINS, 2017, 23, 78-89).

A shift to glycolysis accompanies the inflammatory changes in PBMCs from individuals with an IQ-discrepant memory.

PubMed

Wolfe, Hannah; Hannigan, Caoimhe; O'Sullivan, Michael; Carroll, Liam Barry; Brennan, Sabina; Lawlor, Brian; Robertson, Ian H; Lynch, Marina

2018-04-15

Identification of a blood-based biomarker that can detect early cognitive decline presents a significant healthcare challenge. We prepared peripheral blood mononuclear cells (PBMCs) from individuals who had a poorer than predicted performance in their delayed recall performance on the Logical Memory II Subtest of the Wechsler Memory Scale (WMS) relative to their IQ estimated by the National Adult Reading Test (NART); we described these individuals as IQ-discrepant, compared with IQ-consistent, individuals. Stimulation with Aβ + LPS increased production of TNFα to a greater extent in cells from IQ-discrepant, compared with IQ-consistent, individuals. This was associated with a shift towards glycolysis and the evidence indicates that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)3 plays a role in driving glycolysis. A similar shift towards glycolysis was observed in MDMs prepared from IQ-discrepant, compared with IQ-consistent, individuals. The important finding here is that we have established an increased sensitivity to Aβ + LPS stimulation in PBMCs from individuals that under-perform on a memory task, relative to their estimated premorbid IQ, which may be an indicator of early cognitive decline. This may be a useful tool in determining the presence of early cognitive dysfunction. Copyright © 2018 Elsevier B.V. All rights reserved.

Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease.

PubMed

Cunnane, Stephen C; Courchesne-Loyer, Alexandre; St-Pierre, Valérie; Vandenberghe, Camille; Pierotti, Tyler; Fortier, Mélanie; Croteau, Etienne; Castellano, Christian-Alexandre

2016-03-01

Brain glucose uptake is impaired in Alzheimer's disease (AD). A key question is whether cognitive decline can be delayed if this brain energy defect is at least partly corrected or bypassed early in the disease. The principal ketones (also called ketone bodies), β-hydroxybutyrate and acetoacetate, are the brain's main physiological alternative fuel to glucose. Three studies in mild-to-moderate AD have shown that, unlike with glucose, brain ketone uptake is not different from that in healthy age-matched controls. Published clinical trials demonstrate that increasing ketone availability to the brain via moderate nutritional ketosis has a modest beneficial effect on cognitive outcomes in mild-to-moderate AD and in mild cognitive impairment. Nutritional ketosis can be safely achieved by a high-fat ketogenic diet, by supplements providing 20-70 g/day of medium-chain triglycerides containing the eight- and ten-carbon fatty acids octanoate and decanoate, or by ketone esters. Given the acute dependence of the brain on its energy supply, it seems reasonable that the development of therapeutic strategies aimed at AD mandates consideration of how the underlying problem of deteriorating brain fuel supply can be corrected or delayed. © 2016 New York Academy of Sciences.

Low intakes of carotene, vitamin B2 , pantothenate and calcium predict cognitive decline among elderly patients with diabetes mellitus: The Japanese Elderly Diabetes Intervention Trial.

PubMed

Araki, Atsushi; Yoshimura, Yukio; Sakurai, Takashi; Umegaki, Hiroyuki; Kamada, Chiemi; Iimuro, Satoshi; Ohashi, Yasuo; Ito, Hideki

2017-08-01

The present study aimed to examine whether nutrient intakes predicted cognitive decline among elderly patients with diabetes mellitus. This study evaluated data from a 6-year prospective follow up of 237 elderly patients (aged ≥65 years) with diabetes mellitus, and the associations of baseline nutrient intakes with cognitive decline. Cognitive decline was defined as a ≥2-point decrease in the Mini-Mental State Examination (MMSE) score. Intakes of food and nutrients were assessed using a validated food frequency questionnaire, and were compared between patients with cognitive decline and intact cognition. Analysis of covariance and logistic regression analysis were used to compare the changes in the MMSE score during the follow up among intake tertile groups for each nutrient. Compared with men with intact cognition, the men with cognitive decline had lower baseline intakes of calcium, vitamin A, vitamin B 2 , pantothenate, soluble fiber, green vegetables and milk. However, no significant associations between cognitive decline and nutrient intakes were observed among women. After adjusting for age, body mass index, glycated hemoglobin levels, history of severe hypoglycemia, previous stroke and baseline MMSE score, we found that cognitive decline was significantly associated with low intakes of carotene, vitamin B 2 , pantothenate, calcium and green vegetables. Multiple logistic regression analysis showed that intakes of nutrients and green vegetables predicted cognitive decline after adjusting for age, body mass index, glycated hemoglobin levels, baseline MMSE score, and incident stroke during the follow up. These findings suggest that sufficient intakes of carotene, vitamin B 2 , pantothenate, calcium and vegetables could help prevent cognitive decline among elderly men with diabetes mellitus. Geriatr Gerontol Int 2017; 17: 1168-1175. © 2016 Japan Geriatrics Society.

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.

A preclinical cognitive test battery to parallel the National Institute of Health Toolbox in humans: bridging the translational gap.

PubMed

Snigdha, Shikha; Milgram, Norton W; Willis, Sherry L; Albert, Marylin; Weintraub, S; Fortin, Norbert J; Cotman, Carl W

2013-07-01

A major goal of animal research is to identify interventions that can promote successful aging and delay or reverse age-related cognitive decline in humans. Recent advances in standardizing cognitive assessment tools for humans have the potential to bring preclinical work closer to human research in aging and Alzheimer's disease. The National Institute of Health (NIH) has led an initiative to develop a comprehensive Toolbox for Neurologic Behavioral Function (NIH Toolbox) to evaluate cognitive, motor, sensory and emotional function for use in epidemiologic and clinical studies spanning 3 to 85 years of age. This paper aims to analyze the strengths and limitations of animal behavioral tests that can be used to parallel those in the NIH Toolbox. We conclude that there are several paradigms available to define a preclinical battery that parallels the NIH Toolbox. We also suggest areas in which new tests may benefit the development of a comprehensive preclinical test battery for assessment of cognitive function in animal models of aging and Alzheimer's disease. Copyright © 2013 Elsevier Inc. All rights reserved.

A preclinical cognitive test battery to parallel the National Institute of Health Toolbox in humans: bridging the translational gap

PubMed Central

Snigdha, Shikha; Milgram, Norton W.; Willis, Sherry L.; Albert, Marylin; Weintraub, S.; Fortin, Norbert J.; Cotman, Carl W.

2013-01-01

A major goal of animal research is to identify interventions that can promote successful aging and delay or reverse age-related cognitive decline in humans. Recent advances in standardizing cognitive assessment tools for humans have the potential to bring preclinical work closer to human research in aging and Alzheimer’s disease. The National Institute of Health (NIH) has led an initiative to develop a comprehensive Toolbox for Neurologic Behavioral Function (NIH Toolbox) to evaluate cognitive, motor, sensory and emotional function for use in epidemiologic and clinical studies spanning 3 to 85 years of age. This paper aims to analyze the strengths and limitations of animal behavioral tests that can be used to parallel those in the NIH Toolbox. We conclude that there are several paradigms available to define a preclinical battery that parallels the NIH Toolbox. We also suggest areas in which new tests may benefit the development of a comprehensive preclinical test battery for assessment of cognitive function in animal models of aging and Alzheimer’s disease. PMID:23434040

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.

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.

Gait Rather Than Cognition Predicts Decline in Specific Cognitive Domains in Early Parkinson's Disease.

PubMed

Morris, Rosie; Lord, Sue; Lawson, Rachael A; Coleman, Shirley; Galna, Brook; Duncan, Gordon W; Khoo, Tien K; Yarnall, Alison J; Burn, David J; Rochester, Lynn

2017-11-09

Dementia is significant in Parkinson's disease (PD) with personal and socioeconomic impact. Early identification of risk is of upmost importance to optimize management. Gait precedes and predicts cognitive decline and dementia in older adults. We aimed to evaluate gait characteristics as predictors of cognitive decline in newly diagnosed PD. One hundred and nineteen participants recruited at diagnosis were assessed at baseline, 18 and 36 months. Baseline gait was characterized by variables that mapped to five domains: pace, rhythm, variability, asymmetry, and postural control. Cognitive assessment included attention, fluctuating attention, executive function, visual memory, and visuospatial function. Mixed-effects models tested independent gait predictors of cognitive decline. Gait characteristics of pace, variability, and postural control predicted decline in fluctuating attention and visual memory, whereas baseline neuropsychological assessment performance did not predict decline. This provides novel evidence for gait as a clinical biomarker for PD cognitive decline in early disease. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.

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.

Cognitively Engaging Activity Is Associated with Greater Cortical and Subcortical Volumes

PubMed Central

Seider, Talia R.; Fieo, Robert A.; O’Shea, Andrew; Porges, Eric C.; Woods, Adam J.; Cohen, Ronald A.

2016-01-01

As the population ages and dementia becomes a growing healthcare concern, it is increasingly important to identify targets for intervention to delay or attenuate cognitive decline. Research has shown that the most successful interventions aim at altering lifestyle factors. Thus, this study examined how involvement in physical, cognitive, and social activity is related to brain structure in older adults. Sixty-five adults (mean age = 71.4 years, standard deviation = 8.9) received the Community Healthy Activities Model Program for Seniors (CHAMPS), a questionnaire that polls everyday activities in which older adults may be involved, and also underwent structural magnetic resonance imaging. Stepwise regression with backward selection was used to predict weekly time spent in either social, cognitive, light physical, or heavy physical activity from the volume of one of the cortical or subcortical regions of interest (corrected by intracranial volume) as well as age, education, and gender as control variables. Regressions revealed that more time spent in cognitive activity was associated with greater volumes of all brain regions studied: total cortex (β = 0.289, p = 0.014), frontal (β = 0.276, p = 0.019), parietal (β = 0.305, p = 0.009), temporal (β = 0.275, p = 0.020), and occipital (β = 0.256, p = 0.030) lobes, and thalamus (β = 0.310, p = 0.010), caudate (β = 0.233, p = 0.049), hippocampus (β = 0.286, p = 0.017), and amygdala (β = 0.336, p = 0.004). These effects remained even after accounting for the positive association between cognitive activity and education. No other activity variable was associated with brain volumes. Results indicate that time spent in cognitively engaging activity is associated with greater cortical and subcortical brain volume. Findings suggest that interventions aimed at increasing levels of cognitive activity may delay cognitive consequences of aging and decrease the risk of developing dementia. PMID:27199740

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

Montmorency Tart cherries (Prunus cerasus L.) modulate vascular function acutely, in the absence of improvement in cognitive performance.

PubMed

Keane, K M; Haskell-Ramsay, C F; Veasey, R C; Howatson, G

2016-12-01

Cerebral blood volume and metabolism of oxygen decline as part of human ageing, and this has been previously shown to be related to cognitive decline. There is some evidence to suggest that polyphenol-rich foods can play an important role in delaying the onset or halting the progression of age-related health disorders such as CVD and Alzheimer's disease and to improve cognitive function. In the present study, an acute, placebo-controlled, double-blinded, cross-over, randomised Latin-square design study with a washout period of at least 14 d was conducted on twenty-seven, middle-aged (defined as 45-60 years) volunteers. Participants received either a 60 ml dose of Montmorency tart cherry concentrate (MC), which contained 68·0 (sd 0·26) mg cyanidin-3-glucoside/l, 160·75 (sd 0·55) mean gallic acid equivalent/l and 0·59 (sd 0·02) mean Trolox equivalent/l, respectively, or a placebo. Cerebrovascular responses, cognitive performance and blood pressure were assessed at baseline and 1, 2, 3 and 5 h following consumption. There were significant differences in concentrations of total Hb and oxygenated Hb during the task period 1 h after MC consumption (P≤0·05). Furthermore, MC consumption significantly lowered systolic blood pressure (P≤0·05) over a period of 3 h, with peak reductions of 6±2 mmHg at 1 h after MC consumption relative to the placebo. Cognitive function and mood were not affected. These results show that a single dose of MC concentrate can modulate certain variables of vascular function; however, this does not translate to improvements in cognition or mood.

Exposure to air pollution and cognitive functioning across the life course--A systematic literature review.

PubMed

Clifford, Angela; Lang, Linda; Chen, Ruoling; Anstey, Kaarin J; Seaton, Anthony

2016-05-01

Air pollution is associated with increased risk of respiratory, cardiovascular and cerebrovascular disease, but its association with cognitive functioning and impairment is unclear. The aim of this systematic review was to examine whether a relationship exists between these variables across the life course. We searched Web of Knowledge, Pubmed, SciVerse Scopus, CINAHL, PsychInfo and Science Direct up to October 2015 to identify studies that investigated the association between air pollution and performance on neurocognitive tests. Variations in exposure assessment and outcome measures make meta-analysis impossible. Thirty one studies published between 2006 and 2015, from the Americas (n=15), Asia (n=5) and Europe (n=11), met the criteria for inclusion. Many showed weak but quantified relationships between various air pollutants and cognitive function. Pollution exposure in utero has been associated with increased risk of neuro-developmental delay. Exposure in childhood has been inversely associated with neuro-developmental outcomes in younger children and with academic achievement and neurocognitive performance in older children. In older adults, air pollution has been associated with accelerated cognitive decline. The evidence to date is coherent in that exposure to a range of largely traffic-related pollutants has been associated with quantifiable impairment of brain development in the young and cognitive decline in the elderly. There is insufficient evidence at present to comment on consistency, in view of the different indices of pollution and end-points measured, the limited number of studies, and the probability at this stage of publication bias. However, plausible toxicological mechanisms have been demonstrated and the evidence as a whole suggests that vehicular pollution, at least, contributes to cognitive impairment, adding to pressure on governments and individuals to continue to reduce air pollution. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Acute cocaine induced deficits in cognitive performance in rhesus macaque monkeys treated with baclofen

PubMed Central

Porrino, Linda J.; Hampson, Robert E.; Opris, Ioan; Deadwyler, Samuel A.

2013-01-01

Rationale Acute and/or chronic exposure to cocaine can affect cognitive performance, which may influence rate of recovery during treatment. Objective Effects of the GABA-B receptor agonist baclofen were assessed for potency to reverse the negative influence of acute, pre-session, intravenous (IV) injection of cocaine on cognitive performance in Macaca mulatta nonhuman primates. Methods Animals were trained to perform a modified delayed match to sample (DMS) task incorporating two types of trials with varying degrees of cognitive load that had different decision requirements in order to correctly utilize information retained over the delay interval. The effects of cocaine (0.2, 0.4, and 0.6 mg/kg, IV) alone and in combination with baclofen (0.29 and 0.40 mg/kg, IV) were examined with respect to sustained performance levels. Brain metabolic activity during performance of the task was assessed using PET imaged uptake of [18F]-fluorodeoxyglucose. Results Acute cocaine injections produced a dose-dependent decline in DMS performance selective for trials of high cognitive load. The GABA-receptor agonist baclofen, co-administered with cocaine, reversed task performance back to nondrug (saline IV) control levels. Simultaneous assessment of PET-imaged brain metabolic activity in prefrontal cortex (PFC) showed alterations by cocaine compared to PFC metabolic activation in nondrug (saline, IV) control DMS sessions, but like performance, PFC activation was returned to control levels by baclofen (0.40 mg/kg, IV) injected with cocaine. Conclusions The results show that baclofen, administered at a relatively high dose, reversed the cognitive deficits produced by acute cocaine intoxication that may have implications for use in chronic drug exposure. PMID:22836369

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

Predictors of parenting stress among Vietnamese mothers of young children with and without cognitive delay.

PubMed

Shin, Jin Y; Nhan, Nguyen Viet

2009-03-01

The study examined whether Vietnamese mothers of children with cognitive delay experienced more parenting stress compared to mothers of children without delay, and the factors that contribute to the parenting stress. The study sample included 225 mothers of children with and without cognitive delays from Hue City in Vietnam. The study protocol included mothers reporting on the scales of parenting stress and perceived social support, and on demographic questions. Mothers of children with cognitive delay experienced more stress. They were poorer and less educated, and perceived less social support. More mothers of these children had health issues. Having a child with cognitive delay was the strongest predictor of stress after controlling other demographic and psychosocial variables. Special education and early intervention services should be developed and available to educate the children with cognitive delay and support their mothers in Vietnam. Effective services also need to address their poverty and health care needs.

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.

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

Brain Health: The Importance of Recognizing Cognitive Impairment: An IAGG Consensus Conference

PubMed Central

Morley, John E.; Morris, John C.; Berg-Weger, Marla; Borson, Soo; Carpenter, Brian D.; del Campo, Natalia; Dubois, Bruno; Fargo, Keith; Fitten, L. Jaime; Flaherty, Joseph H.; Ganguli, Mary; Grossberg, George T.; Malmstrom, Theodore K.; Petersen, Ronald D.; Rodriguez, Carroll; Saykin, Andrew J.; Scheltens, Philip; Tangalos, Eric G.; Verghese, Joe; Wilcock, Gordon; Winblad, Bengt; Woo, Jean; Vellas, Bruno

2016-01-01

Cognitive impairment creates significant challenges for patients, their families and friends, and clinicians who provide their health care. Early recognition allows for diagnosis and appropriate treatment, education, psychosocial support, and engagement in shared decision-making regarding life planning, health care, involvement in research, and financial matters. An IAGG-GARN consensus panel examined the importance of early recognition of impaired cognitive health. Their major conclusion was that case-finding by physicians and health professionals is an important step toward enhancing brain health for aging populations throughout the world. This conclusion is in keeping with the position of the United States’ Centers for Medicare and Medicaid Services that reimburses for detection of cognitive impairment as part the of Medicare Annual Wellness Visit and with the international call for early detection of cognitive impairment as a patient’s right. The panel agreed on the following specific findings: (1) validated screening tests are available that take 3 to 7 minutes to administer; (2) a combination of patient- and informant-based screens is the most appropriate approach for identifying early cognitive impairment; (3) early cognitive impairment may have treatable components; and (4) emerging data support a combination of medical and lifestyle interventions as a potential way to delay or reduce cognitive decline. PMID:26315321

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

BioAge: Toward A Multi-Determined, Mechanistic Account of Cognitive Aging

PubMed Central

DeCarlo, Correne A.; Tuokko, Holly A.; Williams, Dorothy; Dixon, Roger A.; MacDonald, Stuart W.S.

2014-01-01

The search for reliable early indicators of age-related cognitive decline represents a critical avenue for progress in aging research. Chronological age is a commonly used developmental index; however, it offers little insight into the mechanisms underlying cognitive decline. In contrast, biological age (BioAge), reflecting the vitality of essential biological systems, represents a promising operationalization of developmental time. Current BioAge models have successfully predicted age-related cognitive deficits. Research on aging-related cognitive function indicates that the interaction of multiple risk and protective factors across the human lifespan confers individual risk for late-life cognitive decline, implicating a multi-causal explanation. In this review, we explore current BioAge models, describe three broad yet pathologically relevant biological processes linked to cognitive decline, and propose a novel operationalization of BioAge accounting for both moderating and causal mechanisms of cognitive decline and dementia. We argue that a multivariate and mechanistic BioAge approach will lead to a greater understanding of disease pathology as well as more accurate prediction and early identification of late-life cognitive decline. PMID:25278166

BioAge: toward a multi-determined, mechanistic account of cognitive aging.

PubMed

DeCarlo, Correne A; Tuokko, Holly A; Williams, Dorothy; Dixon, Roger A; MacDonald, Stuart W S

2014-11-01

The search for reliable early indicators of age-related cognitive decline represents a critical avenue for progress in aging research. Chronological age is a commonly used developmental index; however, it offers little insight into the mechanisms underlying cognitive decline. In contrast, biological age (BioAge), reflecting the vitality of essential biological systems, represents a promising operationalization of developmental time. Current BioAge models have successfully predicted age-related cognitive deficits. Research on aging-related cognitive function indicates that the interaction of multiple risk and protective factors across the human lifespan confers individual risk for late-life cognitive decline, implicating a multi-causal explanation. In this review, we explore current BioAge models, describe three broad yet pathologically relevant biological processes linked to cognitive decline, and propose a novel operationalization of BioAge accounting for both moderating and causal mechanisms of cognitive decline and dementia. We argue that a multivariate and mechanistic BioAge approach will lead to a greater understanding of disease pathology as well as more accurate prediction and early identification of late-life cognitive decline. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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

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.

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.

Cross-linked fibrin degradation products (D-dimer), plasma cytokines, and cognitive decline in community-dwelling elderly persons.

PubMed

Wilson, Craig J; Cohen, Harvey Jay; Pieper, Carl F

2003-10-01

To investigate the effect of coagulation and inflammatory pathway activation on future cognitive decline in older persons. Prospective cohort study. Rural and urban communities in North Carolina. Community-dwelling older people enrolled in the Duke Established Populations for Epidemiologic Studies of the Elderly in 1986. In 1992, blood was drawn for assay of D-dimer (1,723 subjects), Interleukin-6 (1,726 subjects), and other cytokines (1,551 subjects). Cognitive and functional assessments were performed in 1986, 1989, 1992, and 1996. Cognition was measured using the Short Portable Mental Status Questionnaire. Cognitive decline over a 4-year period was significantly correlated (P<.001) with D-dimer, age, race, and physical performance status as measured using the Rosow-Breslau and Nagi instruments. After controlling for demographics, functional status, and comorbidities, D-dimer remained predictive of cognitive decline. Proinflammatory cytokines were not associated with current cognitive status in cross-sectional analyses or with incident cognitive decline in prospective analyses. In a large sample of community-dwelling elders, higher levels of D-dimer were predictive of cognitive decline over a 4-year period. No clinically significant associations were found between age-related peripheral cytokine dysregulation and cognition.

Postural complexity influences development in infants born preterm with brain injury: relating perception-action theory to 3 cases.

PubMed

Dusing, Stacey C; Izzo, Theresa; Thacker, Leroy R; Galloway, James Cole

2014-10-01

Perception-action theory suggests a cyclical relationship between movement and perceptual information. In this case series, changes in postural complexity were used to quantify an infant's action and perception during the development of early motor behaviors. Three infants born preterm with periventricular white matter injury were included. Longitudinal changes in postural complexity (approximate entropy of the center of pressure), head control, reaching, and global development, measured with the Test of Infant Motor Performance and the Bayley Scales of Infant and Toddler Development, were assessed every 0.5 to 3 months during the first year of life. All 3 infants demonstrated altered postural complexity and developmental delays. However, the timing of the altered postural complexity and the type of delays varied among the infants. For infant 1, reduced postural complexity or limited action while learning to control her head in the midline position may have contributed to her motor delay. However, her ability to adapt her postural complexity eventually may have supported her ability to learn from her environment, as reflected in her relative cognitive strength. For infant 2, limited early postural complexity may have negatively affected his learning through action, resulting in cognitive delay. For infant 3, an increase in postural complexity above typical levels was associated with declining neurological status. Postural complexity is proposed as a measure of perception and action in the postural control system during the development of early behaviors. An optimal, intermediate level of postural complexity supports the use of a variety of postural control strategies and enhances the perception-action cycle. Either excessive or reduced postural complexity may contribute to developmental delays in infants born preterm with white matter injury. © 2014 American Physical Therapy Association.

Latent Class Analysis of Early Developmental Trajectory in Baby Siblings of Children with Autism

PubMed Central

Landa, Rebecca J.; Gross, Alden L.; Stuart, Elizabeth A.; Bauman, Margaret

2012-01-01

Background Siblings of children with autism (sibs-A) are at increased genetic risk for autism spectrum disorders (ASD) and milder impairments. To elucidate diversity and contour of early developmental trajectories exhibited by sibs-A, regardless of diagnostic classification, latent class modeling was used. Methods Sibs-A (n=204) were assessed with the Mullen Scales of Early Learning from age 6–36 months. Mullen T scores served as dependent variables. Outcome classifications at age 36 months included: ASD (n=52); non-ASD social/communication delay (broader autism phenotype; BAP) (n=31); and unaffected (n=121). Child-specific patterns of performance were studied using latent class growth analysis. Latent class membership was then related to diagnostic outcome through estimation of within-class proportions of children assigned to each diagnostic classification. Results A 4-class model was favored. Class 1 represented accelerated development and consisted of 25.7% of the sample, primarily unaffected children. Class 2 (40.0% of the sample), was characterized by normative development with above-average nonverbal cognitive outcome. Class 3 (22.3% of the sample) was characterized by receptive language, and gross and fine motor delay. Class 4 (12.0% of the sample), was characterized by widespread delayed skill acquisition, reflected by declining trajectories. Children with an outcome diagnosis of ASD were spread across Classes 2, 3, and 4. Conclusions Results support a category of ASD that involves slowing in early non-social development. Receptive language and motor development is vulnerable to early delay in sibs-A with and without ASD outcomes. Non-ASD sibs-A are largely distributed across classes depicting average or accelerated development. Developmental trajectories of motor, language, and cognition appear independent of communication and social delays in non-ASD sibs-A. PMID:22574686

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.

Effect of Nutrients, Dietary Supplements and Vitamins on Cognition: a Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Forbes, Scott C.; Holroyd-Leduc, Jayna M.; Poulin, Marc J.; Hogan, David B.

2015-01-01

Background Observational studies have suggested that various nutrients, dietary supplements, and vitamins may delay the onset of age-associated cognitive decline and dementia. We systematically reviewed recent randomized controlled trials investigating the effect of nutritional interventions on cognitive performance in older non-demented adults. Methods We searched MEDLINE, CINAHL, Embase, and the Cochrane Library for articles published between 2003 and 2013. We included randomized trials of ≥ 3 months’ duration that examined the cognitive effects of a nutritional intervention in non-demented adults > 40 years of age. Meta-analyses were done when sufficient trials were available. Results Twenty-four trials met inclusion criteria (six omega-3 fatty acids, seven B vitamins, three vitamin E, eight other interventions). In the meta-analyses, omega-3 fatty acids showed no significant effect on Mini-Mental State Examination (MMSE) scores (four trials, mean difference 0.06, 95% CI −0.08 – 0.19) or digit span forward (three trials, mean difference −0.02, 95% CI −0.30 – 0.25), while B vitamins showed no significant effect on MMSE scores (three trials, mean difference 0.02, 95% CI −0.22 – 0.25). None of the vitamin E studies reported significant effects on cognitive outcomes. Among the other nutritional interventions, statistically significant differences between the intervention and control groups on at least one cognitive domain were found in single studies of green tea extract, Concord grape juice, chromium picolinate, beta-carotene, two different combinations of multiple vitamins, and a dietary approach developed for the control of hypertension. Conclusions Omega-3 fatty acids, B vitamins, and vitamin E supplementation did not affect cognition in non-demented middle-aged and older adults. Other nutritional interventions require further evaluation before their use can be advocated for the prevention of age-associated cognitive decline and dementia. PMID:26740832

An innovative intervention for the treatment of cognitive impairment–Emisymmetric bilateral stimulation improves cognitive functions in Alzheimer’s disease and mild cognitive impairment: an open-label study

PubMed Central

Guerriero, Fabio; Botarelli, Emanuele; Mele, Gianni; Polo, Lorenzo; Zoncu, Daniele; Renati, Paolo; Sgarlata, Carmelo; Rollone, Marco; Ricevuti, Giovanni; Maurizi, Niccolo; Francis, Matthew; Rondanelli, Mariangela; Perna, Simone; Guido, Davide; Mannu, Piero

2015-01-01

Background and aims In the last decade, the development of different methods of brain stimulation by electromagnetic fields (EMF) provides a promising therapeutic tool for subjects with impaired cognitive functions. Emisymmetric bilateral stimulation (EBS) is a novel and innovative EMF brain stimulation, whose working principle is to introduce very weak noise-like stimuli through EMF to trigger self-arrangements in the cortex of treated subjects, thereby improving cognitive faculties. The aim of this pilot study was to investigate in patients with cognitive impairment the effectiveness of EBS treatment with respect to global cognitive function, episodic memory, and executive functions. Methods Fourteen patients with cognitive decline (six with mild cognitive impairment and eight with Alzheimer’s disease) underwent three EBS applications per week to both the cerebral cortex and auricular-specific sites for a total of 5 weeks. At baseline, after 2 weeks and 5 weeks, a neuropsychological assessment was performed through mini–mental state examination, free and cued selective reminding tests, and trail making test. As secondary outcomes, changes in behavior, functionality, and quality of life were also evaluated. Results After 5 weeks of standardized EBS therapy, significant improvements were observed in all neurocognitive assessments. Mini–mental state examination score significantly increased from baseline to end treatment (+3.19, P=0.002). Assessment of episodic memory showed an improvement both in immediate and delayed recalls (immediate recall =+7.57, P=0.003; delayed recall =+4.78, P<0.001). Executive functions significantly improved from baseline to end stimulation (trail making test A −53.35 seconds; P=0.001). Of note, behavioral disorders assessed through neuropsychiatric inventory significantly decreased (−28.78, P<0.001). The analysis concerning the Alzheimer’s disease and mild cognitive impairment group confirmed a significant improvement of cognitive functions and behavior after EBS treatment. Conclusion This pilot study has shown EBS to be a promising, effective, and safe tool to treat cognitive impairment, in addition to the drugs presently available. Further investigations and controlled clinical trials are warranted. PMID:26425094

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.

Longitudinal cognitive biomarkers predicting symptom onset in presymptomatic frontotemporal dementia.

PubMed

Jiskoot, Lize C; Panman, Jessica L; van Asseldonk, Lauren; Franzen, Sanne; Meeter, Lieke H H; Donker Kaat, Laura; van der Ende, Emma L; Dopper, Elise G P; Timman, Reinier; van Minkelen, Rick; van Swieten, John C; van den Berg, Esther; Papma, Janne M

2018-06-01

We performed 4-year follow-up neuropsychological assessment to investigate cognitive decline and the prognostic abilities from presymptomatic to symptomatic familial frontotemporal dementia (FTD). Presymptomatic MAPT (n = 15) and GRN mutation carriers (n = 31), and healthy controls (n = 39) underwent neuropsychological assessment every 2 years. Eight mutation carriers (5 MAPT, 3 GRN) became symptomatic. We investigated cognitive decline with multilevel regression modeling; the prognostic performance was assessed with ROC analyses and stepwise logistic regression. MAPT converters declined on language, attention, executive function, social cognition, and memory, and GRN converters declined on attention and executive function (p < 0.05). Cognitive decline in ScreeLing phonology (p = 0.046) and letter fluency (p = 0.046) were predictive for conversion to non-fluent variant PPA, and decline on categorical fluency (p = 0.025) for an underlying MAPT mutation. Using longitudinal neuropsychological assessment, we detected a mutation-specific pattern of cognitive decline, potentially suggesting prognostic value of neuropsychological trajectories in conversion to symptomatic FTD.

Unraveling the "new morbidity": adolescent parenting and developmental delays.

PubMed

Borkowski, J G; Whitman, T L; Passino, A W; Rellinger, E A; Sommer, K; Keogh, D

1992-01-01

Baumeister's concept of the "new morbidity" pertains to the linkages between poverty, adolescent mothers, and a series of developmental delays in their children. Outlined are three possible causes of the mild mental retardation and learning disabilities that are found disproportionately among the offspring of adolescents. First, there may be a direct genetic transmission of mild mental retardation. Second, adolescent mothers are likely to have a lack of support from a social network, be unprepared cognitively and emotionally to assume responsibility for child rearing, and to look to an infant to meet their own needs. Third, the interaction of genetic and environmental deficits leads to a parenting style that deprives the child of stimulation that could potentially overcome these deficits. A secure mother-infant attachment relationship provides the foundation for the development of social, emotional, attentional, and self-regulatory processes. When this attachment relationship is insecure, as a result of the mother's unreadiness to parent, the child cannot proceed to exploration of the environment--a critical component of cognitive development. If the infant has a difficult temperament, the risk of physical and emotional abuse increases, further compromising the child's future development. By 3 years of age, many of these children are showing declines in mental functioning, delays in receptive language skills, and poor motor and social skills. Research is urged to identify events in this chain that can be targeted for early intervention.

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…

Cognition and mortality in older people: the Sydney Memory and Ageing Study.

PubMed

Connors, Michael H; Sachdev, Perminder S; Kochan, Nicole A; Xu, Jing; Draper, Brian; Brodaty, Henry

2015-11-01

Both cognitive ability and cognitive decline have been shown to predict mortality in older people. As dementia, a major form of cognitive decline, has an established association with shorter survival, it is unclear the extent to which cognitive ability and cognitive decline predict mortality in the absence of dementia. To determine whether cognitive ability and decline in cognitive ability predict mortality in older individuals without dementia. The Sydney Memory and Ageing Study is an observational population-based cohort study. Participants completed detailed neuropsychological assessments and medical examinations to assess for risk factors such as depression, obesity, hypertension, diabetes, hypercholesterolaemia, smoking and physical activity. Participants were regularly assessed at 2-year intervals over 8 years. A community sample in Sydney, Australia. One thousand and thirty-seven elderly people without dementia. Overall, 236 (22.8%) participants died within 8 years. Both cognitive ability at baseline and decline in cognitive ability over 2 years predicted mortality. Decline in cognitive ability, but not baseline cognitive ability, was a significant predictor of mortality when depression and other medical risk factors were controlled for. These relationships also held when excluding incident cases of dementia. The findings indicate that decline in cognition is a robust predictor of mortality in older people without dementia at a population level. This relationship is not accounted for by co-morbid depression or other established biomedical risk factors. © 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.

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.

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 ...

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.

Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer’s disease

PubMed Central

Franzmeier, Nicolai; Düzel, Emrah; Jessen, Frank; Buerger, Katharina; Levin, Johannes; Duering, Marco; Dichgans, Martin; Haass, Christian; Suárez-Calvet, Marc; Fagan, Anne M; Paumier, Katrina; Benzinger, Tammie; Masters, Colin L; Morris, John C; Perneczky, Robert; Janowitz, Daniel; Catak, Cihan; Wolfsgruber, Steffen; Wagner, Michael; Teipel, Stefan; Kilimann, Ingo; Ramirez, Alfredo; Rossor, Martin; Jucker, Mathias; Chhatwal, Jasmeer; Spottke, Annika; Boecker, Henning; Brosseron, Frederic; Falkai, Peter; Fliessbach, Klaus; Heneka, Michael T; Laske, Christoph; Nestor, Peter; Peters, Oliver; Fuentes, Manuel; Menne, Felix; Priller, Josef; Spruth, Eike J; Franke, Christiana; Schneider, Anja; Kofler, Barbara; Westerteicher, Christine; Speck, Oliver; Wiltfang, Jens; Bartels, Claudia; Araque Caballero, Miguel Ángel; Metzger, Coraline; Bittner, Daniel; Weiner, Michael; Lee, Jae-Hong; Salloway, Stephen; Danek, Adrian; Goate, Alison; Schofield, Peter R; Bateman, Randall J; Ewers, Michael

2018-01-01

Abstract Patients with Alzheimer’s disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer’s pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer’s disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer’s disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer’s disease, 55 controls from the Dominantly Inherited Alzheimer’s Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer’s disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer’s disease and cerebrospinal fluid tau levels in sporadic Alzheimer’s disease cases. In both autosomal dominant and sporadic Alzheimer’s disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer’s disease, a significant left frontal cortex connectivity × estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer’s disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer’s disease is at least partially attributable to higher left frontal cortex-hub connectivity. PMID:29462334

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.

The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects memory performance in older adults.

PubMed

Azeredo, Lucas A de; De Nardi, Tatiana; Levandowski, Mateus L; Tractenberg, Saulo G; Kommers-Molina, Julia; Wieck, Andrea; Irigaray, Tatiana Q; Silva, Irênio G da; Grassi-Oliveira, Rodrigo

2017-01-01

Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF) is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR), delayed verbal recall (DVR), and memory retention rate. BDNF Met allele carriers had lower DVR scores (p = 0.004) and a decline in memory retention (p = 0.017) when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088). These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

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

Comparison of semantic and episodic memory BOLD fMRI activation in predicting cognitive decline in older adults.

PubMed

Hantke, Nathan; Nielson, Kristy A; Woodard, John L; Breting, Leslie M Guidotti; Butts, Alissa; Seidenberg, Michael; Carson Smith, J; Durgerian, Sally; Lancaster, Melissa; Matthews, Monica; Sugarman, Michael A; Rao, Stephen M

2013-01-01

Previous studies suggest that task-activated functional magnetic resonance imaging (fMRI) can predict future cognitive decline among healthy older adults. The present fMRI study examined the relative sensitivity of semantic memory (SM) versus episodic memory (EM) activation tasks for predicting cognitive decline. Seventy-eight cognitively intact elders underwent neuropsychological testing at entry and after an 18-month interval, with participants classified as cognitively "Stable" or "Declining" based on ≥ 1.0 SD decline in performance. Baseline fMRI scanning involved SM (famous name discrimination) and EM (name recognition) tasks. SM and EM fMRI activation, along with Apolipoprotein E (APOE) ε4 status, served as predictors of cognitive outcome using a logistic regression analysis. Twenty-seven (34.6%) participants were classified as Declining and 51 (65.4%) as Stable. APOE ε4 status alone significantly predicted cognitive decline (R(2) = .106; C index = .642). Addition of SM activation significantly improved prediction accuracy (R(2) = .285; C index = .787), whereas the addition of EM did not (R(2) = .212; C index = .711). In combination with APOE status, SM task activation predicts future cognitive decline better than EM activation. These results have implications for use of fMRI in prevention clinical trials involving the identification of persons at-risk for age-associated memory loss and Alzheimer's disease.

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

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.

Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease

PubMed Central

Wang, Fen; Gordon, Brian A.; Ryman, Davis C.; Ma, Shengmei; Xiong, Chengjie; Hassenstab, Jason; Goate, Alison; Fagan, Anne M.; Cairns, Nigel J.; Marcus, Daniel S.; McDade, Eric; Ringman, John M.; Graff-Radford, Neill R.; Ghetti, Bernardino; Farlow, Martin R.; Sperling, Reisa; Salloway, Steve; Schofield, Peter R.; Masters, Colin L.; Martins, Ralph N.; Rossor, Martin N.; Jucker, Mathias; Danek, Adrian; Förster, Stefan; Lane, Christopher A.S.; Morris, John C.; Bateman, Randall J.

2015-01-01

Objective: To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Methods: Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89–4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. Results: In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Conclusions: Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials. PMID:26245925

Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease.

PubMed

Wang, Fen; Gordon, Brian A; Ryman, Davis C; Ma, Shengmei; Xiong, Chengjie; Hassenstab, Jason; Goate, Alison; Fagan, Anne M; Cairns, Nigel J; Marcus, Daniel S; McDade, Eric; Ringman, John M; Graff-Radford, Neill R; Ghetti, Bernardino; Farlow, Martin R; Sperling, Reisa; Salloway, Steve; Schofield, Peter R; Masters, Colin L; Martins, Ralph N; Rossor, Martin N; Jucker, Mathias; Danek, Adrian; Förster, Stefan; Lane, Christopher A S; Morris, John C; Benzinger, Tammie L S; Bateman, Randall J

2015-09-01

To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89-4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials. © 2015 American Academy of Neurology.

Decline in word-finding: The objective cognitive finding most relevant to patients after mesial temporal lobe epilepsy surgery.

PubMed

Pauli, Carla; de Oliveira Thais, Maria Emilia Rodrigues; Guarnieri, Ricardo; Schwarzbold, Marcelo Liborio; Diaz, Alexandre Paim; Ben, Juliana; Linhares, Marcelo Neves; Markowitsch, Hans Joachim; Wolf, Peter; Wiebe, Samuel; Lin, Katia; Walz, Roger

2017-10-01

The purpose of this study was to investigate the following: i) the objective impairment in neuropsychological tests that were associated with the subjective perception of cognitive function decline in Brazilian patients who underwent mesial temporal lobe epilepsy (MTLE) surgery and ii) the predictive variables for those impaired objective neuropsychological tests. Forty-eight adults with MTLE (27 right HS and 23 male) were divided according to their perception of changes (Decline or No-decline) of cognitive function domain of the QOLIE-31 questionnaire applied before and 1year after the ATL. The mean (SD) of changes in the raw score difference of the neuropsychological tests before and after the ATL was compared between Decline and No-decline groups. Receiver Operating Characteristic curves, sensitivity, specificity, and predictive values were used to assess the optimum cutoff points of neuropsychological test score changes to predict patient-reported subjective cognitive decline. Six (12.5%) patients reported a perception of cognitive function decline after ATL. Among the 25 cognitive tests analyzed, only changes in the Boston Naming Test (BNT) were associated with subjective cognitive decline reported by patients. A reduction of ≥8 points in the raw score of BNT after surgery had 91% of sensitivity and 45% specificity for predicting subjective perception of cognitive function decline by the patient. Left side surgery and age older than 40years were more associated with an important BNT reduction with overall accuracy of 91.7%, 95% predictive ability for no impairment, and 75% for impairment of cognitive function. Impairment in word-finding seems to be the objective cognitive finding most relevant to Brazilian patients after mesial temporal lobe epilepsy surgery. Similar to American patients, the side of surgery and age are good predictors for no decline in the BNT, but shows a lower accuracy to predict its decline. If replicated in other populations, the results may have wider implications for the surgical management of patients with drug-resistant MTLE. Copyright © 2017 Elsevier Inc. All rights reserved.

Better verbal memory in women than men in MCI despite similar levels of hippocampal atrophy.

PubMed

Sundermann, Erin E; Biegon, Anat; Rubin, Leah H; Lipton, Richard B; Mowrey, Wenzhu; Landau, Susan; Maki, Pauline M

2016-04-12

To examine sex differences in the relationship between clinical symptoms related to Alzheimer disease (AD) (verbal memory deficits) and neurodegeneration (hippocampal volume/intracranial volume ratio [HpVR]) across AD stages. The sample included 379 healthy participants, 694 participants with amnestic mild cognitive impairment (aMCI), and 235 participants with AD and dementia from the Alzheimer's Disease Neuroimaging Initiative who completed the Rey Auditory Verbal Learning Test (RAVLT). Cross-sectional analyses were conducted using linear regression to examine the interaction between sex and HpVR on RAVLT across and within diagnostic groups adjusting for age, education, and APOE ε4 status. Across groups, there were significant sex × HpVR interactions for immediate and delayed recall (p < 0.01). Women outperformed men among individuals with moderate to larger HpVR, but not among individuals with smaller HpVR. In diagnosis-stratified analyses, the HpVR × sex interaction was significant in the aMCI group, but not in the control or AD dementia groups, for immediate and delayed recall (p < 0.01). Among controls, women outperformed men on both outcomes irrespective of HpVR (p < 0.001). In AD dementia, better RAVLT performance was independently associated with female sex (immediate, p = 0.04) and larger HpVR (delayed, p = 0.001). Women showed an advantage in verbal memory despite evidence of moderate hippocampal atrophy. This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages. © 2016 American Academy of Neurology.

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

No Effects of Non-invasive Brain Stimulation on Multiple Sessions of Object-Location-Memory Training in Healthy Older Adults.

PubMed

Külzow, Nadine; Cavalcanti de Sousa, Angelica Vieira; Cesarz, Magda; Hanke, Julie-Marie; Günsberg, Alida; Harder, Solvejg; Koblitz, Swantje; Grittner, Ulrike; Flöel, Agnes

2017-01-01

Object-location memory (OLM) is known to decline with normal aging, a process accelerated in pathological conditions like mild cognitive impairment (MCI). In order to maintain cognitive health and to delay the transition from healthy to pathological conditions, novel strategies are being explored. Tentative evidence suggests that combining cognitive training and anodal transcranial direct current stimulation (atDCS), both reported to induce small and often inconsistent behavioral improvements, could generate larger or more consistent improvements or both, compared to each intervention alone. Here, we explored the combined efficacy of these techniques on OLM. In a subject-blind sham-controlled cross-over design 32 healthy older adults underwent a 3-day visuospatial training paired with either anodal (20 min) or sham (30 s) atDCS (1 mA, temporoparietal). Subjects were asked to learn the correct object-location pairings on a street map, shown over five learning blocks on each training day. Acquisition performance was assessed by accuracy on a given learning block in terms of percentage of correct responses. Training success (performance on last training day) and delayed memory after 1-month were analyzed by mixed model analysis and were controlled for gender, age, education, sequence of stimulation and baseline performance. Exploratory analysis of atDCS effects on within-session (online) and between-session (offline) memory performance were conducted. Moreover, transfer effects on similar trained (visuospatial) and less similar (visuo-constructive, verbal) untrained memory tasks were explored, both immediately after training, and on follow-up. We found that atDCS paired with OLM-training did not enhance success in training or performance in 1-month delayed memory or transfer tasks. In sum, this study did not support the notion that the combined atDCS-training approach improves immediate or delayed OLM in older adults. However, specifics of the experimental design, and a non-optimal timing of atDCS between sessions might have masked beneficial effects and should be more systematically addressed in future studies.

Memory performance on the story recall test and prediction of cognitive dysfunction progression in mild cognitive impairment and Alzheimer's dementia.

PubMed

Park, Jong-Hwan; Park, Hyuntae; Sohn, Sang Wuk; Kim, Sungjae; Park, Kyung Won

2017-10-01

To determine the factors that influence diagnosis and differentiation of patients with mild cognitive impairment (MCI) and Alzheimer's dementia (AD) by comparing memory test results at baseline with those at 1-2-year follow up. We consecutively recruited 23 healthy participants, 44 MCI patients and 27 patients with very mild AD according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorder Association criteria for probable Alzheimer's disease and Petersen's clinical diagnostic criteria. We carried out detailed neuropsychological tests, including the Story Recall Test (SRT) and the Seoul Verbal Learning Test, for all participants. We defined study participants as the "progression group" as follows: (i) participants who showed conversion to dementia from the MCI state; and (ii) those with dementia who showed more than a three-point decrement in their Mini-Mental State Examination scores with accompanying functional decline from baseline status, which were ascertained by physician's clinical judgment. The SRT delayed recall scores were significantly lower in the patients with mild AD than in those with MCI and after progression. Lower (relative risk 1.1, 95% confidence interval 0.1-1.6) and higher SRT delayed recall scores (relative risk 2.1, confidence interval 1.0-2.8), and two-test combined immediate and delayed recall scores (relative risk 2.0, confidence interval 0.9-2.3; and relative risk 2.8, confidence interval 1.1-4.2, respectively) were independent predictors of progression in a stepwise multiple adjusted Cox proportional hazards model, with age, sex, depression and educational level forced into the model. The present study suggests that the SRT delayed recall score independently predicts progression to dementia in patients with MCI. Geriatr Gerontol Int 2017; 17: 1603-1609. © 2016 Japan Geriatrics Society.

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…

Predictors of Parenting Stress among Vietnamese Mothers of Young Children with and without Cognitive Delay

ERIC Educational Resources Information Center

Shin, Jin Y.; Nhan, Nguyen Viet

2009-01-01

Background: The study examined whether Vietnamese mothers of children with cognitive delay experienced more parenting stress compared to mothers of children without delay, and the factors that contribute to the parenting stress. Method: The study sample included 225 mothers of children with and without cognitive delays from Hue City in Vietnam.…

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.

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

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.

Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model

PubMed Central

Lockrow, Jason; Prakasam, Annamalai; Huang, Peng; Bimonte-Nelson, Heather; Sambamurti, Kumar; Granholm, Ann-Charlotte

2009-01-01

Down syndrome (DS) individuals develop several neuropathological hallmarks seen in Alzheimer's disease, including cognitive decline and the early loss of cholinergic markers in the basal forebrain. These deficits are replicated in the Ts65Dn mouse, which contains a partial trisomy of murine chromosome 16, the orthologous genetic segment to human chromosome 21. Oxidative stress levels are elevated early in DS, and may contribute to the neurodegeneration seen in these individuals. We evaluated oxidative stress in Ts65Dn mice, and assessed the efficacy of long-term antioxidant supplementation on memory and basal forebrain pathology. We report that oxidative stress was elevated in the adult Ts65Dn brain, and that supplementation with the antioxidant vitamin E effectively reduced these markers. Also, Ts65Dn mice receiving vitamin E exhibited improved performance on a spatial working memory task and showed an attenuation of cholinergic neuron pathology in the basal forebrain. This study provides evidence that vitamin E delays onset of cognitive and morphological abnormalities in a mouse model of DS, and may represent a safe and effective treatment early in the progression of DS neuropathology. PMID:19135442

Memory load as a cognitive antidote to performance decrements in data entry.

PubMed

Chapman, Mary J; Healy, Alice F; Kole, James A

2016-10-01

In two experiments, subjects trained in data entry, typing one 4-digit number at a time. At training, subjects either typed the numbers immediately after they appeared (immediate) or typed the previous number from memory while viewing the next number (delayed). In Experiment 2 stimulus presentation time was limited and either nothing or a space (gap) was inserted between the second and third digits. In both experiments after training, all subjects completed a test with no gap and typed numbers immediately. Training with a memory load improved speed across training blocks (Experiment 1) and eliminated the decline in accuracy across training blocks (Experiment 2), thus serving as a cognitive antidote to performance decrements. An analysis of each keystroke revealed different underlying processes and strategies for the two training conditions, including when encoding took place. Chunking (in which the first and last two digits are treated separately) was more evident in the immediate than in the delayed condition and was exaggerated with a gap, even at test when there was no gap. These results suggest that such two-digit chunking is due to stimulus encoding and motor planning processes as well as memory, and those processes transferred from training to testing.

Older adults get episodic memory boosting from noninvasive stimulation of prefrontal cortex during learning.

PubMed

Sandrini, Marco; Manenti, Rosa; Brambilla, Michela; Cobelli, Chiara; Cohen, Leonardo G; Cotelli, Maria

2016-03-01

Episodic memory displays the largest degree of age-related decline, a process that is accelerated in pathological conditions such as amnestic mild cognitive impairment and Alzheimer's disease. Previous studies have shown that the left lateral prefrontal cortex (PFC) contributes to the encoding of episodic memories along the life span. The aim of this randomized, double-blind, placebo-controlled study was to test the hypothesis that anodal trascranial direct current stimulation (tDCS) over the left lateral PFC during the learning phase would enhance delayed recall of verbal episodic memories in elderly individuals. Older adults learned a list of words while receiving anodal or placebo (sham) tDCS. Memory recall was tested 48 hours and 1 month later. The results showed that anodal tDCS strengthened episodic memories, an effect indicated by enhanced delayed recall (48 hours) compared to placebo stimulation (Cohen's d effect size = 1.01). The observation that PFC-tDCS during learning can boost verbal episodic memory in the elderly opens up the possibility to design-specific neurorehabilitation protocols targeted to conditions that affect episodic memory such as mild cognitive impairment. Copyright © 2016 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

Integrative Transcriptome Profiling of Cognitive Aging and Its Preservation through Ser/Thr Protein Phosphatase Regulation.

PubMed

Park, C Sehwan; Valomon, Amandine; Welzl, Hans

2015-01-01

Environmental enrichment has been reported to delay or restore age-related cognitive deficits, however, a mechanism to account for the cause and progression of normal cognitive decline and its preservation by environmental enrichment is lacking. Using genome-wide SAGE-Seq, we provide a global assessment of differentially expressed genes altered with age and environmental enrichment in the hippocampus. Qualitative and quantitative proteomics in naïve young and aged mice was used to further identify phosphorylated proteins differentially expressed with age. We found that increased expression of endogenous protein phosphatase-1 inhibitors in aged mice may be characteristic of long-term environmental enrichment and improved cognitive status. As such, hippocampus-dependent performances in spatial, recognition, and associative memories, which are sensitive to aging, were preserved by environmental enrichment and accompanied by decreased protein phosphatase activity. Age-associated phosphorylated proteins were also found to correspond to the functional categories of age-associated genes identified through transcriptome analysis. Together, this study provides a comprehensive map of the transcriptome and proteome in the aging brain, and elucidates endogenous protein phosphatase-1 inhibition as a potential means through which environmental enrichment may ameliorate age-related cognitive deficits.

Associations between depressive symptoms and memory deficits vary as a function of insulin-like growth factor (IGF-1) levels in healthy older adults.

PubMed

Lin, Feng; Suhr, Julie; Diebold, Stephanie; Heffner, Kathi L

2014-04-01

Accumulating evidence suggests an adverse association between depressive symptoms and cognition, but a positive association between insulin-like growth factor (IGF)-1 and cognition. The present study examined the influence of IGF-1 in the relationship between depressive symptoms and learning and memory. A cross-sectional study of 94 healthy fit older adults. Blood was collected and plasma IGF-1 was measured. Depressive symptoms were assessed with the Geriatric Depression Scale (GDS), and learning and memory were assessed using the Rey Auditory Verbal Learning Test (AVLT). Among older adults with lower IGF-1 levels, higher depressive symptoms scores were associated with lower AVLT delayed recall and recognition. Older adults with higher IF-1 levels showed no associations between depressive symptoms and memory. The association between depressive symptoms and cognition is stronger among older adults with lower levels of circulating IGF-1. Further validation studies on groups with depression or different stages of cognitive impairment are needed. IGF-1 may be a novel intervention target for slowing cognitive decline in older adults with depressive symptoms. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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.

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.

Subjective Cognitive Decline Is Associated With Altered Default Mode Network Connectivity in Individuals With a Family History of Alzheimer's Disease.

PubMed

Verfaillie, Sander C J; Pichet Binette, Alexa; Vachon-Presseau, Etienne; Tabrizi, Shirin; Savard, Mélissa; Bellec, Pierre; Ossenkoppele, Rik; Scheltens, Philip; van der Flier, Wiesje M; Breitner, John C S; Villeneuve, Sylvia

2018-05-01

Both subjective cognitive decline (SCD) and a family history of Alzheimer's disease (AD) portend risk of brain abnormalities and progression to dementia. Posterior default mode network (pDMN) connectivity is altered early in the course of AD. It is unclear whether SCD predicts similar outcomes in cognitively normal individuals with a family history of AD. We studied 124 asymptomatic individuals with a family history of AD (age 64 ± 5 years). Participants were categorized as having SCD if they reported that their memory was becoming worse (SCD + ). We used extensive neuropsychological assessment to investigate five different cognitive domain performances at baseline (n = 124) and 1 year later (n = 59). We assessed interconnectivity among three a priori defined ROIs: pDMN, anterior ventral DMN, medial temporal memory system (MTMS), and the connectivity of each with the rest of brain. Sixty-eight (55%) participants reported SCD. Baseline cognitive performance was comparable between groups (all false discovery rate-adjusted p values > .05). At follow-up, immediate and delayed memory improved across groups, but the improvement in immediate memory was reduced in SCD + compared with SCD - (all false discovery rate-adjusted p values < .05). When compared with SCD - , SCD + subjects showed increased pDMN-MTMS connectivity (false discovery rate-adjusted p < .05). Higher connectivity between the MTMS and the rest of the brain was associated with better baseline immediate memory, attention, and global cognition, whereas higher MTMS and pDMN-MTMS connectivity were associated with lower immediate memory over time (all false discovery rate-adjusted p values < .05). SCD in cognitively normal individuals is associated with diminished immediate memory practice effects and a brain connectivity pattern that mirrors early AD-related connectivity failure. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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.

Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer's Disease.

PubMed

Liu-Seifert, Hong; Siemers, Eric; Price, Karen; Han, Baoguang; Selzler, Katherine J; Henley, David; Sundell, Karen; Aisen, Paul; Cummings, Jeffrey; Raskin, Joel; Mohs, Richard

2015-01-01

The temporal relationship of cognitive deficit and functional impairment in Alzheimer's disease (AD) is not well characterized. Recent analyses suggest cognitive decline predicts subsequent functional decline throughout AD progression. To better understand the relationship between cognitive and functional decline in mild AD using autoregressive cross-lagged (ARCL) panel analyses in several clinical trials. Data included placebo patients with mild AD pooled from two multicenter, double-blind, Phase 3 solanezumab (EXPEDITION/2) or semagacestat (IDENTITY/2) studies, and from AD patients participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitive and functional outcomes were assessed using AD Assessment Scale-Cognitive subscale (ADAS-Cog), AD Cooperative Study-Activities of Daily Living instrumental subscale (ADCS-iADL), or Functional Activities Questionnaire (FAQ), respectively. ARCL panel analyses evaluated relationships between cognitive and functional impairment over time. In EXPEDITION, ARCL panel analyses demonstrated cognitive scores significantly predicted future functional impairment at 5 of 6 time points, while functional scores predicted subsequent cognitive scores in only 1 of 6 time points. Data from IDENTITY and ADNI programs yielded consistent results whereby cognition predicted subsequent function, but not vice-versa. Analyses from three databases indicated cognitive decline precedes and predicts subsequent functional decline in mild AD dementia, consistent with previously proposed hypotheses, and corroborate recent publications using similar methodologies. Cognitive impairment may be used as a predictor of future functional impairment in mild AD dementia and can be considered a critical target for prevention strategies to limit future functional decline in the dementia process.

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.

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

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.

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.

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

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.

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

Omega-3 fatty acids and brain resistance to ageing and stress: body of evidence and possible mechanisms.

PubMed

Denis, I; Potier, B; Vancassel, S; Heberden, C; Lavialle, M

2013-03-01

The increasing life expectancy in the populations of rich countries raises the pressing question of how the elderly can maintain their cognitive function. Cognitive decline is characterised by the loss of short-term memory due to a progressive impairment of the underlying brain cell processes. Age-related brain damage has many causes, some of which may be influenced by diet. An optimal diet may therefore be a practical way of delaying the onset of age-related cognitive decline. Nutritional investigations indicate that the ω-3 poyunsaturated fatty acid (PUFA) content of western diets is too low to provide the brain with an optimal supply of docosahexaenoic acid (DHA), the main ω-3 PUFA in cell membranes. Insufficient brain DHA has been associated with memory impairment, emotional disturbances and altered brain processes in rodents. Human studies suggest that an adequate dietary intake of ω-3 PUFA can slow the age-related cognitive decline and may also protect against the risk of senile dementia. However, despite the many studies in this domain, the beneficial impact of ω-3 PUFA on brain function has only recently been linked to specific mechanisms. This review examines the hypothesis that an optimal brain DHA status, conferred by an adequate ω-3 PUFA intake, limits age-related brain damage by optimizing endogenous brain repair mechanisms. Our analysis of the abundant literature indicates that an adequate amount of DHA in the brain may limit the impact of stress, an important age-aggravating factor, and influences the neuronal and astroglial functions that govern and protect synaptic transmission. This transmission, particularly glutamatergic neurotransmission in the hippocampus, underlies memory formation. The brain DHA status also influences neurogenesis, nested in the hippocampus, which helps maintain cognitive function throughout life. Although there are still gaps in our knowledge of the way ω-3 PUFA act, the mechanistic studies reviewed here indicate that ω-3 PUFA may be a promising tool for preventing age-related brain deterioration. Copyright © 2013 Elsevier B.V. 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.

Advanced Age Dissociates Dual Functions of the Perirhinal Cortex

PubMed Central

Burke, Sara N.; Maurer, Andrew P.; Nematollahi, Saman; Uprety, Ajay; Wallace, Jenelle L.

2014-01-01

The perirhinal cortex (PRC) is proposed to both represent high-order sensory information and maintain those representations across delays. These cognitive processes are required for recognition memory, which declines during normal aging. Whether or not advanced age affects the ability of PRC principal cells to support these dual roles, however, is not known. The current experiment recorded PRC neurons as young and aged rats traversed a track. When objects were placed on the track, a subset of the neurons became active at discrete locations adjacent to objects. Importantly, the aged rats had a lower proportion of neurons that were activated by objects. Once PRC activity patterns in the presence of objects were established, however, both age groups maintained these representations across delays up to 2 h. These data support the hypothesis that age-associated deficits in stimulus recognition arise from impairments in high-order stimulus representation rather than difficulty in sustaining stable activity patterns over time. PMID:24403147

Advanced age dissociates dual functions of the perirhinal cortex.

PubMed

Burke, Sara N; Maurer, Andrew P; Nematollahi, Saman; Uprety, Ajay; Wallace, Jenelle L; Barnes, Carol A

2014-01-08

The perirhinal cortex (PRC) is proposed to both represent high-order sensory information and maintain those representations across delays. These cognitive processes are required for recognition memory, which declines during normal aging. Whether or not advanced age affects the ability of PRC principal cells to support these dual roles, however, is not known. The current experiment recorded PRC neurons as young and aged rats traversed a track. When objects were placed on the track, a subset of the neurons became active at discrete locations adjacent to objects. Importantly, the aged rats had a lower proportion of neurons that were activated by objects. Once PRC activity patterns in the presence of objects were established, however, both age groups maintained these representations across delays up to 2 h. These data support the hypothesis that age-associated deficits in stimulus recognition arise from impairments in high-order stimulus representation rather than difficulty in sustaining stable activity patterns over time.

Impact of County Disadvantage on Behavior Problems Among US Children With Cognitive Delay

PubMed Central

Park, Hyojun; Robert, Stephanie A.; Palta, Mari; Witt, Whitney P.

2014-01-01

Objectives. We investigated relationships among cognitive delay, community factors, and behavior problems over 2 years in early childhood with a national sample of US families. Methods. Data were from 3 waves of the Early Childhood Longitudinal Study, Birth Cohort (2001–2005; n = 7650). We defined cognitive delay as the lowest 10% of mental scores from the Bayley Short Form–Research Edition, administered at 9 and 24 months. At 24 months, we classified children as typically developing or as having resolved, newly developed, or persistent cognitive delays. Behavior was measured at age 4 years with the Preschool and Kindergarten Behavior Scales (range = 0–36). Community factors included perceived neighborhood safety and an index of county disadvantage. Results. Behavior scores at age 4 years (mean = 12.4; SD = 4.9) were higher among children with resolved (Β = 0.70; SE = 0.20), newly developed (Β = 1.92; SE = 0.25), and persistent (Β = 2.96; SE = 0.41) cognitive delays than for typically developing children. The interaction between county disadvantage and cognitive delay status was statistically significant (P < .01), suggesting that county disadvantage was particularly detrimental for children with persistent delays. Conclusions. The community context may provide an opportunity for public health interventions to improve the behavioral health of children with cognitive delays. PMID:25211742

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.

Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment.

PubMed

Schneider, Christine B; Donix, Markus; Linse, Katharina; Werner, Annett; Fauser, Mareike; Klingelhoefer, Lisa; Löhle, Matthias; von Kummer, Rüdiger; Reichmann, Heinz; Storch, Alexander

2017-09-01

Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. Irrespective of the study participants' cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.

Olfactory discrimination predicts cognitive decline among community-dwelling older adults

PubMed Central

Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

2012-01-01

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46–86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio=0.869; P<0.05; 95% confidence interval=0.764−0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia. PMID:22832962

Olfactory discrimination predicts cognitive decline among community-dwelling older adults.

PubMed

Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

2012-05-22

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio = 0.869; P<0.05; 95% confidence interval = 0.764-0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia.

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.

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

Changes in brain anatomy during the course of PTSD

PubMed Central

Cardenas, Valerie A.; Samuelson, Kristin; Lenoci, Maryann; Studholme, Colin; Neylan, Thomas C.; Marmar, Charles R.; Schuff, Norbert; Weiner, Michael W.

2011-01-01

The goal of this study was to determine whether PTSD was associated with an increase in time-related decline in macrostructural brain volume and whether these changes were associated with accelerated cognitive decline. To quantify brain structure, 3 dimensional T1-weighted MRI scans were performed at baseline and again after a minimum of 24 months in 25 patients with PTSD and 22 controls. Longitudinal changes in brain volume were measured using deformation morphometry. For the group as a whole PTSD+ patients did not show significant ongoing brain atrophy compared to PTSD-. PTSD+ patients were then subgrouped into those with decreasing or increasing symptoms. We found little evidence for brain markers of accelerated atrophy in PTSD+ veterans whose symptoms improved over time, with only a small left parietal region showing greater ongoing tissue loss than PTSD-. PTSD patients whose symptoms increased over time showed accelerated atrophy throughout the brain, particularly brainstem and frontal and temporal lobes. Lastly, for the sample as a whole greater rates of brain atrophy were associated with greater rates of decline in verbal memory and delayed facial recognition. PMID:21683556

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.

Cardiorespiratory Fitness and Cognitive Function in Midlife: Neuroprotection or Neuroselection?

PubMed Central

Belsky, Daniel W.; Caspi, Avshalom; Israel, Salomon; Blumenthal, James A.; Poulton, Richie; Moffitt, Terrie E.

2015-01-01

Objective To determine if better cognitive functioning at midlife among more physically fit individuals reflects “neuroprotection,” in which fitness protects against age-related cognitive decline, or “neuroselection,” in which children with higher cognitive functioning select into more active lifestyles. Methods Children in the Dunedin Longitudinal Study (N=1,037) completed the Wechsler Intelligence Scales and the Trail-Making, Rey-Delayed-Recall, and Grooved-Pegboard tasks as children and again at midlife (age-38). Adult cardiorespiratory fitness was assessed using a submaximal exercise test to estimate maximum-oxygen-consumption-adjusted-for-body-weight in milliliters/minute/kilogram (VO2max). We tested if more-fit individuals had better cognitive functioning than their less-fit counterparts (which could be consistent with neuroprotection), and if better childhood cognitive functioning predisposed to better adult cardiorespiratory fitness (neuroselection). Finally, we examined possible mechanisms of neuroselection. Results Participants with better cardiorespiratory fitness had higher cognitive test scores at midlife. However, fitness-associated advantages in cognitive functioning were present already in childhood. After accounting for childhood-baseline performance on the same cognitive tests, there was no association between cardiorespiratory fitness and midlife cognitive functioning. Socioeconomic and health advantages in childhood, and healthier lifestyles during young adulthood explained most of the association between childhood cognitive functioning and adult cardiorespiratory fitness. Interpretation We found no evidence for a neuroprotective effect of cardiorespiratory fitness as of midlife. Instead, children with better cognitive functioning are selecting into healthier lives. Fitness interventions may enhance cognitive functioning. But, observational and experimental studies testing neuroprotective effects of physical fitness should consider confounding by neuroselection. PMID:25601795

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

A Systematic Review for Functional Neuroimaging Studies of Cognitive Reserve Across the Cognitive Aging Spectrum.

PubMed

Anthony, Mia; Lin, Feng

2017-12-13

Cognitive reserve has been proposed to explain the discrepancy between clinical symptoms and the effects of aging or Alzheimer's pathology. Functional magnetic resonance imaging (fMRI) may help elucidate how neural reserve and compensation delay cognitive decline and identify brain regions associated with cognitive reserve. This systematic review evaluated neural correlates of cognitive reserve via fMRI (resting-state and task-related) studies across the cognitive aging spectrum (i.e., normal cognition, mild cognitive impairment, and Alzheimer's disease). This review examined published articles up to March 2017. There were 13 cross-sectional observational studies that met the inclusion criteria, including relevance to cognitive reserve, subjects 60 years or older with normal cognition, mild cognitive impairment, and/or Alzheimer's disease, at least one quantitative measure of cognitive reserve, and fMRI as the imaging modality. Quality assessment of included studies was conducted using the Newcastle-Ottawa Scale adapted for cross-sectional studies. Across the cognitive aging spectrum, medial temporal regions and an anterior or posterior cingulate cortex-seeded default mode network were associated with neural reserve. Frontal regions and the dorsal attentional network were related to neural compensation. Compared to neural reserve, neural compensation was more common in mild cognitive impairment and Alzheimer's disease. Neural reserve and compensation both support cognitive reserve, with compensation more common in later stages of the cognitive aging spectrum. Longitudinal and intervention studies are needed to investigate changes between neural reserve and compensation during the transition between clinical stages, and to explore the causal relationship between cognitive reserve and potential neural substrates. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial.

PubMed

Valls-Pedret, Cinta; Sala-Vila, Aleix; Serra-Mir, Mercè; Corella, Dolores; de la Torre, Rafael; Martínez-González, Miguel Ángel; Martínez-Lapiscina, Elena H; Fitó, Montserrat; Pérez-Heras, Ana; Salas-Salvadó, Jordi; Estruch, Ramon; Ros, Emilio

2015-07-01

Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline, a strong risk factor for development of dementia. Epidemiologic studies suggest that a Mediterranean diet, an antioxidant-rich cardioprotective dietary pattern, delays cognitive decline, but clinical trial evidence is lacking. To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet. Parallel-group randomized clinical trial of 447 cognitively healthy volunteers from Barcelona, Spain (233 women [52.1%]; mean age, 66.9 years), at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1, 2003, through December 31, 2009. All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study. Participants were randomly assigned to a Mediterranean diet supplemented with extravirgin olive oil (1 L/wk), a Mediterranean diet supplemented with mixed nuts (30 g/d), or a control diet (advice to reduce dietary fat). Rates of cognitive change over time based on a neuropsychological test battery: Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT), Animals Semantic Fluency, Digit Span subtest from the Wechsler Adult Intelligence Scale, Verbal Paired Associates from the Wechsler Memory Scale, and the Color Trail Test. We used mean z scores of change in each test to construct 3 cognitive composites: memory, frontal (attention and executive function), and global. Follow-up cognitive tests were available in 334 participants after intervention (median, 4.1 years). In multivariate analyses adjusted for confounders, participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT (P = .049) and Color Trail Test part 2 (P = .04) compared with controls; no between-group differences were observed for the other cognitive tests. Similarly adjusted cognitive composites (mean z scores with 95% CIs) for changes above baseline of the memory composite were 0.04 (-0.09 to 0.18) for the Mediterranean diet plus olive oil, 0.09 (-0.05 to 0.23; P = .04 vs controls) for the Mediterranean diet plus nuts, and -0.17 (-0.32 to -0.01) for the control diet. Respective changes from baseline of the frontal cognition composite were 0.23 (0.03 to 0.43; P = .003 vs controls), 0.03 (-0.25 to 0.31), and -0.33 (-0.57 to -0.09). Changes from baseline of the global cognition composite were 0.05 (-0.11 to 0.21; P = .005 vs controls) for the Mediterranean diet plus olive oil, -0.05 (-0.27 to 0.18) for the Mediterranean diet plus nuts, and -0.38 (-0.57 to -0.18) for the control diet. All cognitive composites significantly (P < .05) decreased from baseline in controls. In an older population, a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function. isrctn.org Identifier: ISRCTN35739639.

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/

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.

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.

Short-term memory deficits correlate with hippocampal-thalamic functional connectivity alterations following acute sleep restriction.

PubMed

Chengyang, Li; Daqing, Huang; Jianlin, Qi; Haisheng, Chang; Qingqing, Meng; Jin, Wang; Jiajia, Liu; Enmao, Ye; Yongcong, Shao; Xi, Zhang

2017-08-01

Acute sleep restriction heavily influences cognitive function, affecting executive processes such as attention, response inhibition, and memory. Previous neuroimaging studies have suggested a link between hippocampal activity and short-term memory function. However, the specific contribution of the hippocampus to the decline of short-term memory following sleep restriction has yet to be established. In the current study, we utilized resting-state functional magnetic resonance imaging (fMRI) to examine the association between hippocampal functional connectivity (FC) and the decline of short-term memory following total sleep deprivation (TSD). Twenty healthy adult males aged 20.9 ± 2.3 years (age range, 18-24 years) were enrolled in a within-subject crossover study. Short-term memory and FC were assessed using a Delay-matching short-term memory test and a resting-state fMRI scan before and after TSD. Seed-based correlation analysis was performed using fMRI data for the left and right hippocampus to identify differences in hippocampal FC following TSD. Subjects demonstrated reduced alertness and a decline in short-term memory performance following TSD. Moreover, fMRI analysis identified reduced hippocampal FC with the superior frontal gyrus (SFG), temporal regions, and supplementary motor area. In addition, an increase in FC between the hippocampus and bilateral thalamus was observed, the extent of which correlated with short-term memory performance following TSD. Our findings indicate that the disruption of hippocampal-cortical connectivity is linked to the decline in short-term memory observed after acute sleep restriction. Such results provide further evidence that support the cognitive impairment model of sleep deprivation.

Bilingualism in older Mexican-American immigrants is associated with higher scores on cognitive screening.

PubMed

Padilla, Claudia; Mendez, Mario F; Jimenez, Elvira E; Teng, Edmond

2016-11-24

Bilingualism may protect against cognitive aging and delay the onset of dementia. However, studies comparing monolinguals and bilinguals on such metrics have produced inconsistent results complicated by confounding variables and methodological concerns. We addressed this issue by comparing cognitive performance in a more culturally homogeneous cohort of older Spanish-speaking monolingual (n = 289) and Spanish-English bilingual (n = 339) Mexican-American immigrants from the Sacramento Longitudinal Study on Aging. After adjusting for demographic differences and depressive symptoms, both groups performed similarly at baseline on verbal memory but the bilingual group performed significantly better than the monolingual group on a cognitive screening test, the Modified Mini-Mental State Examination (3MS; p < 0.001). Group differences on the 3MS were driven by language/executive and language/praxis factors. Within the bilingual group, neither language of testing nor degree of bilingualism was significantly associated with 3MS or verbal memory scores. Amongst individuals who performed in the normal or better range on both tests at baseline and were followed for an average of 6 years, both monolinguals and bilinguals exhibited similar rates of cognitive decline on both measures. These findings suggest that bilingualism is associated with modest benefits in cognitive screening performance in older individuals in cross-sectional analyses that persist across longitudinal analyses. The effects of bilingualism should be considered when cognitively screening is performed in aging immigrant populations.

Advances in Alzheimer's imaging are changing the experience of Alzheimer's disease.

PubMed

Stites, Shana D; Milne, Richard; Karlawish, Jason

2018-01-01

Neuroimaging is advancing a new definition of Alzheimer's disease (AD). Using imaging biomarkers, clinicians may begin to diagnose the disease by identifying pathology and neurodegeneration in either cognitively impaired or unimpaired adults. This "biomarker-based" diagnosis may allow clinicians novel opportunities to use interventions that either delay the onset or slow the progression of cognitive decline, but it will also bring novel challenges. How will changing the definition of AD from a clinical to a biomarker construct change the experience of living with the disease? Knowledge of AD biomarker status can affect how individuals feel about themselves (internalized stigma) and how others judge them (public stigma). Following a review of AD stigma, we appraise how advances in diagnosis may enable or interrupt its transfer from clinical to preclinical stages and then explore conceptual and pragmatic challenges to addressing stigma in routine care.

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

Phase Measurement of Cognitive Impairment Specific to Radiotherapy

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

Armstrong, Carol L., E-mail: armstrongc@email.chop.edu; Department of Pediatrics, Division of Neuro-Oncology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania; Shera, David M.

Purpose: Memory impairment is an early-delayed effect of radiotherapy (RT). The prospective longitudinal measurement of the cognitive phase effects from RT was conducted on treated and untreated brain tumor patients. The study design investigated semantic vs. perceptual and visual vs. verbal memory to determine the most disease-specific measure of RT-related changes and understanding of the neurotoxicity from RT to the brain. Methods and Materials: Tests of memory that had previously shown RT-related phasic changes were compared with experimental tests of memory to test hypotheses about cognition targeted to the neural toxicity of RT. The results from 41 irradiated and 29more » nonirradiated patients with low-grade, supratentorial tumors were analyzed. The methods controlled for comorbid white matter risk, recurrence, interval after treatment, and age (18-69 years). The effects were examined before RT and at three points after RT to 1 year using a mixed effects model that included interval, group, surgical status, medication use, practice, and individual random effects. Four new tests of memory and other candidate cognitive tests were investigated, and a post hoc analysis of a comprehensive battery of tests was performed to identify the cognitive processes most specific to RT. Results: The RT effects on memory were identified in the treated group only; among the new tests of memory and the complete neurocognitive battery, the RT effects were significant only for delayed recall (p < 0.009) and interval to recognize (p < 0.002). Tumor location was not related to the treatment effect. Memory decline was specific to retrieval of semantic memories; a double dissociation of semantic from perceptual visual memory was demonstrated in the RT group. Conclusions: These results implicate memory dependent on the semantic cortex and the hippocampal memory system. A cognitive measurement that is brief but specific to neural mechanisms is effective and feasible for studies of RT damage.« less

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.

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.

Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease.

PubMed

Stout, Julie C; Jones, Rebecca; Labuschagne, Izelle; O'Regan, Alison M; Say, Miranda J; Dumas, Eve M; Queller, Sarah; Justo, Damian; Santos, Rachelle Dar; Coleman, Allison; Hart, Ellen P; Dürr, Alexandra; Leavitt, Blair R; Roos, Raymund A; Langbehn, Doug R; Tabrizi, Sarah J; Frost, Chris

2012-07-01

Deterioration of cognitive functioning is a debilitating symptom in many neurodegenerative diseases, such as Huntington's disease (HD). To date, there are no effective treatments for the cognitive problems associated with HD. Cognitive assessment outcomes will have a central role in the efforts to develop treatments to delay onset or slow the progression of the disease. The TRACK-HD study was designed to build a rational basis for the selection of cognitive outcomes for HD clinical trials. There were a total of 349 participants, including controls (n=116), premanifest HD (n=117) and early HD (n=116). A standardised cognitive assessment battery (including nine cognitive tests comprising 12 outcome measures) was administered at baseline, and at 12 and 24 months, and consisted of a combination of paper and pencil and computerised tasks selected to be sensitive to cortical-striatal damage or HD. Each cognitive outcome was analysed separately using a generalised least squares regression model. Results are expressed as effect sizes to permit comparisons between tasks. 10 of the 12 cognitive outcomes showed evidence of deterioration in the early HD group, relative to controls, over 24 months, with greatest sensitivity in Symbol Digit, Circle Tracing direct and indirect, and Stroop word reading. In contrast, there was very little evidence of deterioration in the premanifest HD group relative to controls. The findings describe tests that are sensitive to longitudinal cognitive change in HD and elucidate important considerations for selecting cognitive outcomes for clinical trials of compounds aimed at ameliorating cognitive decline in HD.

Repeated cognitive stimulation alleviates memory impairments in an Alzheimer's disease mouse model.

PubMed

Martinez-Coria, Hilda; Yeung, Stephen T; Ager, Rahasson R; Rodriguez-Ortiz, Carlos J; Baglietto-Vargas, David; LaFerla, Frank M

2015-08-01

Alzheimer's disease is a neurodegenerative disease associated with progressive memory and cognitive decline. Previous studies have identified the benefits of cognitive enrichment on reducing disease pathology. Additionally, epidemiological and clinical data suggest that repeated exercise, and cognitive and social enrichment, can improve and/or delay the cognitive deficiencies associated with aging and neurodegenerative diseases. In the present study, 3xTg-AD mice were exposed to a rigorous training routine beginning at 3 months of age, which consisted of repeated training in the Morris water maze spatial recognition task every 3 months, ending at 18 months of age. At the conclusion of the final Morris water maze training session, animals subsequently underwent testing in another hippocampus-dependent spatial task, the Barnes maze task, and on the more cortical-dependent novel object recognition memory task. Our data show that periodic cognitive enrichment throughout aging, via multiple learning episodes in the Morris water maze task, can improve the memory performance of aged 3xTg-AD mice in a separate spatial recognition task, and in a preference memory task, when compared to naïve aged matched 3xTg-AD mice. Furthermore, we observed that the cognitive enrichment properties of Morris water maze exposer, was detectable in repeatedly trained animals as early as 6 months of age. These findings suggest early repeated cognitive enrichment can mitigate the diverse cognitive deficits observed in Alzheimer's disease. Published by Elsevier Inc.

Developmental fMRI study of episodic verbal memory encoding in children.

PubMed

Maril, A; Davis, P E; Koo, J J; Reggev, N; Zuckerman, M; Ehrenfeld, L; Mulkern, R V; Waber, D P; Rivkin, M J

2010-12-07

Understanding the maturation and organization of cognitive function in the brain is a central objective of both child neurology and developmental cognitive neuroscience. This study focuses on episodic memory encoding of verbal information by children, a cognitive domain not previously studied using fMRI. Children from 7 to 19 years of age were scanned at 1.5-T field strength using event-related fMRI while performing a novel verbal memory encoding paradigm in which words were incidentally encoded. A subsequent memory analysis was performed. SPM2 was utilized for whole brain and region-of-interest analyses of data. Both whole-sample intragroup analyses and intergroup analyses of the sample divided into 2 subgroups by age were conducted. Importantly, behavioral memory performance was equal across the age range of children studied. Encoding-related activation in the left hippocampus and bilateral basal ganglia declined as age increased. In addition, while robust blood oxygen level-dependent signal was found in left prefrontal cortex with task performance, no encoding-related age-modulated prefrontal activation was observed in either hemisphere. These data are consistent with a developmental pattern of verbal memory encoding function in which left hippocampal and bilateral basal ganglionic activations are more robust earlier in childhood but then decline with age. No encoding-related activation was found in prefrontal cortex which may relate to this region's recognized delay in biologic maturation in humans. These data represent the first fMRI demonstration of verbal encoding function in children and are relevant developmentally and clinically.

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

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.

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.

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.

Quality of education and memory test performance in older men: the New York University Paragraph Recall Test normative data.

PubMed

Mathews, Melissa; Abner, Erin; Caban-Holt, Allison; Dennis, Brandon C; Kryscio, Richard; Schmitt, Frederick

2013-09-01

Memory evaluation is a key component in the accurate diagnosis of cognitive disorders.One memory procedure that has shown promise in discriminating disease-related cognitive decline from normal cognitive aging is the New York University Paragraph Recall Test; however, the effects of education have been unexamined as they pertain to one's literacy level. The current study provides normative data stratified by estimated quality of education as indexed by irregular word reading skill. Conventional norms were derived from a sample (N = 385) of cognitively intact elderly men who were initially recruited for participation in the PREADViSE clinical trial. A series of multiple linear regression models were constructed to assess the influence of demographic variables on mean NYU Paragraph Immediate and Delayed Recall scores. Test version, assessment site, and estimated quality of education were significant predictors of performance on the NYU Paragraph Recall Test. Findings indicate that estimated quality of education is a better predictor of memory performance than ethnicity and years of total education. Normative data stratified according to estimated quality of education are presented. The current study provides evidence and support for normativedata stratified by quality of education as opposed to years of education.

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

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

Does cognition improve following LVAD implantation?

PubMed

Pavol, Marykay A; Willey, Joshua Z; Wei, Ying; Yuzefpolskaya, Melana; Marshall, Randolph S; Marascalco, Philip J; Harwood, Jason; Lazar, Ronald M

2018-05-23

Studies of cognition after LVAD surgery have produced mixed results. To explore whether cognition would improve, decline, or remain stable after LVAD surgery, we examined cognition before and 1- and 3-months after LVAD surgery. Patients with post-surgical stroke were excluded. 28 subjects (mean age = 54.31 ± 12 years) comprised an observational case series from the DuraHeart LVAS device® trial. Cognitive testing was performed at baseline, 1-month, and 3-month post-surgery, and included tests of attention, memory, language, visualmotor speed (TMT) and visualconstruction. No difference in cognition was found between baseline and 1-month exams (means z score improvement = 0.06, p = 0.43) but cognition improved significantly between baseline and 3-month exams (mean z score improvement = 0.34, p < 0.00001). Examination of individual test scores found, after correction for multiple comparisons, only the TMT variable was significantly different at the 3-month exam. We found significantly improved cognition 3 months after LVAD surgery in a subset of patients without post-surgical stroke. The reasons for the lack of cognitive improvement at the 1-month post-surgical assessment may include ongoing medical and physiological disruptions in the immediate post-operative period. Further research into the sources of delayed improvement is warranted. Cognitive assessments performed immediately after surgery should be interpreted with caution because the results may not reflect longer term cognitive outcomes. LVAD patients may require additional support to successfully manage their health in the weeks immediately following surgery but assistance needs may decrease over time.

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.

Towards onset prevention of cognition decline in adults with Down syndrome (The TOP-COG study): A pilot randomised controlled trial.

PubMed

Cooper, Sally-Ann; Ademola, Temitope; Caslake, Muriel; Douglas, Elizabeth; Evans, Jonathan; Greenlaw, Nicola; Haig, Caroline; Hassiotis, Angela; Jahoda, Andrew; McConnachie, Alex; Morrison, Jill; Ring, Howard; Starr, John; Stiles, Ciara; Sirisena, Chammy; Sullivan, Frank

2016-07-29

Dementia is very common in Down syndrome (trisomy 21) adults. Statins may slow brain amyloid β (Aβ, coded on chromosome 21) deposition and, therefore, delay Alzheimer disease onset. One prospective cohort study with Down syndrome adults found participants on statins had reduced risk of incident dementia, but there are no randomised controlled trials (RCTs) on this issue. Evidence is sparse on the best instruments to detect longitudinal cognitive decline in older Down syndrome adults. TOP-COG was a feasibility/pilot, double-blind RCT of 12 months simvastatin 40 mg versus placebo for the primary prevention of dementia in Alzheimer disease in Down syndrome adults aged 50 years or older. Group allocation was stratified by age, apolipoprotein E (APOE) ε4 allele status, and cholesterol level. Recruitment was from multiple general community sources over 12 months. Adults with dementia, or simvastatin contraindications, were excluded. Main outcomes were recruitment and retention rates. Cognitive decline was measured with a battery of tests; secondary measures were adaptive behaviour skills, general health, and quality of life. Assessments were conducted pre randomisation and at 12 months post randomisation. Blood Aβ40/Aβ42 levels were investigated as a putative biomarker. Results were analysed on an intention-to-treat basis. A qualitative sub-study was conducted and analysed using the Framework Approach to determine recruitment motivators/barriers, and participation experience. We identified 181 (78 %) of the likely eligible Down syndrome population, and recruited 21 (11.6 %), from an area with a general population size of 3,135,974. Recruitment was highly labour-intensive. Thirteen (62 %) participants completed the full year. Results favoured the simvastatin group. The most appropriate cognitive instrument (regarding ease of completion and detecting change over time) was the Memory for Objects test from the Neuropsychological Assessment of Dementia in Individuals with Intellectual Disabilities battery. Cognitive testing appeared more sensitive than proxy-rated adaptive behaviour, quality of life, or general health scores. Aβ40 levels changed less for the simvastatin group (not statistically significant). People mostly declined to participate because of not wanting to take medication, and not knowing if they would receive simvastatin or placebo. Participants reported enjoying taking part. A full-scale RCT is feasible. It will need 37 % UK population coverage to recruit the required 160 participants. Information/education about the importance of RCT participation is needed for this population. ISRCTN67338640 .

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.

The Memory Fitness Program: Cognitive Effects of a Healthy Aging Intervention

PubMed Central

Miller, Karen J.; Siddarth, Prabha; Gaines, Jean M.; Parrish, John M.; Ercoli, Linda M.; Marx, Katherine; Ronch, Judah; Pilgram, Barbara; Burke, Kasey; Barczak, Nancy; Babcock, Bridget; Small, Gary W.

2014-01-01

Context Age-related memory decline affects a large proportion of older adults. Cognitive training, physical exercise, and other lifestyle habits may help to minimize self-perception of memory loss and a decline in objective memory performance. Objective The purpose of this study was to determine whether a 6-week educational program on memory training, physical activity, stress reduction, and healthy diet led to improved memory performance in older adults. Design A convenience sample of 115 participants (mean age: 80.9 [SD: 6.0 years]) was recruited from two continuing care retirement communities. The intervention consisted of 60-minute classes held twice weekly with 15–20 participants per class. Testing of both objective and subjective cognitive performance occurred at baseline, preintervention, and postintervention. Objective cognitive measures evaluated changes in five domains: immediate verbal memory, delayed verbal memory, retention of verbal information, memory recognition, and verbal fluency. A standardized metamemory instrument assessed four domains of memory self-awareness: frequency and severity of forgetting, retrospective functioning, and mnemonics use. Results The intervention program resulted in significant improvements on objective measures of memory, including recognition of word pairs (t[114] = 3.62, p < 0.001) and retention of verbal information from list learning (t[114] = 2.98, p < 0.01). No improvement was found for verbal fluency. Regarding subjective memory measures, the retrospective functioning score increased significantly following the intervention (t[114] = 4.54, p < 0.0001), indicating perception of a better memory. Conclusions These findings indicate that a 6-week healthy lifestyle program can improve both encoding and recalling of new verbal information, as well as self-perception of memory ability in older adults residing in continuing care retirement communities. PMID:21765343

The Tyrosine Phosphatase STEP Is Involved in Age-Related Memory Decline.

PubMed

Castonguay, David; Dufort-Gervais, Julien; Ménard, Caroline; Chatterjee, Manavi; Quirion, Rémi; Bontempi, Bruno; Schneider, Jay S; Arnsten, Amy F T; Nairn, Angus C; Norris, Christopher M; Ferland, Guylaine; Bézard, Erwan; Gaudreau, Pierrette; Lombroso, Paul J; Brouillette, Jonathan

2018-04-02

Cognitive disabilities that occur with age represent a growing and expensive health problem. Age-associated memory deficits are observed across many species, but the underlying molecular mechanisms remain to be fully identified. Here, we report elevations in the levels and activity of the striatal-enriched phosphatase (STEP) in the hippocampus of aged memory-impaired mice and rats, in aged rhesus monkeys, and in people diagnosed with amnestic mild cognitive impairment (aMCI). The accumulation of STEP with aging is related to dysfunction of the ubiquitin-proteasome system that normally leads to the degradation of STEP. Higher level of active STEP is linked to enhanced dephosphorylation of its substrates GluN2B and ERK1/2, CREB inactivation, and a decrease in total levels of GluN2B and brain-derived neurotrophic factor (BDNF). These molecular events are reversed in aged STEP knockout and heterozygous mice, which perform similarly to young control mice in the Morris water maze (MWM) and Y-maze tasks. In addition, administration of the STEP inhibitor TC-2153 to old rats significantly improved performance in a delayed alternation T-maze memory task. In contrast, viral-mediated STEP overexpression in the hippocampus is sufficient to induce memory impairment in the MWM and Y-maze tests, and these cognitive deficits are reversed by STEP inhibition. In old LOU/C/Jall rats, a model of healthy aging with preserved memory capacities, levels of STEP and GluN2B are stable, and phosphorylation of GluN2B and ERK1/2 is unaltered. Altogether, these data suggest that elevated levels of STEP that appear with advancing age in several species contribute to the cognitive declines associated with aging. Copyright © 2018 Elsevier Ltd. All rights reserved.

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).

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.

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

Latent class analysis of early developmental trajectory in baby siblings of children with autism.

PubMed

Landa, Rebecca J; Gross, Alden L; Stuart, Elizabeth A; Bauman, Margaret

2012-09-01

Siblings of children with autism (sibs-A) are at increased genetic risk for autism spectrum disorders (ASD) and milder impairments. To elucidate diversity and contour of early developmental trajectories exhibited by sibs-A, regardless of diagnostic classification, latent class modeling was used. Sibs-A (N = 204) were assessed with the Mullen Scales of Early Learning from age 6 to 36 months. Mullen T scores served as dependent variables. Outcome classifications at age 36 months included: ASD (N = 52); non-ASD social/communication delay (broader autism phenotype; BAP; N = 31); and unaffected (N = 121). Child-specific patterns of performance were studied using latent class growth analysis. Latent class membership was then related to diagnostic outcome through estimation of within-class proportions of children assigned to each diagnostic classification. A 4-class model was favored. Class 1 represented accelerated development and consisted of 25.7% of the sample, primarily unaffected children. Class 2 (40.0% of the sample), was characterized by normative development with above-average nonverbal cognitive outcome. Class 3 (22.3% of the sample) was characterized by receptive language, and gross and fine motor delay. Class 4 (12.0% of the sample), was characterized by widespread delayed skill acquisition, reflected by declining trajectories. Children with an outcome diagnosis of ASD were spread across Classes 2, 3, and 4. Results support a category of ASD that involves slowing in early non-social development. Receptive language and motor development is vulnerable to early delay in sibs-A with and without ASD outcomes. Non-ASD sibs-A are largely distributed across classes depicting average or accelerated development. Developmental trajectories of motor, language, and cognition appear independent of communication and social delays in non-ASD sibs-A. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

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.

Loss of Cognitive Skill across Delays: Constraints for Theories of Cognitive Skill Acquisition

ERIC Educational Resources Information Center

Wilkins, Nicolas J.; Rawson, Katherine A.

2010-01-01

Mastering a cognitive skill requires many practice sessions, occurring over a period of days, weeks, months, or even years. Although a large body of research describes and explains gains made within a given practice session, few studies have investigated what happens to these gains across a delay, and none have examined effects of delays on…

Parenting Stress of Mothers and Fathers of Young Children with Cognitive Delays in Vietnam

ERIC Educational Resources Information Center

Shin, J.; Nhan, N. V.; Crittenden, K. S.; Hong, H. T. D.; Flory, M.; Ladinsky, J.

2006-01-01

Background: This research examined the effects of child and family variables on stress experienced by mothers and fathers of young children with cognitive delays in Vietnam. Methods: The mothers (n=106) and fathers (n=93) whose children (age range= 3-6 years) were identified as having cognitive delays participated in the interview survey. The…

Structural and Functional Aspects of Social Support for Mothers of Children with and without Cognitive Delays in Vietnam

ERIC Educational Resources Information Center

Park, So-Youn; Glidden, Laraine M.; Shin, Jin Y.

2010-01-01

Background: This study reports development of a social support scale appropriate to the Vietnamese culture and the impact of social support on mothers of children with cognitive delays by using the developing scale. Method: Interview surveys were conducted with 225 mothers of children with and without cognitive delays in Vietnam. The structural…

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.

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.

Treating cognitive impairment with transcranial low level laser therapy.

PubMed

de la Torre, Jack C

2017-03-01

This report examines the potential of low level laser therapy (LLLT) to alter brain cell function and neurometabolic pathways using red or near infrared (NIR) wavelengths transcranially for the prevention and treatment of cognitive impairment. Although laser therapy on human tissue has been used for a number of medical conditions since the late 1960s, it is only recently that several clinical studies have shown its value in raising neurometabolic energy levels that can improve cerebral hemodynamics and cognitive abilities in humans. The rationale for this approach, as indicated in this report, is supported by growing evidence that neurodegenerative damage and cognitive impairment during advanced aging is accelerated or triggered by a neuronal energy crisis generated by brain hypoperfusion. We have previously proposed that chronic brain hypoperfusion in the elderly can worsen in the presence of one or more vascular risk factors, including hypertension, cardiac disease, atherosclerosis and diabetes type 2. Although many unanswered questions remain, boosting neurometabolic activity through non-invasive transcranial laser biostimulation of neuronal mitochondria may be a valuable tool in preventing or delaying age-related cognitive decline that can lead to dementia, including its two major subtypes, Alzheimer's and vascular dementia. The technology to achieve significant improvement of cognitive dysfunction using LLLT or variations of this technique is moving fast and may signal a new chapter in the treatment and prevention of neurocognitive disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of guar gum on hunger and satiety after meals of differing fat content: relationship with gastric emptying.

PubMed

French, S J; Read, N W

1994-01-01

To determine whether the satiating effects of fiber are due to delaying gastric emptying or slowing absorption of meals, 3% guar gum was added to high- and low-fat soups and gastric emptying rate, hunger, and satiety were measured in eight male volunteers. Guar gum delayed the emptying of the low-fat soup but the small delays in the return of hunger and decline of fullness were significantly correlated with the gastric emptying, suggesting mediation by gastric mechanoreceptors. The high-fat soup also emptied more slowly but this had no effect on the return of hunger or the decline in fullness. The delays in the return of hunger and decline of fullness were far greater when guar gum was added to the fatty soup; these delays were not correlated with the small additional delay in gastric emptying. This is more compatible with slowed absorption and prolonged contact of nutrients with intestinal chemoreceptors.

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.

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

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.

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.

Predicting early cognitive decline in newly-diagnosed Parkinson's patients: A practical model.

PubMed

Hogue, Olivia; Fernandez, Hubert H; Floden, Darlene P

2018-06-19

To create a multivariable model to predict early cognitive decline among de novo patients with Parkinson's disease, using brief, inexpensive assessments that are easily incorporated into clinical flow. Data for 351 drug-naïve patients diagnosed with idiopathic Parkinson's disease were obtained from the Parkinson's Progression Markers Initiative. Baseline demographic, disease history, motor, and non-motor features were considered as candidate predictors. Best subsets selection was used to determine the multivariable baseline symptom profile that most accurately predicted individual cognitive decline within three years. Eleven per cent of the sample experienced cognitive decline. The final logistic regression model predicting decline included five baseline variables: verbal memory retention, right-sided bradykinesia, years of education, subjective report of cognitive impairment, and REM behavior disorder. Model discrimination was good (optimism-adjusted concordance index = .749). The associated nomogram provides a tool to determine individual patient risk of meaningful cognitive change in the early stages of the disease. Through the consideration of easily-implemented or routinely-gathered assessments, we have identified a multidimensional baseline profile and created a convenient, inexpensive tool to predict cognitive decline in the earliest stages of Parkinson's disease. The use of this tool would generate prediction at the individual level, allowing clinicians to tailor medical management for each patient and identify at-risk patients for clinical trials aimed at disease modifying therapies. Copyright © 2018. Published by Elsevier Ltd.

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.

No Effects of Non-invasive Brain Stimulation on Multiple Sessions of Object-Location-Memory Training in Healthy Older Adults

PubMed Central

Külzow, Nadine; Cavalcanti de Sousa, Angelica Vieira; Cesarz, Magda; Hanke, Julie-Marie; Günsberg, Alida; Harder, Solvejg; Koblitz, Swantje; Grittner, Ulrike; Flöel, Agnes

2018-01-01

Object-location memory (OLM) is known to decline with normal aging, a process accelerated in pathological conditions like mild cognitive impairment (MCI). In order to maintain cognitive health and to delay the transition from healthy to pathological conditions, novel strategies are being explored. Tentative evidence suggests that combining cognitive training and anodal transcranial direct current stimulation (atDCS), both reported to induce small and often inconsistent behavioral improvements, could generate larger or more consistent improvements or both, compared to each intervention alone. Here, we explored the combined efficacy of these techniques on OLM. In a subject-blind sham-controlled cross-over design 32 healthy older adults underwent a 3-day visuospatial training paired with either anodal (20 min) or sham (30 s) atDCS (1 mA, temporoparietal). Subjects were asked to learn the correct object-location pairings on a street map, shown over five learning blocks on each training day. Acquisition performance was assessed by accuracy on a given learning block in terms of percentage of correct responses. Training success (performance on last training day) and delayed memory after 1-month were analyzed by mixed model analysis and were controlled for gender, age, education, sequence of stimulation and baseline performance. Exploratory analysis of atDCS effects on within-session (online) and between-session (offline) memory performance were conducted. Moreover, transfer effects on similar trained (visuospatial) and less similar (visuo-constructive, verbal) untrained memory tasks were explored, both immediately after training, and on follow-up. We found that atDCS paired with OLM-training did not enhance success in training or performance in 1-month delayed memory or transfer tasks. In sum, this study did not support the notion that the combined atDCS-training approach improves immediate or delayed OLM in older adults. However, specifics of the experimental design, and a non-optimal timing of atDCS between sessions might have masked beneficial effects and should be more systematically addressed in future studies. PMID:29375290

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.

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.

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.

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

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.

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.

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).

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.

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.

High-Density Lipoprotein Cholesterol Level Relates to Working Memory, Immediate and Delayed Cued Recall in Brazilian Older Adults: The Role of Cognitive Reserve.

PubMed

Ihle, Andreas; Gouveia, Élvio R; Gouveia, Bruna R; Freitas, Duarte L; Jurema, Jefferson; Tinôco, Maria A; Kliegel, Matthias

2017-01-01

The present study set out to investigate the relation of the high-density lipoprotein cholesterol (HDL-C) level to cognitive performance and its interplay with key markers of cognitive reserve in a large sample of older adults. We assessed tests of working memory, immediate and delayed cued recall in 701 older adults from Amazonas, Brazil. The HDL-C level was derived from fasting blood samples. In addition, we interviewed individuals on their education, past occupation, and cognitive leisure activity. A critically low HDL-C level (<40 mg/dL) was significantly related to lower performance in working memory, immediate and delayed cued recall. Moderation analyses suggested that the relations of the HDL-C level to working memory and delayed cued recall were negligible in individuals with longer education, a higher cognitive level of the job, and greater engagement in cognitive leisure activity. Cognitive reserve accumulated during the life course may reduce the detrimental influences of a critically low HDL-C level on cognitive functioning in old age. © 2017 S. Karger AG, Basel.

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

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.

Everyday episodic memory in amnestic mild cognitive impairment: a preliminary investigation.

PubMed

Irish, Muireann; Lawlor, Brian A; Coen, Robert F; O'Mara, Shane M

2011-08-04

Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time.

The impact of bilingualism on brain reserve and metabolic connectivity in Alzheimer's dementia

PubMed Central

Perani, Daniela; Farsad, Mohsen; Ballarini, Tommaso; Lubian, Francesca; Malpetti, Maura; Fracchetti, Alessandro; Magnani, Giuseppe; March, Albert; Abutalebi, Jubin

2017-01-01

Cognitive reserve (CR) prevents cognitive decline and delays neurodegeneration. Recent epidemiological evidence suggests that lifelong bilingualism may act as CR delaying the onset of dementia by ∼4.5 y. Much controversy surrounds the issue of bilingualism and its putative neuroprotective effects. We studied brain metabolism, a direct index of synaptic function and density, and neural connectivity to shed light on the effects of bilingualism in vivo in Alzheimer’s dementia (AD). Eighty-five patients with probable AD and matched for disease duration (45 German-Italian bilingual speakers and 40 monolingual speakers) were included. Notably, bilingual individuals were on average 5 y older than their monolingual peers. In agreement with our predictions and with models of CR, cerebral hypometabolism was more severe in the group of bilingual individuals with AD. The metabolic connectivity analyses crucially supported the neuroprotective effect of bilingualism by showing an increased connectivity in the executive control and the default mode networks in the bilingual, compared with the monolingual, AD patients. Furthermore, the degree of lifelong bilingualism (i.e., high, moderate, or low use) was significantly correlated to functional modulations in crucial neural networks, suggesting both neural reserve and compensatory mechanisms. These findings indicate that lifelong bilingualism acts as a powerful CR proxy in dementia and exerts neuroprotective effects against neurodegeneration. Delaying the onset of dementia is a top priority of modern societies, and the present in vivo neurobiological evidence should stimulate social programs and interventions to support bilingual or multilingual education and the maintenance of the second language among senior citizens. PMID:28137833

The impact of bilingualism on brain reserve and metabolic connectivity in Alzheimer's dementia.

PubMed

Perani, Daniela; Farsad, Mohsen; Ballarini, Tommaso; Lubian, Francesca; Malpetti, Maura; Fracchetti, Alessandro; Magnani, Giuseppe; March, Albert; Abutalebi, Jubin

2017-02-14

Cognitive reserve (CR) prevents cognitive decline and delays neurodegeneration. Recent epidemiological evidence suggests that lifelong bilingualism may act as CR delaying the onset of dementia by ∼4.5 y. Much controversy surrounds the issue of bilingualism and its putative neuroprotective effects. We studied brain metabolism, a direct index of synaptic function and density, and neural connectivity to shed light on the effects of bilingualism in vivo in Alzheimer's dementia (AD). Eighty-five patients with probable AD and matched for disease duration (45 German-Italian bilingual speakers and 40 monolingual speakers) were included. Notably, bilingual individuals were on average 5 y older than their monolingual peers. In agreement with our predictions and with models of CR, cerebral hypometabolism was more severe in the group of bilingual individuals with AD. The metabolic connectivity analyses crucially supported the neuroprotective effect of bilingualism by showing an increased connectivity in the executive control and the default mode networks in the bilingual, compared with the monolingual, AD patients. Furthermore, the degree of lifelong bilingualism (i.e., high, moderate, or low use) was significantly correlated to functional modulations in crucial neural networks, suggesting both neural reserve and compensatory mechanisms. These findings indicate that lifelong bilingualism acts as a powerful CR proxy in dementia and exerts neuroprotective effects against neurodegeneration. Delaying the onset of dementia is a top priority of modern societies, and the present in vivo neurobiological evidence should stimulate social programs and interventions to support bilingual or multilingual education and the maintenance of the second language among senior citizens.

Language Delay in 3-Year-Old Children With ADHD Symptoms.

PubMed

Rohrer-Baumgartner, Nina; Zeiner, Pål; Eadie, Patricia; Egeland, Jens; Gustavson, Kristin; Reichborn-Kjennerud, Ted; Aase, Heidi

2016-10-01

Little is known about cognition in preschoolers with ADHD and language delay (LD). The objective was to investigate cognitive functions in preschoolers with ADHD symptoms and LD compared with children with ADHD symptoms only and to estimate the frequency of children with ADHD symptoms, co-occurring language delay, and delays on cognitive measures. Participants were recruited from the Norwegian Mother and Child Cohort Study. The teacher report of expressive language and the cognitive tests from 119 3-year-old children with parent reported ADHD symptoms and LD were compared with those of 258 children with ADHD symptoms only. The ADHD + LD group performed significantly worse than the ADHD group on most language-related measures. There were no differences between the groups on most nonverbal measures. Single measures had a limited potential of differentiating between the groups. ADHD symptoms and co-occurring LD in preschoolers were characterized by cognitive deficits associated with both disorders, not with global neurodevelopmental delay. © The Author(s) 2013.

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

Long-term intake of nuts in relation to cognitive function in older women.

PubMed

O'Brien, J; Okereke, O; Devore, E; Rosner, B; Breteler, M; Grodstein, F

2014-05-01

Nuts contain nutrients that may benefit brain health; thus, we examined long-term intake of nuts in relation to cognition in older women. Population-based prospective cohort study. Academic research using data from the Nurses' Health Study. Nut intake was assessed in a food-frequency questionnaire beginning in1980, and approximately every four years thereafter. Between 1995-2001, 16,010 women age 70 or older (mean age = 74 years) without a history of stroke were administered 4 repeated telephone-based cognitive interviews over 6 years. Our final sample included 15,467 women who completed an initial cognitive interview and had complete information on nut intake. The Telephone Interview for Cognitive Status (TICS), 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 tests of verbal recall. In multivariable-adjusted linear regression models, higher long-term total nut intake was associated with better average cognitive status for all cognitive outcomes. For the global composite score combining all tests, women consuming at least 5 servings of nuts/week had higher scores than non-consumers (mean difference=0.08 standard units, 95% confidence interval 0.00-0.15; p-trend=0.003). This mean difference of 0.08 is equivalent to the mean difference we find between women 2 years apart in age. Long-term intake of nuts was not associated with rates of cognitive decline. Higher nut intake may be related to better overall cognition at older ages, and could be an easily-modifiable public health intervention.

Association between mental demands at work and cognitive functioning in the general population - results of the health study of the Leipzig research center for civilization diseases (LIFE).

PubMed

Then, Francisca S; Luck, Tobias; Luppa, Melanie; Arélin, Katrin; Schroeter, Matthias L; Engel, Christoph; Löffler, Markus; Thiery, Joachim; Villringer, Arno; Riedel-Heller, Steffi G

2014-01-01

The level of mental demands in the workplace is rising. The present study investigated whether and how mental demands at work are associated with cognitive functioning in the general population. The analysis is based on data of the Health Study of the Leipzig Research Centre for Civilization Disease (LIFE). 2,725 participants aged 40-80 years underwent cognitive testing (Trail-Making Test, Verbal Fluency Test) and provided information on their occupational situation. Participants over the age of 65 years additionally completed the Mini-Mental State Examination. Mental demands at work were rated by a standardized classification system (O*NET). The association between mental demands and cognitive functioning was analyzed using Generalized Linear Modeling (GENLIN) adjusted for age, gender, self-regulation, working hour status, education, and health-related factors. Univariate as well as multivariate analyses demonstrated significant and highly consistent effects of higher mental demands on better performance in cognitive testing. The results also indicated that the effects are independent of education and intelligence. Moreover, analyses of retired individuals implied a significant association between high mental demands at work of the job they once held and a better cognitive functioning in old age. In sum, our findings suggest a significant association between high mental demands at work and better cognitive functioning. In this sense, higher levels of mental demands - as brought about by technological changes in the working environment - may also have beneficial effects for the society as they could increase cognitive capacity levels and might even delay cognitive decline in old age.

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.

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.

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

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.

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.

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.

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

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

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.

Revisiting Metchnikoff: Age-related alterations in microbiota-gut-brain axis in the mouse.

PubMed

Scott, Karen A; Ida, Masayuki; Peterson, Veronica L; Prenderville, Jack A; Moloney, Gerard M; Izumo, Takayuki; Murphy, Kiera; Murphy, Amy; Ross, R Paul; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

2017-10-01

Over the last decade, there has been increased interest in the role of the gut microbiome in health including brain health. This is by no means a new theory; Elie Metchnikoff proposed over a century ago that targeting the gut by consuming lactic acid bacteria such as those in yogurt, could improve or delay the onset of cognitive decline associated with ageing. However, there is limited information characterising the relationship between the behavioural and physiological sequelae of ageing and alterations in the gut microbiome. To this end, we assessed the behavioural, physiological and caecal microbiota profile of aged male mice. Older mice (20-21months old) exhibited deficits in spatial memory and increases in anxiety-like behaviours compared to younger mice (2-3months old). They also exhibited increased gut permeability, which was directly correlated with elevations in peripheral pro-inflammatory cytokines. Furthermore, stress exacerbated the gut permeability of aged mice. Examination of the caecal microbiota revealed significant increases in phylum TM7, family Porphyromonadaceae and genus Odoribacter of aged mice. This represents a shift of aged microbiota towards a profile previously associated with inflammatory disease, particularly gastrointestinal and liver disorders. Furthermore, Porphyromonadaceae, which has also been associated with cognitive decline and affective disorders, was directly correlated with anxiety-like behaviour in aged mice. These changes suggest that changes in the gut microbiota and associated increases in gut permeability and peripheral inflammation may be important mediators of the impairments in behavioural, affective and cognitive functions seen in ageing. Copyright © 2017 Elsevier Inc. All rights reserved.

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 .

Relative value of diverse brain MRI and blood-based biomarkers for predicting cognitive decline in the elderly

NASA Astrophysics Data System (ADS)

Madsen, Sarah K.; Ver Steeg, Greg; Daianu, Madelaine; Mezher, Adam; Jahanshad, Neda; Nir, Talia M.; Hua, Xue; Gutman, Boris A.; Galstyan, Aram; Thompson, Paul M.

2016-03-01

Cognitive decline accompanies many debilitating illnesses, including Alzheimer's disease (AD). In old age, brain tissue loss also occurs along with cognitive decline. Although blood tests are easier to perform than brain MRI, few studies compare brain scans to standard blood tests to see which kinds of information best predict future decline. In 504 older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we first used linear regression to assess the relative value of different types of data to predict cognitive decline, including 196 blood panel biomarkers, 249 MRI biomarkers obtained from the FreeSurfer software, demographics, and the AD-risk gene APOE. A subset of MRI biomarkers was the strongest predictor. There was no specific blood marker that increased predictive accuracy on its own, we found that a novel unsupervised learning method, CorEx, captured weak correlations among blood markers, and the resulting clusters offered unique predictive power.

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.

Immediate and Delayed Effects of Meta-Cognitive Instruction on Regulation of Cognition and Mathematics Achievement

ERIC Educational Resources Information Center

Mevarech, Zemira R.; Amrany, Chagit

2008-01-01

The present study addressed two research questions: (a) the extent to which students who were exposed to meta-cognitive instruction are able to implement meta-cognitive processes in a delayed, stressful situation, in our case--being examined on the matriculation exam; and (b) whether students preparing themselves for the matriculation exam in…

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

Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis.

PubMed

Northey, Joseph Michael; Cherbuin, Nicolas; Pumpa, Kate Louise; Smee, Disa Jane; Rattray, Ben

2018-02-01

Physical exercise is seen as a promising intervention to prevent or delay cognitive decline in individuals aged 50 years and older, yet the evidence from reviews is not conclusive. To determine if physical exercise is effective in improving cognitive function in this population. Systematic review with multilevel meta-analysis. Electronic databases Medline (PubMed), EMBASE (Scopus), PsychINFO and CENTRAL (Cochrane) from inception to November 2016. Randomised controlled trials of physical exercise interventions in community-dwelling adults older than 50 years, with an outcome measure of cognitive function. The search returned 12 820 records, of which 39 studies were included in the systematic review. Analysis of 333 dependent effect sizes from 36 studies showed that physical exercise improved cognitive function (0.29; 95% CI 0.17 to 0.41; p<0.01). Interventions of aerobic exercise, resistance training, multicomponent training and tai chi, all had significant point estimates. When exercise prescription was examined, a duration of 45-60 min per session and at least moderate intensity, were associated with benefits to cognition. The results of the meta-analysis were consistent and independent of the cognitive domain tested or the cognitive status of the participants. Physical exercise improved cognitive function in the over 50s, regardless of the cognitive status of participants. To improve cognitive function, this meta-analysis provides clinicians with evidence to recommend that patients obtain both aerobic and resistance exercise of at least moderate intensity on as many days of the week as feasible, in line with current exercise guidelines. © 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.

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

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.

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.

[Theoretical reflection on the place of memory and temporal cognitive mechanisms in addictive disorders].

PubMed

Lalanne, L; Laprevote, V; Danion, J-M; Bacon, E

2016-06-01

Addictions can be regarded as cognitive disorders related to neurobiological impairments. On the one hand, some cognitive impairments occur as a result of substance intake and withdrawal upon stopping intake, while, on the other hand, cognitive mechanisms are responsible for initiating and maintaining addiction. In this review, we detail the memory and temporal mechanisms involved in this pathology. We reviewed the literature dedicated to the mechanisms of conditioning association between a substance and a context, and the memory and temporal mechanisms involved in the maintenance of addiction. Cognitive impairments in this context are accompanied by both short-term and long-term neurobiological disorders. Drug-context conditioning is dependent on learning abilities in rats and humans, and it is the first step towards the development of an addiction. In fact, with the beginning of an addiction, it is the context associated with the substance intake, which determines the reinforcing factors (such as pleasure in the case of drug consumption) for the development of an addiction. Maintenance of addiction is related to the persistence of this association between context and substance. Furthermore, the impulsiveness of patients renders them unable to delay their gratification. Consequently, even if delayed gratifications are more valuable, patients prefer immediate gratification such as substance use. The memory and temporal mechanisms of addiction are central to the initiation and maintenance of drug addiction. They also affect patients' ability to develop projects for the future. The salience of the memory association between drug and context is accompanied by a decline in autobiographical memories, which become poor and lacking in detail. It is probably these impairments which are responsible for the difficulty that the patients have while investigating their story during psychotherapy. On the other hand, given that even though delayed gratification is greater patients prefer immediate gratification, they have difficulty making plans for the future and constructing their own personality. These cognitive impairments are sustained by neurobiological correlates such as dopamine dysregulation in the short-term and changes in neural plasticity in the cortico-meso-limbic system in the long term. We reviewed full arguments which highlight that addiction is mediated by cognitive mechanisms which are related on the one hand to clinical symptoms and, on the other hand, to neurobiological alterations. According to the literature, memory and time mechanisms seem to be central to the initiation and maintenance of addictive behaviours. More research is needed to improve our knowledge of the cognitive mechanisms of addiction and to develop new tools for treating patients. Copyright © 2015 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

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.

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

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.

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.

Multiple Imputation of Cognitive Performance as a Repeatedly Measured Outcome

PubMed Central

Rawlings, Andreea M.; Sang, Yingying; Sharrett, A. Richey; Coresh, Josef; Griswold, Michael; Kucharska-Newton, Anna M.; Palta, Priya; Wruck, Lisa M.; Gross, Alden L.; Deal, Jennifer A.; Power, Melinda C.; Bandeen-Roche, Karen

2016-01-01

Background Longitudinal studies of cognitive performance are sensitive to dropout, as participants experiencing cognitive deficits are less likely to attend study visits, which may bias estimated associations between exposures of interest and cognitive decline. Multiple imputation is a powerful tool for handling missing data, however its use for missing cognitive outcome measures in longitudinal analyses remains limited. Methods We use multiple imputation by chained equations (MICE) to impute cognitive performance scores of participants who did not attend the 2011-2013 exam of the Atherosclerosis Risk in Communities Study. We examined the validity of imputed scores using observed and simulated data under varying assumptions. We examined differences in the estimated association between diabetes at baseline and 20-year cognitive decline with and without imputed values. Lastly, we discuss how different analytic methods (mixed models and models fit using generalized estimate equations) and choice of for whom to impute result in different estimands. Results Validation using observed data showed MICE produced unbiased imputations. Simulations showed a substantial reduction in the bias of the 20-year association between diabetes and cognitive decline comparing MICE (3-4% bias) to analyses of available data only (16-23% bias) in a construct where missingness was strongly informative but realistic. Associations between diabetes and 20-year cognitive decline were substantially stronger with MICE than in available-case analyses. Conclusions Our study suggests when informative data are available for non-examined participants, MICE can be an effective tool for imputing cognitive performance and improving assessment of cognitive decline, though careful thought should be given to target imputation population and analytic model chosen, as they may yield different estimands. PMID:27619926

Visual function and cognitive speed of processing mediate age-related decline in memory span and fluid intelligence

PubMed Central

Clay, Olivio J.; Edwards, Jerri D.; Ross, Lesley A.; Okonkwo, Ozioma; Wadley, Virginia G.; Roth, David L.; Ball, Karlene K.

2010-01-01

Objectives: To evaluate the relationship between sensory and cognitive decline, particularly with respect to speed of processing, memory span, and fluid intelligence. Additionally, the common cause, sensory degradation and speed of processing hypotheses were compared. Methods: Structural equation modeling was used to investigate the complex relationships among age-related decrements in these areas. Results: Cross-sectional data analyses included 842 older adult participants (M = 73 years). After accounting for age-related declines in vision and processing speed, the direct associations between age and memory span and between age and fluid intelligence were nonsignificant. Older age was associated with visual decline, which was associated with slower speed of processing, which in turn was associated with greater cognitive deficits. Discussion: The findings support both the sensory degradation and speed of processing accounts of age-related cognitive decline. Further, the findings highlight positive aspects of normal cognitive aging in that older age may not be associated with a loss of fluid intelligence if visual sensory functioning and processing speed can be maintained. PMID:19436063

Hypoglycaemia and cognitive function.

PubMed

Warren, Roderick E; Frier, Brian M

2005-09-01

Acute hypoglycaemia impairs cerebral function, and available data indicate that cognitive performance becomes impaired at a blood glucose level of 2.6-3.0 mmol/l in healthy subjects. Methodological problems limit comparisons between studies, but in general complex tasks are more sensitive to hypoglycaemia than simple tasks, and some cognitive abilities are completely abolished. The onset of hypoglycaemic cognitive dysfunction is immediate, but recovery may be considerably delayed. There is persuasive evidence of adaptation to hypoglycaemia, partly due to increased brain glucose uptake capacity, although other mechanisms may exist. Patients who are exposed to chronic or recurrent hypoglycaemia become remarkably tolerant to the state, but this is insufficient to prevent severe hypoglycaemia with neuroglycopenic decompensation, probably because symptomatic and counterregulatory responses adapt even more. During experimental hypoglycaemia, administration of non-glucose cerebral fuels preserves cognitive function. However, little progress has been made as yet towards protecting cognitive function during hypoglycaemia in clinical practice. The chronic effects of recurrent hypoglycaemia remain contentious. There are numerous case reports of hypoglycaemic brain damage and of cognitive deterioration attributed to repeated severe hypoglycaemia. The major prospective studies, including the Diabetes Control and Complications Trial, did not report cognitive declines in intensively treated patients, but had unrepresentative study populations and may have been too short to detect such effects. Structural and functional brain changes are not only associated with recurrent severe hypoglycaemia, but also with hyperglycaemia and early disease onset and may in part be due to hyperglycaemic microvascular disease. Children may be more prone to acute metabolic insults, and there is evidence of developmental disadvantage associated with hypoglycaemic episodes.

Cognitive function and the agreement between self-reported and accelerometer-accessed physical activity.

PubMed

Herbolsheimer, Florian; Riepe, Matthias W; Peter, Richard

2018-02-21

Numerous studies have reported weak or moderate correlations between self-reported and accelerometer-assessed physical activity. One explanation is that self-reported physical activity might be biased by demographic, cognitive or other factors. Cognitive function is one factor that could be associated with either overreporting or underreporting of daily physical activity. Difficulties in remembering past physical activities might result in recall bias. Thus, the current study examines whether the cognitive function is associated with differences between self-reported and accelerometer-assessed physical activity. Cross-sectional data from the population-based Activity and Function in the Elderly in Ulm study (ActiFE) were used. A total of 1172 community-dwelling older adults (aged 65-90 years) wore a uniaxial accelerometer (activPAL unit) for a week. Additionally, self-reported physical activity was assessed using the LASA Physical Activity Questionnaire (LAPAQ). Cognitive function was measured with four items (immediate memory, delayed memory, recognition memory, and semantic fluency) from the Consortium to Establish a Registry for Alzheimer's Disease Total Score (CERAD-TS). Mean differences of self-reported and accelerometer-assessed physical activity (MPA) were associated with cognitive function in men (r s  = -.12, p = .002) but not in women. Sex-stratified multiple linear regression analyses showed that MPA declined with high cognitive function in men (β = -.13; p = .015). Results suggest that self-reported physical activity should be interpreted with caution in older populations, as cognitive function was one factor that explained the differences between objective and subjective physical activity measurements.

The Effect of Cognitive Restructuring on Delay of Gratification.

ERIC Educational Resources Information Center

Nisan, Mordecai; Koriat, Asher

1984-01-01

Two experiments evaluated predictions derived from a cognitive-developmental approach to delay of gratification. In the first, kindergarten children were asked to make a choice between a small immediate and a large delayed reward. In the second, children were presented with either an objective-rational or a subjective-emotional argument…

Monkeys perform as well as apes and humans in a size discrimination task.

PubMed

Schmitt, Vanessa; Kröger, Iris; Zinner, Dietmar; Call, Josep; Fischer, Julia

2013-09-01

Whether the cognitive competences of monkeys and apes are rather similar or whether the larger-brained apes outperform monkeys in cognitive experiments is a highly debated topic. Direct comparative analyses are therefore essential to examine similarities and differences among species. We here compared six primate species, including humans, chimpanzees, bonobos, gorillas (great apes), olive baboons, and long-tailed macaques (Old World monkeys) in a task on fine-grained size discrimination. Except for gorillas, subjects of all taxa (i.e. humans, apes, and monkeys) were able to discriminate three-dimensional cubes with a volume difference of only 10 % (i.e. cubes of 50 and 48 mm side length) and performed only slightly worse when the cubes were presented successively. The minimal size discriminated declined further with increasing time delay between presentations of the cubes, highlighting the difficulty to memorize exact size differences. The results suggest that differences in brain size, as a proxy for general cognitive abilities, did not account for variation in performance, but that differential socio-ecological pressures may better explain species differences. Our study highlights the fact that differences in cognitive abilities do not always map neatly onto phylogenetic relationships and that in a number of cognitive experiments monkeys do not fare significantly worse than apes, casting doubt on the assumption that larger brains per se confer an advantage in such kinds of tests.

Prospective memory training in older adults and its relevance for successful aging.

PubMed

Hering, Alexandra; Rendell, Peter G; Rose, Nathan S; Schnitzspahn, Katharina M; Kliegel, Matthias

2014-11-01

In research on cognitive plasticity, two training approaches have been established: (1) training of strategies to improve performance in a given task (e.g., encoding strategies to improve episodic memory performance) and (2) training of basic cognitive processes (e.g., working memory, inhibition) that underlie a range of more complex cognitive tasks (e.g., planning) to improve both the training target and the complex transfer tasks. Strategy training aims to compensate or circumvent limitations in underlying processes, while process training attempts to augment or to restore these processes. Although research on both approaches has produced some promising findings, results are still heterogeneous and the impact of most training regimes for everyday life is unknown. We, therefore, discuss recent proposals of training regimes aiming to improve prospective memory (i.e., forming and realizing delayed intentions) as this type of complex cognition is highly relevant for independent living. Furthermore, prospective memory is associated with working memory and executive functions and age-related decline is widely reported. We review initial evidence suggesting that both training regimes (i.e., strategy and/or process training) can successfully be applied to improve prospective memory. Conceptual and methodological implications of the findings for research on age-related prospective memory and for training research in general are discussed.

Synergistic Increase of Serum BDNF in Alzheimer Patients Treated with Cerebrolysin and Donepezil: Association with Cognitive Improvement in ApoE4 Cases

PubMed Central

Alvarez, Irene; Iglesias, Olalla; Crespo, Ignacio; Figueroa, Jesus; Aleixandre, Manuel; Linares, Carlos; Granizo, Elias; Garcia-Fantini, Manuel; Marey, Jose; Masliah, Eliezer; Winter, Stefan; Muresanu, Dafin; Moessler, Herbert

2016-01-01

Background: Low circulating brain derived neurotrophic factor may promote cognitive deterioration, but the effects of neurotrophic and combination drug therapies on serum brain derived neurotrophic factor were not previously investigated in Alzheimer’s disease. Methods: We evaluated the effects of Cerebrolysin, donepezil, and the combined therapy on brain derived neurotrophic factor serum levels at week 16 (end of Cerebrolysin treatment) and week 28 (endpoint) in mild-to-moderate Alzheimer’s disease patients. Results: Cerebrolysin, but not donepezil, increased serum brain derived neurotrophic factor at week 16, while the combination therapy enhanced it at both week 16 and study endpoint. Brain derived neurotrophic factor responses were significantly higher in the combination therapy group than in donepezil and Cerebrolysin groups at week 16 and week 28, respectively. Brain derived neurotrophic factor increases were greater in apolipoprotein E epsilon-4 allele carriers, and higher brain derived neurotrophic factor levels were associated with better cognitive improvements in apolipoprotein E epsilon-4 allele patients treated with Cerebrolysin and the combined therapy. Conclusion: Our results indicate a synergistic action of Cerebrolysin and donepezil to increase serum brain derived neurotrophic factor and delaying cognitive decline, particularly in Alzheimer’s disease cases with apolipoprotein E epsilon-4 allele. PMID:27207906

Modifiable factors that alter the size of the hippocampus with ageing.

PubMed

Fotuhi, Majid; Do, David; Jack, Clifford

2012-03-13

The hippocampus is particularly vulnerable to the neurotoxic effects of obesity, diabetes mellitus, hypertension, hypoxic brain injury, obstructive sleep apnoea, bipolar disorder, clinical depression and head trauma. Patients with these conditions often have smaller hippocampi and experience a greater degree of cognitive decline than individuals without these comorbidities. Moreover, hippocampal atrophy is an established indicator for conversion from the normal ageing process to developing mild cognitive impairment and dementia. As such, an important aim is to ascertain which modifiable factors can have a positive effect on the size of the hippocampus throughout life. Observational studies and preliminary clinical trials have raised the possibility that physical exercise, cognitive stimulation and treatment of general medical conditions can reverse age-related atrophy in the hippocampus, or even expand its size. An emerging concept--the dynamic polygon hypothesis--suggests that treatment of modifiable risk factors can increase the volume or prevent atrophy of the hippocampus. According to this hypothesis, a multidisciplinary approach, which involves strategies to both reduce neurotoxicity and increase neurogenesis, is likely to be successful in delaying the onset of cognitive impairment with ageing. Further research on the constellation of interventions that could be most effective is needed before recommendations can be made for implementing preventive and therapeutic strategies.

Obstructive sleep apnoea and dementia: is there a link?

PubMed

Shastri, Abhishek; Bangar, Santosh; Holmes, John

2016-04-01

Obstructive sleep apnoea is a common sleep disturbance in people of all ages, while dementia is an increasing entity among the ageing population of the world. Recent studies have established a link between sleep apnoea and cognitive decline. This literature review explores this relationship and examines the mechanisms, neurobiology and treatment modalities. The study was conducted with the use of narrative literature overview. While there are numerous studies that establish a clear relationship between obstructive sleep apnoea, cognitive decline and dementia, more work is needed in understanding the mechanism and processes involved. A detailed understanding of pathophysiology of sleep and the relationship with cognitive decline will be vital in addressing the possibility of averting a likely reversible cause of dementia or cognitive decline. Copyright © 2015 John Wiley & Sons, Ltd.

The role of B-vitamins in preventing and treating cognitive impairment and decline

USDA-ARS?s Scientific Manuscript database

Many epidemiologic studies have considered the question of whether markers of B-vitamin status are associated with cognitive function and cognitive decline. This avenue of research was sparked by the homocysteine (Hcy) theory of cardiovascular disease (CVD), which was extended to Alzheimer’s disease...

Dementia and Depression in Elders with Mental Retardation: A Pilot Study.

ERIC Educational Resources Information Center

Harper, Dennis C.; Wadsworth, John S.

1990-01-01

This article investigates cognitive decline and depressive symptomatology among older adults with mental retardation. A pilot study of assessment instruments is reported. Findings reveal that decreasing cognitive ability is associated with higher rates of observed depression and reported behavioral problems. Cognitive decline was associated with…

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

Working Memory Delay Activity Predicts Individual Differences in Cognitive Abilities

PubMed Central

Unsworth, Nash; Fukuda, Keisuke; Awh, Edward; Vogel, Edward K.

2015-01-01

A great deal of prior research has examined the relation between estimates of working memory and cognitive abilities. Yet, the neural mechanisms that account for these relations are still not very well understood. The current study explored whether individual differences in working memory delay activity would be a significant predictor of cognitive abilities. A large number of participants performed multiple measures of capacity, attention control, long-term memory, working memory span, and fluid intelligence, and latent variable analyses were used to examine the data. During two working memory change detection tasks, we acquired EEG data and examined the contra-lateral delay activity. The results demonstrated that the contralateral delay activity was significantly related to cognitive abilities, and importantly these relations were because of individual differences in both capacity and attention control. These results suggest that individual differences in working memory delay activity predict individual differences in a broad range of cognitive abilities, and this is because of both differences in the number of items that can be maintained and the ability to control access to working memory. PMID:25436671

Working memory delay activity predicts individual differences in cognitive abilities.

PubMed

Unsworth, Nash; Fukuda, Keisuke; Awh, Edward; Vogel, Edward K

2015-05-01

A great deal of prior research has examined the relation between estimates of working memory and cognitive abilities. Yet, the neural mechanisms that account for these relations are still not very well understood. The current study explored whether individual differences in working memory delay activity would be a significant predictor of cognitive abilities. A large number of participants performed multiple measures of capacity, attention control, long-term memory, working memory span, and fluid intelligence, and latent variable analyses were used to examine the data. During two working memory change detection tasks, we acquired EEG data and examined the contralateral delay activity. The results demonstrated that the contralateral delay activity was significantly related to cognitive abilities, and importantly these relations were because of individual differences in both capacity and attention control. These results suggest that individual differences in working memory delay activity predict individual differences in a broad range of cognitive abilities, and this is because of both differences in the number of items that can be maintained and the ability to control access to working memory.

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.

Effect of Aging on ERP Components of Cognitive Control

PubMed Central

Kropotov, Juri; Ponomarev, Valery; Tereshchenko, Ekaterina P.; Müller, Andreas; Jäncke, Lutz

2016-01-01

As people age, their performance on tasks requiring cognitive control often declines. Such a decline is frequently explained as either a general or specific decline in cognitive functioning with age. In the context of hypotheses suggesting a general decline, it is often proposed that processing speed generally declines with age. A further hypothesis is that an age-related compensation mechanism is associated with a specific cognitive decline. One prominent theory is the compensation hypothesis, which proposes that deteriorated functions are compensated for by higher performing functions. In this study, we used event-related potentials (ERPs) in the context of a GO/NOGO task to examine the age-related changes observed during cognitive control in a large group of healthy subjects aged between 18 and 84 years. The main question we attempted to answer was whether we could find neurophysiological support for either a general decline in processing speed or a compensation strategy. The subjects performed a relatively demanding cued GO/NOGO task with similar omissions and reaction times across the five age groups. The ERP waves of cognitive control, such as N2, P3cue and CNV, were decomposed into latent components by means of a blind source separation method. Based on this decomposition, it was possible to more precisely delineate the different neurophysiological and psychological processes involved in cognitive control. These data support the processing speed hypothesis because the latencies of all cognitive control ERP components increased with age, by 8 ms per decade for the early components (<200 ms) and by 20 ms per decade for the late components. At the same time, the compensatory hypothesis of aging was also supported, as the amplitudes of the components localized in posterior brain areas decreased with age, while those localized in the prefrontal cortical areas increased with age in order to maintain performance on this simple task at a relatively stable level. PMID:27092074

Improvement of short-term memory performance in aged beagles by a nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine

PubMed Central

Araujo, Joseph A.; Landsberg, Gary M.; Milgram, Norton W.; Miolo, Alda

2008-01-01

Aged dogs demonstrate cognitive decline that is linked to brain aging. The purpose of the present study was to examine if a commercially available nutraceutical supplement that may be neuroprotective and contains phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine could improve cognitive function in aged beagles. Nine aged beagles were tested on performance on a delayed-non-matching-to-position task, which is a neuropsychological test of short-term visuospatial memory. All subjects were tested on 5 baseline sessions; then, to assess the supplement, a crossover design was used in which 1 group received the supplement and the other a control substance in the 1st phase, with treatment conditions being reversed in the 2nd phase. Performance accuracy was significantly improved in supplemented dogs compared with control dogs and the effect was long lasting. These findings suggest that the nutraceutical supplement can improve memory in aged dogs. PMID:18481547

Health span approximates life span among many supercentenarians: compression of morbidity at the approximate limit of life span.

PubMed

Andersen, Stacy L; Sebastiani, Paola; Dworkis, Daniel A; Feldman, Lori; Perls, Thomas T

2012-04-01

We analyze the relationship between age of survival, morbidity, and disability among centenarians (age 100-104 years), semisupercentenarians (age 105-109 years), and supercentenarians (age 110-119 years). One hundred and four supercentenarians, 430 semisupercentenarians, 884 centenarians, 343 nonagenarians, and 436 controls were prospectively followed for an average of 3 years (range 0-13 years). The older the age group, generally, the later the onset of diseases, such as cancer, cardiovascular disease, dementia, and stroke, as well as of cognitive and functional decline. The hazard ratios for these individual diseases became progressively less with older and older age, and the relative period of time spent with disease was lower with increasing age group. We observed a progressive delay in the age of onset of physical and cognitive function impairment, age-related diseases, and overall morbidity with increasing age. As the limit of human life span was effectively approached with supercentenarians, compression of morbidity was generally observed.

Health Span Approximates Life Span Among Many Supercentenarians: Compression of Morbidity at the Approximate Limit of Life Span

PubMed Central

Andersen, Stacy L.; Sebastiani, Paola; Dworkis, Daniel A.; Feldman, Lori

2012-01-01

We analyze the relationship between age of survival, morbidity, and disability among centenarians (age 100–104 years), semisupercentenarians (age 105–109 years), and supercentenarians (age 110–119 years). One hundred and four supercentenarians, 430 semisupercentenarians, 884 centenarians, 343 nonagenarians, and 436 controls were prospectively followed for an average of 3 years (range 0–13 years). The older the age group, generally, the later the onset of diseases, such as cancer, cardiovascular disease, dementia, and stroke, as well as of cognitive and functional decline. The hazard ratios for these individual diseases became progressively less with older and older age, and the relative period of time spent with disease was lower with increasing age group. We observed a progressive delay in the age of onset of physical and cognitive function impairment, age-related diseases, and overall morbidity with increasing age. As the limit of human life span was effectively approached with supercentenarians, compression of morbidity was generally observed. PMID:22219514

Patterns of verbal memory performance in mild cognitive impairment, Alzheimer disease, and normal aging.

PubMed

Greenaway, Melanie C; Lacritz, Laura H; Binegar, Dani; Weiner, Myron F; Lipton, Anne; Munro Cullum, C

2006-06-01

Individuals with mild cognitive impairment (MCI) typically demonstrate memory loss that falls between normal aging (NA) and Alzheimer disease (AD), but little is known about the pattern of memory dysfunction in MCI. To explore this issue, California Verbal Learning Test (CVLT) performance was examined across groups of MCI, AD, and NA. MCI subjects displayed a pattern of deficits closely resembling that of AD, characterized by reduced learning, rapid forgetting, increased recency recall, elevated intrusion errors, and poor recognition discriminability with increased false-positives. MCI performance was significantly worse than that of controls and better than that of AD patients across memory indices. Although qualitative analysis of CVLT profiles may be useful in individual cases, discriminant function analysis revealed that delayed recall and total learning were the best aspects of learning/memory on the CVLT in differentiating MCI, AD, and NA. These findings support the position that amnestic MCI represents an early point of decline on the continuum of AD that is different from normal aging.

USHERING IN THE STUDY AND TREATMENT OF PRECLINICAL ALZHEIMER DISEASE

PubMed Central

Langbaum, Jessica B.S.; Fleisher, Adam S.; Chen, Kewei; Ayutyanont, Napatkamon; Lopera, Francisco; Quiroz, Yakeel T.; Caselli, Richard J.; Tariot, Pierre N.; Reiman, Eric M.

2014-01-01

Researchers have begun to characterize the subtle biological and cognitive processes that precede the clinical onset of Alzheimer disease (AD), and to set the stage for accelerated evaluation of experimental treatments to delay the onset, reduce the risk of or completely prevent clinical decline. Here, we provide an overview of the experimental strategies, and brain imaging and cerebrospinal fluid biomarker measures that are used in early detection and tracking of AD, highlighting at-risk individuals who could be suitable for preclinical monitoring. We discuss how these advances have contributed to reconceptualization of AD as a sequence of biological changes that occur during progression from preclinical AD, to mild cognitive impairment and finally dementia, and we review recently proposed research criteria for preclinical AD. Advances in the study of preclinical AD have driven the recognition that efficacy of at least some AD therapies may depend on initiation of treatment before clinical manifestation of disease, leading to a new era of AD prevention research. PMID:23752908

Ushering in the study and treatment of preclinical Alzheimer disease.

PubMed

Langbaum, Jessica B; Fleisher, Adam S; Chen, Kewei; Ayutyanont, Napatkamon; Lopera, Francisco; Quiroz, Yakeel T; Caselli, Richard J; Tariot, Pierre N; Reiman, Eric M

2013-07-01

Researchers have begun to characterize the subtle biological and cognitive processes that precede the clinical onset of Alzheimer disease (AD), and to set the stage for accelerated evaluation of experimental treatments to delay the onset, reduce the risk of, or completely prevent clinical decline. In this Review, we provide an overview of the experimental strategies, and brain imaging and cerebrospinal fluid biomarker measures that are used in early detection and tracking of AD, highlighting at-risk individuals who could be suitable for preclinical monitoring. We discuss how advances in the field have contributed to reconceptualization of AD as a sequence of biological changes that occur during progression from preclinical AD, to mild cognitive impairment and finally dementia, and we review recently proposed research criteria for preclinical AD. Advances in the study of preclinical AD have driven the recognition that efficacy of at least some AD therapies may depend on initiation of treatment before clinical manifestation of disease, leading to a new era of AD prevention research.

Effectiveness of Occupational Therapy Interventions to Enhance Occupational Performance for Adults With Alzheimer's Disease and Related Major Neurocognitive Disorders: A Systematic Review.

PubMed

Smallfield, Stacy; Heckenlaible, Cindy

The purpose of this systematic review was to describe the evidence for the effectiveness of interventions designed to establish, modify, and maintain occupations for adults with Alzheimer's disease (AD) and related neurocognitive disorders. Titles and abstracts of 2,597 articles were reviewed, of which 256 were retrieved for full review and 52 met inclusion criteria. U.S. Preventive Services Task Force levels of certainty and grade definitions were used to describe the strength of evidence. Articles were categorized into five themes: occupation-based, sleep, cognitive, physical exercise, and multicomponent interventions. Strong evidence supports the benefits of occupation-based interventions, physical exercise, and error-reduction learning. Occupational therapy practitioners should integrate daily occupations, physical exercise, and error-reduction techniques into the daily routine of adults with AD to enhance occupational performance and delay functional decline. Future research should focus on establishing consensus on types and dosage of exercise and cognitive interventions. Copyright © 2017 by the American Occupational Therapy Association, Inc.

Which Neuropsychological Tests Predict Progression to Alzheimer’s Disease in Hispanics?

PubMed Central

Weissberger, Gali H.; Salmon, David P.; Bondi, Mark W.; Gollan, Tamar H.

2013-01-01

Objective To investigate which neuropsychological tests predict eventual progression to Alzheimer’s disease (AD) in both Hispanic and non-Hispanic individuals. Although our approach was exploratory, we predicted that tests that underestimate cognitive ability in healthy aging Hispanics might not be sensitive to future cognitive decline in this cultural group. Method We compared first-year data of 22 older adults (11 Hispanic) who were diagnosed as cognitively normal but eventually developed AD (decliners), to 60 age- and education-matched controls (27 Hispanic) who remained cognitively normal. To identify tests that may be culturally biased in our sample, we compared Hispanic with non-Hispanic controls on all tests and asked which tests were sensitive to future decline in each cultural group. Results Compared to age-, education-, and gender-matched non-Hispanic controls, Hispanic controls obtained lower scores on tests of language, executive function, and some measures of global cognition. Consistent with our predictions, some tests identified non-Hispanic, but not Hispanic, decliners (vocabulary, semantic fluency). Contrary to our predictions, a number of tests on which Hispanics obtained lower scores than non-Hispanics nevertheless predicted eventual progression to AD in both cultural groups (e.g., Boston Naming Test [BNT], Trails A and B). Conclusions Cross-cultural variation in test sensitivity to decline may reflect greater resistance of medium difficulty items to decline and bilingual advantages that initially protect Hispanics against some aspects of cognitive decline commonly observed in non-Hispanics with preclinical AD. These findings highlight a need for further consideration of cross-cultural differences in neuropsychological test performance and development of culturally unbiased measures. PMID:23688216

Mechanisms of age-related cognitive change and targets for intervention: social interactions and stress.

PubMed

Kremen, William S; Lachman, Margie E; Pruessner, Jens C; Sliwinski, Martin; Wilson, Robert S

2012-06-01

The effects of biological and physical factors on cognitive aging are widely studied. Less is known about the role of psychosocial factors such as stress and social relationships for cognitive functioning. Speakers in Session IV of the Summit focused on possible mechanisms linking social interactions and stressful experiences to cognitive changes with aging. Elevated cortisol, repetitive thinking, negative emotions, neuroticism, chronic stress, and early life adversity were negatively associated with memory and other cognitive dimensions in later life. In contrast, supportive social relationships were found to be positively related to cognitive functioning. Some evidence was provided for multidirectional, causal relationships involving stress and negative affect as both antecedents and consequences of cognitive decline. The findings contribute to understanding the potential underlying causal processes linking psychosocial factors and cognitive aging with a developmental focus on the etiology of declines and onset of cognitive impairments. This work provides an important foundation for future research to identify modifiable factors and to design interventions to minimize cognitive declines and optimize cognitive health in adulthood.

Neural Dynamics of Multiple Object Processing in Mild Cognitive Impairment and Alzheimer's Disease: Future Early Diagnostic Biomarkers?

PubMed

Bagattini, Chiara; Mazza, Veronica; Panizza, Laura; Ferrari, Clarissa; Bonomini, Cristina; Brignani, Debora

2017-01-01

The aim of this study was to investigate the behavioral and electrophysiological dynamics of multiple object processing (MOP) in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and to test whether its neural signatures may represent reliable diagnostic biomarkers. Behavioral performance and event-related potentials [N2pc and contralateral delay activity (CDA)] were measured in AD, MCI, and healthy controls during a MOP task, which consisted in enumerating a variable number of targets presented among distractors. AD patients showed an overall decline in accuracy for both small and large target quantities, whereas in MCI patients, only enumeration of large quantities was impaired. N2pc, a neural marker of attentive individuation, was spared in both AD and MCI patients. In contrast, CDA, which indexes visual short term memory abilities, was altered in both groups of patients, with a non-linear pattern of amplitude modulation along the continuum of the disease: a reduction in AD and an increase in MCI. These results indicate that AD pathology shows a progressive decline in MOP, which is associated to the decay of visual short-term memory mechanisms. Crucially, CDA may be considered as a useful neural signature both to distinguish between healthy and pathological aging and to characterize the different stages along the AD continuum, possibly becoming a reliable candidate for an early diagnostic biomarker of AD pathology.

Suppressing aberrant GluN3A expression rescues NMDA receptor dysfunction, synapse loss and motor and cognitive decline in Huntington's disease models

PubMed Central

Marco, Sonia; Giralt, Albert; Petrovic, Milos M.; Pouladi, Mahmoud A.; Martínez-Turrillas, Rebeca; Martínez-Hernández, José; Kaltenbach, Linda S.; Torres-Peraza, Jesús; Graham, Rona K.; Watanabe, Masahiko; Luján, Rafael; Nakanishi, Nobuki; Lipton, Stuart A.; Lo, Donald C.; Hayden, Michael R.; Alberch, Jordi; Wesseling, John F.

2013-01-01

Huntington's disease is caused by an expanded polyglutamine repeat in huntingtin (Htt), but the pathophysiological sequence of events that trigger synaptic failure and neuronal loss are not fully understood. Alterations in NMDA-type glutamate receptors (NMDARs) have been implicated, yet it remains unclear how the Htt mutation impacts NMDAR function and direct evidence for a causative role is missing. Here we show that mutant Htt re-directs an intracellular store of juvenile NMDARs to the surface of striatal neurons by sequestering and disrupting the subcellular localization of the GluN3A subunit-specific endocytic adaptor PACSIN1. Overexpressing GluN3A in wild-type striatum mimicked the synapse loss observed in Huntington's disease mouse models, whereas genetic deletion of GluN3A prevented synapse degeneration, ameliorated motor and cognitive decline, and reduced striatal atrophy and neuronal loss in the YAC128 model. Furthermore, GluN3A deletion corrected the abnormally enhanced NMDAR currents, which have been linked to cell death in Huntington's disease and other neurodegenerative conditions. Our findings reveal an early pathogenic role of GluN3A dysregulation in Huntington's disease, and suggest that therapies targeting GluN3A or pathogenic Htt-PACSIN1 interactions might prevent or delay disease progression. PMID:23852340

Using an eHealth Intervention to Stimulate Health Behavior for the Prevention of Cognitive Decline in Dutch Adults: A Study Protocol for the Brain Aging Monitor.

PubMed

Aalbers, Teun; Baars, Maria Ae; Qin, Li; de Lange, Annet; Kessels, Roy Pc; Olde Rikkert, Marcel Gm

2015-11-10

Internet-delivered intervention programs are an effective way of changing health behavior in an aging population. The same population has an increasing number of people with cognitive decline or cognitive impairments. Modifiable lifestyle risk factors such as physical activity, nutrition, smoking, alcohol consumption, sleep, and stress all influence the probability of developing neurodegenerative diseases such as Alzheimer's disease. This study aims to answer two questions: (1) Is the use of a self-motivated, complex eHealth intervention effective in changing multiple health behaviors related to cognitive aging in Dutch adults in the work force, especially those aged 40 and over? and (2) Does this health behavior change result in healthier cognitive aging patterns and contribute to preventing or delaying future onset of neurodegenerative syndromes? The Brain Aging Monitor study uses a quasi-experimental 2-year pre-posttest design. The Brain Aging Monitor is an online, self-motivated lifestyle intervention program. Recruitment is done both in medium to large organizations and in the Dutch general population over the age of 40. The main outcome measure is the relationship between lifestyle change and cognitive aging. The program uses different strategies and modalities such as Web content, email, online newsletters, and online games to aid its users in behavior change. To build self-regulatory skills, the Brain Aging Monitor offers its users goal-setting activities, skill-building activities, and self-monitoring. Study results are expected to be published in early 2016. This study will add to the body of evidence on the effectiveness of eHealth intervention programs with the combined use of state-of-the-art applied games and established behavior change techniques. This will lead to new insights on how to use behavior change techniques and theory in multidimensional lifestyle eHealth research, and how these techniques and theories apply when they are used in a setting where no professional back-end is available. Nederlands Trial Register: NTR4144; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4144 (Archived by WebCite at http://www.webcitation.org/6cZzwZSg3).

Examining the association between late-life leisure activity participation and global cognitive decline in community-dwelling elderly Chinese in Hong Kong.

PubMed

Leung, Grace Tak Yu; Fung, Ada Wai Tung; Tam, Cindy Woon Chi; Lui, Victor Wing Cheong; Chiu, Helen Fung Kum; Chan, Wai Man; Lam, Linda Chiu Wa

2011-01-01

This study examines the association between late-life leisure activity participation and global cognitive decline in community-dwelling elderly Chinese in Hong Kong. Five hundred and five participants, not clinically demented at the baseline, were analysed in the follow-up study of a population-based community survey among Hong Kong Chinese aged 60 and over. Information regarding leisure activity participation, global cognitive function and important sociodemographic variables was collected. Late life leisure activity profiles were classified into intellectual, social, physical and recreational categories, and were measured by total hours per week, total frequency and total number of subtypes. Multivariate logistic regression analyses were used to evaluate the association between leisure activity participation at the baseline and the incidence of global cognitive decline at the 22-month follow-up. The incidence of global cognitive decline was defined as a one-point drop in z-score of the Cantonese version of the mini-mental state examination (CMMSE). At the follow-up, a higher level of participation in intellectual activities was significantly associated with a lower incidence of global cognitive decline as measured by both the total hours per week (multivariate-adjusted OR 0.97 (95% CI 0.94-0.99, p=0.003)), and the total number of subtypes (multivariate-adjusted OR 0.74 (95% CI 0.58-0.95, p=0.018)). A higher level of late-life intellectual activity participation was associated with less global cognitive decline among community-dwelling elderly Chinese in Hong Kong. Copyright © 2010 John Wiley & Sons, Ltd.

Fasting insulin levels and cognitive decline in older women without diabetes.

PubMed

van Oijen, Marieke; Okereke, Olivia I; Kang, Jae Hee; Pollak, Michael N; Hu, Frank B; Hankinson, Susan E; Grodstein, Francine

2008-01-01

Type 2 diabetes has been associated with an increased risk of dementia. To assess possible independent effects of insulin, we investigated the relation of insulin levels to cognitive decline in nondiabetic women. Fasting plasma insulin levels were measured in mid-life in 1,416 nondiabetic Nurses' Health Study participants, who also completed cognitive testing that began 10 years later (current age: 70-75 years). Over 4 years, 3 assessments of general cognition, verbal memory, category fluency and attention were administered. Primary outcomes were the Telephone Interview for Cognitive Status (TICS) performance, the global score (average of all tests) and verbal memory (average of verbal recall tests). Linear mixed-effects models were used to calculate the association between insulin and cognitive decline. Higher insulin levels were associated with a faster decline on the TICS and verbal memory. For analysis, batch-specific quartiles of insulin levels were constructed. Compared to the lowest quartile, adjusted differences in the annual rates of decline (with 95% CI values in parentheses) for the second, third and fourth quartiles were: TICS, -0.06 (-0.16, 0.03), -0.14 (-0.24, -0.04), and -0.09 (-0.19, 0.01) points (p trend = 0.04); verbal memory, -0.01 (-0.04, 0.02), -0.05 (-0.08, -0.02), and -0.02 (-0.05, 0.01) units (p trend = 0.02). These associations remained after multivariable adjustment. Our study provides evidence for a potential role of higher fasting insulin levels in cognitive decline, possibly independent of diabetes. (c) 2008 S. Karger AG, Basel

Habitual coffee consumption and risk of cognitive decline/dementia: A systematic review and meta-analysis of prospective cohort studies.

PubMed

Liu, Qing-Ping; Wu, Yan-Feng; Cheng, Hong-Yu; Xia, Tao; Ding, Hong; Wang, Hui; Wang, Ze-Mu; Xu, Yun

2016-06-01

Findings from epidemiologic studies of coffee consumption and risk for cognitive decline or dementia are inconclusive. The aim of this study was to conduct a meta-analysis of prospective studies to assess the association between coffee consumption and the risk for cognitive decline and dementia. Relevant studies were identified by searching PubMed and Embase databases between 1966 and December 2014. Prospective cohorts that reported relative risk (RRs) and 95% confidence intervals (CIs) for the association of coffee consumption with dementia incidence or cognitive changing were eligible. Study-specific RRs were combined by using a random-effects model. Eleven prospective studies, including 29,155 participants, were included in the meta-analysis. The combined RR indicated that high coffee consumption was not associated with the different measures of cognitive decline or dementia (summary RR, 0.97; 95% CI, 0.84-1.11). Subgroup analyses suggested a significant inverse association between highest coffee consumption and the risk for Alzheimer disease (summary RR, 0.73; 95% CI, 0.55-0.97). The dose-response analysis, including eight studies, did not show an association between the increment of coffee intake and cognitive decline or dementia risk (an increment of 1 cup/d of coffee consumed; summary RR, 1.00; 95% CI, 0.98-1.02). The present study suggests that higher coffee consumption is associated with reduced risk for Alzheimer disease. Further randomized controlled trials or well-designed cohort studies are needed to determine the association between coffee consumption and cognitive decline or dementia. Copyright © 2016 Elsevier Inc. All rights reserved.

Older driver support system.

DOT National Transportation Integrated Search

2016-04-01

A significant factor impinging on older drivers ability to maintain safe and efficient mobility as : they age is the decline in behavioral, cognitive, and perceptual functions. Declines in vision, : hearing, cognitive processing, physical strength...

Effects of Family History and APOE ε4 Status on Cognitive Decline in the Absence of AD: The Cache County Study

PubMed Central

Hayden, Kathleen M.; Zandi, Peter P.; West, Nancy A.; Tschanz, JoAnn T.; Norton, Maria C.; Corcoran, Chris; Breitner, John C. S.; Welsh-Bohmer, Kathleen A.

2010-01-01

Context Studies have shown that the APOE ε4 genotype is associated with cognitive decline and increased risk of Alzheimer’s dementia (AD). Other genes are probably associated with both outcomes. Family history of AD (FhxAD) may represent genetic factors or shared environmental factors that increase the risk of cognitive decline. Objective To evaluate the influences of FhxAD and APOE ε4 on cognitive decline. Design, Setting, and Participants Residents of Cache County, Utah, aged 65+ were invited to participate. At baseline 2,957 participants provided DNA for genotyping at APOE and a detailed family history of AD. They also completed the Modified Mini-Mental State Examination (3MS). Cognitive status was re-examined after three and seven years. We used mixed models to examine the association between FhxAD, APOE ε4, and cognitive trajectories. Main Outcome Measure 3MS score trajectories over time. Results Compared with participants who had neither APOE ε4 nor FhxAD, those with APOE ε4 scored lower at baseline (−0.70 points on 3MS, 95% confidence interval (CI) −1.15 to −0.24). Participants with both FhxAD and APOE ε4 differed less, if at all, in baseline score (−0.46, 95% CI −1.09 to 0.16) but declined faster over 7 years (− 9.75, CI −10.82 -- 8.67) vs.(−2.91, CI −3.37 to −2.44). After exclusion of participants who developed prodromal AD or incident dementia, the group with FhxAD and APOE ε4 declined much less over 7 years (−1.54, CI −2.59 to −0.50). Conclusions These results suggest that much of the association between FhxAD, APOE ε4, and cognitive decline is attributed to undetected incipient (latent) disease. Absent this association, the two factors do not appear individually to be associated with cognitive decline although they may be additive. PMID:19901170

Bayley-III Cognitive and Language Scales in Preterm Children.

PubMed

Spencer-Smith, Megan M; Spittle, Alicia J; Lee, Katherine J; Doyle, Lex W; Anderson, Peter J

2015-05-01

This study aimed to assess the sensitivity and specificity of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), Cognitive and Language scales at 24 months for predicting cognitive impairments in preterm children at 4 years. Children born <30 weeks' gestation completed the Bayley-III at 24 months and the Differential Ability Scale, Second Edition (DAS-II), at 4 years to assess cognitive functioning. Test norms and local term-born reference data were used to classify delay on the Bayley-III Cognitive and Language scales. Impairment on the DAS-II Global Conceptual Ability, Verbal, and Nonverbal Reasoning indices was classified relative to test norms. Scores < -1 SD relative to the mean were classified as mild/moderate delay or impairment, and scores < -2 SDs were classified as moderate delay or impairment. A total of 105 children completed the Bayley-III and DAS-II. The sensitivity of mild/moderate cognitive delay on the Bayley-III for predicting impairment on DAS-II indices ranged from 29.4% to 38.5% and specificity ranged from 92.3% to 95.5%. The sensitivity of mild/moderate language delay on the Bayley-III for predicting impairment on DAS-II indices ranged from 40% to 46.7% and specificity ranged from 81.1% to 85.7%. The use of local reference data at 24 months to classify delay increased sensitivity but reduced specificity. Receiver operating curve analysis identified optimum cut-point scores for the Bayley-III that were more consistent with using local reference data than Bayley-III normative data. In our cohort of very preterm children, delay on the Bayley-III Cognitive and Language scales was not strongly predictive of future impairments. More children destined for later cognitive impairment were identified by using cut-points based on local reference data than Bayley-III norms. Copyright © 2015 by the American Academy of Pediatrics.

Global Developmental Delay and Its Relationship to Cognitive Skills

ERIC Educational Resources Information Center

Riou, Emilie M.; Ghosh, Shuvo; Francoeur, Emmett; Shevell, Michael I.

2009-01-01

Global developmental delay (GDD) is defined as evidence of significant delays in two or more developmental domains. Our study determined the cognitive skills of a cohort of young children with GDD. A retrospective chart review of all children diagnosed with GDD within a single developmental clinic was carried out. Scores on fine motor (Peabody…

Preservation of cognitive and functional ability as markers of longevity.

PubMed

Schupf, Nicole; Costa, Rosann; Tang, Ming-Xin; Andrews, Howard; Tycko, Benjamin; Lee, Joseph H; Mayeux, Richard

2004-10-01

Longevity is a complex biological process for which the phenotypes have not been established. Preservation of cognitive and physical function may be important and preservation of these functions is, in part, inherited. We investigated the relation between rate of change in cognitive and functional abilities in probands and risk of death in their siblings. Probands were classified as showing no decline, slow, medium, or rapid rate of decline, based on the slope of change in cognitive and physical/functional factors over three or more assessments. Siblings of probands who did not decline on measures of memory, visuospatial/cognitive function or ADL skills were approximately half as likely to die as siblings of probands who had the most rapid decline. The reduction in risk of death in siblings of probands who did not decline in was primarily observed among siblings of probands who were older than 75 years, suggesting that genetic influences on life span may be greater at older ages. There was no association between probands' rate of change in language, IADL skills, upper or lower extremity mobility and risk of death in siblings. The results of the present study identify phenotypes associated with preserved cognitive and functional abilities which may serve as markers for longevity.

Aging children of long-lived parents experience slower cognitive decline.

PubMed

Dutta, Ambarish; Henley, William; Robine, Jean-Marie; Llewellyn, David; Langa, Kenneth M; Wallace, Robert B; Melzer, David

2014-10-01

Parental longevity confers lower risks for some age-related diseases in offspring. We tested the association between parental longevity and late-life cognitive decline or dementia. Data were from the Health and Retirement Study (HRS), a US national sample. Biennial cognitive assessment (Telephone Interview of Cognitive Status-Modified [TICS-m]) occurred for ages 64 years or older in 1996 through 2008 (maximum, 79 years), including physician-diagnosed memory disorder. Offspring were categorized into parental longevity groups based on gender-specific distributional cut points. Model covariates included race, respondents' education, and income status during childhood and adulthood. Offspring groups did not differ on TICS-m scores at baseline. During follow-up, offspring of two long-lived parents experienced 40% slower rates of TICS-m decline than those with no long-lived parents (95% confidence interval, 12-72; P=.003; n=4731). Increased parental longevity was also associated with lower risk of physician-diagnosed memory disorder. Estimates did not change after controlling for environmental variables. Parental longevity is associated inversely with cognitive decline and self-reported diagnosed memory disorders in aging offspring. Parental longevity may be a valuable trait for identifying early biomarkers for resistance to cognitive decline in aging. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Development and validation of a parent-report measure for detection of cognitive delay in infancy.

PubMed

Schafer, Graham; Genesoni, Lucia; Boden, Greg; Doll, Helen; Jones, Rosamond A K; Gray, Ron; Adams, Eleri; Jefferson, Ros

2014-12-01

To develop a brief, parent-completed instrument (ERIC - Early Report by Infant Caregivers) for detection of cognitive delay in 10- to 24-month-olds born preterm, or of low birthweight, or with perinatal complications, and to establish ERIC's diagnostic properties. Scores for ERIC were collected from the parents of 317 children meeting ≥inclusion criterion (birthweight <1500 g, gestational age <34 completed weeks, 5 min Apgar score <7, or presence of hypoxic-ischaemic encephalopathy) and no exclusion criteria. Children were assessed using a criterion score of below 80 on the Bayley Scales of Infant and Toddler Development-III cognitive scale. Items were retained according to their individual associations with delay. Sensitivity, specificity, and positive and negative predictive values were estimated and a truncated ERIC was developed for use in children <14 months old. ERIC correctly detected developmental delay in 17 out of 18 children in the sample, with 94.4% sensitivity, 76.9% specificity, 19.8% positive predictive value, 99.6% negative predictive value, 4.09 likelihood ratio positive, and 0.07 likelihood ratio negative. ERIC has potential value as a quickly administered diagnostic instrument for the absence of early cognitive delay in 10- to 24-month-old preterm infants and as a screen for cognitive delay. © 2014 Mac Keith Press.

Association of physical fitness and fatness with cognitive function in women with fibromyalgia.

PubMed

Soriano-Maldonado, Alberto; Artero, Enrique G; Segura-Jiménez, Víctor; Aparicio, Virgina A; Estévez-López, Fernando; Álvarez-Gallardo, Inmaculada C; Munguía-Izquierdo, Diego; Casimiro-Andújar, Antonio J; Delgado-Fernández, Manuel; Ortega, Francisco B

2016-09-01

This study assessed the association of fitness and fatness with cognitive function in women with fibromyalgia, and the independent influence of their single components on cognitive tasks. A total of 468 women with fibromyalgia were included. Speed of information processing and working memory (Paced Auditory Serial Addition Task), as well as immediate and delayed recall, verbal learning and delayed recognition (Rey Auditory Verbal Learning Test) were assessed. Aerobic fitness, muscle strength, flexibility and motor agility were assessed with the Senior Fitness Test battery. Body mass index, percent body fat, fat-mass index and waist circumference were measured. Aerobic fitness was associated with attention and working memory (all, p < 0.05). All fitness components were generally associated with delayed recall, verbal learning and delayed recognition (all, p < 0.05). Aerobic fitness showed the most powerful association with attention, working memory, delayed recall and verbal learning, while motor agility was the most powerful indicator of delayed recognition. None of the fatness parameters were associated with any of the outcomes (all, p > 0.05). Our results suggest that fitness, but not fatness, is associated with cognitive function in women with fibromyalgia. Aerobic fitness appears to be the most powerful fitness component regarding the cognitive tasks evaluated.

Causes, effects and connectivity changes in MS-related cognitive decline.

PubMed

Rimkus, Carolina de Medeiros; Steenwijk, Martijn D; Barkhof, Frederik

2016-01-01

Cognitive decline is a frequent but undervalued aspect of multiple sclerosis (MS). Currently, it remains unclear what the strongest determinants of cognitive dysfunction are, with grey matter damage most directly related to cognitive impairment. Multi-parametric studies seem to indicate that individual factors of MS-pathology are highly interdependent causes of grey matter atrophy and permanent brain damage. They are associated with intermediate functional effects (e.g. in functional MRI) representing a balance between disconnection and (mal) adaptive connectivity changes. Therefore, a more comprehensive MRI approach is warranted, aiming to link structural changes with functional brain organization. To better understand the disconnection syndromes and cognitive decline in MS, this paper reviews the associations between MRI metrics and cognitive performance, by discussing the interactions between multiple facets of MS pathology as determinants of brain damage and how they affect network efficiency.

C-reactive protein and genetic variants and cognitive decline in old age: The PROSPER Study

USDA-ARS?s Scientific Manuscript database

Plasma concentrations of C-reactive protein (CRP), a marker of chronic inflammation, have been associated with cognitive impairment in old age. However, it is unknown whether CRP is causally linked to cognitive decline. Within the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) tri...

Relationships between performance on the Cogstate Brief Battery, neurodegeneration, and Aβ accumulation in cognitively normal older adults and adults with MCI.

PubMed

Lim, Yen Ying; Pietrzak, Robert H; Bourgeat, Pierrick; Ames, David; Ellis, Kathryn A; Rembach, Alan; Harrington, Karra; Salvado, Olivier; Martins, Ralph N; Snyder, Peter J; Masters, Colin L; Rowe, Christopher C; Villemagne, Victor L; Maruff, Paul

2015-02-01

We investigated the extent to which decline in memory and working memory in beta-amyloid (Aβ) positive non-demented individuals was related to hippocampal atrophy and Aβ accumulation over 36 months. Cognitively normal older adults (CN) (n = 178) and adults with mild cognitive impairment (MCI) (n = 49) underwent positron emission tomography neuroimaging, magnetic resonance imaging, and cognitive assessments at baseline, 18- and 36-months. Relative to Aβ- CNs, Aβ+ CNs and Aβ+ MCIs showed greater rates of cognitive decline, Aβ accumulation, and hippocampal atrophy. Analysis of interrelationships between these Alzheimer's disease markers in Aβ+ CNs and MCIs indicated that rate of Aβ accumulation was associated with rate of hippocampal atrophy (β = -0.05, p = .037), which was in turn associated independently with rate of decline in memory (β = -0.03, p = .032). This suggests that Aβ accumulation precedes any neurodegeneration or clinical symptoms, and that the relationship between Aβ and cognitive decline is mediated by hippocampal atrophy. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cognitive and behavioral assessment in dogs and pet food market applications.

PubMed

Zicker, Steven C

2005-03-01

A multi-disciplinary program was developed to assess the efficacy of antioxidant inclusion in a canine pet food on cognitive decline in aged beagles. A systematic approach to development of the food was used prior to beginning the cognitive studies. Comprehensive evaluation of antioxidant ingredients included assessments of commodities with naturally occurring antioxidants and synthetic antioxidants not commonly utilized, or at different concentrations than what was commonly utilized, in commercial pet foods. Studies were conducted to insure stability through processing, absorption from the gastrointestinal tract, safety, and tests for potential antioxidant biological benefit by ex vivo tests. Testing of the antioxidant-fortified food in aged beagles slowed the rate of cognitive decline in aged dogs. In addition, environmental enrichment also slowed the rate of cognitive decline. Importantly, the combination of dietary antioxidants and environmental enrichment was synergistic and resulted in the least amount of cognitive decline over the 30-month study period. Finally, a clinical study showed that antioxidant fortified food improved age-related behavioral changes in older pet dogs at in-home situations.

Vitamin K Status Is not Associated with Cognitive Decline in Middle Aged Adults.

PubMed

van den Heuvel, E G H M; van Schoor, N M; Vermeer, C; Zwijsen, R M L; den Heijer, M; Comijs, H C

2015-11-01

The aim of this study was to examine the association between dephospho-uncarboxylated matrix Gla protein (dp-ucMGP), an indicator of vitamin K status, and cognitive decline, and the modifying role of 25(OH)D. Longitudinal study with six years follow-up. Community based. 599 participants of the Longitudinal Aging Study Amsterdam (aged 55-65 years). Information processing speed and a composite Z-score by combining three domains of cognition reflecting general cognitive functioning. Generalized estimating equations (GEE) showed no significant associations between dp-ucMGP and decline in general cognitive functioning. Vitamin D modified the association between dp-ucMGP and speed of information processing (p<0.05). In the group with a 25(OH)D concentration > 50 nmol/l, the highest tertile of dp-ucMGP (>406 pmol/l), which corresponds to lower vitamin K levels, was associated with 1.5 higher score on information processing speed (p=0.023) as compared to the lowest tertile of dp-ucMGP. In contrast to our hypothesis, a suboptimal vitamin K was not associated with cognitive decline in middle-aged adults.

Epidemiologic Evidence of a Relationship between Tea, Coffee, or Caffeine Consumption and Cognitive Decline12

PubMed Central

Arab, Lenore; Khan, Faraz; Lam, Helen

2013-01-01

A systematic literature review of human studies relating caffeine or caffeine-rich beverages to cognitive decline reveals only 6 studies that have collected and analyzed cognition data in a prospective fashion that enables study of decline across the spectrum of cognition. These 6 studies, in general, evaluate cognitive function using the Mini Mental State Exam and base their beverage data on FFQs. Studies included in our review differed in their source populations, duration of study, and most dramatically in how their analyses were done, disallowing direct quantitative comparisons of their effect estimates. Only one of the studies reported on all 3 exposures, coffee, tea, and caffeine, making comparisons of findings across studies more difficult. However, in general, it can be stated that for all studies of tea and most studies of coffee and caffeine, the estimates of cognitive decline were lower among consumers, although there is a lack of a distinct dose response. Only a few measures showed a quantitative significance and, interestingly, studies indicate a stronger effect among women than men. PMID:23319129

Epidemiologic evidence of a relationship between tea, coffee, or caffeine consumption and cognitive decline.

PubMed

Arab, Lenore; Khan, Faraz; Lam, Helen

2013-01-01

A systematic literature review of human studies relating caffeine or caffeine-rich beverages to cognitive decline reveals only 6 studies that have collected and analyzed cognition data in a prospective fashion that enables study of decline across the spectrum of cognition. These 6 studies, in general, evaluate cognitive function using the Mini Mental State Exam and base their beverage data on FFQs. Studies included in our review differed in their source populations, duration of study, and most dramatically in how their analyses were done, disallowing direct quantitative comparisons of their effect estimates. Only one of the studies reported on all 3 exposures, coffee, tea, and caffeine, making comparisons of findings across studies more difficult. However, in general, it can be stated that for all studies of tea and most studies of coffee and caffeine, the estimates of cognitive decline were lower among consumers, although there is a lack of a distinct dose response. Only a few measures showed a quantitative significance and, interestingly, studies indicate a stronger effect among women than men.

Testosterone Deficiency Accelerates Neuronal and Vascular Aging of SAMP8 Mice: Protective Role of eNOS and SIRT1

PubMed Central

Ota, Hidetaka; Akishita, Masahiro; Akiyoshi, Takuyu; Kahyo, Tomoaki; Setou, Mitsutoshi; Ogawa, Sumito; Iijima, Katsuya; Eto, Masato; Ouchi, Yasuyoshi

2012-01-01

Oxidative stress and atherosclerosis-related vascular disorders are risk factors for cognitive decline with aging. In a small clinical study in men, testosterone improved cognitive function; however, it is unknown how testosterone ameliorates the pathogenesis of cognitive decline with aging. Here, we investigated whether the cognitive decline in senescence-accelerated mouse prone 8 (SAMP8), which exhibits cognitive impairment and hypogonadism, could be reversed by testosterone, and the mechanism by which testosterone inhibits cognitive decline. We found that treatment with testosterone ameliorated cognitive function and inhibited senescence of hippocampal vascular endothelial cells of SAMP8. Notably, SAMP8 showed enhancement of oxidative stress in the hippocampus. We observed that an NAD+-dependent deacetylase, SIRT1, played an important role in the protective effect of testosterone against oxidative stress-induced endothelial senescence. Testosterone increased eNOS activity and subsequently induced SIRT1 expression. SIRT1 inhibited endothelial senescence via up-regulation of eNOS. Finally, we showed, using co-culture system, that senescent endothelial cells promoted neuronal senescence through humoral factors. Our results suggest a critical role of testosterone and SIRT1 in the prevention of vascular and neuronal aging. PMID:22238626

A call for comparative effectiveness research to learn whether routine clinical care decisions can protect from dementia and cognitive decline.

PubMed

Dacks, Penny A; Armstrong, Joshua J; Brannan, Stephen K; Carman, Aaron J; Green, Allan M; Kirkman, M Sue; Krakoff, Lawrence R; Kuller, Lewis H; Launer, Lenore J; Lovestone, Simon; Merikle, Elizabeth; Neumann, Peter J; Rockwood, Kenneth; Shineman, Diana W; Stefanacci, Richard G; Velentgas, Priscilla; Viswanathan, Anand; Whitmer, Rachel A; Williamson, Jeff D; Fillit, Howard M

2016-08-20

Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer's and other dementia. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer's Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia.

Brain volume change and cognitive trajectories in aging.

PubMed

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

2018-05-01

Examine how longitudinal cognitive trajectories relate to brain baseline measures and change in lobar volumes in a racially/ethnically and cognitively diverse sample of older adults. Participants were 460 older adults enrolled in a longitudinal aging study. Cognitive outcomes were measures of episodic memory, semantic memory, executive function, and spatial ability derived from the Spanish and English Neuropsychological Assessment Scales (SENAS). Latent variable multilevel modeling of the four cognitive outcomes as parallel longitudinal processes identified intercepts for each outcome and a second order global change factor explaining covariance among the highly correlated slopes. We examined how baseline brain volumes (lobar gray matter, hippocampus, and white matter hyperintensity) and change in brain volumes (lobar gray matter) were associated with cognitive intercepts and global cognitive change. Lobar volumes were dissociated into global and specific components using latent variable methods. Cognitive change was most strongly associated with brain gray matter volume change, with strong independent effects of global gray matter change and specific temporal lobe gray matter change. Baseline white matter hyperintensity and hippocampal volumes had significant incremental effects on cognitive decline beyond gray matter change. Baseline lobar gray matter was related to cognitive decline, but did not contribute beyond gray matter change. Cognitive decline was strongly influenced by gray matter volume change and, especially, temporal lobe change. The strong influence of temporal lobe gray matter change on cognitive decline may reflect involvement of temporal lobe structures that are critical for late life cognitive health but also are vulnerable to diseases of aging. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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.

Value of FDG-PET scans of non-demented patients in predicting rates of future cognitive and functional decline.

PubMed

Torosyan, Nare; Mason, Kelsey; Dahlbom, Magnus; Silverman, Daniel H S

2017-08-01

The aim of this study was to examine the value of fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting subsequent rates of functional and cognitive decline among subjects considered cognitively normal (CN) or clinically diagnosed with mild cognitive impairment (MCI). Analyses of 276 subjects, 92 CN subjects and 184 with MCI, who were enrolled in the Alzheimer's Disease Neuroimaging Initiative, were conducted. Functional decline was assessed using scores on the Functional Activities Questionnaire (FAQ) obtained over a period of 36 months, while cognitive decline was determined using the Alzheimer's disease Assessment Scale-Cognitive subscale (ADAS-Cog) and Mini-Mental State Examination (MMSE) scores. PET images were analyzed using clinically routine brain quantification software. A dementia prognosis index (DPI), derived from a ratio of uptake values in regions of interest known to be hypometabolic in Alzheimer's disease to regions known to be stable, was generated for each baseline FDG-PET scan. The DPI was correlated with change in scores on the neuropsychological examinations to examine the predictive value of baseline FDG-PET. DPI powerfully predicted rate of functional decline among MCI patients (t = 5.75, p < 1.0E-8) and pooled N + MCI patient groups (t = 7.02, p < 1.0E-11). Rate of cognitive decline on MMSE was also predicted by the DPI among MCI (t = 6.96, p < 1.0E-10) and pooled N + MCI (t = 8.78, p < 5.0E-16). Rate of cognitive decline on ADAS-cog was powerfully predicted by the DPI alone among N (p < 0.001), MCI (t = 6.46, p < 1.0E-9) and for pooled N + MCI (t = 8.85, p = 1.1E-16). These findings suggest that an index, derivable from automated regional analysis of brain PET scans, can be used to help predict rates of functional and cognitive deterioration in the years following baseline PET.

HbA1c, diabetes and cognitive decline: the English Longitudinal Study of Ageing.

PubMed

Zheng, Fanfan; Yan, Li; Yang, Zhenchun; Zhong, Baoliang; Xie, Wuxiang

2018-04-01

The aim of the study was to evaluate longitudinal associations between HbA 1c levels, diabetes status and subsequent cognitive decline over a 10 year follow-up period. Data from wave 2 (2004-2005) to wave 7 (2014-2015) of the English Longitudinal Study of Ageing (ELSA) were analysed. Cognitive function was assessed at baseline (wave 2) and reassessed every 2 years at waves 3-7. Linear mixed models were used to evaluate longitudinal associations. The study comprised 5189 participants (55.1% women, mean age 65.6 ± 9.4 years) with baseline HbA 1c levels ranging from 15.9 to 126.3 mmol/mol (3.6-13.7%). The mean follow-up duration was 8.1 ± 2.8 years and the mean number of cognitive assessments was 4.9 ± 1.5. A 1 mmol/mol increment in HbA 1c was significantly associated with an increased rate of decline in global cognitive z scores (-0.0009 SD/year, 95% CI -0.0014, -0.0003), memory z scores (-0.0005 SD/year, 95% CI -0.0009, -0.0001) and executive function z scores (-0.0008 SD/year, 95% CI -0.0013, -0.0004) after adjustment for baseline age, sex, total cholesterol, HDL-cholesterol, triacylglycerol, high-sensitivity C-reactive protein, BMI, education, marital status, depressive symptoms, current smoking, alcohol consumption, hypertension, CHD, stroke, chronic lung disease and cancer. Compared with participants with normoglycaemia, the multivariable-adjusted rate of global cognitive decline associated with prediabetes and diabetes was increased by -0.012 SD/year (95% CI -0.022, -0.002) and -0.031 SD/year (95% CI -0.046, -0.015), respectively (p for trend <0.001). Similarly, memory, executive function and orientation z scores showed an increased rate of cognitive decline with diabetes. Significant longitudinal associations between HbA 1c levels, diabetes status and long-term cognitive decline were observed in this study. Future studies are required to determine the effects of maintaining optimal glucose control on the rate of cognitive decline in people with diabetes.

Brain Metastases Treatment Worsens Cognitive Decline

Cancer.gov

In some patients with cancer that has spread to the brain, whole brain radiation following radiosurgery causes more severe cognitive decline and does not improve survival compared with radiosurgery alone, a new study has found.

Opportunities for New Insights on the Life-Course Risks and Outcomes of Cognitive Decline in the Kavli HUMAN Project.

PubMed

Langa, Kenneth M; Cutler, David

2015-09-01

The Kavli HUMAN Project (KHP) will provide groundbreaking insights into how biological, medical, and social factors interact and impact the risks for cognitive decline from birth through older age. It will richly measure the effect of cognitive decline on the ability to perform key activities of daily living. In addition, due to its family focus, the KHP will measure the impact on family members, including the amount of time that family members spend providing care to older adults with dementia. It will also clarify the division of caregiving duties among family members and the effects on caregivers' work, family life, and balance thereof. At the same time, for care that the family cannot provide, it will clarify the extent to which cognitive decline impacts healthcare utilization and end-of-life decision making.

Strategies for Preventing Cognitive Decline in Healthy Older Adults

PubMed Central

2017-01-01

Objective: Many advances have been made in the understanding of age-related changes in cognition. As research details the cognitive and neurobiological changes that occur in aging, there is increased interest in developing and understanding methods to prevent, slow, or reverse the cognitive decline that may occur in normal healthy older adults. The Institute of Medicine has recently recognized cognitive aging as having important financial and public health implications for society with the increasing older adult population worldwide. Cognitive aging is not dementia and does not result in the loss of neurons but rather changes in neurotransmission that affect brain functioning. The fact that neurons are structurally intact but may be functionally affected by increased age implies that there is potential for remediation. Method and Results: This review article presents recent work using medication-based strategies for slowing cognitive changes in aging. The primary method presented is a hormonal approach for affecting cognition in older women. In addition, a summary of the work examining modifiable lifestyle factors that have shown promise in benefiting cognition in both older men and women is described. Conclusions: Much work remains to be done so that evidence-based recommendations can be made for slowing cognitive decline in healthy older adults. The success of some of these methods thus far indicates that the brains of healthy older adults are plastic enough to be able to respond to these cognitive decline prevention strategies, and further work is needed to define the most beneficial methods. PMID:28703016

The Addenbrooke's Cognitive Examination-Revised accurately detects cognitive decline in Huntington's disease.

PubMed

Begeti, Faye; Tan, Adrian Y K; Cummins, Gemma A; Collins, Lucy M; Guzman, Natalie Valle; Mason, Sarah L; Barker, Roger A

2013-11-01

Cognitive features, which begin before manifestation of the motor features, are an integral part of Huntington's disease and profoundly affect quality of life. A number of neuropsychological batteries have been used to assess this aspect of the condition, many of which are difficult to administer and time consuming, especially in advanced disease. We, therefore, investigated a simple and practical way to monitor cognition using the Addenbrooke's Cognitive Examination-Revised (ACE-R) in 126 manifest Huntington's disease patients, 28 premanifest gene carriers and 21 controls. Using this test, we demonstrated a selective decrease in phonemic, but not semantic, fluency in premanifest participants Cognitive decline in manifest Huntington's disease varied according to disease severity with extensive cognitive decline observed in early-stage Huntington's disease patients, indicating that this would be an optimal stage for interventions designed to halt cognitive decline, and lesser changes in the advanced cases. We next examined cognitive performance in patients prescribed antidopaminergic drugs as these drugs are known to decrease cognition when administered to healthy volunteers. We paradoxically found that these drugs may be beneficial, as early-stage Huntington's disease participants in receipt of them had improved attention and Mini-Mental State Examination scores. In conclusion, this is the first study to test the usefulness of the ACE-R in a Huntington's disease population and demonstrates that this is a brief, inexpensive and practical way to measure global cognitive performance in clinical practice with potential use in clinical trials.

Surgery results in exaggerated and persistent cognitive decline in a rat model of the Metabolic Syndrome.

PubMed

Feng, Xiaomei; Degos, Vincent; Koch, Lauren G; Britton, Steven L; Zhu, Yinggang; Vacas, Susana; Terrando, Niccolò; Nelson, Jeffrey; Su, Xiao; Maze, Mervyn

2013-05-01

Postoperative cognitive decline can be reproduced in animal models. In a well-validated rat model of the Metabolic Syndrome, we sought to investigate whether surgery induced a more severe and persistent form of cognitive decline similar to that noted in preliminary clinical studies. In rats that had been selectively bred for low and high exercise endurance, the low capacity runners (LCR) exhibited features of Metabolic Syndrome (obesity, dyslipidemia, insulin resistance, and hypertension). Tibial fracture surgery was performed under isoflurane anesthesia in LCR and high capacity runner (HCR) rats and cognitive function was assessed postoperatively in a trace-fear conditioning paradigm and Morris Water Maze; non-operated rats were exposed to anesthesia and analgesia (sham). Group sizes were n = 6. On postoperative D7, LCR rats had shorter freezing times than postoperative HCR rats. Five months postoperatively, LCR rats had a flatter learning trajectory and took longer to locate the submerged platform than postoperative HCR rats; dwell-time in the target quadrant in a probe trial was shorter in the postoperative LCR compared to HCR rats. LCR and HCR sham rats did not differ in any test. Postoperatively, LCR rats diverged from HCR rats exhibiting a greater decline in memory, acutely, with persistent learning and memory decline, remotely; this could not be attributed to changes in locomotor or swimming performance. This Metabolic Syndrome animal model of surgery-induced cognitive decline corroborates, with high fidelity, preliminary findings of postoperative cognitive dysfunction in Metabolic Syndrome patients.

Anesthetic effects in Alzheimer transgenic mouse models.

PubMed

Tang, Junxia X; Eckenhoff, Maryellen F

2013-12-02

Research has improved the diagnosis of Alzheimer's disease, and at earlier stages, but effective therapy continues to be elusive. Current effort is focused on delay. Environmental factors are thought to interact with genetics to modulate the progression of the disease, and one such environmental factor is exposure to general anesthetics. The possibility that some anesthetic effects have long-term consequences is of general interest and concern. The difficulty of studying a chronic, age-related disease in humans combined with the fact that anesthetics are rarely given without surgery, has led to a focus on animal models. Transgenic mouse models have been developed to mimic the hallmarks of Alzheimer's disease, including amyloid beta accumulation (plaque), neurofibrillary tangles, and cognitive dysfunction. While none of the models recapitulate the human disease with high fidelity, they allow a first look at anesthetic-Alzheimer interactions in a reasonable time frame. In studies found to date, none have concluded that anesthetics alone cause a significant change in cognitive decline, but rather an acceleration in Alzheimer neuropathology. Further studies are required to define the best anesthetic paradigm for our elderly population to mitigate changes in neuropathology and potentially cognition. Copyright © 2012 Elsevier Inc. All rights reserved.

Association between mental demands at work and cognitive functioning in the general population – results of the health study of the Leipzig research center for civilization diseases (LIFE)

PubMed Central

2014-01-01

Background The level of mental demands in the workplace is rising. The present study investigated whether and how mental demands at work are associated with cognitive functioning in the general population. Methods The analysis is based on data of the Health Study of the Leipzig Research Centre for Civilization Disease (LIFE). 2,725 participants aged 40–80 years underwent cognitive testing (Trail-Making Test, Verbal Fluency Test) and provided information on their occupational situation. Participants over the age of 65 years additionally completed the Mini-Mental State Examination. Mental demands at work were rated by a standardized classification system (O*NET). The association between mental demands and cognitive functioning was analyzed using Generalized Linear Modeling (GENLIN) adjusted for age, gender, self-regulation, working hour status, education, and health-related factors. Results Univariate as well as multivariate analyses demonstrated significant and highly consistent effects of higher mental demands on better performance in cognitive testing. The results also indicated that the effects are independent of education and intelligence. Moreover, analyses of retired individuals implied a significant association between high mental demands at work of the job they once held and a better cognitive functioning in old age. Conclusions In sum, our findings suggest a significant association between high mental demands at work and better cognitive functioning. In this sense, higher levels of mental demands – as brought about by technological changes in the working environment – may also have beneficial effects for the society as they could increase cognitive capacity levels and might even delay cognitive decline in old age. PMID:24914403

LONG-TERM INTAKE OF NUTS IN RELATION TO COGNITIVE FUNCTION IN OLDER WOMEN

PubMed Central

O’BRIEN, J.; OKEREKE, O.; DEVORE, E.; ROSNER, B.; BRETELER, M.; GRODSTEIN, F.

2014-01-01

Objective Nuts contain nutrients that may benefit brain health; thus, we examined long-term intake of nuts in relation to cognition in older women. Design Population-based prospective cohort study. Setting Academic research using data from the Nurses’ Health Study. Participants Nut intake was assessed in a food-frequency questionnaire beginning in1980, and approximately every four years thereafter. Between 1995–2001, 16,010 women age 70 or older (mean age = 74 years) without a history of stroke were administered 4 repeated telephone-based cognitive interviews over 6 years. Our final sample included 15,467 women who completed an initial cognitive interview and had complete information on nut intake. Main Outcome Measures The Telephone Interview for Cognitive Status (TICS), 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 tests of verbal recall. Results In multivariable-adjusted linear regression models, higher long-term total nut intake was associated with better average cognitive status for all cognitive outcomes. For the global composite score combining all tests, women consuming at least 5 servings of nuts/week had higher scores than non-consumers (mean difference=0.08 standard units, 95% confidence interval 0.00–0.15; p-trend=0.003). This mean difference of 0.08 is equivalent to the mean difference we find between women 2 years apart in age. Long-term intake of nuts was not associated with rates of cognitive decline. Conclusions Higher nut intake may be related to better overall cognition at older ages, and could be an easily-modifiable public health intervention. PMID:24886736

Pre-clinical cognitive phenotypes for Alzheimer disease: a latent profile approach.

PubMed

Hayden, Kathleen M; Kuchibhatla, Maragatha; Romero, Heather R; Plassman, Brenda L; Burke, James R; Browndyke, Jeffrey N; Welsh-Bohmer, Kathleen A

2014-11-01

Cognitive profiles for pre-clinical Alzheimer disease (AD) can be used to identify groups of individuals at risk for disease and better characterize pre-clinical disease. Profiles or patterns of performance as pre-clinical phenotypes may be more useful than individual test scores or measures of global decline. To evaluate patterns of cognitive performance in cognitively normal individuals to derive latent profiles associated with later onset of disease using a combination of factor analysis and latent profile analysis. The National Alzheimer Coordinating Centers collect data, including a battery of neuropsychological tests, from participants at 29 National Institute on Aging-funded Alzheimer Disease Centers across the United States. Prior factor analyses of this battery demonstrated a four-factor structure comprising memory, attention, language, and executive function. Factor scores from these analyses were used in a latent profile approach to characterize cognition among a group of cognitively normal participants (N = 3,911). Associations between latent profiles and disease outcomes an average of 3 years later were evaluated with multinomial regression models. Similar analyses were used to determine predictors of profile membership. Four groups were identified; each with distinct characteristics and significantly associated with later disease outcomes. Two groups were significantly associated with development of cognitive impairment. In post hoc analyses, both the Trail Making Test Part B, and a contrast score (Delayed Recall - Trails B), significantly predicted group membership and later cognitive impairment. Latent profile analysis is a useful method to evaluate patterns of cognition in large samples for the identification of preclinical AD phenotypes; comparable results, however, can be achieved with very sensitive tests and contrast scores. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Glycemic control, cognitive function, and family support among middle-aged and older Hispanics with diabetes: The Hispanic Community Health Study/Study of Latinos.

PubMed

Strizich, Garrett; Kaplan, Robert C; González, Hector M; Daviglus, Martha L; Giachello, Aida L; Teng, Yanping; Lipton, Richard B; Grober, Ellen

2016-07-01

To examine among Hispanics in the U.S., a population with increased reliance on informal healthcare support structures, (1) the association between cognitive function and control of diabetes; and (2) whether this association is modified by family support. The Digit Symbol Substitution Test (DSST), word fluency, and learning and delayed recall components of the Spanish English Verbal Learning Test were administered to 1794 Hispanic adults aged 45-76years with diagnosed diabetes. An executive function index and global cognitive function index (GCFI) were derived. Uncontrolled diabetes (HbA1c⩾7% [53mmol/mol]) was compared across quartiles of cognitive function using multivariable logit models with interaction terms for cognitive function and family support. After adjustment, lower DSST scores were associated with uncontrolled diabetes (P=0.03). Family support modified the relationship between other measures of cognition and diabetes control (Pinteraction: 0.002, 0.09). Among individuals with low family support, as cognitive function declined, the odds of uncontrolled diabetes increased (P-trend across quartiles of the GCFI, 0.015). Among those with low family support, persons in the lowest quartile of global cognitive function were more than twice as likely to have uncontrolled diabetes as those in the highest performing quartile (OR=2.31; 95% CI: 1.17, 4.55). There was no similar effect among those with high family support. Family support may buffer the negative association between low cognitive functioning and diabetes control in US Hispanics/Latinos. Educational programs targeted at family members of middle-age and older persons with diabetes regardless of neurocognitive status may help improve population-level glycemic control. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Influence of Cognitive Functioning on Age-Related Performance Declines in Visuospatial Sequence Learning.

PubMed

Krüger, Melanie; Hinder, Mark R; Puri, Rohan; Summers, Jeffery J

2017-01-01

Objectives: The aim of this study was to investigate how age-related performance differences in a visuospatial sequence learning task relate to age-related declines in cognitive functioning. Method: Cognitive functioning of 18 younger and 18 older participants was assessed using a standardized test battery. Participants then undertook a perceptual visuospatial sequence learning task. Various relationships between sequence learning and participants' cognitive functioning were examined through correlation and factor analysis. Results: Older participants exhibited significantly lower performance than their younger counterparts in the sequence learning task as well as in multiple cognitive functions. Factor analysis revealed two independent subsets of cognitive functions associated with performance in the sequence learning task, related to either the processing and storage of sequence information (first subset) or problem solving (second subset). Age-related declines were only found for the first subset of cognitive functions, which also explained a significant degree of the performance differences in the sequence learning task between age-groups. Discussion: The results suggest that age-related performance differences in perceptual visuospatial sequence learning can be explained by declines in the ability to process and store sequence information in older adults, while a set of cognitive functions related to problem solving mediates performance differences independent of age.

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.

Cognitive training and Bacopa monnieri: Evidence for a combined intervention to alleviate age associated cognitive decline.

PubMed

McPhee, Grace M; Downey, Luke A; Noble, Anthony; Stough, Con

2016-10-01

As the elderly population grows the impact of age associated cognitive decline as well as neurodegenerative diseases such as Alzheimer's disease and dementia will increase. Ageing is associated with consistent impairments in cognitive processes (e.g., processing speed, memory, executive function and learning) important for work, well-being, life satisfaction and overall participation in society. Recently, there has been increased effort to conduct research examining methods to improve cognitive function in older citizens. Cognitive training has been shown to improve performance in some cognitive domains; including memory, processing speed, executive function and attention in older adults. These cognitive changes are thought to be related to improvements in brain connectivity and neural circuitry. Bacopa monnieri has also been shown to improve specific domains of cognition, sensitive to age associated cognitive decline (particularly processing speed and memory). These Bacopa monnieri dependent improvements may be due to the increase in specific neuro-molecular mechanisms implicated in the enhancement of neural connections in the brain (i.e. synaptogenesis). In particular, a number of animal studies have shown Bacopa monnieri consumption upregulates calcium dependent kinases in the synapse and post-synaptic cell, crucial for strengthening and growing connections between neurons. These effects have been shown to occur in areas important for cognitive processes, such as the hippocampus. As Bacopa monnieri has shown neuro-molecular mechanisms that encourage synaptogenesis, while cognitive training enhances brain connectivity, Bacopa monnieri supplementation could theoretically enhance and strengthen synaptic changes acquired through cognitive training. Therefore, the current paper hypothesises that the combination of these two interventions could improve cognitive outcomes, over and above the effects of administrating these interventions independently, as an effective treatment to ameliorate age associated cognitive decline. Copyright © 2016 Elsevier Ltd. All rights reserved.