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

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

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

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

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

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.

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

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

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

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

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

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

PubMed Central

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

2014-01-01

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

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

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.

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

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.

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

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.

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.

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

Fibrillar amyloid correlates of preclinical cognitive decline.

PubMed

Stonnington, Cynthia M; Chen, Kewei; Lee, Wendy; Locke, Dona E C; Dueck, Amylou C; Liu, Xiaofen; Roontiva, Auttawut; Fleisher, Adam S; Caselli, Richard J; Reiman, Eric M

2014-01-01

It is not known whether preclinical cognitive decline is associated with fibrillar β-amyloid (Aβ) deposition irrespective of apolipoprotein E (APOE) ε4 status. From a prospective observational study of 623 cognitively normal individuals, we identified all subjects who showed preclinical decline of at least 2 standard deviations beyond the decline of the entire group in memory or executive function. Fourteen decliners were matched by APOE ε4 gene dose, age, sex, and education with 14 nondecliners. Dynamic Pittsburgh compound B (PiB) positron emission tomography (PET) scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest were used to characterize and compare cerebral-to-cerebellar PiB distribution volume ratios (DVRs), reflecting fibrillar Aβ burden. At P < .005 (uncorrected), decliners had significantly greater DVRs in comparison to nondecliners. Asymptomatic longitudinal neuropsychological decline is associated with subsequent increased fibrillar amyloid deposition, even when controlling for APOE ε4 genotype. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Should general anaesthesia be avoided in the elderly?

PubMed Central

Strøm, C.; Rasmussen, L. S.; Sieber, F. E.

2016-01-01

Summary Surgery and anaesthesia exert comparatively greater adverse effects on the elderly than on the younger brain, manifest by the higher prevalence of postoperative delirium and cognitive dysfunction. Postoperative delirium and cognitive dysfunction delay rehabilitation, and are associated with increases in morbidity and mortality among elderly surgical patients. We review the aetiology of postoperative delirium and cognitive dysfunction in the elderly with a particular focus on anaesthesia and sedation, discuss methods of diagnosing and monitoring postoperative cognitive decline, and describe the treatment strategies by which such decline may be prevented. PMID:24303859

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

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

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

Validation analysis of informant's ratings of cognitive function in African Americans and Nigerians

PubMed Central

Shen, Jianzhao; Gao, Sujuan; Unverzagt, Frederick W.; Ogunniyi, Adesola; Baiyewu, Olusegun; Gureje, Oye; Hendrie, Hugh C.; Hall, Kathleen S.

2011-01-01

SUMMARY Objectives To examine informant validity using the Community Screening Interview for Dementia (CSI ‘D’) both cross-sectionally and longitudinally in two very different cultures and to explore the effects of informants and study participants’ characteristics on the validity of informants’ reports. Methods Elderly African Americans age 65 years and older residing in Indianapolis, USA and elderly Yoruba Nigerians age 65 years and older residing in Ibadan, Nigeria were assessed on cognitive functioning using the CSI ‘D’ at baseline (1992–1993) and five-year follow-up (1997–1998). At baseline, the informant validity in both samples was evaluated against participants’ cognitive tests using Pearson correlation and regular regression models. At follow-up, informants ratings on cognitive decline were assessed against participants’ cognitive decline scores from baseline to follow-up using biserial correlation and logistic regressions. Results At baseline, informants’ reports on cognitive functioning significantly correlated with cognitive scores in both samples (Indianapolis:r = –0.43, p < 0.001; Ibadan:r = –0.47, p < 0.001). The participant–informant relationships significantly affected the informants’ reports in the two samples with different patterns (p = 0.005 for Indianapolis and p < 0.001 for Ibadan) at a given level of cognitive functioning. African Americans spouses reported more cognitive problems, while siblings reported more problems for the Yoruba Nigerians. At follow-up, informants’ ratings on cognitive decline significantly correlated with the cognitive decline scores (Indianapolis r = 0.38, p < 0.001; Ibadan r = 0.32, p < 0.001). The characteristics of study participants and informants had little impact on the informants’ ratings on cognitive decline. Conclusions Informant reports are valid in assessing the cognitive functioning of study participants both cross-sectionally and longitudinally in two very different cultures, languages and environments. PMID:16802282

Disease Progression in Mild Dementia due to Alzheimer Disease in an 18-Month Observational Study (GERAS): The Impact on Costs and Caregiver Outcomes

PubMed Central

Jones, Roy W.; Lebrec, Jeremie; Kahle-Wrobleski, Kristin; Dell'Agnello, Grazia; Bruno, Giuseppe; Vellas, Bruno; Argimon, Josep M.; Dodel, Richard; Haro, Josep Maria; Wimo, Anders; Reed, Catherine

2017-01-01

Background/Aims We assessed whether cognitive and functional decline in community-dwelling patients with mild Alzheimer disease (AD) dementia were associated with increased societal costs and caregiver burden and time outcomes. Methods Cognitive decline was defined as a ≥3-point reduction in the Mini-Mental State Examination and functional decline as a decrease in the ability to perform one or more basic items of the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) or ≥20% of instrumental ADL items. Total societal costs were estimated from resource use and caregiver hours using 2010 costs. Caregiver burden was assessed using the Zarit Burden Interview (ZBI); caregiver supervision and total hours were collected. Results Of 566 patients with mild AD enrolled in the GERAS study, 494 were suitable for the current analysis. Mean monthly total societal costs were greater for patients showing functional (+61%) or cognitive decline (+27%) compared with those without decline. In relation to a typical mean monthly cost of approximately EUR 1,400 at baseline, this translated into increases over 18 months to EUR 2,254 and 1,778 for patients with functional and cognitive decline, respectively. The number of patients requiring supervision doubled among patients showing functional or cognitive decline compared with those not showing decline, while caregiver total time increased by 70 and 33%, respectively and ZBI total score by 5.3 and 3.4 points, respectively. Conclusion Cognitive and, more notably, functional decline were associated with increases in costs and caregiver outcomes in patients with mild AD dementia. PMID:28611822

Use of Spoken and Written Japanese Did Not Protect Japanese-American Men From Cognitive Decline in Late Life

PubMed Central

Gruhl, Jonathan C.; Erosheva, Elena A.; Gibbons, Laura E.; McCurry, Susan M.; Rhoads, Kristoffer; Nguyen, Viet; Arani, Keerthi; Masaki, Kamal; White, Lon

2010-01-01

Objectives. Spoken bilingualism may be associated with cognitive reserve. Mastering a complicated written language may be associated with additional reserve. We sought to determine if midlife use of spoken and written Japanese was associated with lower rates of late life cognitive decline. Methods. Participants were second-generation Japanese-American men from the Hawaiian island of Oahu, born 1900–1919, free of dementia in 1991, and categorized based on midlife self-reported use of spoken and written Japanese (total n included in primary analysis = 2,520). Cognitive functioning was measured with the Cognitive Abilities Screening Instrument scored using item response theory. We used mixed effects models, controlling for age, income, education, smoking status, apolipoprotein E e4 alleles, and number of study visits. Results. Rates of cognitive decline were not related to use of spoken or written Japanese. This finding was consistent across numerous sensitivity analyses. Discussion. We did not find evidence to support the hypothesis that multilingualism is associated with cognitive reserve. PMID:20639282

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

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

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.

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.

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

PubMed Central

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

2012-01-01

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

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

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

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

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

PubMed

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

2014-01-01

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

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

PubMed

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

2015-09-24

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

Orthopedic Surgery and Post-Operative Cognitive Decline in Idiopathic Parkinson’s Disease: Considerations from a Pilot Study

PubMed Central

Price, Catherine C.; Levy, Shellie-Anne; Tanner, Jared; Garvan, Cyndi; Ward, Jade; Akbar, Farheen; Bowers, Dawn; Rice, Mark; Okun, Michael

2016-01-01

BACKGROUND Post-operative cognitive dysfunction (POCD) demarks cognitive decline after major surgery but has been studied to date in “healthy” adults. Although individuals with neurodegenerative disorders such as Parkinson’s disease (PD) commonly undergo elective surgery, these individuals have yet to be prospectively followed despite hypotheses of increased POCD risk. OBJECTIVE To conduct a pilot study examining cognitive change pre-post elective orthopedic surgery for PD relative to surgery and non-surgery peers. METHODS A prospective one-year longitudinal design. No-dementia idiopathic PD individuals were actively recruited along with non-PD “healthy” controls (HC) undergoing knee replacement surgery. Non-surgical PD and HC controls were also recruited. Attention/processing speed, inhibitory function, memory recall, animal (semantic) fluency, and motor speed were assessed at baseline (pre-surgery), three-weeks, three-months, and one-year post- orthopedic surgery. Reliable change methods examined individual changes for PD individuals relative to control surgery and control non-surgery peers. RESULTS Over two years we screened 152 older adult surgery or non-surgery candidates with 19 of these individuals having a diagnosis of PD. Final participants included 8 PD (5 surgery, 3 non-surgery), 47 Control Surgery, and 21 Control Non-Surgery. Eighty percent (4 of the 5) PD surgery declined greater than 1.645 standard deviations from their baseline performance on measures assessing processing speed and inhibitory function. This was not observed for the non-surgery PD individuals. CONCLUSION This prospective pilot study demonstrated rationale and feasibility for examining cognitive decline in at-risk neurodegenerative populations. We discuss recruitment and design challenges for examining post-operative cognitive decline in neurodegenerative samples. PMID:26683785

Fifteen-Year Follow-Up of 92 Hospitalized Adults with Down's Syndrome: Incidence of Cognitive Decline, Its Relationship to Age and Neuropathology

ERIC Educational Resources Information Center

Margallo-Lana, M. L.; Moore, P. B.; Kay, D. W. K.; Perry, R. H.; Reid, B. E.; Berney, T. P.; Tyrer, S. P.

2007-01-01

Background: The clinical and neuropathological features associated with dementia in Down's syndrome (DS) are not well established. Aims: To examine clinico-pathological correlations and the incidence of cognitive decline in a cohort of adults with DS. Method: A total of 92 hospitalized persons with DS were followed up from 1985 to December 2000.…

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.

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).

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

PubMed Central

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

2013-01-01

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

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

Correlating Cognitive Decline with White Matter Lesion and Brain Atrophy MRI Measurements in Alzheimer’s Disease

PubMed Central

Bilello, Michel; Doshi, Jimit; Nabavizadeh, S. Ali; Toledo, Jon B.; Erus, Guray; Xie, Sharon X.; Trojanowski, John Q.; Han, Xiaoyan; Davatzikos, Christos

2015-01-01

Background Vascular risk factors are increasingly recognized as risks factors for Alzheimer’s disease (AD) and early conversion from mild cognitive impairment (MCI) to dementia. While neuroimaging research in AD has focused on brain atrophy, metabolic function or amyloid deposition, little attention has been paid to the effect of cerebrovascular disease to cognitive decline. Objective To investigate the correlation of brain atrophy and white matter lesions with cognitive decline in AD, MCI, and control subjects. Methods Patients with AD and MCI, and healthy subjects were included in this study. Subjects had a baseline MRI scan, and baseline and follow-up neuropsychological battery (CERAD). Regional volumes were measured, and white matter lesion segmentation was performed. Correlations between rate of CERAD score decline and white matter lesion load and brain structure volume were evaluated. In addition, voxel-based correlations between baseline CERAD scores and atrophy and white matter lesion measures were computed. Results CERAD rate of decline was most significantly associated with lesion loads located in the fornices. Several temporal lobe ROI volumes were significantly associated with CERAD decline. Voxel-based analysis demonstrated strong correlation between baseline CERAD scores and atrophy measures in the anterior temporal lobes. Correlation of baseline CERAD scores with white matter lesion volumes achieved significance in multilobar subcortical white matter. Conclusion Both baseline and declines in CERAD scores correlate with white matter lesion load and gray matter atrophy. Results of this study highlight the dominant effect of volume loss, and underscore the importance of small vessel disease as a contributor to cognitive decline in the elderly. PMID:26402108

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.

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

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.

Long-term cognitive decline in older subjects was not attributable to non-cardiac surgery or major illness

PubMed Central

Avidan, Michael S; FCASA; Searleman, Adam C; Storandt, Martha; Barnett, Kara; Vannucci, Andrea; Saager, Leif; Xiong, Chengjie; Grant, Elizabeth A; Kaiser, Dagmar; Morris, John C; Evers, Alex S

2009-01-01

Background Persistent postoperative cognitive decline is thought to be a public health problem, but its severity may have been overestimated because of limitations in statistical methodology. This study assessed whether long-term cognitive decline occurred after surgery or illness by using an innovative approach and including participants with early Alzheimer's disease to overcome some limitations. Methods In this retrospective cohort study, three groups were identified from participants tested annually at Washington University's Alzheimer Disease Research Center in St. Louis: those with non-cardiac surgery, illness, or neither. This enabled long-term tracking of cognitive function before and after surgery and illness. The effect of surgery and illness on longitudinal cognitive course was analyzed using a general linear mixed effects model. For participants without initial dementia, time to dementia onset was analyzed using sequential Cox proportional hazards regression. Results Of the 575 participants, 214 were nondemented and 361 had very mild or mild dementia at enrollment. Cognitive trajectories did not differ among the three groups (surgery, illness, control), although demented participants declined more markedly than nondemented. Of the initially nondemented participants, 23% progressed to a clinical dementia rating greater than zero, but this was not more common following surgery or illness. Conclusions The study did not detect long-term cognitive decline independently attributable to surgery or illness nor were these events associated with accelerated progression to dementia. The decision to proceed with surgery in elderly people, including those with early Alzheimer's disease, may presently be made without factoring in the specter of persistent cognitive deterioration. PMID:19786858

Lifecourse Activity Participation From Early, Mid, and Later Adulthood as Determinants of Cognitive Aging: The Lothian Birth Cohort 1921

PubMed Central

Pattie, Alison; Deary, Ian J.

2017-01-01

Objectives: To examine potential sensitive periods for activity participation across adulthood to reduce cognitive decline and to determine whether associations persist after accounting for the lifetime stability of cognitive ability. Method: The Lothian Birth Cohort 1921 is a longitudinal study of cognitive aging. Participants were born in 1921 and most completed a mental ability test at the age of 11 years. Cognitive assessments were completed at mean ages 79 (N = 550), 83 (N = 321), 87 (N = 235), and 90 years (N = 129). Participants provided retrospective details of their activity participation for young (20–35 years), mid (40–55 years), and later adulthood (60–75 years), and contemporaneously at age 79. Results: Associations between activity and the level of, and change in, cognitive ability in old age were examined with latent growth curve models. Accounting for demographics and childhood cognitive ability, engagement in leisure activities in midlife was positively associated with cognitive ability level (path coefficient = .32), whereas higher physical activity in later adulthood was associated with less cognitive decline (.27). Discussion: The findings support a lifecourse approach in identifying determinants of cognitive aging; leisure and physical activity during different periods of adulthood may enhance cognitive abilities or reduce decline. PMID:27974473

Fasting Insulin Levels and Cognitive Decline in Older Women without Diabetes

PubMed Central

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

2008-01-01

Background 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. Methods 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. Results 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. Conclusions Our study provides evidence for a potential role of higher fasting insulin levels in cognitive decline, possibly independent of diabetes. PMID:18421217

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.

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.

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.

Selective Attrition and Intraindividual Variability in Response Time Moderate Cognitive Change

PubMed Central

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

2016-01-01

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

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.

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

PubMed Central

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

2016-01-01

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

Frontal Gamma-Aminobutyric Acid Concentrations Are Associated With Cognitive Performance in Older Adults

PubMed Central

Porges, Eric C.; Woods, Adam J.; Edden, Richard A.E.; Puts, Nicolaas A.J.; Harris, Ashley D.; Chen, Huaihou; Garcia, Amanda M.; Seider, Talia R.; Lamb, Damon G.; Williamson, John B.; Cohen, Ronald A.

2017-01-01

BACKGROUND Gamma-aminobutyric acid (GABA), the brain’s principal inhibitory neurotransmitter, has been associated with perceptual and attentional functioning. Recent application of magnetic resonance spectroscopy (MRS) provides in vivo evidence for decreasing GABA concentrations during adulthood. It is unclear, however, how age-related decrements in cerebral GABA concentrations contribute to cognitive decline, or whether previously reported declines in cerebral GABA concentrations persist during healthy aging. We hypothesized that participants with higher GABA concentrations in the frontal cortex would exhibit superior cognitive function and that previously reported age-related decreases in cortical GABA concentrations continue into old age. METHODS We measured GABA concentrations in frontal and posterior midline cerebral regions using a Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) 1H-MRS approach in 94 older adults without history or clinical evidence of mild cognitive impairment or dementia (mean age, 73 years). We administered the Montreal Cognitive Assessment to assess cognitive functioning. RESULTS Greater frontal GABA concentrations were associated with superior cognitive performance. This relation remained significant after controlling for age, years of education, and brain atrophy. GABA concentrations in both frontal and posterior regions decreased as a function of age. CONCLUSIONS These novel findings from a large, healthy, older population indicate that cognitive function is sensitive to cerebral GABA concentrations in the frontal cortex, and GABA concentration in frontal and posterior regions continue to decline in later age. These effects suggest that proton MRS may provide a clinically useful method for the assessment of normal and abnormal age-related cognitive changes and the associated physiological contributors. PMID:28217759

Diabetes and Cognitive Decline in Older Adults: The Ginkgo Evaluation of Memory Study.

PubMed

Palta, Priya; Carlson, Michelle C; Crum, Rosa M; Colantuoni, Elizabeth; Sharrett, A Richey; Yasar, Sevil; Nahin, Richard L; DeKosky, Steven T; Snitz, Beth; Lopez, Oscar; Williamson, Jeff D; Furberg, Curt D; Rapp, Stephen R; Golden, Sherita Hill

2017-12-12

Previous studies have shown that individuals with diabetes exhibit accelerated cognitive decline. However, methodological limitations have limited the quality of this evidence. Heterogeneity in study design, cognitive test administration, and methods of analysis of cognitive data have made it difficult to synthesize and translate findings to practice. We analyzed longitudinal data from the Ginkgo Evaluation of Memory Study to test our hypothesis that older adults with diabetes have greater test-specific and domain-specific cognitive declines compared to older adults without diabetes. Tests of memory, visuo-spatial construction, language, psychomotor speed, and executive function were administered. Test scores were standardized to z-scores and averaged to yield domain scores. Linear random effects models were used to compare baseline differences and changes over time in test and domain scores among individuals with and without diabetes. Among the 3,069 adults, aged 72-96 years, 9.3% reported diabetes. Over a median follow-up of 6.1 years, participants with diabetes exhibited greater baseline differences in a test of executive function (trail making test, Part B) and greater declines in a test of language (phonemic verbal fluency). For the composite cognitive domain scores, participants with diabetes exhibited lower baseline executive function and global cognition domain scores, but no significant differences in the rate of decline. Identifying cognitive domains most affected by diabetes can lead to targeted risk modification, possibly in the form of lifestyle interventions such as diet and physical activity, which we know to be beneficial for improving vascular risk factors, such as diabetes, and therefore may reduce the risk of executive dysfunction and possible dementia. © The Author 2017. 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.

Falls and cognitive decline in Mexican Americans 75 years and older

PubMed Central

Padubidri, Anokha; Al Snih, Soham; Samper-Ternent, Rafael; Markides, Kyriakos S; Ottenbacher, Kenneth J; Raji, Mukaila A

2014-01-01

Background Little is known about long-term emotional and cognitive consequences of falls. We examined the association between falls and subsequent cognitive decline, and tested the hypothesis that depression would mediate any falls–cognition association among cognitively intact Hispanic Elders. Methods We used data from the Hispanic Established Population for the Epidemiological Study of the Elderly to examine change in Mini Mental State Examination (MMSE) scores over the 6-year period according to number of falls. All participants (N=1,119) had MMSE scores ≥21 and complete data on Center for Epidemiologic Studies of Depression Scale, social and demographic factors, medical conditions (diabetes, heart attack, stroke, and hypertension), and hand grip muscle strength. Results At baseline, participants’ mean age was 80.8 years (range, 74–109), mean education was 6.3 years (range, 0–17), and mean MMSE was 25.2 (range, 21–30). Of the 1,119 participants, 15.8% experienced one fall and 14.4% had two or more falls. In mixed model analyses, having two or more falls was associated with greater decline in MMSE score (estimate =−0.81, standard error =0.19, P<0.0001) compared to having no fall, after adjusting for age, sex, marital status, and education. The magnitude of the association decreased (estimate =−0.65, standard error =0.19, P=0.0007) when adjustment was made for high depressive symptoms, suggesting a possible mediating effect of depression on the falls–cognition association. Female sex, high level of education, and high performance in hand grip muscle strength were associated with a slower decline in MMSE scores. Conclusion Having two or more falls was independently associated with steeper decline in cognition over 6 years, with a possible mediating effect of depression on the falls–cognition association. PMID:24790424

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.

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

Detecting Cognitive Stress and Impairment Using Keystroke and Linguistic Features of Typed Text: Toward a Method for Continuous Monitoring of Cognitive Status

ERIC Educational Resources Information Center

Vizer, Lisa Michele

2013-01-01

Systems that can detect cognitive decline or harmful levels of stress could assist users in managing their stress and health. However, current assessments are often obtrusive or require specialized equipment, and not suited to continuous monitoring of cognitive status. This research leverages attributes of everyday keyboard interactions to…

Cognitive decline and brain volume loss are signatures of cerebral Aβ deposition identified with PIB

PubMed Central

Storandt, Martha; Mintun, Mark A.; Head, Denise; Morris, John C.

2009-01-01

Objective To examine the relation of amyloid-beta (Aβ) levels in cerebral cortex with structural brain integrity and cognitive performance in older people with a Clinical Dementia Rating (CDR) of 0 (cognitively normal). Methods The relations between mean cortical [11C] PIB binding potential values, proportional to the density of fibrillar Aβ binding sites in the brain, concurrent regional brain volumes as assessed by magnetic resonance imaging, and both concurrent and longitudinal (up to 19 years) cognitive performance in multiple domains were examined in 135 CDR 0 individuals aged 65 to 88 years. Results Elevated cerebral Aβ levels, in some cases comparable to that seen in individuals with Alzheimer's disease, were observed in 29 CDR 0 individuals. Significantly smaller regional volumes in the hippocampus, temporal neocortex, anterior cingulate, and posterior cingulate were observed in these CDR 0 individuals with elevated Aβ levels. Concurrent cognitive performance was unrelated to Aβ levels but was related to regional brain volumes with the exception of caudate. Longitudinal cognitive decline was associated with elevated Aβ levels and decreased hippocampal volume. Decline was not limited to episodic memory but included working memory and visuospatial abilities as well. Interpretation [11C] PIB, an in vivo measure of cerebral amyloidosis, is associated with regionally specific brain atrophy cross-sectionally and a pattern of longitudinal cognitive decline in multiple cognitive domains that occurs prior to the clinical diagnosis of Alzheimer' disease. These findings contribute to the understanding of the cognitive and structural consequences of Aβ levels in CDR 0 older adults. PMID:20008651

Motor Phenotype of Decline in Cognitive Performance among Community-Dwellers without Dementia: Population-Based Study and Meta-Analysis

PubMed Central

Beauchet, Olivier; Allali, Gilles; Montero-Odasso, Manuel; Sejdić, Ervin; Fantino, Bruno; Annweiler, Cédric

2014-01-01

Background Decline in cognitive performance is associated with gait deterioration. Our objectives were: 1) to determine, from an original study in older community-dwellers without diagnosis of dementia, which gait parameters, among slower gait speed, higher stride time variability (STV) and Timed Up & Go test (TUG) delta time, were most strongly associated with lower performance in two cognitive domains (i.e., episodic memory and executive function); and 2) to quantitatively synthesize, with a systematic review and meta-analysis, the association between gait performance and cognitive decline (i.e., mild cognitive impairment (MCI) and dementia). Methods Based on a cross-sectional design, 934 older community-dwellers without dementia (mean±standard deviation, 70.3±4.9years; 52.1% female) were recruited. A score at 5 on the Short Mini-Mental State Examination defined low episodic memory performance. Low executive performance was defined by clock-drawing test errors. STV and gait speed were measured using GAITRite system. TUG delta time was calculated as the difference between the times needed to perform and to imagine the TUG. Then, a systematic Medline search was conducted in November 2013 using the Medical Subject Heading terms “Delirium,” “Dementia,” “Amnestic,” “Cognitive disorders” combined with “Gait” OR “Gait disorders, Neurologic” and “Variability.” Findings A total of 294 (31.5%) participants presented decline in cognitive performance. Higher STV, higher TUG delta time, and slower gait speed were associated with decline in episodic memory and executive performances (all P-values <0.001). The highest magnitude of association was found for higher STV (effect size  =  −0.74 [95% Confidence Interval (CI): −1.05;−0.43], among participants combining of decline in episodic memory and in executive performances). Meta-analysis underscored that higher STV represented a gait biomarker in patients with MCI (effect size  =  0.48 [95% CI: 0.30;0.65]) and dementia (effect size  = 1.06 [95% CI: 0.40;1.72]). Conclusion Higher STV appears to be a motor phenotype of cognitive decline. PMID:24911155

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.

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.

Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial

PubMed Central

Brown, Paul D.; Pugh, Stephanie; Laack, Nadia N.; Wefel, Jeffrey S.; Khuntia, Deepak; Meyers, Christina; Choucair, Ali; Fox, Sherry; Suh, John H.; Roberge, David; Kavadi, Vivek; Bentzen, Soren M.; Mehta, Minesh P.; Watkins-Bruner, Deborah

2013-01-01

Background To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT). Methods Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed. Results Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62–0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks. Conclusions Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852. PMID:23956241

The Longitudinal Impact of Cognitive Speed of Processing Training on Driving Mobility

PubMed Central

Edwards, Jerri D.; Myers, Charlsie; Ross, Lesley A.; Roenker, Daniel L.; Cissell, Gayla M.; McLaughlin, Alexis M.; Ball, Karlene K.

2009-01-01

Purpose: To examine how cognitive speed of processing training affects driving mobility across a 3-year period among older drivers. Design and Methods: Older drivers with poor Useful Field of View (UFOV) test performance (indicating greater risk for subsequent at-fault crashes and mobility declines) were randomly assigned to either a speed of processing training or a social and computer contact control group. Driving mobility of these 2 groups was compared with a group of older adults who did not score poorly on the UFOV test (reference group) across a 3-year period. Results: Older drivers with poor UFOV test scores who did not receive training experienced greater mobility declines as evidenced by decreased driving exposure and space and increased driving difficulty at 3 years. Those at risk for mobility decline who received training did not differ across the 3-year period from older adults in the reference group with regard to driving exposure, space, and most aspects of driving difficulty. Implications: Cognitive speed of processing training can not only improve cognitive performance but also protect against mobility declines among older drivers. Scientifically proven cognitive training regimens have the potential to enhance the everyday lives of older adults. PMID:19491362

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.

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

Postoperative cognitive changes after total knee arthroplasty under regional anesthesia

PubMed Central

Jeon, Young-Tae; Kim, Byung-Gun; Park, Young Ho; Sohn, Hye-Min; Kim, Jungeun; Kim, Seung Chan; An, Seong Soo; Kim, SangYun

2016-01-01

Abstract Background: The type of postoperative cognitive decline after surgery under spinal anesthesia is unknown. We investigated the type of postoperative cognitive decline after total knee arthroplasty (TKA). Neuropsychological testing was conducted and the changes in cerebrospinal fluid (CSF) biomarkers after surgery were evaluated. Methods: Fifteen patients who required bilateral TKA at a 1-week interval under spinal anesthesia were included. Neuropsychological tests were performed twice, once the day before the first operation and just before the second operation (usually 1 week after the first test) to determine cognitive decline. Validated neuropsychological tests were used to examine 4 types of cognitive decline: memory, frontal-executive, language-semantic, and others. Concentrations of CSF amyloid peptide, tau protein, and S100B were measured twice during spinal anesthesia at a 1-week interval. The patients showed poor performance in frontal-executive function (forward digit span, semantic fluency, letter-phonemic fluency, and Stroop color reading) at the second compared to the first neuropsychological assessment. Results: S100B concentration decreased significantly 1 week after the operation compared to the basal value (638 ± 178 vs 509 ± 167 pg/mL) (P = 0.019). Amyloid protein β1–42, total tau, and phosphorylated tau concentrations tended to decrease but the changes were not significant. Conclusion: Our results suggest that frontal-executive function declined 1 week after TKA under spinal anesthesia. The CSF biomarker analysis indicated that TKA under regional anesthesia might not cause neuronal damage. PMID:28033253

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

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.

Seafood Types and Age-Related Cognitive Decline in the Women’s Health Study

PubMed Central

2013-01-01

Background. Seafood consumption may prevent age-related cognitive decline. However, benefits may vary by nutrient contents in different seafood types. We examined associations between total seafood consumption and cognitive decline and whether these associations differ by seafood types. Methods. We conducted a prospective cohort study of 5,988 women (mean age, 72 years) from the Women’s Health Study who self-reported seafood intake at Women’s Health Study baseline and also participated in telephone assessments of general cognition, verbal memory, and category fluency administered 5.6 years after Women’s Health Study baseline and 2 and 4 years thereafter. Primary outcomes were standardized composite scores of global cognition and verbal memory. Results. After adjusting for potential confounders, different amounts of total seafood consumption were not associated with changes in global cognition (p = .56) or verbal memory (p = .29). Considering seafood types, however, compared with women consuming less than once-weekly tuna or dark-meat finfish, those with once-weekly or higher consumption had significantly better verbal memory (0.079 standard units; p < .01) after 4 years—a difference comparable to that for women 2.1 years apart in age. There was also a statistically nonsignificant suggestion of better global cognition (p = .13) with once-weekly or higher tuna or dark-meat fish consumption. No significant associations were observed for light-meat finfish or shellfish. Conclusions. The relation of seafood to cognition may depend on the types consumed. Total consumption levels of seafood were unrelated to cognitive change. However, consumption of tuna and dark-meat fish once weekly or higher was associated with lower decline in verbal memory for a period of 4 years. PMID:23554464

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

PubMed

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

2016-01-01

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

[User friendliness of computer-based cognitive training for psychogeriatric patients with mild to moderate cognitive impairments].

PubMed

van der Ploeg, Eva S; Hoorweg, Angela; van der Lee, Jacqueline

2016-04-01

Cognitive impairment associated with dementia is characterized by a continuous decline. Cognitive training is a method to train specific brain functions such as memory and attention to prevent or slow down cognitive decline. A small number of studies has shown that cognitive training on a computer has a positive effect on both cognition and mood in people with cognitive impairment. This pilot study tested if serious games could be integrated in a psychogeriatric rehabilitation center. Fourteen psychogeriatric patients participated twice weekly in cognitive training sessions on a computer. Both the participants and the facilitator reported positive interactions and outcomes. However, after five weeks only half of the sample still participated in the training. This was partly because of patient turn-over as well as incorporating this new task in the facilitators' daily work. Fear of failure, physical limitations and rapidly decreasing cognitive function led to drop out according to the facilitator. The engagement of patients in the games and the role of the facilitator seemed essential for success, especially monitoring (and adjusting) the difficulty level of the program for every individual participant.

A framework for cognitive monitoring using computer game interactions.

PubMed

Jimison, Holly B; Pavel, Misha; Bissell, Payton; McKanna, James

2007-01-01

Many countries are faced with a rapidly increasing economic and social challenge of caring for their elderly population. Cognitive issues are at the forefront of the list of concerns. People over the age of 75 are at risk for medically related cognitive decline and confusion, and the early detection of cognitive problems would allow for more effective clinical intervention. However, standard cognitive assessments are not diagnostically sensitive and are performed infrequently. To address these issues, we have developed a set of adaptive computer games to monitor cognitive performance in a home environment. Assessment algorithms for various aspects of cognition are embedded in the games. The monitoring of these metrics allows us to detect within subject trends over time, providing a method for the early detection of cognitive decline. In addition, the real-time information on cognitive state is used to adapt the user interface to the needs of the individual user. In this paper we describe the software architecture and methodology for monitoring cognitive performance using data from natural computer interactions in a home setting.

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.

Six-month outcomes of co-occurring delirium, depression, and dementia in long-term care.

PubMed

McCusker, Jane; Cole, Martin G; Voyer, Philippe; Monette, Johanne; Champoux, Nathalie; Ciampi, Antonio; Vu, Minh; Belzile, Eric

2014-12-01

To describe the 6-month outcomes of co-occurring delirium (full syndrome and subsyndromal symptoms), depression, and dementia in a long-term care (LTC) population. Observational, prospective cohort study with 6-month follow-up conducted from 2005 to 2009. Seven LTC facilities in the province of Quebec, Canada. Newly admitted and long-term residents recruited consecutively from lists of residents aged 65 and older admitted for LTC, with stratification into groups with and without severe cognitive impairment. The study sample comprised 274 residents with complete data at baseline on delirium, dementia, and depression. Outcomes were 6-month mortality, functional decline (10-point decline from baseline on 100-point Barthel scale), and cognitive decline (3-point decline on 30-point Mini-Mental State Examination). Predictors included delirium (full syndrome or subsyndromal symptoms, using the Confusion Assessment Method), depression (Cornell Scale for Depression in Dementia), and dementia (chart diagnosis). The baseline prevalences of delirium, subsyndromal symptoms of delirium (SSD), depression, and dementia were 11%, 44%, 19%, and 66%, respectively. By 6 months, 10% of 274 had died, 19% of 233 had experienced functional decline, and 17% of 246 had experienced cognitive decline. An analysis using multivariable generalized linear models found the following significant interaction effects (P < .15): between depression and dementia for mortality, between delirium and depression for functional decline, and between SSD and dementia for cognitive decline. Co-occurrence of delirium, SSD, depression, and dementia in LTC residents appears to affect some 6-month outcomes. Because of limited statistical power, it was not possible to draw conclusions about the effects of the co-occurrence of some syndromes on poorer outcomes. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

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

PubMed Central

Alley, Dawn; Suthers, Kristen; Crimmins, Eileen

2009-01-01

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

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

PubMed

Athey, Richard J; Walker, Richard W

2006-10-01

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

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.

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.

Mediterranean diet and cognitive function in older age: results from the Women’s Health Study

PubMed Central

Samieri, Cécilia; Grodstein, Francine; Rosner, Bernard A.; Kang, Jae H.; Cook, Nancy R.; Manson, JoAnn E.; Buring, Julie E.; Willett, Walter C.; Okereke, Olivia I.

2013-01-01

Background Adherence to a Mediterranean diet may help prevent cognitive decline in older age, but studies are limited. We examined the association of adherence to the Mediterranean diet with cognitive function and decline. Methods We included 6,174 participants, aged 65+ years, from the cognitive sub-study of the Women’s Health Study. Women provided dietary information in 1998 and completed a cognitive battery 5 years later, followed by two assessments at 2-year intervals. The primary outcomes were composite scores of global cognition and verbal memory. The alternate Mediterranean diet adherence 9-point-score was constructed based on intakes of: vegetables, fruits, legumes, whole grains, nuts, fish, red and processed meats, moderate alcohol, and the ratio of monounsaturated-to-saturated fats. Results After multivariable adjustment, the alternate Mediterranean diet score was not associated with trajectories of repeated cognitive scores (P-trend across quintiles=0.26 and 0.40 for global cognition and verbal memory, respectively), nor with overall global cognition and verbal memory at older ages, assessed by averaging the three cognitive measures (P-trend=0.63 and 0.44, respectively). Among alternate Mediterranean diet components, higher monounsaturated-to-saturated fats ratio was associated with more favorable cognitive trajectories (P-trend=0.03 and 0.05 for global cognition and verbal memory, respectively). Greater whole grain intake was not associated with cognitive trajectories, but was related to better average global cognition (P-trend=0.02). Conclusions In this large study of older women, we observed no association of the Mediterranean diet with cognitive decline. Relations between individual Mediterranean diet components, particularly whole grains, and cognitive function merit further study. PMID:23676264

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.

Evidence for age-associated cognitive decline from Internet game scores.

PubMed

Geyer, Jason; Insel, Philip; Farzin, Faraz; Sternberg, Daniel; Hardy, Joseph L; Scanlon, Michael; Mungas, Dan; Kramer, Joel; Mackin, R Scott; Weiner, Michael W

2015-06-01

Lumosity's Memory Match (LMM) is an online game requiring visual working memory. Change in LMM scores may be associated with individual differences in age-related changes in working memory. Effects of age and time on LMM learning and forgetting rates were estimated using data from 1890 game sessions for users aged 40 to 79 years. There were significant effects of age on baseline LMM scores (β = -.31, standard error or SE = .02, P < .0001) and lower learning rates (β = -.0066, SE = .0008, P < .0001). A sample size of 202 subjects/arm was estimated for a 1-year study for subjects in the lower quartile of game performance. Online memory games have the potential to identify age-related decline in cognition and to identify subjects at risk for cognitive decline with smaller sample sizes and lower cost than traditional recruitment methods.

Implementation of Subjective Cognitive Decline criteria in research studies

PubMed Central

Molinuevo, José L; Rabin, Laura A.; Amariglio, Rebecca; Buckley, Rachel; Dubois, Bruno; Ellis, Kathryn A.; Ewers, Michael; Hampel, Harald; Klöppel, Stefan; Rami, Lorena; Reisberg, Barry; Saykin, Andrew J.; Sikkes, Sietske; Smart, Colette M.; Snitz, Beth E.; Sperling, Reisa; van der Flier, Wiesje M.; Wagner, Michael; Jessen, Frank

2017-01-01

INTRODUCTION Subjective Cognitive Decline (SCD) manifesting prior to clinical impairment could serve as a target population for early intervention trials in Alzheimer’s disease (AD). A working group, the Subjective Cognitive Decline Initiative (SCD-I), published SCD research criteria in the context of preclinical AD. To successfully apply them, a number of issues regarding assessment and implementation of SCD needed to be addressed. METHODS Members of the SCD-I met to identify and agree upon topics relevant to SCD criteria operationalization in research settings. Initial ideas and recommendations were discussed with other SCD-I working group members and modified accordingly. RESULTS Topics included SCD inclusion and exclusion criteria, together with the informant’s role in defining SCD presence and the impact of demographic factors. DISCUSSION Recommendations for the operationalization of SCD in differing research settings, with the aim of harmonization of SCD measurement across studies are proposed, to enhance comparability and generalizability across studies. PMID:27825022

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

PubMed

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

2012-02-01

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

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

PubMed

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

2016-10-01

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

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.

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…

Muscle mass decline, arterial stiffness, white matter hyperintensity, and cognitive impairment: Japan Shimanami Health Promoting Program study

PubMed Central

Okada, Yoko; Ochi, Masayuki; Ohara, Maya; Nagai, Tokihisa; Tabara, Yasuharu; Igase, Michiya

2017-01-01

Abstract Background There is a close association between frailty and cognitive impairment. However, the underlying contribution of sarcopenia to the development of cognitive impairment is unclear. We investigated the possible association between muscle mass decline and cognitive impairment in a cross‐sectional study of 1518 subjects aged 55 years or above. We also evaluated arterial stiffness and white matter hyperintensities (WMHs) as possible underlying mechanisms for this association. Methods Two sarcopenic indices were measured: thigh muscle cross‐sectional area (CSA; calculated by computed tomography) and skeletal muscle mass (bioelectric impedance). Muscle mass decline was defined as either the bottom 10% or 20% of participants for each sex. Cognitive function was assessed using the Touch Panel‐type Dementia Assessment Scale, and brachial–ankle pulse wave velocity was measured as an index of arterial stiffness. Results Both sarcopenic indices were modestly but significantly associated with brachial–ankle pulse wave velocity in male and female subjects. The presence of WMHs was significantly associated with low thigh muscle CSA in men and with low skeletal muscle mass in women. The Touch Panel‐type Dementia Assessment Scale score was modestly but significantly and positively associated with thigh muscle CSA in men and skeletal muscle mass in women. Muscle mass decline in the bottom 10% of participants on both sarcopenic indices was significantly and independently related to cognitive impairment in women. Conclusions Lower sarcopenic indices are significantly related to lower cognitive scores. Arterial stiffness and WMHs could account, at least in part, for this association. PMID:28371474

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.

Bidirectional Relationship between Cognitive Function and Pneumonia

PubMed Central

Shah, Faraaz Ali; Pike, Francis; Alvarez, Karina; Angus, Derek; Newman, Anne B.; Lopez, Oscar; Tate, Judith; Kapur, Vishesh; Wilsdon, Anthony; Krishnan, Jerry A.; Hansel, Nadia; Au, David; Avdalovic, Mark; Fan, Vincent S.; Barr, R. Graham

2013-01-01

Rationale: Relationships between chronic health conditions and acute infections remain poorly understood. Preclinical studies suggest crosstalk between nervous and immune systems. Objectives: To determine bidirectional relationships between cognition and pneumonia. Methods: We conducted longitudinal analyses of a population-based cohort over 10 years. We determined whether changes in cognition increase risk of pneumonia hospitalization by trajectory analyses and joint modeling. We then determined whether pneumonia hospitalization increased risk of subsequent dementia using a Cox model with pneumonia as a time-varying covariate. Measurements and Main Results: Of the 5,888 participants, 639 (10.9%) were hospitalized with pneumonia at least once. Most participants had normal cognition before pneumonia. Three cognition trajectories were identified: no, minimal, and severe rapid decline. A greater proportion of participants hospitalized with pneumonia were on trajectories of minimal or severe decline before occurrence of pneumonia compared with those never hospitalized with pneumonia (proportion with no, minimal, and severe decline were 67.1%, 22.8%, and 10.0% vs. 76.0%, 19.3%, and 4.6% for participants with and without pneumonia, respectively; P < 0.001). Small subclinical changes in cognition increased risk of pneumonia, even in those with normal cognition and physical function before pneumonia (β = −0.02; P < 0.001). Participants with pneumonia were subsequently at an increased risk of dementia (hazard ratio, 2.24 [95% confidence interval, 1.62–3.11]; P = 0.01). Associations were independent of demographics, health behaviors, other chronic conditions, and physical function. Bidirectional relationship did not vary based on severity of disease, and similar associations were noted for those with severe sepsis and other infections. Conclusions: A bidirectional relationship exists between pneumonia and cognition and may explain how a single episode of infection in well-appearing older individuals accelerates decline in chronic health conditions and loss of functional independence. PMID:23848267

Impaired renal function is associated with brain atrophy and poststroke cognitive decline.

PubMed

Auriel, Eitan; Kliper, Efrat; Shenhar-Tsarfaty, Shani; Molad, Jeremy; Berliner, Shlomo; Shapira, Itzhak; Ben-Bashat, Dafna; Shopin, Ludmila; Tene, Oren; Rosenberg, Gary A; Bornstein, Natan M; Ben Assayag, Einor

2016-05-24

To evaluate the interrelationship among impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. The Tel Aviv Brain Acute Stroke Cohort study is a prospective cohort of mild-moderate ischemic stroke/TIA survivors without dementia who underwent a 3T MRI and were cognitively assessed at admission and for 24 months following stroke. Renal function was evaluated at admission by creatinine clearance (CCl) estimation. The volumes of ischemic lesions and preexisting white matter hyperintensities (WMH), brain atrophy, and microstructural changes of the normal-appearing white matter tissue were measured using previously validated methods. Baseline data were available for 431 participants. Participants with a CCl <60 mL/min at baseline performed significantly worse in all cognitive tests over time (p = 0.001) than those with a CCl ≥60 mL/min and had larger WMH volume and cortical atrophy and smaller hippocampal volume (all p < 0.001). After 2 years, 15.5% of the participants were diagnosed with cognitive impairment. Multiple logistic regression analysis, controlling for traditional risk factors, suggested CCl <60 mL/min at baseline as a significant predictor for the development of cognitive impairment 2 years after the index stroke (odds ratio 2.01 [95% confidence interval 1.03-3.92], p = 0.041). Impaired renal function is associated with increased WMH volume and cortical atrophy, known biomarkers of the aging brain, and is a predictor for cognitive decline 2 years after stroke/TIA. Decreased renal function may be associated with cerebral small vessel disease underlying poststroke cognitive decline, suggesting a new target for early intervention. © 2016 American Academy of Neurology.

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 ...

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

PubMed Central

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

2009-01-01

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

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.

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

PubMed Central

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

2012-01-01

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

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

PubMed Central

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

2014-01-01

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

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.

Augmenting cognitive training in older adults (The ACT Study): Design and Methods of a Phase III tDCS and cognitive training trial.

PubMed

Woods, Adam J; Cohen, Ronald; Marsiske, Michael; Alexander, Gene E; Czaja, Sara J; Wu, Samuel

2018-02-01

Adults over age 65 represent the fastest growing population in the US. Decline in cognitive abilities is a hallmark of advanced age and is associated with loss of independence and dementia risk. There is a pressing need to develop effective interventions for slowing or reversing the cognitive aging process. While certain forms of cognitive training have shown promise in this area, effects only sometimes transfer to neuropsychological tests within or outside the trained domain. This paper describes a NIA-funded Phase III adaptive multisite randomized clinical trial, examining whether transcranial direct current stimulation (tDCS) of frontal cortices enhances neurocognitive outcomes achieved from cognitive training in older adults experiencing age-related cognitive decline: the Augmenting Cognitive Training in Older Adults study (ACT). ACT will enroll 360 participants aged 65 to 89 with age-related cognitive decline, but not dementia. Participants will undergo cognitive training intervention or education training-control combined with tDCS or sham tDCS control. Cognitive training employs a suite of eight adaptive training tasks focused on attention/speed of processing and working memory from Posit Science BrainHQ. Training control involves exposure to educational nature/history videos and related content questions of the same interval/duration as the cognitive training. Participants are assessed at baseline, after training (12weeks), and 12-month follow-up on our primary outcome measure, NIH Toolbox Fluid Cognition Composite Score, as well as a comprehensive neurocognitive, functional, clinical and multimodal neuroimaging battery. The findings from this study have the potential to significantly enhance efforts to ameliorate cognitive aging and slow dementia. Copyright © 2017 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 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

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.

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.

Impaired olfaction and risk of delirium or cognitive decline after cardiac surgery.

PubMed

Brown, Charles H; Morrissey, Candice; Ono, Masahiro; Yenokyan, Gayane; Selnes, Ola A; Walston, Jeremy; Max, Laura; LaFlam, Andrew; Neufeld, Karin; Gottesman, Rebecca F; Hogue, Charles W

2015-01-01

To determine the prevalence of impaired olfaction in individuals presenting for cardiac surgery and the independent association between impaired olfaction and postoperative delirium and cognitive decline. Nested prospective cohort study. Academic hospital. Individuals undergoing coronary artery bypass, valve surgery, or both (n = 165). Olfaction was measured using the Brief Smell Identification Test, with impaired olfaction defined as an olfactory score below the fifth percentile of normative data. Delirium was assessed using a validated chart review method. Cognitive performance was assessed using a neuropsychological testing battery at baseline and 4 to 6 weeks after surgery. Impaired olfaction was identified in 54 of 165 participants (33%) before surgery. Impaired olfaction was associated with greater adjusted risk of postoperative delirium (relative risk = 1.90, 95% confidence interval = 1.17-3.09, P = .009). There was no association between impaired olfaction and change in composite cognitive score in the overall study population. Impaired olfaction is prevalent in individuals undergoing cardiac surgery and is associated with greater adjusted risk of postoperative delirium but not cognitive decline. Impaired olfaction may identify unrecognized vulnerability to postoperative delirium in individuals undergoing cardiac surgery. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

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

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.

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

PubMed

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

2009-01-01

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

A randomized controlled trial of Kundalini yoga in mild cognitive impairment

PubMed Central

Eyre, Harris A.; Siddarth, Prabha; Acevedo, Bianca; Van Dyk, Kathleen; Paholpak, Pattharee; Ercoli, Linda; Cyr, Natalie St.; Yang, Hongyu; Khalsa, Dharma S.; Lavretsky, Helen

2017-01-01

Background Global population aging will result in increasing rates of cognitive decline and dementia. Thus, effective, low-cost, and low side-effect interventions for the treatment and prevention of cognitive decline are urgently needed. Our study is the first to investigate the effects of Kundalini yoga (KY) training on mild cognitive impairment (MCI). Methods Older participants (≥55 years of age) with MCI were randomized to either a 12-week KY intervention or memory enhancement training (MET; gold-standard, active control). Cognitive (i.e. memory and executive functioning) and mood (i.e. depression, apathy, and resilience) assessments were administered at baseline, 12 weeks and 24 weeks. Results At baseline, 81 participants had no significant baseline group differences in clinical or demographic characteristics. At 12 weeks and 24 weeks, both KY and MET groups showed significant improvement in memory; however, only KY showed significant improvement in executive functioning. Only the KY group showed significant improvement in depressive symptoms and resilience at week 12. Conclusion KY group showed short- and long-term improvements in executive functioning as compared to MET, and broader effects on depressed mood and resilience. This observation should be confirmed in future clinical trials of yoga intervention for treatment and prevention of cognitive decline (NCT01983930). PMID:28088925

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.

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…

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

PubMed

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

2016-04-01

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

Cognitive Decline in a Colombian Kindred With Autosomal Dominant Alzheimer Disease

PubMed Central

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

2017-01-01

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

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

PubMed

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

2018-06-01

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

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

PubMed

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

2012-01-01

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

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.

Cognitive function and advanced kidney disease: longitudinal trends and impact on decision-making.

PubMed

Iyasere, Osasuyi; Okai, David; Brown, Edwina

2017-02-01

Background: Cognitive impairment commonly affects renal patients. But little is known about the influence of dialysis modality on cognitive trends or the influence of cognitive impairment on decision-making in renal patients. This study evaluated cognitive trends amongst chronic kidney disease (CKD), haemodialysis (HD) and peritoneal dialysis (PD) patients. The relationship between cognitive impairment and decision-making capacity (DMC) was also assessed. Methods: Patients were recruited from three outpatient clinics. Cognitive function was assessed 4-monthly for up to 2 years, using the Montreal Cognitive Assessment (MoCA) tool. Cognitive trends were assessed using mixed model analysis. DMC was assessed using the Macarthur Competency Assessment tool (MacCAT-T). MacCAT-T scores were compared between patients with cognitive impairment (MoCA <26) and those without. Results: In total, 102 (41 HD, 25 PD and 36 CKD) patients were recruited into the prospective study. After multivariate analysis, the total MoCA scores declined faster in dialysis compared with CKD patients [coefficient = -0.03, 95% confidence interval (95% CI) = -0.056 to - 0.004; P = 0.025]. The MoCA executive scores declined faster in the HD compared with PD patients (coefficient = -0.12, 95% CI = -0.233 to - 0.007; P = 0.037). DMC was assessed in 10 patients. Those with cognitive impairment had lower MacCAT-T compared with those without [median (interquartile range) 19 (17.9-19.6) versus 17.4 (16.3-18.4); P = 0.049]. Conclusions: Cognition declines faster in dialysis patients compared with CKD patients and in HD patients compared with PD patients. Cognitive impairment affects DMC in patients with advanced kidney disease.

Day-to-Day Variability of Postural Sway and Its Association With Cognitive Function in Older Adults: A Pilot Study

PubMed Central

Leach, Julia M.; Mancini, Martina; Kaye, Jeffrey A.; Hayes, Tamara L.; Horak, Fay B.

2018-01-01

Introduction: Increased variability in motor function has been observed during the initial stages of cognitive decline. However, the natural variability of postural control, as well as its association with cognitive status and decline, remains unknown. The objective of this pilot study was to characterize the day-to-day variability in postural sway in non-demented older adults. We hypothesized that older adults with a lower cognitive status would have higher day-to-day variability in postural sway. Materials and Methods: A Nintendo Wii balance board (WBB) was used to quantify postural sway in the home twice daily for 30 days in 20 non-demented, community-dwelling older adults: once under a single-task condition and once under a dual-task condition (using a daily word search task administered via a Nook tablet). Mean sway distance, velocity, area, centroidal frequency and frequency dispersion were derived from the center of pressure data acquired from the WBB. Results: Linear relationships were observed between the day-to-day variability in postural sway and cognitive status (indexed by cognitive global z-scores). More variability in time-domain postural sway (sway distance and area) and less variability in frequency-domain postural sway (centroidal sway frequency) were associated with a lower cognitive status under both the single- and dual-task conditions. Additionally, lower cognitive performance rates on the daily word search task were related to a lower cognitive status. Discussion: This small pilot study conducted on a short time scale motivates large-scale implementations over more extended time periods. Tracking longitudinal changes in postural sway may further our understanding of early-stage postural decline and its association with cognitive decline and, in turn, may aid in the early detection of dementia during preclinical stages when the utility of disease-modifying therapies would be greatest. PMID:29780319

Day-to-Day Variability of Postural Sway and Its Association With Cognitive Function in Older Adults: A Pilot Study.

PubMed

Leach, Julia M; Mancini, Martina; Kaye, Jeffrey A; Hayes, Tamara L; Horak, Fay B

2018-01-01

Introduction : Increased variability in motor function has been observed during the initial stages of cognitive decline. However, the natural variability of postural control, as well as its association with cognitive status and decline, remains unknown. The objective of this pilot study was to characterize the day-to-day variability in postural sway in non-demented older adults. We hypothesized that older adults with a lower cognitive status would have higher day-to-day variability in postural sway. Materials and Methods : A Nintendo Wii balance board (WBB) was used to quantify postural sway in the home twice daily for 30 days in 20 non-demented, community-dwelling older adults: once under a single-task condition and once under a dual-task condition (using a daily word search task administered via a Nook tablet). Mean sway distance, velocity, area, centroidal frequency and frequency dispersion were derived from the center of pressure data acquired from the WBB. Results : Linear relationships were observed between the day-to-day variability in postural sway and cognitive status (indexed by cognitive global z-scores). More variability in time-domain postural sway (sway distance and area) and less variability in frequency-domain postural sway (centroidal sway frequency) were associated with a lower cognitive status under both the single- and dual-task conditions. Additionally, lower cognitive performance rates on the daily word search task were related to a lower cognitive status. Discussion : This small pilot study conducted on a short time scale motivates large-scale implementations over more extended time periods. Tracking longitudinal changes in postural sway may further our understanding of early-stage postural decline and its association with cognitive decline and, in turn, may aid in the early detection of dementia during preclinical stages when the utility of disease-modifying therapies would be greatest.

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.

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

PubMed Central

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

2010-01-01

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

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.

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.

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

PubMed

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

2001-12-26

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

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

PubMed

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

2016-01-01

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

Bilingualism Does Not Alter Cognitive Decline or Dementia Risk among Spanish-Speaking Immigrants

PubMed Central

Zahodne, Laura B.; Schofield, Peter W.; Farrell, Meagan T.; Stern, Yaakov; Manly, Jennifer J.

2013-01-01

Objective Clinic-based studies suggest that dementia is diagnosed at older ages in bilinguals compared to monolinguals. The current study sought to test this hypothesis in a large, prospective, community-based study of initially non-demented Hispanic immigrants living in a Spanish-speaking enclave of Northern Manhattan. Method Participants included 1,067 participants in the Washington/Hamilton Heights Inwood Columbia Aging Project (WHICAP) who were tested in Spanish and followed at 18–24 month intervals for up to 23 years. Spanish-English bilingualism was estimated via both self-report and an objective measure of English reading level. Multilevel models for change estimated the independent effects of bilingualism on cognitive decline in four domains: episodic memory, language, executive function, and speed. Over the course of the study, 282 participants developed dementia. Cox regression was used to estimate the independent effect of bilingualism on dementia conversion. Covariates included country of origin, gender, education, time spent in the United States, recruitment cohort, and age at enrollment. Results Independent of the covariates, bilingualism was associated with better memory and executive function at baseline. However bilingualism was not independently associated with rates of cognitive decline or dementia conversion. Results were similar whether bilingualism was measured via self-report or an objective test of reading level. Conclusions This study does not support a protective effect of bilingualism on age-related cognitive decline or the development of dementia. In this sample of Hispanic immigrants, bilingualism is related to higher initial scores on cognitive tests and higher educational attainment and may not represent a unique source of cognitive reserve. PMID:24188113

C-reactive protein, APOE genotype and longitudinal cognitive change in an older population

PubMed Central

Lima, Thomas A. S.; Adler, Amanda L.; Minett, Thais; Matthews, Fiona E.; Brayne, Carol; Marioni, Riccardo E.

2014-01-01

Background: circulating measures of inflammatory markers, such as C-reactive protein (CRP) have been associated with an increased risk of future cognitive decline. However, the nature of the relationship among the very old (>75 years) is unclear. Cross-sectional evidence suggests that elevated CRP may even be protective in this age group. This study examines these associations longitudinally. Methods: logistic regression was used to investigate the association between CRP and drop in cognitive performance (≥3 point change on the Mini-Mental State Examination) over a 4-year period in a population of 266 people, mean age 77 years. Results: increased levels of CRP were associated with a decreased risk of a drop in cognitive performance; however, this association was only seen in those without an APOE e4 allele [odds ratio of decline per unit increase in ln(CRP) 0.57, P = 0.04]. The magnitude of the finding remained consistent after adjustment for cardiovascular confounders (smoking, drinking, MI, stroke, diabetes, education, medication and blood pressure). For those with an e4 allele, the relationship with longitudinal cognitive decline was neither statistically significant nor in a consistent direction after controlling for acute inflammation. Conclusions: this study strengthens previous cross-sectional findings and shows elevated levels of CRP to be linked to a decreased risk of longitudinal cognitive decline in the very old. However, as with prior analyses, this was only observed in those not carrying an APOE e4 allele. Future work on larger APOE e4 allele carrying samples is required to determine the nature of the association in this population. PMID:24305621

Leisure-time physical activity associates with cognitive decline

PubMed Central

Willey, Joshua Z.; Gardener, Hannah; Caunca, Michelle R.; Moon, Yeseon Park; Dong, Chuanhui; Cheung, Yuen K.; Sacco, Ralph L.; Elkind, Mitchell S.V.

2016-01-01

Objective: Because leisure-time physical activity (LTPA) is protective against incident dementia, we hypothesized that LTPA is protective against decline in domain-specific cognitive performance. Methods: As part of the Northern Manhattan Study, LTPA was ascertained at enrollment using a validated in-person questionnaire. We assessed cognition in participants in the Northern Manhattan Study MRI substudy using a standard neuropsychological examination (NPE) (n = 1,228), and a repeat examination was performed 5 years later (n = 876). LTPA was summarized as the maximum intensity of any activity performed, classified as none to light intensity (physical inactivity) (90%) vs moderate to heavy intensity (10%). The NPE was subcategorized using standardized z scores over validated domains: processing speed, semantic memory, episodic memory, and executive function. We used multivariable linear regression models to examine the association of LTPA with initial and change in cognitive performance. Analyses were adjusted for sociodemographics, cardiovascular disease risk factors, and MRI findings (white matter hyperintensity volume, silent brain infarcts, cerebral volume). Results: No/low levels of LTPA were associated with worse executive function, semantic memory, and processing speed scores on the first NPE. The associations were slightly attenuated and no longer significant after adjusting for vascular risk factors. Cognitively unimpaired participants reporting no/low LTPA vs moderate/high levels declined more over time in processing speed (β = −0.231 ± 0.112, p = 0.040) and episodic memory (β = −0.223 ± 0.117, p = 0.057) adjusting for sociodemographic and vascular risk factors. Conclusions: A low level of LTPA is independently associated with greater decline in cognitive performance over time across domains. PMID:27009261

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.

Association between late-onset depression and incident dementia in Chinese older persons.

PubMed

Tam, C W C; Lam, L C W

2013-12-01

OBJECTIVE. Previous studies have shown that depression is a precursor / prodrome or susceptible state for the development of dementia. This study aimed to examine the relationship between late-onset depression and subsequent cognitive and functional decline in a cohort of non-demented older Chinese persons at their 2-year follow-up and investigate for possible predictors of cognitive decline. METHODS. A total of 81 depressed subjects and 468 non-depressed community controls were recruited. RESULTS. Subjects with late-onset depression showed significantly more incident Clinical Dementia Rating (CDR) scale decline (odds ratio = 3.87, 95% confidence interval = 2.23-6.70) and dementia (odds ratio = 3.44, 95% confidence interval = 1.75-6.77) than those without depression. A higher proportion of depressed CDR 0 subjects had CDR and functional decline than their non-depressed counterparts. Depressed CDR 0.5 subjects had significantly higher rates of functional decline and lower rates of improvement in CDR than their non-depressed counterparts. CONCLUSION. Diagnosis of depression was a robust predictor of incident very mild dementia (i.e. CDR of 0.5) and depression severity was a predictor of progression to dementia from CDR of 0.5. The association between depression and the risk of CDR decline and dementia was observed in non-demented Chinese subjects. Depression was also associated with persistent mild cognitive deficits in CDR 0.5 subjects.

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

Optimizing Functional Network Representation of Multivariate Time Series

NASA Astrophysics Data System (ADS)

Zanin, Massimiliano; Sousa, Pedro; Papo, David; Bajo, Ricardo; García-Prieto, Juan; Pozo, Francisco Del; Menasalvas, Ernestina; Boccaletti, Stefano

2012-09-01

By combining complex network theory and data mining techniques, we provide objective criteria for optimization of the functional network representation of generic multivariate time series. In particular, we propose a method for the principled selection of the threshold value for functional network reconstruction from raw data, and for proper identification of the network's indicators that unveil the most discriminative information on the system for classification purposes. We illustrate our method by analysing networks of functional brain activity of healthy subjects, and patients suffering from Mild Cognitive Impairment, an intermediate stage between the expected cognitive decline of normal aging and the more pronounced decline of dementia. We discuss extensions of the scope of the proposed methodology to network engineering purposes, and to other data mining tasks.

Optimizing Functional Network Representation of Multivariate Time Series

PubMed Central

Zanin, Massimiliano; Sousa, Pedro; Papo, David; Bajo, Ricardo; García-Prieto, Juan; Pozo, Francisco del; Menasalvas, Ernestina; Boccaletti, Stefano

2012-01-01

By combining complex network theory and data mining techniques, we provide objective criteria for optimization of the functional network representation of generic multivariate time series. In particular, we propose a method for the principled selection of the threshold value for functional network reconstruction from raw data, and for proper identification of the network's indicators that unveil the most discriminative information on the system for classification purposes. We illustrate our method by analysing networks of functional brain activity of healthy subjects, and patients suffering from Mild Cognitive Impairment, an intermediate stage between the expected cognitive decline of normal aging and the more pronounced decline of dementia. We discuss extensions of the scope of the proposed methodology to network engineering purposes, and to other data mining tasks. PMID:22953051

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

PubMed

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

2015-04-01

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

Cognitive 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.

The Potential Utility of Eye Movements in the Detection and Characterization of Everyday Functional Difficulties in Mild Cognitive Impairment.

PubMed

Seligman, Sarah C; Giovannetti, Tania

2015-06-01

Mild cognitive impairment (MCI) refers to the intermediate period between the typical cognitive decline of normal aging and more severe decline associated with dementia, and it is associated with greater risk for progression to dementia. Research has suggested that functional abilities are compromised in MCI, but the degree of impairment and underlying mechanisms remain poorly understood. The development of sensitive measures to assess subtle functional decline poses a major challenge for characterizing functional limitations in MCI. Eye-tracking methodology has been used to describe visual processes in everyday, naturalistic action among healthy older adults as well as several case studies of severely impaired individuals, and it has successfully differentiated healthy older adults from those with MCI on specific visual tasks. These studies highlight the promise of eye-tracking technology as a method to characterize subtle functional decline in MCI. However, to date no studies have examined visual behaviors during completion of naturalistic tasks in MCI. This review describes the current understanding of functional ability in MCI, summarizes findings of eye-tracking studies in healthy individuals, severe impairment, and MCI, and presents future research directions to aid with early identification and prevention of functional decline in disorders of aging.

The Feldenkrais Method(®) can enhance cognitive function in independent living older adults: A case-series.

PubMed

Ullmann, Gerhild; Williams, Harriet G

2016-07-01

Poor cognitive health a major concern of aging individuals, can compromise independent living. More than 16 million people in the United States are affected by cognitive impairment. We have studied the effects of the Feldenkrais Method(®) on cognitive function. In this case series with three participants cognitive function was assessed with the Trail Making Test A and B at baseline and after the Feldenkrais intervention. All participants improved performance on Trail Making Test A and B after completing the Feldenkrais intervention indicating that Feldenkrais lessons may offset age-related decline in cognitive function. The results of this case series warrant larger scale studies on cognitive outcomes of Feldenkrais interventions in clinical and non-clinical populations. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2017-01-01

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

Brain Pathology Contributes to Simultaneous Change in Physical Frailty and Cognition in Old Age

PubMed Central

Yu, Lei; Wilson, Robert S.; Boyle, Patricia A.; Schneider, Julie A.; Bennett, David. A.

2014-01-01

Objective. First, we tested the hypothesis that the rate of change of physical frailty and cognitive function in older adults are correlated. Next, we examined if their rates of change are associated with the same brain pathologies. Methods. About 2,167 older adults participating in the Religious Orders Study and the Rush Memory and Aging Project had annual clinical evaluations. Bivariate random coefficient models were used to estimate simultaneously the rates of change in both frailty and cognition, and the correlation of change was characterized by a joint distribution of the random effects. Then, we examined whether postmortem indices from deceased were associated with the rate of change of frailty and cognition. Results. During an average follow-up of 6 years, frailty worsened by 0.09 unit/y and cognition declined by 0.08 unit/y. Most individuals showed worsening frailty and cognition (82.8%); 17% showed progressive frailty alone and <1% showed only cognitive decline. The rates of change of frailty and cognition were strongly correlated (ρ = −0.73, p < .001). Among deceased (N = 828), Alzheimer’s disease pathology, macroinfarcts, and nigral neuronal loss showed independent associations with the rate of change in both frailty and cognition (all ps < .001). In these models, demographics explained about 9% of the variation in individual rate of change in frailty, and neuropathologies explained about 8%. In contrast, demographics and neuropathologies accounted for 2% and 30%, respectively, of the variance in the cognitive decline. Conclusion. The rates of change in frailty and cognition are strongly correlated and this may be due in part because they share a common pathologic basis. PMID:25136002

Recruitment of Chinese American Elders into Dementia Research: The UCSF ADRC Experience

ERIC Educational Resources Information Center

Chao, Steven Z.; Lai, Ngan B.; Tse, Marian M.; Ho, Rachel J.; Kong, Joanne P.; Matthews, Brandy R.; Miller, Bruce L.; Rosen, Howard J.

2011-01-01

Purpose: To describe the results of efforts to recruit Asian Americans into longitudinal research on cognitive decline in aging. Design and Methods: Recruitment strategies include clinics for assessment of cognitive impairment at the University of California, San Francisco campus and San Francisco's Chinatown, lectures to local health care…

Frontal Gamma-Aminobutyric Acid Concentrations Are Associated With Cognitive Performance in Older Adults.

PubMed

Porges, Eric C; Woods, Adam J; Edden, Richard A E; Puts, Nicolaas A J; Harris, Ashley D; Chen, Huaihou; Garcia, Amanda M; Seider, Talia R; Lamb, Damon G; Williamson, John B; Cohen, Ronald A

2017-01-01

Gamma-aminobutyric acid (GABA), the brain's principal inhibitory neurotransmitter, has been associated with perceptual and attentional functioning. Recent application of magnetic resonance spectroscopy (MRS) provides in vivo evidence for decreasing GABA concentrations during adulthood. It is unclear, however, how age-related decrements in cerebral GABA concentrations contribute to cognitive decline, or whether previously reported declines in cerebral GABA concentrations persist during healthy aging. We hypothesized that participants with higher GABA concentrations in the frontal cortex would exhibit superior cognitive function and that previously reported age-related decreases in cortical GABA concentrations continue into old age. We measured GABA concentrations in frontal and posterior midline cerebral regions using a Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) 1 H-MRS approach in 94 older adults without history or clinical evidence of mild cognitive impairment or dementia (mean age, 73 years). We administered the Montreal Cognitive Assessment to assess cognitive functioning. Greater frontal GABA concentrations were associated with superior cognitive performance. This relation remained significant after controlling for age, years of education, and brain atrophy. GABA concentrations in both frontal and posterior regions decreased as a function of age. These novel findings from a large, healthy, older population indicate that cognitive function is sensitive to cerebral GABA concentrations in the frontal cortex, and GABA concentration in frontal and posterior regions continue to decline in later age. These effects suggest that proton MRS may provide a clinically useful method for the assessment of normal and abnormal age-related cognitive changes and the associated physiological contributors.

Attention and Off-Topic Speech in the Recounts of Middle-Age and Elderly Adults: A Pilot Investigation

PubMed Central

Wills, Courtney L.; Capilouto, Gilson J.; Wright, Heather Harris

2013-01-01

Purpose The discourse of healthy older adults is commonly described as being lengthy and off-topic and is thought to be associated with a general cognitive decline that accompanies healthy aging. The purpose of this preliminary study was to investigate the overall decline in attention associated with healthy aging and its relationship to instances of off-topic speech (OTS). Method Thirty cognitively healthy adults divided into 5 age cohorts (40–80) completed cognitive measures of attention and several discourse tasks that included recounting personal events. Results Cohorts differed significantly with respect to the measures of attention. However, no significant differences in the incidence of OTS were detected between the cohorts. Attention and the incidence of OTS were not significantly correlated within any of the cohorts. Conclusion No significant differences in the incidence of OTS and its relation to attention measures were found. However, the relationship between age-related declines in attention and increased OTS approached significance, suggesting the need for further study. PMID:23420319

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.

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.

Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study

PubMed Central

Lipnicki, Darren M.; Crawford, John D.; Thalamuthu, Anbupalam; Castro-Costa, Erico; Stephan, Blossom C. M.; Lipton, Richard B.; Katz, Mindy J.; Ritchie, Karen; Scali, Jacqueline; Ancelin, Marie-Laure; Scarmeas, Nikolaos; Yannakoulia, Mary; Dardiotis, Efthimios; Lam, Linda C. W.; Fung, Ada W. T.; Vaccaro, Roberta; Davin, Annalisa; Kim, Ki Woong; Han, Ji Won; Kim, Tae Hui; Cherbuin, Nicolas; Butterworth, Peter; Scazufca, Marcia; Kumagai, Shuzo; Chen, Sanmei; Narazaki, Kenji; Lobo, Antonio; Lopez-Anton, Raúl; Santabárbara, Javier; Sachdev, Perminder S.

2017-01-01

Background The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. Methods and findings We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China. Conclusions Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data. PMID:28323832

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.

The Relationship of Bilingualism Compared to Monolingualism to the Risk of Cognitive Decline or Dementia: A Systematic Review and Meta-Analysis.

PubMed

Mukadam, Naaheed; Sommerlad, Andrew; Livingston, Gill

2017-01-01

Bilingualism may contribute to cognitive reserve, protect against cognitive decline, and delay the onset of dementia. We systematically reviewed evidence about the effect of bilingualism on subsequent cognitive decline or dementia. We searched electronic databases and references for longitudinal studies comparing cognitive decline in people who were bilingual with those who were monolingual and evaluated study quality. We conducted meta-analyses using random effects models to calculate pooled odds ratio of incident dementia. We included 13/1,156 eligible articles. Meta-analysis of prospective studies of the effects of bilingualism on future dementia gave a combined Odds Ratio of dementia of 0.96 (95% CI 0.74-1.23) in bilingual participants (n = 5,527) compared to monolinguals. Most retrospective studies found that bilingual people were reported to develop symptoms of cognitive decline at a later age than monolingual participants. We did not find that bilingualism protects from cognitive decline or dementia from prospective studies. Retrospective studies are more prone to confounding by education, or cultural differences in presentation to dementia services and are therefore not suited to establishing causative links between risk factors and outcomes.

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.

Internet use, social engagement and health literacy decline during ageing in a longitudinal cohort of older English adults

PubMed Central

Kobayashi, Lindsay C; Wardle, Jane; von Wagner, Christian

2015-01-01

Background Health literacy skills tend to decline during ageing, which is often attributed to age-related cognitive decline. Whether health literacy skills may be influenced by technological and social factors during ageing is unknown. Methods We investigated whether internet use and social engagement protect against health literacy decline during ageing, independent of cognitive decline. We used prospective data from 4368 men and women aged ≥52 years in the English Longitudinal Study of Ageing from 2004 to 2011. Health literacy was measured at baseline (2004–2005) and at follow-up (2010–2011) using a reading comprehension test of a fictitious medicine label. The influences of consistent internet use and engagement in each of the civic, leisure and cultural activities on health literacy decline over the follow-up were estimated. Results After adjusting for cognitive decline and other covariates, consistent internet use (1379/4368; 32%) was protectively associated with health literacy decline (OR=0.77; 95% CI 0.60 to 0.99), as was consistent engagement in cultural activities (1715/4368; 39%; OR=0.73; 95% CI 0.56 to 0.93). As the number of activities engaged in increased, the likelihood of health literacy decline steadily decreased (ptrend<0.0001), with OR=0.51 (95% CI 0.33 to 0.79) for engaging in all four of the internet use and civic, leisure and cultural activities versus none. Conclusions Internet use and social engagement, particularly in cultural activities (eg, attending the cinema, art galleries, museums and the theatre), may help older adults to maintain health literacy during ageing. Support for older adults to maintain socially engaged lives and to access the internet should help promote the maintenance of functional literacy skills during ageing. PMID:25428933

The Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes Study (ACCORD-MIND): rationale, design, and methods.

PubMed

Williamson, Jeff D; Miller, Michael E; Bryan, R Nick; Lazar, Ronald M; Coker, Laura H; Johnson, Janice; Cukierman, Tali; Horowitz, Karen R; Murray, Anne; Launer, Lenore J

2007-06-18

Type 2 diabetes mellitus and cognitive impairment are 2 of the most common chronic conditions found in persons aged > or = 60 years. Clinical studies have shown a greater prevalence of global cognitive impairment, incidence of cognitive decline, and incidence of Alzheimer disease in patients with type 2 diabetes. To date, there have been no randomized trials of the effects of long-term glycemic control on cognitive function and structural brain changes in patients with type 2 diabetes. The primary aim of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Memory in Diabetes Study (ACCORD-MIND) is to test whether there is a difference in the rate of cognitive decline and structural brain change in patients with diabetes treated with standard-care guidelines compared with those treated with intensive-care guidelines. This comparison will be made in a subsample of 2,977 patients with diabetes participating in the ongoing ACCORD trial, a clinical trial sponsored by the National Heart, Lung, and Blood Institute (NHLBI) with support from the National Institute on Aging (NIA). Data from this ACCORD substudy on the possible beneficial or adverse effects of intensive treatment on cognitive function will be obtained from a 30-minute test battery, administered at baseline and 20-month and 40-month visits. In addition, full-brain magnetic resonance imaging will be performed on 630 participants at baseline and at 40 months to assess the relation between the ACCORD treatments and structural brain changes. The general aim of ACCORD-MIND is to determine whether the intensive treatment of diabetes, a major risk factor for Alzheimer disease and vascular dementia, can reduce the early decline in cognitive function that could later evolve into more cognitively disabling conditions. This report presents the design, rationale, and methods of the ACCORD-MIND substudy.

Cognitive decline following incident and preexisting diabetes mellitus in a population sample.

PubMed

Rajan, Kumar B; Arvanitakis, Zoe; Lynch, Elizabeth B; McAninch, Elizabeth A; Wilson, Robert S; Weuve, Jennifer; Barnes, Lisa L; Bianco, Antonio C; Evans, Denis A

2016-10-18

To examine if incident and preexisting diabetes mellitus (DM) were associated with cognitive decline among African Americans (AAs) and European Americans (EAs). Based on a prospective study of 7,740 older adults (mean age 72.3 years, 64% AA, 63% female), DM was ascertained by hypoglycemic medication use and Medicare claims during physician or hospital visits, and cognition by performance on a brief battery for executive functioning, episodic memory, and Mini-Mental State Examination (MMSE). Decline in composite and individual tests among those with incident DM, with preexisting DM, and without DM was studied using a linear mixed effects model with and without change point. At baseline, 737 (15%) AAs and 269 (10%) EAs had preexisting DM. Another 721 (17%) AAs and 289 (12%) EAs had incident DM in old age. Following incident DM, cognitive decline increased by 36% among AAs and by 40% among EAs compared to those without DM. No significant difference was observed between AAs and EAs (p = 0.64). However, cognitive decline increased by 17% among AAs with preexisting DM compared to those without DM, but no increased decline was observed among EAs with preexisting DM. In secondary analyses, faster decline in executive functioning and episodic memory was observed following incident DM. In old age, faster cognitive decline was present among AAs and EAs following incident DM, compared to cognitive decline prior to DM, and among those without DM. This underscores the need for stronger prevention and control of DM in old age. © 2016 American Academy of Neurology.

Association of Crossword Puzzle Participation with Memory Decline in Persons Who Develop Dementia

PubMed Central

Pillai, Jagan A.; Hall, Charles B.; Dickson, Dennis W.; Buschke, Herman; Lipton, Richard B.; Verghese, Joe

2013-01-01

Participation in cognitively stimulating leisure activities such as crossword puzzles may delay onset of the memory decline in the preclinical stages of dementia, possibly via its effect on improving cognitive reserve. We followed 488 initially cognitively intact community residing individuals with clinical and cognitive assessments every 12–18 months in the Bronx Aging Study. We assessed the influence of crossword puzzle participation on the onset of accelerated memory decline as measured by the Buschke Selective Reminding Test in 101 individuals who developed incident dementia using a change point model. Crossword puzzle participation at baseline delayed onset of accelerated memory decline by 2.54 years. Inclusion of education or participation in other cognitively stimulating activities did not significantly add to the fit of the model beyond the effect of puzzles. Our findings show that late life crossword puzzle participation, independent of education, was associated with delayed onset of memory decline in persons who developed dementia. Given the wide availability and accessibility of crossword puzzles, their role in preventing cognitive decline should be validated in future clinical trials. PMID:22040899

Associations between cognitively stimulating leisure activities, cognitive function and age-related cognitive decline.

PubMed

Ferreira, Nicola; Owen, Adrian; Mohan, Anita; Corbett, Anne; Ballard, Clive

2015-04-01

Emerging literature suggests that lifestyle factors may play an important role in reducing age-related cognitive decline. There have, however, been few studies investigating the role of cognitively stimulating leisure activities in maintaining cognitive health. This study sought to identify changes in cognitive performance with age and to investigate associations of cognitive performance with several key cognitively stimulating leisure activities. Over 65,000 participants provided demographic and lifestyle information and completed tests of grammatical reasoning, spatial working memory, verbal working memory and episodic memory. Regression analyses suggested that frequency of engaging in Sudoku or similar puzzles was significantly positively associated with grammatical reasoning, spatial working memory and episodic memory scores. Furthermore, for participants aged under 65 years, frequency of playing non-cognitive training computer games was also positively associated with performance in the same cognitive domains. The results also suggest that grammatical reasoning and episodic memory are particularly vulnerable to age-related decline. Further investigation to determine the potential benefits of participating in Sudoku puzzles and non-cognitive computer games is indicated, particularly as they are associated with grammatical reasoning and episodic memory, cognitive domains found to be strongly associated with age-related cognitive decline. Results of this study have implications for developing improved guidance for the public regarding the potential value of cognitively stimulating leisure activities. The results also suggest that grammatical reasoning and episodic memory should be targeted in developing appropriate outcome measures to assess efficacy of future interventions, and in developing cognitive training programmes to prevent or delay cognitive decline. Copyright © 2014 John Wiley & Sons, Ltd.

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/

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.

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.

Apathy and Reduced Speed of Processing Underlie Decline in Verbal Fluency following DBS.

PubMed

Foley, Jennifer A; Foltynie, Tom; Zrinzo, Ludvic; Hyam, Jonathan A; Limousin, Patricia; Cipolotti, Lisa

2017-01-01

Objective . Reduced verbal fluency is a strikingly uniform finding following deep brain stimulation (DBS) for Parkinson's disease (PD). The precise cognitive mechanism underlying this reduction remains unclear, but theories have suggested reduced motivation, linguistic skill, and/or executive function. It is of note, however, that previous reports have failed to consider the potential role of any changes in speed of processing. Thus, the aim of this study was to examine verbal fluency changes with a particular focus on the role of cognitive speed. Method . In this study, 28 patients with PD completed measures of verbal fluency, motivation, language, executive functioning, and speed of processing, before and after DBS. Results . As expected, there was a marked decline in verbal fluency but also in a timed test of executive functions and two measures of speed of processing. Verbal fluency decline was associated with markers of linguistic and executive functioning, but not after speed of processing was statistically controlled for. In contrast, greater decline in verbal fluency was associated with higher levels of apathy at baseline, which was not associated with changes in cognitive speed. Discussion . Reduced generativity and processing speed may account for the marked reduction in verbal fluency commonly observed following DBS.

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.

Examining the impact of grape consumption on brain metabolism and cognitive function in patients with mild decline in cognition: A double-blinded placebo controlled pilot study.

PubMed

Lee, Jooyeon; Torosyan, Nare; Silverman, Daniel H

2017-01-01

Natural compounds in grapes such as resveratrol are known for their antioxidant and anti-inflammatory properties. Some studies have shown a potential role for grapes or wine in slowing cognitive decline and other effects of aging. However, well-controlled experimental data obtained in human subjects are still in need of further development. Here we aimed to systematically assess effects of grapes on regional cerebral metabolism. Ten subjects with mild decline in cognition (mean, 72.2±4.7years; 50% female) were included in this analysis. Participants were randomized into an active grape formulation arm or a placebo arm which consumed a formulation free of polyphenols for six months. Cognitive performance was measured through neuropsychological assessments performed at baseline and 6months after initiation of therapy. Changes in brain metabolism occurring with each therapy regimen were assessed by brain PET scans with the radiotracer [F-18] fluorodeoxyglucose (FDG), obtained during initial evaluation and 6months later. Standardized volumes of interest (sVOI) and statistical parametric mapping (SPM) methods were applied to FDG-PET scans to identify significant regional cerebral metabolic changes. In contrast to participants taking the active grape formulation, who displayed no significant decline in metabolism, the placebo arm underwent significant metabolic decline in sVOI's of the right posterior cingulate cortex (p=0.01), and left superior posterolateral temporal cortex (p=0.04). SPM analyses also found significant declines in the placebo group, particularly in left prefrontal, cingulate, and left superior posterolateral temporal cortex (p<0.01) with stable brain metabolism in the active formulation arm. No significant differences were seen in scores on the neuropsychological battery of tests between the two groups. However, metabolism in right superior parietal cortex and left inferior anterior temporal cortex was correlated with improvements in attention/working memory, as measured with WAIS-III Digital Span within the active formulation group (r=-0.69, p=0.04). The placebo arm had declines in regions of the brain known to be significantly affected in the early stages of Alzheimer's disease, while the active formulation group was spared such decline. This suggests a protective effect of grapes against early pathologic metabolic decline. Copyright © 2016 Elsevier Inc. All rights reserved.

Examining the Association between Patient-Reported Symptoms of Attention and Memory Dysfunction with Objective Cognitive Performance: A Latent Regression Rasch Model Approach.

PubMed

Li, Yuelin; Root, James C; Atkinson, Thomas M; Ahles, Tim A

2016-06-01

Patient-reported cognition generally exhibits poor concordance with objectively assessed cognitive performance. In this article, we introduce latent regression Rasch modeling and provide a step-by-step tutorial for applying Rasch methods as an alternative to traditional correlation to better clarify the relationship of self-report and objective cognitive performance. An example analysis using these methods is also included. Introduction to latent regression Rasch modeling is provided together with a tutorial on implementing it using the JAGS programming language for the Bayesian posterior parameter estimates. In an example analysis, data from a longitudinal neurocognitive outcomes study of 132 breast cancer patients and 45 non-cancer matched controls that included self-report and objective performance measures pre- and post-treatment were analyzed using both conventional and latent regression Rasch model approaches. Consistent with previous research, conventional analysis and correlations between neurocognitive decline and self-reported problems were generally near zero. In contrast, application of latent regression Rasch modeling found statistically reliable associations between objective attention and processing speed measures with self-reported Attention and Memory scores. Latent regression Rasch modeling, together with correlation of specific self-reported cognitive domains with neurocognitive measures, helps to clarify the relationship of self-report with objective performance. While the majority of patients attribute their cognitive difficulties to memory decline, the Rash modeling suggests the importance of processing speed and initial learning. To encourage the use of this method, a step-by-step guide and programming language for implementation is provided. Implications of this method in cognitive outcomes research are discussed. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

PubMed

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

2009-12-01

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

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.

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

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.

Impaired Olfaction and Risk for Delirium or Cognitive Decline After Cardiac Surgery

PubMed Central

Brown, Charles H.; Morrissey, Candice; Ono, Masahiro; Yenokyan, Gayane; Selnes, Ola A.; Walston, Jeremy; Max, Laura; LaFlam, Andrew; Neufeld, Karin; Gottesman, Rebecca F.; Hogue, Charles W.

2014-01-01

Summary Statement Impaired olfaction, identified in 33% of patients undergoing cardiac surgery, was associated with the adjusted risk for postoperative delirium but not cognitive decline. Objectives The prevalence and significance of impaired olfaction is not well characterized in patients undergoing cardiac surgery. Because impaired olfaction has been associated with underlying neurologic disease, impaired olfaction may identify patients who are vulnerable to poor neurological outcomes in the perioperative period. The objective of this study was to determine the prevalence of impaired olfaction among patients presenting for cardiac surgery and the independent association of impaired olfaction with postoperative delirium and cognitive decline. Design Nested prospective cohort study Setting Academic hospital Participants 165 patients undergoing coronary artery bypass and/or valve surgery Measurements Olfaction was measured using the Brief Smell Identification Test, with impaired olfaction defined as an olfactory score < 5th percentile of normative data. Delirium was assessed using a validated chart-review method. Cognitive performance was assessed using a neuropsychological testing battery at baseline and 4–6 weeks after surgery. Results Impaired olfaction was identified in 54 of 165 patients (33%) prior to surgery. Impaired olfaction was associated with increased adjusted risk for postoperative delirium (relative risk [RR] 1.90, 95% CI 1.17–3.09; P=0.009). There was no association between impaired olfaction and change in composite cognitive score in the overall study population. Conclusion Impaired olfaction is prevalent in patients undergoing cardiac surgery and is associated with increased adjusted risk for postoperative delirium, but not cognitive decline. Impaired olfaction may identify unrecognized vulnerability for postoperative delirium among patients undergoing cardiac surgery. PMID:25597555

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

Age-related reduction in microcolumnar structure correlates with cognitive decline in ventral but not dorsal area 46 of the rhesus monkey.

PubMed

Cruz, L; Roe, D L; Urbanc, B; Inglis, A; Stanley, H E; Rosene, D L

2009-02-18

The age-related decline in cognitive function that is observed in normal aging monkeys and humans occurs without significant loss of cortical neurons. This suggests that cognitive impairment results from subtle, sub-lethal changes in the cortex. Recently, changes in the structural coherence in mini- or microcolumns without loss of neurons have been linked to loss of function. Here we use a density map method to quantify microcolumnar structure in both banks of the sulcus principalis (prefrontal cortical area 46) of 16 (ventral) and 19 (dorsal) behaviorally tested female rhesus monkeys from 6 to 33 years of age. While total neuronal density does not change with age in either of these banks, there is a significant age-related reduction in the strength of microcolumns in both regions on the order of 40%. This likely reflects a subtle but definite loss of organization in the structure of the cortical microcolumn. The reduction in strength in ventral area 46 correlates with cognitive impairments in learning and memory while the reduction in dorsal area 46 does not. This result is congruent with published data attributing cognitive functions to ventral area 46 that are similar to our particular cognitive battery which does not optimally tap cognitive functions attributed to dorsal area 46. While the exact mechanisms underlying this loss of microcolumnar organization remain to be determined, it is plausible that they reflect age-related alterations in dendritic and/or axonal organization which alter connectivity and may contribute to age-related declines in cognitive performance.

The Longitudinal Impact of Cognitive Speed of Processing Training on Driving Mobility

ERIC Educational Resources Information Center

Edwards, Jerri D.; Myers, Charlsie; Ross, Lesley A.; Roenker, Daniel L.; Cissell, Gayla M.; McLaughlin, Alexis M.; Ball, Karlene K.

2009-01-01

Purpose: To examine how cognitive speed of processing training affects driving mobility across a 3-year period among older drivers. Design and Methods: Older drivers with poor Useful Field of View (UFOV) test performance (indicating greater risk for subsequent at-fault crashes and mobility declines) were randomly assigned to either a speed of…

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.

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

PubMed Central

Teixeira-Leite, Homero; Manhães, Alex C.

2012-01-01

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

Adverse Childhood and Recent Negative Life Events: Contrasting Associations With Cognitive Decline in Older Persons.

PubMed

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

2014-06-01

To examine whether persons who experienced adverse childhood events or recent negative life events have a worse cognitive performance and faster cognitive decline and the role of depression and apolipoprotein E-∊4 in this relationship. The community-based sample consisted of 10-year follow-up data of 1312 persons participating in the Longitudinal Aging Study Amsterdam (age range 65-85 years). Persons who experienced adverse childhood events showed a faster 10-year decline in processing speed but only when depressive symptoms were experienced. Persons with more recent negative life events showed slower processing speed at baseline but no faster decline. Childhood adversity may cause biological or psychological vulnerability, which is associated with both depressive symptoms and cognitive decline in later life. The accumulation of recent negative life events did not affect cognitive functioning over a longer time period. © The Author(s) 2014.

Higher Blood Vitamin C Levels are Associated with Reduction of Apolipoprotein E E4-related Risks of Cognitive Decline in Women: The Nakajima Study.

PubMed

Noguchi-Shinohara, Moeko; Abe, Chiemi; Yuki-Nozaki, Sohshi; Dohmoto, Chiaki; Mori, Ayaka; Hayashi, Koji; Shibata, Syutaro; Ikeda, Yoshihisa; Sakai, Kenji; Iwasa, Kazuo; Yokogawa, Masami; Ishimiya, Mai; Nakamura, Hiroyuki; Yokoji, Hidehiro; Komai, Kiyonobu; Nakamura, Hiroyuki; Yamada, Masahito

2018-05-11

Antioxidants like vitamins C and E may minimize the risk for Alzheimer's disease. We examined whether vitamins C and E modify the apolipoprotein E (APOE) E4-related risks for developing cognitive decline. We conducted a population-based prospective study including Japanese residents aged 65 years from Nakajima, Japan. The participants received an evaluation of cognitive function and underwent blood tests including tests for vitamins C and E levels and APOE phenotypes. The APOE E4-by-gender-by-vitamin C or E interactions on developing cognitive decline were analyzed. Of 606 participants with normal cognitive function determined using a baseline survey (2007-2008), 349 completed the follow up survey between 2014 and 2016. In women with APOE E4, significantly reduced risk for cognitive decline was observed for the highest blood vitamin C concentration tertile [multivariate OR 0.10 (95% CI 0.01-0.93)] compared with the lowest tertile. In men without APOE E4, significantly reduced risk for cognitive decline was observed for the highest blood vitamin E concentration tertile [multivariate OR 0.19 (0.05-0.74)] as compared with the lowest tertile. Our results demonstrate significant beneficial effects of vitamins C and E in reducing the risk of cognitive decline in women with APOE E4 and men without APOE E4, respectively.

Left Ventricular Hypertrophy and Cognitive Decline in Old Age.

PubMed

Mahinrad, Simin; Vriend, Annelotte E; Jukema, J Wouter; van Heemst, Diana; Sattar, Naveed; Blauw, Gerard Jan; Macfarlane, Peter W; Clark, Elaine N; de Craen, Anton J M; Sabayan, Behnam

2017-01-01

Patients with advanced heart failure run a greater risk of dementia. Whether early cardiac structural changes also associate with cognitive decline is yet to be determined. We tested whether left ventricular hypertrophy (LVH) derived from electrocardiogram associates with cognitive decline in older subjects at risk of cardiovascular disease. We included 4,233 participants (mean age 75.2 years, 47.8% male) from PROSPER (PROspective Study of Pravastatin in the Elderly at Risk). LVH was assessed from baseline electrocardiograms by measuring the Sokolow-Lyon index. Higher levels of Sokolow-Lyon index indicate higher degrees of LVH. Cognitive domains involving selective attention, processing speed, and immediate and delayed memory were measured at baseline and repeated during a mean follow-up of 3.2 years. At baseline, LVH was not associated with worse cognitive function. During follow-up, participants with higher levels of LVH had a steeper decline in cognitive function including in selective attention (p = 0.009), processing speed (p = 0.010), immediate memory (p < 0.001), and delayed memory (p = 0.002). These associations were independent of cardiovascular risk factors, co-morbidities, and medications. LVH assessed by electrocardiogram associates with steeper decline in cognitive function of older subjects independent of cardiovascular risk factors and co-morbidities. This study provides further evidence on the link between subclinical cardiac structural changes and cognitive decline in older subjects.

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.

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

PubMed Central

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

2012-01-01

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

Analysis of brief language tests in the detection of cognitive decline and dementia

PubMed Central

Radanovic, Marcia; Carthery-Goulart, Maria Teresa; Charchat-Fichman, Helenice; Herrera Jr., Emílio; Lima, Edson Erasmo Pereira; Smid, Jerusa; Porto, Cláudia Sellitto; Nitrini, Ricardo

2007-01-01

Lexical access difficulties are frequent in normal aging and initial stages of dementia.Verbal fluency tests are valuable to detect cognitive decline, evidencing lexico-semantic and executive dysfunction. Objectives To establish which language tests can contribute in detecting dementia and to verify schooling influence on subject performance. Method 74 subjects: 33 controls, 17 Clinical Dementia Rating (CDR) 0.5 and 24 (Brief Cognitive Battery - BCB e Boston Naming Test - BNT) 1 were compared in tests of semantic verbal fluency (animal and fruit), picture naming (BCB and BNT) and the language items of Mini Mental State Examination (MMSE). Results There were significant differences between the control group and both CDR 0.5 and CDR 1 in all tests. Cut-off scores were: 11 and 10 for animal fluency, 8 for fruit fluency (in both), 8 and 9 for BCB naming. The CDR 0.5 group performed better than the CDR 1 group only in animal fluency. Stepwise multiple regression revealed fruit fluency, animal fluency and BCB naming as the best discriminators between patients and controls (specificity: 93.8%; sensitivity: 91.3%). In controls, comparison between illiterates and literates evidenced schooling influence in all tests, except for fruit fluency and BCB naming. In patients with dementia, only fruit fluency was uninfluenced by schooling. Conclusion The combination of verbal fluency tests in two semantic categories along with a simple picture naming test is highly sensitive in detecting cognitive decline. Comparison between literate and illiterate subjects shows a lesser degree of influence of schooling on the selected tests, thus improving discrimination between low performance and incipient cognitive decline. PMID:29213366

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).

Mindfulness-based stress reduction in middle-aged and older adults with memory complaints: a mixed-methods study.

PubMed

Berk, Lotte; Hotterbeekx, Rafke; van Os, Jim; van Boxtel, Martin

2017-07-19

In a rapidly aging world population, an increasingly large group faces age-related decline in cognitive functioning. Cognitive complaints of older adults are often related to worries and concerns associated with age-related functional decline. Mindfulness-Based Stress Reduction (MBSR) can successfully target stress, worry and ruminative thinking, but the applicability of this method in middle-aged and older adults with memory complaints is unclear. Patients of a university hospital memory clinic (n = 13), aged 45-85 years, with memory complaints but no diagnosis of cognitive disorder, participated in a standard 8-week MBSR program, consisting of weekly group meetings and a one-day silent retreat. After completion, semi-structured qualitative interviews were conducted. Questionnaires (administered before, one week after and five weeks after the intervention) assessed quality of life, psychological distress (stress, anxiety and depressive symptoms), mindfulness, self-compassion, and subjective memory functioning. Neurocognitive functioning was assessed online, before and after the intervention. The qualitative analysis showed positive effects of the training (e.g. increased serenity), many participants worrying less about memory complaints. The self-reported measures were in line with the results of the qualitative analysis. This exploratory mixed-methods study suggests that MBSR is feasible and well received among older individuals with cognitive complaints.

Randomized control trial of computer-based training targeting alertness in older adults: the ALERT trial protocol.

PubMed

VanVleet, Thomas; Voss, Michelle; Dabit, Sawsan; Mitko, Alex; DeGutis, Joseph

2018-05-03

Healthy aging is associated with a decline in multiple functional domains including perception, attention, short and long-term memory, reasoning, decision-making, as well as cognitive and motor control functions; all of which are significantly modulated by an individual's level of alertness. The control of alertness also significantly declines with age and contributes to increased lapses of attention in everyday life, ranging from minor memory slips to a lack of vigilance and increased risk of falls or motor-vehicle accidents. Several experimental behavioral therapies designed to remediate age-related cognitive decline have been developed, but differ widely in content, method and dose. Preliminary studies demonstrate that Tonic and Phasic Alertness Training (TAPAT) can improve executive functions in older adults and may be a useful adjunct treatment to enhance benefits gained in other clinically validated treatments. The purpose of the current trial (referred to as the Attention training for Learning Enhancement and Resilience Trial or ALERT) is to compare TAPAT to an active control training condition, include a larger sample of patients, and assess both cognitive and functional outcomes. We will employ a multi-site, longitudinal, blinded randomized controlled trial (RCT) design with a target sample of 120 patients with age-related cognitive decline. Patients will be asked to complete 36 training sessions remotely (30 min/day, 5 days a week, over 3 months) of either the experimental TAPAT training program or an active control computer games condition. Patients will be assessed on a battery of cognitive and functional outcomes at four time points, including: a) immediately before training, b) halfway through training, c) within forty-eight hours post completion of total training, and d) after a three-month no-contact period post completion of total training, to assess the longevity of potential training effects. The strengths of this protocol are that it tests an innovative, in-home administered treatment that targets a fundamental deficit in adults with age-related cognitive decline; employs highly sensitive computer-based assessments of cognition as well as functional abilities, and incorporates a large sample size in an RCT design. ClinicalTrials.gov identifier: NCT02416401.

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.

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 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.

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.

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.

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.

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.

Treatment effects in multiple cognitive domains in Alzheimer’s disease: a two-year cohort study

PubMed Central

2014-01-01

Introduction Despite widespread use of second-generation cholinesterase inhibitors for the symptomatic treatment of Alzheimer’s disease (AD), little is known about the long term effects of cholinergic treatment on global cognitive function and potential specific effects in different cognitive domains. The objectives of this study were to determine the association between cholinergic treatment and global cognitive function over one and two years in a cohort of patients with mild or moderate AD and identify potential differences in domain-specific cognitive outcomes within this cohort. Methods A cohort of patients meeting the revised National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for mild or moderate AD, including patients both on treatment with a cholinesterase inhibitor and untreated controls (treated = 65, untreated = 65), were recruited from the Cognitive Neurology Clinic at Sunnybrook Health Sciences Centre, as part of the Sunnybrook Dementia Study. Patients were followed for one to two years and underwent standardized neuropsychological assessments to evaluate global and domain-specific cognitive function. Associations between cholinesterase inhibitor use and global and domain-specific cognitive outcome measures at one and two years of follow-up were estimated using mixed model linear regression, adjusting for age, education, and baseline mini mental state examination (MMSE). Results At one year, treated patients showed significantly less decline in global cognitive function, and treatment and time effects across tests of executive and visuospatial function. At two years, there was a significant trend towards less decline in global cognition for treated patients. Moreover, treated patients showed significant treatment and time effects across tests of executive functioning, memory, and visuospatial function. Conclusions The present study offers two important contributions to knowledge of the effectiveness of cholinesterase inhibitor treatment in patients with mild-moderate AD: 1) that second-generation cholinesterase inhibitors demonstrate long-term effectiveness for reducing global cognitive decline over one to two years of follow-up, and 2) that decline in function for cognitive domains, including executive function, memory, and visuospatial skill that are primarily mediated by frontal networks and by the cholinergic system, rather than memory, may be slowed by treatment targeting the cholinergic system. PMID:25484926

Cognitive Experiences Reported by Borderline Patients and Axis II Comparison Subjects: A 16-year Prospective Follow-up Study

PubMed Central

Zanarini, Mary C.; Frankenburg, Frances R.; Wedig, Michelle M.; Fitzmaurice, Garrett M.

2013-01-01

Objective This study assesses three main types of cognition: nonpsychotic thought (odd thinking, unusual perceptual experiences, and non-delusional paranoia), quasi-psychotic thought, and true-psychotic thought in borderline patients followed prospectively for 16 years. It also compares the rates of these disturbed cognitions to those reported by axis II comparison subjects. Method The cognitive experiences of 362 inpatients—290 borderline patients and 72 axis II comparison subjects—were assessed at study entry using the cognitive section of the Revised Diagnostic Interview for Borderlines. Their cognitive experiences were reassessed every two years using the same interview. Results Each of the five main types of thought studied was reported by a significantly higher percentage of borderline patients than axis II comparison subjects over time. Each of these types of thought, except true-psychotic thought, declined significantly over time for those in both groups. Eleven of the 17 more specific forms of thought studied were also reported by a significantly higher percentage of borderline patients over the years of follow-up: magical thinking, overvalued ideas, recurrent illusions, depersonalization, derealization, undue suspiciousness, ideas of reference, other paranoid ideation, quasi-psychotic delusions, quasi-psychotic hallucinations, and true-psychotic hallucinations. Fourteen specific forms of thought were found to decline significantly over time for those in both groups: all forms of thought mentioned above except true-psychotic hallucinations plus marked superstitiousness, sixth sense, telepathy, and clairvoyance. Conclusions Disturbed cognitions are common among borderline patients and distinguishing for the disorder. They also decline substantially over time but remain a problem, particularly those of a nonpsychotic nature. PMID:23558452

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.

MIND diet slows cognitive decline with aging.

PubMed

Morris, Martha Clare; Tangney, Christy C; Wang, Yamin; Sacks, Frank M; Barnes, Lisa L; Bennett, David A; Aggarwal, Neelum T

2015-09-01

The Mediterranean and dash diets have been shown to slow cognitive decline; however, neither diet is specific to the nutrition literature on dementia prevention. We devised the Mediterranean-Dietary Approach to Systolic Hypertension (DASH) diet intervention for neurodegenerative delay (MIND) diet score that specifically captures dietary components shown to be neuroprotective and related it to change in cognition over an average 4.7 years among 960 participants of the Memory and Aging Project. In adjusted mixed models, the MIND score was positively associated with slower decline in global cognitive score (β = 0.0092; P < .0001) and with each of five cognitive domains. The difference in decline rates for being in the top tertile of MIND diet scores versus the lowest was equivalent to being 7.5 years younger in age. The study findings suggest that the MIND diet substantially slows cognitive decline with age. Replication of these findings in a dietary intervention trial would be required to verify its relevance to brain health. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2012-01-01

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

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.

Indication of Cognitive Change and Associated Risk Factor after Thoracic Surgery in the Elderly: A Pilot Study.

PubMed

Kulason, Kay; Nouchi, Rui; Hoshikawa, Yasushi; Noda, Masafumi; Okada, Yoshinori; Kawashima, Ryuta

2017-01-01

Background: This pilot study investigated the effects of partial pulmonary lobectomy lung surgery on cognitive functions of elderly Japanese patients. It is recognized that elderly patients undergoing surgery have increased risk of Postoperative Cognitive Decline (POCD), a condition in which learning, memory, and processing speed is greatly reduced after surgery. Since elderly patients are more likely to exhibit symptoms of POCD, the incidence is increasing as the population receiving surgery is aging. Methods: Cognitive function was measured for all subjects ( n = 12) before and after surgery using three different cognitive tests: Mini-Mental Status Exam-Japanese (MMSE-J), Frontal Assessment Battery (FAB), and a computerized Cogstate Brief Battery (CBB). Changes in these measures indicate changes in cognitive function. In addition, the 12-item General Health Questionnaire (GHQ-12), the Geriatric Depression Scale (GDS), and the 5-item Quality of Life questionnaire (QOL-5) were administered at each time point to measure mental and emotional state. Changes in outcome measures were analyzed via Wilcoxon signed-rank test. Exploratory correlation analysis was conducted using Spearman's rho. Results: Data show a decline in detection (DET; p = 0.045) and identification (IDN; p = 0.038). Spearman's correlation coefficient show a significant correlation between postoperative DET scores and postoperative IDN scores (ρ = 0.78, p = 0.005), a significant correlation between change in IDN and baseline GHQ-12 scores (ρ = -0.595, p = 0.027), and a significant correlation between change in one-back (OBK) scores and duration of anesthesia (ρ = -0.72, p = 0.012). Discussion: This was the first report to examine cognitive decline after major thoracic surgery in Japanese patients. Previous studies have evidenced that POCD is a common phenomenon after surgery, and that age is a major risk factor. The CCB measured significant change in two cognitive domains: attention and psycomotor function. This study clarified that decline in cognition is detectable in certain measures after thoracic surgery in the elderly Japanese patient population. Additionally, longer anesthetic exposure may negatively impact attention and working memory, and preoperative mental wellbeing is a possible predictor of POCD. These preliminary results have important implications and support the need for future studies.

Childhood Cognitive Ability and Age-Related Changes in Physical Capability From Midlife: Findings From a British Birth Cohort Study.

PubMed

Cooper, Rachel; Richards, Marcus; Kuh, Diana

2017-09-01

The aim of the study was to test the hypothesis that higher childhood cognitive ability is associated with reduced risk of decline in physical capability in late midlife. Participants were 1954 men and women from the Medical Research Council National Survey of Health and Development with complete data on cognitive ability at age of 15 years and measures of grip strength and chair rise speed at ages of 53 and 60 to 64 years. Using multinomial logistic regression, associations of childhood cognitive ability with categories of change in grip strength and chair rise speed (i.e., decline, stable high, stable low, reference) were investigated. Adjustments were made for potential confounders from early life and adult mediators including health behaviors, educational level, and cognitive ability at age of 53 years. Higher childhood cognitive scores were associated with reduced risks of decline in grip strength and chair rise speed, for example, the sex-adjusted relative-risk ratio of decline (versus reference) in grip strength per 1SD increase in childhood cognitive score was 0.82 (95% confidence interval = 0.73-0.92). Higher childhood cognitive scores were also associated with reduced risk of stable low and increased likelihood of stable high chair rise speed. These findings suggest that childhood cognitive ability may be related to decline in physical capability in late midlife. A number of life course pathways are implicated, including those linking childhood and adult cognitive ability. Future research aiming to identify new opportunities to prevent or minimize age-related declines in physical capability may benefit from considering the potential role of neurodevelopmental as well as neurodegenerative pathways.

Decline in cognitive function and risk of elder self-neglect: finding from the Chicago Health Aging Project.

PubMed

Dong, XinQi; Simon, Melissa A; Wilson, Robert S; Mendes de Leon, Carlos F; Rajan, K Bharat; Evans, Denis A

2010-12-01

To examine the longitudinal association between decline in cognitive function and risk of elder self-neglect in a community-dwelling population. Prospective population-based study. Geographically defined community in Chicago. Community-dwelling subjects reported to the social services agency from 1993 to 2005 for self-neglect who also participated in the Chicago Health Aging Project (CHAP). Of the 5,519 participants in CHAP, 1,017 were reported to social services agency for suspected elder self-neglect from 1993 to 2005. Social services agency identified reported elder self-neglect. The primary predictor was decline in cognitive function assessed using the Mini-Mental State Examination (MMSE), the Symbol Digit Modalities Test (Executive Function), and immediate and delayed recall of the East Boston Memory Test (Episodic Memory). An index of global cognitive function scores was derived by averaging z-scores of all tests. Outcome of interest was elder self-neglect. Logistic and linear regression models were used to assess these longitudinal associations. After adjusting for potential confounding factors, decline in global cognitive function, MMSE score, and episodic memory were not independently associated with greater risk of reported and confirmed elder self-neglect. Decline in executive function was associated with greater risk of reported and confirmed elder self-neglect. Decline in global cognitive function was associated with greater risk of greater self-neglect severity (parameter estimate=0.76, standard error=0.31, P=.01). Decline in executive function was associated with risk of reported and confirmed elder self-neglect. Decline in global cognitive function was associated with risk of greater self-neglect severity. © 2010, Copyright the Authors. Journal compilation © 2010, The American Geriatrics Society.

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.

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.

The method of educational assessment affects children's neural processing and performance: behavioural and fMRI Evidence

NASA Astrophysics Data System (ADS)

Howard, Steven J.; Burianová, Hana; Calleia, Alysha; Fynes-Clinton, Samuel; Kervin, Lisa; Bokosmaty, Sahar

2017-08-01

Standardised educational assessments are now widespread, yet their development has given comparatively more consideration to what to assess than how to optimally assess students' competencies. Existing evidence from behavioural studies with children and neuroscience studies with adults suggest that the method of assessment may affect neural processing and performance, but current evidence remains limited. To investigate the impact of assessment methods on neural processing and performance in young children, we used functional magnetic resonance imaging to identify and quantify the neural correlates during performance across a range of current approaches to standardised spelling assessment. Results indicated that children's test performance declined as the cognitive load of assessment method increased. Activation of neural nodes associated with working memory further suggests that this performance decline may be a consequence of a higher cognitive load, rather than the complexity of the content. These findings provide insights into principles of assessment (re)design, to ensure assessment results are an accurate reflection of students' true levels of competency.

The level of cognitive function and recognition of emotions in older adults

PubMed Central

Singh-Manoux, Archana; Batty, G. David; Ebmeier, Klaus P.; Jokela, Markus; Harmer, Catherine J.; Kivimäki, Mika

2017-01-01

Background The association between cognitive decline and the ability to recognise emotions in interpersonal communication is not well understood. We aimed to investigate the association between cognitive function and the ability to recognise emotions in other people’s facial expressions across the full continuum of cognitive capacity. Methods Cross-sectional analysis of 4039 participants (3016 men, 1023 women aged 59 to 82 years) in the Whitehall II study. Cognitive function was assessed using a 30-item Mini-Mental State Examination (MMSE), further classified into 8 groups: 30, 29, 28, 27, 26, 25, 24, and <24 (possible dementia) MMSE points. The Facial Expression Recognition Task (FERT) was used to examine recognition of anger, fear, disgust, sadness, and happiness. Results The multivariable adjusted difference in the percentage of accurate recognition between the highest and lowest MMSE group was 14.9 (95%CI, 11.1–18.7) for anger, 15.5 (11.9–19.2) for fear, 18.5 (15.2–21.8) for disgust, 11.6 (7.3–16.0) for sadness, and 6.3 (3.1–9.4) for happiness. However, recognition of several emotions was reduced already after 1 to 2-point reduction in MMSE and with further points down in MMSE, the recognition worsened at an accelerated rate. Conclusions The ability to recognize emotion in facial expressions is affected at an early stage of cognitive impairment and might decline at an accelerated rate with the deterioration of cognitive function. Accurate recognition of happiness seems to be less affected by a severe decline in cognitive performance than recognition of negatively valued emotions. PMID:28977015

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

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

PubMed Central

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

2012-01-01

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

Apathy and Reduced Speed of Processing Underlie Decline in Verbal Fluency following DBS

PubMed Central

Foltynie, Tom; Zrinzo, Ludvic; Hyam, Jonathan A.; Limousin, Patricia

2017-01-01

Objective. Reduced verbal fluency is a strikingly uniform finding following deep brain stimulation (DBS) for Parkinson's disease (PD). The precise cognitive mechanism underlying this reduction remains unclear, but theories have suggested reduced motivation, linguistic skill, and/or executive function. It is of note, however, that previous reports have failed to consider the potential role of any changes in speed of processing. Thus, the aim of this study was to examine verbal fluency changes with a particular focus on the role of cognitive speed. Method. In this study, 28 patients with PD completed measures of verbal fluency, motivation, language, executive functioning, and speed of processing, before and after DBS. Results. As expected, there was a marked decline in verbal fluency but also in a timed test of executive functions and two measures of speed of processing. Verbal fluency decline was associated with markers of linguistic and executive functioning, but not after speed of processing was statistically controlled for. In contrast, greater decline in verbal fluency was associated with higher levels of apathy at baseline, which was not associated with changes in cognitive speed. Discussion. Reduced generativity and processing speed may account for the marked reduction in verbal fluency commonly observed following DBS. PMID:28408788

Internet Searches and Their Relationship to Cognitive Function in Older Adults: Cross-Sectional Analysis

PubMed Central

Hollingshead, Kristy; Kaye, Jeffrey

2017-01-01

Background Alzheimer disease (AD) is a very challenging experience for all those affected. Unfortunately, detection of Alzheimer disease in its early stages when clinical treatments may be most effective is challenging, as the clinical evaluations are time-consuming and costly. Recent studies have demonstrated a close relationship between cognitive function and everyday behavior, an avenue of research that holds great promise for the early detection of cognitive decline. One area of behavior that changes with cognitive decline is language use. Multiple groups have demonstrated a close relationship between cognitive function and vocabulary size, verbal fluency, and semantic ability, using conventional in-person cognitive testing. An alternative to this approach which is inherently ecologically valid may be to take advantage of automated computer monitoring software to continually capture and analyze language use while on the computer. Objective The aim of this study was to understand the relationship between Internet searches as a measure of language and cognitive function in older adults. We hypothesize that individuals with poorer cognitive function will search using fewer unique terms, employ shorter words, and use less obscure words in their searches. Methods Computer monitoring software (WorkTime, Nestersoft Inc) was used to continuously track the terms people entered while conducting searches in Google, Yahoo, Bing, and Ask.com. For all searches, punctuation, accents, and non-ASCII characters were removed, and the resulting search terms were spell-checked before any analysis. Cognitive function was evaluated as a z-normalized summary score capturing five unique cognitive domains. Linear regression was used to determine the relationship between cognitive function and Internet searches by controlling for variables such as age, sex, and education. Results Over a 6-month monitoring period, 42 participants (mean age 81 years [SD 10.5], 83% [35/42] female) conducted 2915 searches using these top search engines. Participants averaged 3.08 words per search (SD 1.6) and 5.77 letters per word (SD 2.2). Individuals with higher cognitive function used more unique terms per search (beta=.39, P=.002) and employed less common terms in their searches (beta=1.39, P=.02). Cognitive function was not significantly associated with the length of the words used in the searches. Conclusions These results suggest that early decline in cognitive function may be detected from the terms people search for when they use the Internet. By continuously tracking basic aspects of Internet search terms, it may be possible to detect cognitive decline earlier than currently possible, thereby enabling proactive treatment and intervention. PMID:28877864

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.

Blood Glucose, Diet-Based Glycemic Load and Cognitive Aging Among Dementia-Free Older Adults

PubMed Central

Andel, Ross; McEvoy, Cathy; Dahl Aslan, Anna K.; Finkel, Deborah; Pedersen, Nancy L.

2015-01-01

Background. Although evidence indicates that Type II Diabetes is related to abnormal brain aging, the influence of elevated blood glucose on long-term cognitive change is unclear. In addition, the relationship between diet-based glycemic load and cognitive aging has not been extensively studied. The focus of this study was to investigate the influence of diet-based glycemic load and blood glucose on cognitive aging in older adults followed for up to 16 years. Methods. Eight-hundred and thirty-eight cognitively healthy adults aged ≥50 years (M = 63.1, SD = 8.3) from the Swedish Adoption/Twin Study of Aging were studied. Mixed effects growth models were utilized to assess overall performance and change in general cognitive functioning, perceptual speed, memory, verbal ability, and spatial ability as a function of baseline blood glucose and diet-based glycemic load. Results. High blood glucose was related to poorer overall performance on perceptual speed as well as greater rates of decline in general cognitive ability, perceptual speed, verbal ability, and spatial ability. Diet-based glycemic load was related to poorer overall performance in perceptual speed and spatial ability. Conclusion. Diet-based glycemic load and, in particular, elevated blood glucose appear important for cognitive performance/cognitive aging. Blood glucose control (perhaps through low glycemic load diets) may be an important target in the detection and prevention of age-related cognitive decline. PMID:25149688

Meta-Analysis of the Association between Tea Intake and the Risk of Cognitive Disorders

PubMed Central

Ma, Qing-Ping; Huang, Chen; Cui, Qiao-Yun; Yang, Ding-Jun; Sun, Kang; Chen, Xuan; Li, Xing-Hui

2016-01-01

Background Alzheimer’s disease is a common neurodegenerative disorder in elderly. This study was aimed to systematically evaluate the association between tea intake and the risk of cognitive disorders by meta-analysis. Methods and Findings PubMed, Embase and Wanfang databases were systematically searched and a total of 26 observational studies were included in this study. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated and pooled by using fixed or random effects models according to the degree of heterogeneity. Results The overall pooled analysis indicated that tea intake could significantly reduce the risk of cognitive disorders (OR = 0.65, 95%CI = 0.58–0.73). Subgroup analyses were conducted based on study design, population, frequency of tea drinking and type of cognitive disorders. The results showed that tea drinking was significantly associated with the reduced incidence of cognitive disorders in all of subgroups based on study design and frequency of tea drinking. In particular, tea drinking was inversely associated with the risk of cognitive impairment (CoI), mild cognitive impairment (MCI), cognitive decline and ungrouped cognitive disorders. Moreover, for population subgroups, the significant association was only found in Chinese people. Conclusion Our study suggests that daily tea drinking is associated with decreased risk of CoI, MCI and cognitive decline in the elderly. However, the association between tea intake and Alzheimer’s disease remains elusive. PMID:27824892

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.

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

PubMed Central

2012-01-01

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

Evaluation of post-surgical cognitive function and protein fingerprints in the cerebro-spinal fluid utilizing surface-enhanced laser Desorption/Ionization time-of-flight mass-spectrometry (SELDI-TOF MS) after coronary artery bypass grafting: review of proteomic analytic tools and introducing a new syndrome.

PubMed

Reis, H J; Wang, L; Verano-Braga, T; Pimenta, A M C; Kálmán, J; Bogáts, G; Babik, B; Vieira, L B; Teixeira, A L; Mukhamedyarov, M A; Zefirov, A L; Kiyasov, A P; Rizvanov, A A; Matin, K; Palotás, M; Guimarães, M M; Ferreira, C N; Yalvaç, M E; Janka, Z; Palotás, A

2011-01-01

Cognitive dysfunction following surgery is a common complication, which increases the incidence of other co-morbid conditions, hospital and health-care costs. The reported rate of the occurrence of post-operative cognitive decline varies with different studies, depending on population profile, type of surgery, definition of cognitive disorder and detection methods, design of study, etc. It remains unclear whether these psychiatric signs and symptoms are direct results of the effects of surgery or general anesthesia. Nonetheless they are more frequent after cardiac surgery and are likely to be multi-factorial, but the patho-mechanisms are not yet fully characterized. This communication provides a synopsis of proteomics tools and delineates novel SELDI-TOF results to evaluate biomarkers in this regard. Presented for the first time is a classification of the clinically relevant forms of post-operative cognitive decline with the advent of a novel subclass.

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.

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

Dietary Patterns High in Red Meat, Potato, Gravy, and Butter Are Associated with Poor Cognitive Functioning but Not with Rate of Cognitive Decline in Very Old Adults1234

PubMed Central

Davies, Karen; Adamson, Ashley; Kirkwood, Thomas; Hill, Tom R; Siervo, Mario; Mathers, John C; Jagger, Carol

2016-01-01

Background: Healthy dietary patterns (DPs) have been linked to better cognition and reduced risk of dementia in older adults, but their role in cognitive functioning and decline in the very old (aged ≥85 y) is unknown. Objective: We investigated the association between previously established DPs from the Newcastle 85+ Study and global and attention-specific cognition over 5 y. Methods: We followed up with 302 men and 489 women (1921 birth cohort from Northeast United Kingdom) for change in global cognition [measured by the Standardized Mini-Mental State Examination (SMMSE)] over 5 y and attention (assessed by the cognitive drug research attention battery) over 3 y. We used 2-step clustering to derive DPs and mixed models to determine the relation between DPs and cognition in the presence of the dementia susceptibility gene. Results: Previously, we characterized 3 DPs that differed in intake of red meat, potato, gravy, and butter and varied with key health measures. When compared with participants in DP1 (high red meat) and DP3 (high butter), participants in DP2 (low meat) had higher SMMSE scores at baseline (P < 0.001) and follow-ups, and better initial attention (P < 0.05). Membership in DP1 and DP3 was associated with overall worse SMMSE scores (β = 0.09, P = 0.01 and β = 0.08, P = 0.02, respectively) than membership in DP2 after adjustment for sociodemographic factors, lifestyle, multimorbidity, and body mass index (BMI). Additional adjustment for apolipoprotein (apoE) ε4 genotype attenuated the association to nonsignificant in women but not in men in DP1 (β = 0.13, P = 0.02). Participants in DP1 and DP3 also had overall worse concentration (β = 0.04, P = 0.002 and β = 0.028, P = 0.03, respectively) and focused attention (β = 0.02, P = 0.01 and β = 0.02, P = 0.03, respectively), irrespective of apoE ε4 genotype, but similar rate of decline in all cognitive measures over time. Conclusion: DPs high in red meat, potato, gravy (DP1), or butter (DP3) were associated with poor cognition but not with the rate of cognitive decline in very old adults. PMID:26740685

Neuroticism Combined With Slower and More Variable Reaction Time: Synergistic Risk Factors for 7-Year Cognitive Decline in Females

PubMed Central

Shickle, Darren A.; Roberts, Beverly A.; Deary, Ian J.

2012-01-01

Objective. Among adults, slower and more variable reaction times are associated with worse cognitive function and increased mortality risk. Therefore, it is important to elucidate risk factors for reaction time change over the life course. Method. Data from the Health and Lifestyle Survey (HALS) were used to examine predictors of 7-year decline in reaction time (N = 4,260). Regression-derived factor scores were used to summarize general change across 4 reaction time variables: simple mean, 4-choice mean, simple variability, and 4-choice variability (53.52% of variance). Results. Age (B = .02, p < .001) and HALS1 baseline reaction time (B = −.10, p = .001) were significant risk factors for males (N = 1,899). In addition to these variables, in females (N = 2,361), neuroticism was significant and interacted synergistically with baseline reaction time (B = .06, p = .04). Adjustment for physiological variables explained the interaction with neuroticism, suggesting that candidate mechanisms had been identified. Discussion. A priority for future research is to replicate interactions between personality and reaction time in other samples and find specific mechanisms. Stratification of population data on cognitive health by personality and reaction time could improve strategies for identifying those at greater risk of cognitive decline. PMID:22367712

A Longitudinal Examination of Agitation and Resident Characteristics in the Nursing Home

ERIC Educational Resources Information Center

Burgio, Louis D.; Park, Nan Sook; Hardin, J. Michael; Sun, Fei

2007-01-01

Purpose: Agitation frequently accompanies cognitive decline among nursing home residents. This study used cross-sectional and longitudinal (up to 18 months) methods to examine agitation among profoundly and moderately impaired residents using both staff report and direct observation methods. Design and Methods: The study included participants (N =…

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.

Future directions in treatment of brain metastases

PubMed Central

Barani, Igor J.; Larson, David A.; Berger, Mitchel S.

2013-01-01

Background: Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT. Methods: A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text. Results: The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline. Conclusions: Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT. PMID:23717793

Linking Biological and Cognitive Aging: Toward Improving Characterizations of Developmental Time

PubMed Central

DeCarlo, Correne A.; Dixon, Roger A.

2011-01-01

Objectives. Chronological age is the most frequently employed predictor in life-span developmental research, despite repeated assertions that it is best conceived as a proxy for true mechanistic changes that influence cognition across time. The present investigation explores the potential that selected functional biomarkers may contribute to the more effective conceptual and operational definitions of developmental time. Methods. We used data from the Victoria Longitudinal Study to explore both static and dynamic biological or physiological markers that arguably influence process-specific mechanisms underlying cognitive changes in late life. Multilevel models were fit to test the dynamic coupling between change in theoretically relevant biomarkers (e.g., grip strength, pulmonary function) and change in select cognitive measures (e.g., executive function, episodic and semantic memory). Results. Results showed that, independent of the passage of developmental time (indexed as years in study), significant time-varying covariation was observed linking corresponding declines for select cognitive outcomes and biological markers. Discussion. Our findings support the interpretation that cognitive decline is not due to chronological aging per se but rather reflects multiple causal factors from a broad range of biological and physical health domains that operate along the age continuum. PMID:21743053

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

PubMed

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

2017-06-01

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

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.

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.

Effect of Vitamin Intake on Cognitive Decline in Older Adults: Evaluation of the Evidence.

PubMed

Krause, D; Roupas, P

2015-08-01

The objective of this review was to evaluate the evidence from human studies on the intake of vitamins, either as monotherapies or in combination with other vitamins, as neuroprotective agents that may delay the onset of cognitive decline in older adults. Evidence-based methodologies were used to capture and evaluate the highest levels of evidence. The current evidence available showed no association for cognitive benefits of vitamins B6 or B12 as a monotherapy, and recent systematic reviews provide no clear evidence that supplementation with vitamin B6, B12 and/or folic acid improves dementia outcomes or slows cognitive decline, even though it may normalise homocysteine levels. Meta-analyses from systematic reviews have shown an association between low vitamin D levels and diminished cognitive function, although causality cannot be confirmed from the available evidence. There is no convincing evidence for an association of vitamin A, vitamin C or vitamin E either as a monotherapy or in combination with other antioxidant vitamins such as β-carotene and the prevention of cognitive decline. The appraisal of nineteen systematic reviews and meta-analyses has highlighted the heterogeneity between studies, and the need for better consensus on definitions of cognitive decline, duration of testing and agreement on which specific endpoints are clinically relevant. Evaluation of the totality of the currently available evidence indicates that intake of the above vitamins, either as a monotherapy, or in combination with other vitamins, has no clinically-relevant effect on delaying cognitive decline or delaying the onset of dementia in older adults.

Accelerated cognitive decline in a rodent model for temporal lobe epilepsy.

PubMed

Schipper, Sandra; Aalbers, Marlien W; Rijkers, Kim; Lagiere, Melanie; Bogaarts, Jan G; Blokland, Arjan; Klinkenberg, Sylvia; Hoogland, Govert; Vles, Johan S H

2016-12-01

Cognitive impairment is frequently observed in patients with temporal lobe epilepsy. It is hypothesized that cumulative seizure exposure causes accelerated cognitive decline in patients with epilepsy. We investigated the influence of seizure frequency on cognitive decline in a rodent model for temporal lobe epilepsy. Neurobehavioral assessment was performed before and after surgery, after the induction of self-sustaining limbic status epilepticus (SSLSE), and in the chronic phase in which rats experienced recurrent seizures. Furthermore, we assessed potential confounders of memory performance. Rats showed a deficit in spatial working memory after the induction of the SSLSE, which endured in the chronic phase. A progressive decline in recognition memory developed in SSLSE rats. Confounding factors were absent. Seizure frequency and also the severity of the status epilepticus were not correlated with the severity of cognitive deficits. The effect of the seizure frequency on cognitive comorbidity in epilepsy has long been debated, possibly because of confounders such as antiepileptic medication and the heterogeneity of epileptic etiologies. In an animal model of temporal lobe epilepsy, we showed that a decrease in spatial working memory does not relate to the seizure frequency. This suggests for other mechanisms are responsible for memory decline and potentially a common pathophysiology of cognitive deterioration and the occurrence and development of epileptic seizures. Identifying this common denominator will allow development of more targeted interventions treating cognitive decline in patients with epilepsy. The treatment of interictal symptoms will increase the quality of life of many patients with epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Stressful life events and cognitive decline in late life: moderation by education and age. The Cache County Study.

PubMed

Tschanz, Joann T; Pfister, Roxane; Wanzek, Joseph; Corcoran, Chris; Smith, Ken; Tschanz, Brian T; Steffens, David C; Østbye, Truls; Welsh-Bohmer, Kathleen A; Norton, Maria C

2013-08-01

Stressful life events (SLE) have been associated with increased dementia risk, but their association with cognitive decline has been inconsistent. In a longitudinal population-based study of older individuals, we examined the association between SLE and cognitive decline, and the role of potential effect modifiers. A total of 2665 non-demented participants of the Cache County Memory Study completed an SLE questionnaire at Wave 2 and were revisited 4 and 7 years later. The events were represented via several scores: total number, subjective rating (negative, positive, and unexpected), and a weighted summary based on their impact. Cognition was assessed at each visit with the modified Mini-Mental State Exam. General linear models were used to examine the association between SLE scores and cognition. Effect modification by age, education, and APOE genotype was tested. Years of formal education (p = 0.006) modified the effect of number of SLE, and age (p = 0.009) modified the effect of negative SLE on the rate of cognitive decline. Faster decline was observed among those with fewer years of education experiencing more SLE and also among younger participants experiencing more negative SLE. There was no association between other indicators of SLE and cognitive decline. APOE genotype did not modify any of the aforementioned associations. The effects of SLE on cognition in late life are complex and vary by individual factors such as age and education. These results may explain some of the contradictory findings in the literature. Copyright © 2012 John Wiley & Sons, Ltd.

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.

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.

Amyloid-β, anxiety, and cognitive decline in preclinical Alzheimer disease: a multicenter, prospective cohort study.

PubMed

Pietrzak, Robert H; Lim, Yen Ying; Neumeister, Alexander; Ames, David; Ellis, Kathryn A; Harrington, Karra; Lautenschlager, Nicola T; Restrepo, Carolina; Martins, Ralph N; Masters, Colin L; Villemagne, Victor L; Rowe, Christopher C; Maruff, Paul

2015-03-01

Alzheimer disease (AD) is now known to have a long preclinical phase in which pathophysiologic processes develop many years, even decades, before the onset of clinical symptoms. Although the presence of abnormal levels of amyloid-β (Aβ) is associated with higher rates of progression to clinically classified mild cognitive impairment or dementia, little research has evaluated potentially modifiable moderators of Aβ-related cognitive decline, such as anxiety and depressive symptoms. To evaluate the association between Aβ status and cognitive changes, and the role of anxiety and depressive symptoms in moderating Aβ-related cognitive changes in the preclinical phase of AD. In this multicenter, prospective cohort study with baseline and 18-, 36-, and 54-month follow-up assessments, we studied 333 healthy, older adults at hospital-based research clinics. Carbon 11-labeled Pittsburgh Compound B (PiB)-, florbetapir F 18-, or flutemetamol F 18-derived measures of Aβ, Hospital Anxiety and Depression Scale scores, and comprehensive neuropsychological evaluation that yielded measures of global cognition, verbal memory, visual memory, attention, language, executive function, and visuospatial ability. A positive Aβ (Aβ+) status at baseline was associated with a significant decline in global cognition, verbal memory, language, and executive function, and elevated anxiety symptoms moderated these associations. Compared with the Aβ+, low-anxiety group, slopes of cognitive decline were significantly more pronounced in the Aβ+, high-anxiety group, with Cohen d values of 0.78 (95% CI, 0.33-1.23) for global cognition, 0.54 (95% CI, 0.10-0.98) for verbal memory, 0.51 (95% CI, 0.07-0.96) for language, and 0.39 (95% CI, 0.05-0.83) for executive function. These effects were independent of age, educational level, IQ, APOE genotype, subjective memory complaints, vascular risk factors, and depressive symptoms; furthermore, depressive symptoms and subjective memory complaints did not moderate the association between Aβ and cognitive decline. These results provide additional support for the deleterious effect of elevated Aβ levels on cognitive function in preclinical AD. They further suggest that elevated anxiety symptoms moderate the effect of Aβ on cognitive decline in preclinical AD, resulting in more rapid decline in several cognitive domains. Given that there is currently no standard antiamyloid therapy and that anxiety symptoms are amenable to treatment, these findings may help inform risk stratification and management of the preclinical phase of AD.

Rationale and design of the CAROLINA® - cognition substudy: a randomised controlled trial on cognitive outcomes of linagliptin versus glimepiride in patients with type 2 diabetes mellitus.

PubMed

Biessels, Geert Jan; Janssen, Jolien; van den Berg, Esther; Zinman, Bernard; Espeland, Mark A; Mattheus, Michaela; Johansen, Odd Erik

2018-01-15

Type 2 diabetes mellitus is associated with cognitive dysfunction and an increased risk of dementia. Linagliptin is a glucose-lowering agent of the dipeptidyl peptidase-IV (DPP-IV) inhibitor class that is of particular interest for the prevention of accelerated cognitive decline, because it may potentially benefit the brain through pleiotropic effects, beyond glucose lowering. This paper presents the design of a study that aims to establish if linagliptin is superior to the sulfonylurea glimepiride in the prevention of accelerated cognitive decline in patients with type 2 diabetes mellitus. The cognition substudy is an integral part of the ongoing event-driven, randomised, double blind CARdiOvascular safety of LINAgliptin (CAROLINA®) trial, which evaluates the effect of treatment with linagliptin versus glimepiride on cardiovascular outcomes. CAROLINA® includes patients with type 2 diabetes mellitus with sub-optimal glycaemic control at elevated cardiovascular risk. The substudy will evaluate patients randomised and treated who have a baseline Mini Mental State Examination (MMSE) score ≥ 24, documented years of formal education with at least one valid cognitive assessment at baseline and during follow-up. The primary cognitive outcome is the occurrence of accelerated cognitive decline at the end of follow-up. The two treatment groups will be compared by using a logistic regression. Accelerated cognitive decline is defined as a rate of cognitive decline that falls at or below the 16th percentile of decline for the whole cohort on either the MMSE or a combined score of the trail making and verbal fluency test. Potential confounders are taken into account at an individual patient level, using a regression based index. Between December 2010 and December 2012, 6042 patients were randomised and treated with either linagliptin (5 mg) or glimepiride (1-4 mg) once daily in CAROLINA®. Cognitive tests were conducted in nearly 4500 participants at baseline and are scheduled for two subsequent assessments, after 160 weeks of follow-up and end of follow-up. This substudy of the ongoing CAROLINA® trial will establish if linagliptin is superior to glimepiride in the prevention of accelerated cognitive decline in patients with type 2 diabetes mellitus. Final results are expected in 2019. ClinicalTrials.gov Identifier: NCT 01243424 .

Patterns of brain atrophy associated with episodic memory and semantic fluency decline in aging.

PubMed

Pelletier, Amandine; Bernard, Charlotte; Dilharreguy, Bixente; Helmer, Catherine; Le Goff, Melanie; Chanraud, Sandra; Dartigues, Jean-François; Allard, Michèle; Amieva, Hélène; Catheline, Gwénaëlle

2017-03-09

The cerebral substratum of age-related cognitive decline was evaluated in an elderly-cohort followed for 12 years (n=306). Participants, free of dementia, received neuropsychological assessments every two years and an MRI exam at baseline and four years later. Cognitive decline was evaluated on two broadly used tests to detect dementia: the Free and Cued Selective Reminding Test (FCSRT), a verbal episodic memory task, and the Isaacs Set Test (IST), a semantic fluency task. Using voxel-based approach, the relationship between cognitive decline with 1/ baseline grey matter volumes and 2/ grey matter volume loss between the two scans was explored. Baseline volumes analysis revealed that FCSRT and IST declines were both associated with lower volumes of the medial temporal region. Volumes loss analysis confirmed that both declines are related to medial temporal lobe atrophy and revealed that FCSRT decline was specifically associated with atrophy of the posterior cingulate cortex whereas IST decline was specifically related to temporal pole atrophy. These results suggest that cognitive decline across aging is firstly related to structural modifications of the medial temporal lobe, followed by an atrophy in the posterior midline structures for episodic memory and an atrophy of the temporal pole for semantic fluency.

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.

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

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.

Relations between Recent Past Leisure Activities with Risks of Dementia and Cognitive Functions after Stroke

PubMed Central

Wong, Adrian; Lau, Alexander Y. L.; Lo, Eugene; Tang, Michael; Wang, Zhaolu; Liu, Wenyan; Tanner, Nicole; Chau, Natalie; Law, Lorraine; Shi, Lin; Chu, Winnie C. W.; Yang, Jie; Xiong, Yun-yun; Lam, Bonnie Y. K.; Au, Lisa; Chan, Anne Y. Y.; Soo, Yannie; Leung, Thomas W. H.; Wong, Lawrence K. S.; Lam, Linda C. W.; Mok, Vincent C. T.

2016-01-01

Background Leisure activity participation has been shown to lower risks of cognitive decline in non-stroke populations. However, effects of leisure activities participation upon cognitive functions and risk of dementia after stroke are unclear. The purpose of this study is to examine the effects of recent past leisure activities participation upon cognitive functions and risk of incident dementia after stroke. Methods Hospital-based, retrospective cohort study. 88 of 1,013 patients with stroke or TIA having no prestroke dementia were diagnosed to have incident poststroke dementia (PSD) 3–6 months after stroke. Regular participation (≥3 times per week) in intellectual, recreational, social and physical activities over the year before the index stroke was retrospectively recorded at 3–6 months after stroke. Results Logistic regression analyses showed that regular participation in intellectual (RR 0.36, 95%CI 0.20–0.63) and stretching & toning physical exercise (0.37, 0.21–0.64) was significantly associated with a reduced risk of PSD after controlling for age, education, prestroke cognitive decline, stroke subtype, prior strokes and chronic brain changes including white matter changes, old infarcts and global atrophy. Results were similar in patients with past strokes in unadjusted models. Participation in increased number of activities in general (r = 0.41, p<0.01) and in intellectual (r = 0.40, p<0.01), recreational (r = 0.24, p<0.01), strenuous aerobic (r = 0.23, p<0.01) and mind-body (r = 0.10, p<0.01) activities was associated with higher poststroke Mini-mental State Examination scores in models adjusted for prestroke cognitive decline. Conclusions Regular participation in intellectual activities and stretching & toning exercise was associated with a significantly reduced short-term risk of PSD in patients with and without recurrent strokes. Participation in greater number of recent past leisure activities was associated with better poststroke cognitive performance. Findings of this retrospective cohort study call for studies of activity intervention for prevention of cognitive decline in individuals at elevated risk of stroke. PMID:27454124

Development of Support Service for Prevention and Recovery from Dementia and Science of Lethe

NASA Astrophysics Data System (ADS)

Otake, Mihoko

Purpose of this study is to explore service design method through the development of support service for prevention and recovery from dementia towards science of lethe. We designed and implemented conversation support service via coimagination method based on multiscale service design method, both were proposed by the author. Multiscale service model consists of tool, event, human, network, style and rule. Service elements at different scales are developed according to the model. Interactive conversation supported by coimagination method activates cognitive functions so as to prevent progress of dementia. This paper proposes theoretical bases for science of lethe. Firstly, relationship among coimagination method and three cognitive functions including division of attention, planning, episodic memory which decline at mild cognitive imparement. Secondly, thought state transition model during conversation which describes cognitive enhancement via interactive communication. Thirdly, Set Theoretical Measure of Interaction is proposed for evaluating effectiveness of conversation to cognitive enhancement. Simulation result suggests that the ideas which cannot be explored by each speaker are explored during interactive conversation. Finally, coimagination method compared with reminiscence therapy and its possibility for collaboration is discussed.

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.

Effects on Cognition of Stereotactic Lesional Surgery For the Treatment of Tremor in Multiple Sclerosis

PubMed Central

Jahanshahi, Marjan; Pieter, Socorro; Alusi, Sundus H.; Jones, Catherine R. G.; Glickman, Scott; Stein, John; Aziz, Tipu; Bain, Peter G.

2008-01-01

Objective: To assess the effect of stereotactic lesional surgery for treatment of tremor in multiple sclerosis on cognition. Methods: Eleven patients (3 males, 8 females) with multiple sclerosis participated in the study. Six subjects comprised the surgical group and five the matched control group. All patients were assessed at baseline and three months using a neuropsychological test battery that included measures of intellectual ability, memory, language, perception and executive function. Results: There were no significant differences between the surgical and control groups and no change from pre to post testing except for a decline in scores on the Mini-Mental State Examination (MMSE), WAIS-R Digit Span and Verbal Fluency in the surgical group. Conclusions: The results indicate that stereotactic lesional surgery does not result in major cognitive impairment in multiple sclerosis. However, the decline in MMSE scores, digit span and verbal fluency require further investigation in a larger sample. PMID:19491469

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

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

PubMed

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

2018-01-01

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

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

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

Ginkgo Biloba Extract and Long-Term Cognitive Decline: A 20-Year Follow-Up Population-Based Study

PubMed Central

Amieva, Hélène; Meillon, Céline; Helmer, Catherine; Barberger-Gateau, Pascale; Dartigues, Jean François

2013-01-01

Background Numerous studies have looked at the potential benefits of various nootropic drugs such as Ginkgo biloba extract (EGb761®; Tanakan®) and piracetam (Nootropyl®) on age-related cognitive decline often leading to inconclusive results due to small sample sizes or insufficient follow-up duration. The present study assesses the association between intake of EGb761® and cognitive function of elderly adults over a 20-year period. Methods and Findings The data were gathered from the prospective community-based cohort study ‘Paquid’. Within the study sample of 3612 non-demented participants aged 65 and over at baseline, three groups were compared: 589 subjects reporting use of EGb761® at at least one of the ten assessment visits, 149 subjects reporting use of piracetam at one of the assessment visits and 2874 subjects not reporting use of either EGb761® or piracetam. Decline on MMSE, verbal fluency and visual memory over the 20-year follow-up was analysed with a multivariate mixed linear effects model. A significant difference in MMSE decline over the 20-year follow-up was observed in the EGb761® and piracetam treatment groups compared to the ‘neither treatment’ group. These effects were in opposite directions: the EGb761® group declined less rapidly than the ‘neither treatment’ group, whereas the piracetam group declined more rapidly (β = −0.6). Regarding verbal fluency and visual memory, no difference was observed between the EGb761® group and the ‘neither treatment’ group (respectively, β = 0.21 and β = −0.03), whereas the piracetam group declined more rapidly (respectively, β = −1.40 and β = −0.44). When comparing the EGb761® and piracetam groups directly, a different decline was observed for the three tests (respectively β = −1.07, β = −1.61 and β = −0.41). Conclusion Cognitive decline in a non-demented elderly population was lower in subjects who reported using EGb761® than in those who did not. This effect may be a specific medication effect of EGb761®, since it was not observed for another nootropic medication, piracetam. PMID:23326356

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.

Longitudinal Cognitive Trajectories of Women Veterans from the Women’s Health Initiative Memory Study

PubMed Central

Padula, Claudia B.; Weitlauf, Julie C.; Rosen, Allyson C.; Reiber, Gayle; Cochrane, Barbara B.; Naughton, Michelle J.; Li, Wenjun; Rissling, Michelle; Yaffe, Kristine; Hunt, Julie R.; Stefanick, Marcia L.; Goldstein, Mary K.; Espeland, Mark A.

2016-01-01

Purpose of the Study: A comparison of longitudinal global cognitive functioning in women Veteran and non-Veteran participants in the Women’s Health Initiative (WHI). Design and Methods: We studied 7,330 women aged 65–79 at baseline who participated in the WHI Hormone Therapy Trial and its ancillary Memory Study (WHIMS). Global cognitive functioning (Modified Mini-Mental State Examination [3MSE]) in Veterans (n = 279) and non-Veterans (n = 7,051) was compared at baseline and annually for 8 years using generalized linear modeling methods. Results: Compared with non-Veterans, Veteran women were older, more likely to be Caucasian, unmarried, and had higher rates of educational and occupational attainment. Results of unadjusted baseline analyses suggest 3MSE scores were similar between groups. Longitudinal analyses, adjusted for age, education, ethnicity, and WHI trial assignment revealed differences in the rate of cognitive decline between groups over time, such that scores decreased more in Veterans relative to non-Veterans. This relative difference was more pronounced among Veterans who were older, had higher educational/occupational attainment and greater baseline prevalence of cardiovascular risk factors (e.g., smoking) and cardiovascular disease (e.g., angina, stroke). Implications: Veteran status was associated with higher prevalence of protective factors that may have helped initially preserve cognitive functioning. However, findings ultimately revealed more pronounced cognitive decline among Veteran relative to non-Veteran participants, likely suggesting the presence of risks that may impact neuropathology and the effects of which were initially masked by Veterans’ greater cognitive reserve. PMID:26615021

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.

Alzheimer Disease: Pharmacologic and Nonpharmacologic Therapies for Cognitive and Functional Symptoms.

PubMed

Epperly, Ted; Dunay, Megan A; Boice, Jack L

2017-06-15

Alzheimer disease comprises a syndrome of progressive cognitive and functional decline. Treatments should target cognitive and functional symptoms. Cholinesterase inhibitors, memantine, and a combination of a cholinesterase inhibitor and memantine have produced statistically significant but clinically small delays in various domains of cognitive and functional decline in select patients with Alzheimer disease. Vitamin E has been shown to delay functional decline in patients with mild to moderate Alzheimer disease, especially when taken in combination with a cholinesterase inhibitor. Structured programs of physical exercise improve physical function and reduce rates of neuropsychiatric symptoms in patients with mild to severe Alzheimer disease. Cognitive stimulation programs show benefit in maintenance of cognitive function and improved self-reported quality of life in patients with mild to moderate Alzheimer disease.

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.

Brain reserve and cognitive reserve in multiple sclerosis

PubMed Central

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

2013-01-01

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

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

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

PubMed Central

2013-01-01

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

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.

The Problems with Problem Solving: Reflections on the Rise, Current Status, and Possible Future of a Cognitive Research Paradigm

ERIC Educational Resources Information Center

Ohlsson, Stellan

2012-01-01

The research paradigm invented by Allen Newell and Herbert A. Simon in the late 1950s dominated the study of problem solving for more than three decades. But in the early 1990s, problem solving ceased to drive research on complex cognition. As part of this decline, Newell and Simon's most innovative research practices--especially their method for…

The Beneficial Effects of Cognitive Training With Simple Calculation and Reading Aloud (SCRA) in the Elderly Postoperative Population: A Pilot Randomized Controlled Trial.

PubMed

Kulason, Kay; Nouchi, Rui; Hoshikawa, Yasushi; Noda, Masafumi; Okada, Yoshinori; Kawashima, Ryuta

2018-01-01

Background: There has been little research conducted regarding cognitive treatments for the elderly postsurgical population. Patients aged ≥60 years have an increased risk of postoperative cognitive decline, a condition in which cognitive functions are negatively affected. This cognitive decline can lead to a decline in quality of life. In order to maintain a high quality of life, the elderly postsurgical population may benefit from treatment to maintain and/or improve their cognitive functions. This pilot study investigates the effect of simple calculation and reading aloud (SCRA) cognitive training in elderly Japanese postsurgical patients. Methods: Elderly patients undergoing non-cardiovascular thoracic surgery under general anesthesia were recruited ( n = 12). Subjects were randomly divided into two groups-one that receives 12 weeks of SCRA intervention, and a waitlisted control group. Before and after the intervention, we measured cognitive function [Mini-Mental Status Exam-Japanese (MMSE-J), Frontal Assessment Battery (FAB), computerized Cogstate Brief Battery (CBB)] and emotional state [General Health Questionnaire-12 (GHQ-12), Geriatric Depression Scale (GDS), Quality of Life Scale-5 (QOL-5)]. Results: Group difference analyses using ANCOVA with permutation test showed that the intervention SCRA group had a significant improvement in FAB motor programming sub-score, GDS, and QOL-5 compared to the control group. Within-group analyses using Wilcoxon signed-rank test to compare baseline and follow-up showed that the SCRA intervention group total FAB scores, FAB motor programming sub-scores, and QOL-5 scores were significantly improved. Discussion: This pilot study showed that there are important implications for the beneficial effects of SCRA intervention on cognitive function and emotional state in the postoperative elderly population; however, further investigations are necessary to reach any conclusions. Trial registration: This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN000019832).

The Beneficial Effects of Cognitive Training With Simple Calculation and Reading Aloud (SCRA) in the Elderly Postoperative Population: A Pilot Randomized Controlled Trial

PubMed Central

Kulason, Kay; Nouchi, Rui; Hoshikawa, Yasushi; Noda, Masafumi; Okada, Yoshinori; Kawashima, Ryuta

2018-01-01

Background: There has been little research conducted regarding cognitive treatments for the elderly postsurgical population. Patients aged ≥60 years have an increased risk of postoperative cognitive decline, a condition in which cognitive functions are negatively affected. This cognitive decline can lead to a decline in quality of life. In order to maintain a high quality of life, the elderly postsurgical population may benefit from treatment to maintain and/or improve their cognitive functions. This pilot study investigates the effect of simple calculation and reading aloud (SCRA) cognitive training in elderly Japanese postsurgical patients. Methods: Elderly patients undergoing non-cardiovascular thoracic surgery under general anesthesia were recruited (n = 12). Subjects were randomly divided into two groups—one that receives 12 weeks of SCRA intervention, and a waitlisted control group. Before and after the intervention, we measured cognitive function [Mini-Mental Status Exam-Japanese (MMSE-J), Frontal Assessment Battery (FAB), computerized Cogstate Brief Battery (CBB)] and emotional state [General Health Questionnaire-12 (GHQ-12), Geriatric Depression Scale (GDS), Quality of Life Scale-5 (QOL-5)]. Results: Group difference analyses using ANCOVA with permutation test showed that the intervention SCRA group had a significant improvement in FAB motor programming sub-score, GDS, and QOL-5 compared to the control group. Within-group analyses using Wilcoxon signed-rank test to compare baseline and follow-up showed that the SCRA intervention group total FAB scores, FAB motor programming sub-scores, and QOL-5 scores were significantly improved. Discussion: This pilot study showed that there are important implications for the beneficial effects of SCRA intervention on cognitive function and emotional state in the postoperative elderly population; however, further investigations are necessary to reach any conclusions. Trial registration: This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN000019832). PMID:29643802

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.

Cognitive performance and engagement in physical, social and intellectual activities in older adults: The FIBRA study

PubMed Central

Sposito, Giovana; Neri, Anita Liberalesso; Yassuda, Mônica Sanches

2015-01-01

Cognitive decline in aging can negatively impact quality of life in the elderly. However, studies have shown that elderly engaged in advanced activities of daily living (AADLs) can maintain or enhance global cognitive function or specific domains. Objective To investigate the relationship between engagement in AADLs and domains of cognition in elderly from seven different locations in Brazil. Methods A cross-sectional study involving 2,549 elderly without cognitive deficits suggestive of dementia was conducted. Data were collected on sociodemographic characteristics, health status, the Mini-Mental State Exam (MMSE) by subdomain (orientation, memory, attention/calculus, language and constructional praxis), and engagement in AADL grouped under physical, social and intellectual activities. Results Multivariate linear regression analysis revealed an association, albeit modest, between intellectual AADLs and the domains orientation, attention/calculus, language and constructional praxis (R2=0.005, 0.008, 0.021, and 0.021 respectively). Social AADLs were correlated with memory (R2=0.002) and language (R2=0.004) domains. No association was found between physical AADLs and MMSE domains. Schooling and family income were the sociodemographic variables exhibiting the strongest relationship with cognitive domains. Conclusion The study found associations between intellectual and social AADLs with higher cognitive performance, suggesting that active aging can provide opportunities to attenuate cognitive decline in aging. PMID:29213972

Walking Stroop carpet: an innovative dual-task concept for detecting cognitive impairment

PubMed Central

Perrochon, A; Kemoun, G; Watelain, E; Berthoz, A

2013-01-01

Background Several studies have reported the potential value of the dual-task concept during locomotion in clinical evaluation because cognitive decline is strongly associated with gait abnormalities. However, current dual-task tests appear to be insufficient for early diagnosis of cognitive impairment. Methods Forty-nine subjects (young, old, with or without mild cognitive impairment) underwent cognitive evaluation (Mini-Mental State Examination, Frontal Assessment Battery, five-word test, Stroop, clock-drawing) and single-task locomotor evaluation on an electronic walkway. They were then dual-task-tested on the Walking Stroop carpet, which is an adaptation of the Stroop color–word task for locomotion. A cluster analysis, followed by an analysis of variance, was performed to assess gait parameters. Results Cluster analysis of gait parameters on the Walking Stroop carpet revealed an interaction between cognitive and functional abilities because it made it possible to distinguish dysexecutive cognitive fragility or decline with a sensitivity of 89% and a specificity of 94%. Locomotor abilities differed according to the group and dual-task conditions. Healthy subjects performed less well on dual-tasking under reading conditions than when they were asked to distinguish colors, whereas dysexecutive subjects had worse motor performances when they were required to dual task. Conclusion The Walking Stroop carpet is a dual-task test that enables early detection of cognitive fragility that has not been revealed by traditional neuropsychological tests or single-task walking analysis. PMID:23682211

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...

Bipolar patients with vascular risk display a steeper age-related negative slope in inhibitory performance but not processing speed: A preliminary study

PubMed Central

Dev, Sheena I.; Eyler, Lisa T.

2017-01-01

Objective Bipolar disorder (BD) is associated with cognitive deficits, yet little is known about associations between cognition, vascular risk (VR) and age in this population. This study investigated whether BD patients with VR demonstrate stronger apparent age-related decline in inhibitory performance and processing speed (PS). Methods A full medical history was obtained for 34 euthymic BD and 41 healthy comparison (HC) individuals. The Delis-Kaplan Executive Functions Color Word Interference Subtests was administered to all participants to assess for inhibitory performance (condition 3) and PS (condition 1 and 2). VR positive (VRPos) and VR negative (VRNeg) groups were created based on the presence of one or more VR factors. Results VRPos-BD participants demonstrated significantly worse inhibitory performance with older age, while age and inhibition were not significantly related in the VRPOS-HC group or in those who were VRNeg. The same was not true for PS. Conclusion BD patients with VR may also be at risk for greater decline in inhibitory performance, but not PS, with age. Longitudinal studies are needed to further investigate the contributions of VR to cognitive decline among older BD patients. PMID:28041763

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

PubMed Central

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

2010-01-01

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

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

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

Physical Activity Interventions in Preventing Cognitive Decline and Alzheimer-Type Dementia: A Systematic Review.

PubMed

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

2018-01-02

The prevalence of cognitive impairment and dementia is expected to increase dramatically as the population ages, creating burdens on families and health care systems. To assess the effectiveness of physical activity interventions in slowing cognitive decline and delaying the onset of cognitive impairment and dementia in adults without diagnosed cognitive impairments. Several electronic databases from January 2009 to July 2017 and bibliographies of systematic reviews. Trials published in English that lasted 6 months or longer, enrolled adults without clinically diagnosed cognitive impairments, and compared cognitive and dementia outcomes between physical activity interventions and inactive controls. Extraction by 1 reviewer and confirmed by a second; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence. Of 32 eligible trials, 16 with low to moderate risk of bias compared a physical activity intervention with an inactive control. Most trials had 6-month follow-up; a few had 1- or 2-year follow-up. Evidence was insufficient to draw conclusions about the effectiveness of aerobic training, resistance training, or tai chi for improving cognition. Low-strength evidence showed that multicomponent physical activity interventions had no effect on cognitive function. Low-strength evidence showed that a multidomain intervention comprising physical activity, diet, and cognitive training improved several cognitive outcomes. Evidence regarding effects on dementia prevention was insufficient for all physical activity interventions. Heterogeneous interventions and cognitive test measures, small and underpowered studies, and inability to assess the clinical significance of cognitive test outcomes. Evidence that short-term, single-component physical activity interventions promote cognitive function and prevent cognitive decline or dementia in older adults is largely insufficient. A multidomain intervention showed a delay in cognitive decline (low-strength evidence). Agency for Healthcare Research and Quality.

Latent Cognitive Phenotypes in De Novo Parkinson's Disease: A Person-Centered Approach.

PubMed

LaBelle, Denise R; Walsh, Ryan R; Banks, Sarah J

2017-08-01

Cognitive impairment is an important aspect of Parkinson's disease (PD), but there is considerable heterogeneity in its presentation. This investigation aims to identify and characterize latent cognitive phenotypes in early PD. Latent class analysis, a data-driven, person-centered, cluster analysis was performed on cognitive data from the Parkinson's Progressive Markers Initiative baseline visit. This analytic method facilitates identification of naturally occurring endophenotypes. Resulting classes were compared across biomarker, symptom, and demographic data. Six cognitive phenotypes were identified. Three demonstrated consistent performance across indicators, representing poor ("Weak-Overall"), average ("Typical-Overall"), and strong ("Strong-Overall") cognition. The remaining classes demonstrated unique patterns of cognition, characterized by "Strong-Memory," "Weak-Visuospatial," and "Amnestic" profiles. The Amnestic class evidenced greater tremor severity and anosmia, but was unassociated with biomarkers linked with Alzheimer's disease. The Weak-Overall class was older and reported more non-motor features associated with cognitive decline, including anxiety, depression, autonomic dysfunction, anosmia, and REM sleep behaviors. The Strong-Overall class was younger, more female, and reported less dysautonomia and anosmia. Classes were unrelated to disease duration, functional independence, or available biomarkers. Latent cognitive phenotypes with focal patterns of impairment were observed in recently diagnosed individuals with PD. Cognitive profiles were found to be independent of traditional biomarkers and motoric indices of disease progression. Only globally impaired class was associated with previously reported indicators of cognitive decline, suggesting this group may drive the effects reported in studies using variable-based analysis. Longitudinal and neuroanatomical characterization of classes will yield further insight into the evolution of cognitive change in the disease. (JINS, 2017, 23, 551-563).

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.

Indication of Cognitive Change and Associated Risk Factor after Thoracic Surgery in the Elderly: A Pilot Study

PubMed Central

Kulason, Kay; Nouchi, Rui; Hoshikawa, Yasushi; Noda, Masafumi; Okada, Yoshinori; Kawashima, Ryuta

2017-01-01

Background: This pilot study investigated the effects of partial pulmonary lobectomy lung surgery on cognitive functions of elderly Japanese patients. It is recognized that elderly patients undergoing surgery have increased risk of Postoperative Cognitive Decline (POCD), a condition in which learning, memory, and processing speed is greatly reduced after surgery. Since elderly patients are more likely to exhibit symptoms of POCD, the incidence is increasing as the population receiving surgery is aging. Methods: Cognitive function was measured for all subjects (n = 12) before and after surgery using three different cognitive tests: Mini-Mental Status Exam-Japanese (MMSE-J), Frontal Assessment Battery (FAB), and a computerized Cogstate Brief Battery (CBB). Changes in these measures indicate changes in cognitive function. In addition, the 12-item General Health Questionnaire (GHQ-12), the Geriatric Depression Scale (GDS), and the 5-item Quality of Life questionnaire (QOL-5) were administered at each time point to measure mental and emotional state. Changes in outcome measures were analyzed via Wilcoxon signed-rank test. Exploratory correlation analysis was conducted using Spearman’s rho. Results: Data show a decline in detection (DET; p = 0.045) and identification (IDN; p = 0.038). Spearman’s correlation coefficient show a significant correlation between postoperative DET scores and postoperative IDN scores (ρ = 0.78, p = 0.005), a significant correlation between change in IDN and baseline GHQ-12 scores (ρ = -0.595, p = 0.027), and a significant correlation between change in one-back (OBK) scores and duration of anesthesia (ρ = -0.72, p = 0.012). Discussion: This was the first report to examine cognitive decline after major thoracic surgery in Japanese patients. Previous studies have evidenced that POCD is a common phenomenon after surgery, and that age is a major risk factor. The CCB measured significant change in two cognitive domains: attention and psycomotor function. This study clarified that decline in cognition is detectable in certain measures after thoracic surgery in the elderly Japanese patient population. Additionally, longer anesthetic exposure may negatively impact attention and working memory, and preoperative mental wellbeing is a possible predictor of POCD. These preliminary results have important implications and support the need for future studies. PMID:29259553

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.

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.

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

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.

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.

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.

Amyloid and APOE ε4 interact to influence short-term decline in preclinical Alzheimer disease.

PubMed

Mormino, Elizabeth C; Betensky, Rebecca A; Hedden, Trey; Schultz, Aaron P; Ward, Andrew; Huijbers, Willem; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A

2014-05-20

To examine whether β-amyloid (Aβ) and APOE ε4 status independently contribute or interact to influence longitudinal cognitive decline in clinically normal older individuals (CN). Data from 490 CNs were aggregated across 3 observational cohort studies (Harvard Aging Brain Study, Alzheimer's Disease Neuroimaging Initiative, and Australian Imaging Biomarkers and Lifestyle Study of Ageing; median age = 75.0 years, 255 female), and the contributions of APOE ε4 and Aβ on longitudinal change over a median of 1.49 years were examined. Cognitive decline was assessed with the Mini-Mental State Examination (MMSE) and Logical Memory (immediate and delayed recall scores). High Aβ participants were more likely to be APOE ε4+ than low Aβ participants. CNs who were both high Aβ and APOE ε4+ showed greater decline in Logical Memory immediate recall (p < 0.087), Logical Memory delayed recall (p < 0.024), and MMSE (p < 0.034) compared to all other groups (low Aβ/APOE ε4-, low Aβ/APOE ε4+, and high Aβ/APOE ε4-). No other pairwise contrast was significant for any cognitive measure. Clinically normal individuals who are APOE ε4+ and have high Aβ showed the highest cognitive decline. These results suggest that Aβ and APOE ε4 are not redundant contributors of decline in aging but rather interact to promote decline during the short follow-up period examined in this study. Longer follow-up periods will be essential to fully elucidate the influence of Alzheimer disease risk factors on cognitive decline in aging. © 2014 American Academy of Neurology.

Functional network integrity presages cognitive decline in preclinical Alzheimer disease.

PubMed

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

2017-07-04

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

Correlating Cognitive Decline with White Matter Lesion and Brain Atrophy Magnetic Resonance Imaging Measurements in Alzheimer's Disease.

PubMed

Bilello, Michel; Doshi, Jimit; Nabavizadeh, S Ali; Toledo, Jon B; Erus, Guray; Xie, Sharon X; Trojanowski, John Q; Han, Xiaoyan; Davatzikos, Christos

2015-01-01

Vascular risk factors are increasingly recognized as risks factors for Alzheimer's disease (AD) and early conversion from mild cognitive impairment (MCI) to dementia. While neuroimaging research in AD has focused on brain atrophy, metabolic function, or amyloid deposition, little attention has been paid to the effect of cerebrovascular disease to cognitive decline. To investigate the correlation of brain atrophy and white matter lesions with cognitive decline in AD, MCI, and control subjects. Patients with AD and MCI, and healthy subjects were included in this study. Subjects had a baseline MRI scan, and baseline and follow-up neuropsychological battery (CERAD). Regional volumes were measured, and white matter lesion segmentation was performed. Correlations between rate of CERAD score decline and white matter lesion load and brain structure volume were evaluated. In addition, voxel-based correlations between baseline CERAD scores and atrophy and white matter lesion measures were computed. CERAD rate of decline was most significantly associated with lesion loads located in the fornices. Several temporal lobe ROI volumes were significantly associated with CERAD decline. Voxel-based analysis demonstrated strong correlation between baseline CERAD scores and atrophy measures in the anterior temporal lobes. Correlation of baseline CERAD scores with white matter lesion volumes achieved significance in multilobar subcortical white matter. Both baseline and declines in CERAD scores correlate with white matter lesion load and gray matter atrophy. Results of this study highlight the dominant effect of volume loss, and underscore the importance of small vessel disease as a contributor to cognitive decline in the elderly.

 Cortical Atrophy is Associated with Accelerated Cognitive Decline in Mild Cognitive Impairment with Subsyndromal Depression.

PubMed

Gonzales, Mitzi M; Insel, Philip S; Nelson, Craig; Tosun, Duygu; Mattsson, Niklas; Mueller, Susanne G; Sacuiu, Simona; Bickford, David; Weiner, Michael W; Mackin, R Scott

2017-09-01

To investigate the association between cognitive decline and cortical atrophy in individuals with mild cognitive impairment (MCI) and chronic subsyndromal symptoms of depression (SSD) over a 4-year period. Prospective cohort study. Multicenter, clinic-based. Within the Alzheimer's Disease Neuroimaging Initiative repository, the Neuropsychiatric Inventory was used to identify individuals with MCI and stable endorsement (SSD group N = 32) or no endorsement (non-SSD group N = 69) of depressive symptoms across time points. Repeated measures of cognitive outcomes, cortical atrophy, and their associations were evaluated with mixed effects models adjusting for age, education, sex, and APOE genotype. The SSD group demonstrated accelerated decline on measures of global cognition (Alzheimer Disease Assessment Scale; df = 421, t = 2.242, p = 0.025), memory (Wechsler Memory Scale-Revised Logical Memory II; df = 244, t = -2.525, p = 0.011), information processing speed (Trail Making Test Parts A [df = 421, t = 2.376, p = 0.018] and B [df = 421, t = 2.533, p = 0.012]), and semantic fluency (Category Fluency; df = 424, t = -2.418, p = 0.016), as well as accelerated frontal lobe (df = 341, t = -2.648, p = 0.008) and anterior cingulate (df = 341, t = -3.786, p < 0.001) atrophy. No group differences were observed for rate of decline on measures of attention, learning, and confrontation naming or for rate of atrophy in any other regions. Accelerated frontal lobe and anterior cingulate atrophy was associated with cognitive decline on measures of global cognition, information processing speed, and semantic fluency (all p < 0.05), but not memory. Individuals with chronic SSD may represent an MCI subgroup that is highly vulnerable to accelerated cognitive decline, an effect that may be governed by frontal lobe and anterior cingulate atrophy. Published by Elsevier Inc.

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

PubMed Central

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

2015-01-01

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

The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment

PubMed Central

Tarawneh, Rawan; Holtzman, David M.

2012-01-01

Alzheimer disease (AD) is the most common cause of dementia in the elderly. Clinicopathological studies support the presence of a long preclinical phase of the disease, with the initial deposition of AD pathology estimated to begin approximately 10–15 years prior to the onset of clinical symptoms. The hallmark clinical phenotype of AD is a gradual and progressive decline in two or more cognitive domains, most commonly involving episodic memory and executive functions, that is sufficient to cause social or occupational impairment. Current diagnostic criteria can accurately identify AD in the majority of cases. As disease-modifying therapies are being developed, there is growing interest in the identification of individuals in the earliest symptomatic, as well as presymptomatic, stages of disease, because it is in this population that such therapies may have the greatest chance of success. The use of informant-based methods to establish cognitive and functional decline of an individual from previously attained levels of performance best allows for the identification of individuals in the very mildest stages of cognitive impairment. PMID:22553492

Potentially modifiable lifestyle factors, cognitive reserve, and cognitive function in later life: A cross-sectional study

PubMed Central

Wu, Yu-Tzu

2017-01-01

Background Potentially modifiable lifestyle factors may influence cognitive health in later life and offer potential to reduce the risk of cognitive decline and dementia. The concept of cognitive reserve has been proposed as a mechanism to explain individual differences in rates of cognitive decline, but its potential role as a mediating pathway has seldom been explored using data from large epidemiological studies. We explored the mediating effect of cognitive reserve on the cross-sectional association between lifestyle factors and cognitive function in later life using data from a population-based cohort of healthy older people. Methods and findings We analysed data from 2,315 cognitively healthy participants aged 65 y and over in the Cognitive Function and Ageing Study Wales (CFAS-Wales) cohort collected in 2011–2013. Linear regression modelling was used to investigate the overall associations between five lifestyle factors—cognitive and social activity, physical activity, diet, alcohol consumption, and smoking—and cognition, adjusting for demographic factors and chronic conditions. Mediation analysis tested for indirect effects of the lifestyle factors on cognition via cognitive reserve. After controlling for age, gender, and the presence of chronic conditions, cognitive and social activity, physical activity, healthy diet, and light-to-moderate alcohol consumption were positively associated with cognitive function, together accounting for 20% (95% CI 17%–23%) of variance in cognitive test scores. Cognitive reserve was an important mediator of this association, with indirect effects via cognitive reserve contributing 21% (95% CI 15%–27%) of the overall effect on cognition. The main limitations of the study derive from the cross-sectional nature of the data and the challenges of accurately measuring the latent construct of cognitive reserve. Conclusions Cross-sectional associations support the view that enhancing cognitive reserve may benefit cognition, and maintenance of cognitive health may be supported by a healthy and active lifestyle, in later life. PMID:28323829

Brain Morphology Links Systemic Inflammation to Cognitive Function in Midlife Adults

PubMed Central

Marsland, Anna L.; Gianaros, Peter J.; Kuan, Dora C-H.; Sheu, Lei K.; Krajina, Katarina; Manuck, Stephen B.

2015-01-01

Background Inflammation is linked to cognitive decline in midlife, but the neural basis for this link is unclear. One possibility is that inflammation associates with adverse changes in brain morphology, which accelerates cognitive aging and later dementia risk. Clear evidence is lacking, however, regarding whether inflammation relates to cognition in midlife via changes in brain morphology. Accordingly, the current study examines whether associations of inflammation with cognitive function are mediated by variation in cortical gray matter volume among midlife adults. Methods Plasma levels of interleukin (IL)-6 and C-reactive protein (CRP), relatively stable markers of peripheral systemic inflammation, were assessed in 408 community volunteers aged 30–54 years. All participants underwent structural neuroimaging to assess global and regional brain morphology and completed neuropsychological tests sensitive to early changes in cognitive function. Measurements of brain morphology (regional tissue volumes and cortical thickness and surface area) were derived using Freesurfer. Results Higher peripheral inflammation was associated with poorer spatial reasoning, short term memory, verbal proficiency, learning and memory, and executive function, as well as lower cortical gray and white matter volumes, hippocampal volume and cortical surface area. Mediation models with age, sex and intracranial volume as covariates showed cortical gray matter volume to partially mediate the association of inflammation with cognitive performance. Exploratory analyses of body mass suggested that adiposity may be a source of the inflammation linking brain morphology to cognition. Conclusions Inflammation and adiposity might relate to cognitive decline via influences on brain morphology. PMID:25882911

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

PubMed

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

2017-10-01

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

Age as a Predictor of Cognitive Decline in Bipolar Disorder

PubMed Central

Lewandowski, Kathryn E.; Sperry, Sarah H.; Malloy, Mary C.; Forester, Brent P.

2013-01-01

Objective Cognitive dysfunction is a core feature of Bipolar Disorder (BD) in both adult and geriatric patients. However, little is known about whether cognitive functioning declines at a faster rate in patients with BD and there are conflicting reports regarding the relationship between age and cognitive functioning in this population. This cross-sectional study examined the relationship between age and cognitive functioning in patients with BD. Methods Patients with BD I (n=113) and healthy adults (n=64) ages 18–87 completed measures of processing speed, attention, executive functioning, verbal fluency, and clinical symptomatology. Groupwise comparisons were used to examine differences between patients and the comparison group and adult and geriatric BD cohorts. A series of linear regressions was conducted to examine the relationship of age and cognitive functioning, and clinical variables and cognition. Results Patients performed significantly worse than the comparison group on all neuropsychological measures. Age was a significant predictor of Trails A scores with older age associated with worse performance. Conclusions Older age was associated with poorer performance on Trails A in patients with BD but not healthy adults. These results are suggestive of greater dysfunction in processing speed with older age in patients with BD compared to a healthy comparison group. As cognitive functioning is associated with community outcomes, these findings suggest a need for treatments targeting cognitive symptoms across the lifespan. Future research exploring neurobiological evidence for neurodegenerative processes in bipolar disorder will pave the way for potential therapeutic interventions. PMID:24262287

Terminal-decline effects for select cognitive tasks after controlling for preclinical dementia.

PubMed

Laukka, Erika J; MacDonald, Stuart W S; Bäckman, Lars

2008-05-01

In a previous study, the authors found no accelerated decline in close proximity to death for a measure of global cognitive functioning, after excluding persons in a preclinical phase of dementia. However, specific cognitive tasks might be more sensitive to terminal-decline effects. The purpose of this study was to explore possible terminal-decline effects for a range of cognitive tasks after controlling for preclinical dementia. Community-based cohort study. The Kungsholmen district of Stockholm. A total of 585 persons (75+ years) were repeatedly assessed over an 11-year period. Level and change in cognitive performance were compared for three groups: persons in close proximity to death, persons in a preclinical phase of dementia, and persons who remained alive and nondemented throughout the study. Tasks assessing primary and episodic memory, verbal ability, and visuospatial skill. Compared with an analysis where all dead subjects were included in the impending-death group, removing the preclinical dementia cases resulted in markedly attenuated mortality-related effects. However, the impending-death group still declined at a faster rate relative to the comparison group on Digit Span-forward, word recognition, and category fluency. Notably, these were tasks for which the comparison group showed no significant decline. A considerable proportion of the terminal-decline effect is accounted for by the impact of preclinical dementia. However, for tasks that are relatively resistant to age-related change, such effects might be detected independently of preclinical dementia.

Assessment of mental competency in community-dwelling elderly.

PubMed

Schmand, B; Gouwenberg, B; Smit, J H; Jonker, C

1999-01-01

We studied the utility of a "vignette method" to assess mental competency for decision making on medical treatment and research participation. A vignette is a description of an imaginary situation in which the subject is asked to decide on a proposed treatment or on participation in research. His or her understanding of the situation and the quality of the reasoning underlying that choice are tested by a short series of questions. Subjects were participants in the Amsterdam Study of the Elderly (AMSTEL), a population-based study on cognitive decline and dementia. The sample consisted of elderly people (70-90 years), who were cognitively intact (n = 176) or had a dementia syndrome (n = 64; mostly Alzheimer disease). Dementia was diagnosed using the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) schedule. Two vignettes were used as competency assessment instruments. The answers to the vignette questions were summed to form a competency score. The reliability (internal consistency) of this score was 0.82 for both vignettes combined. After dichotomization into competent/incompetent (cutoff at the fifth centile of the control group), the agreement between the vignette method and a physician's judgment of competency was poor (kappa = 0.36) in the demented group. There was no agreement whatsoever when subjects with "minimal dementia" (n = 14) were left out of this analysis (kappa = 0.04). As expected, mean competency scores declined with increasing dementia severity. A multiple regression analysis showed that mental competency as measured by the vignette method was determined mainly by recent memory, expressive language, and abstract thinking. In the control group the competency score was only slightly related to education (r = 0.12) and verbal intelligence (r = 0.27). We conclude that the vignette method is a reliable and valid method for the assessment of mental competency in elderly people with cognitive decline. The vignette method is preferred over a physician's judgment, especially in patients with early dementia.

Gait dyspraxia as a clinical marker of cognitive decline in Down syndrome: A review of theory and proposed mechanisms.

PubMed

Anderson-Mooney, Amelia J; Schmitt, Frederick A; Head, Elizabeth; Lott, Ira T; Heilman, Kenneth M

2016-04-01

Down syndrome (DS) is the most common genetic cause of intellectual disability in children. With aging, DS is associated with an increased risk for Alzheimer's disease (AD). The development of AD neuropathology in individuals with DS can result in further disturbances in cognition and behavior and may significantly exacerbate caregiver burden. Early detection may allow for appropriate preparation by caregivers. Recent literature suggests that declines in gait may serve as an early marker of AD-related cognitive disorders; however, this relationship has not been examined in individuals with DS. The theory regarding gait dyspraxia and cognitive decline in the general population is reviewed, and potential applications to the population with individuals with DS are highlighted. Challenges and benefits in the line of inquiry are discussed. In particular, it appears that gait declines in aging individuals with DS may be associated with known declines in frontoparietal gray matter, development of AD-related pathology, and white matter losses in tracts critical to motor control. These changes are also potentially related to the cognitive and functional changes often observed during the same chronological period as gait declines in adults with DS. Gait declines may be an early marker of cognitive change, related to the development of underlying AD-related pathology, in individuals with DS. Future investigations in this area may provide insight into the clinical changes associated with development of AD pathology in both the population with DS and the general population, enhancing efforts for optimal patient and caregiver support and propelling investigations regarding safety/quality of life interventions and disease-modifying interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

Education, bilingualism, and cognitive trajectories: Sacramento Area Latino Aging Study (SALSA).

PubMed

Mungas, Dan; Early, Dawnté R; Glymour, M Maria; Zeki Al Hazzouri, Adina; Haan, Mary N

2018-01-01

This study examined the influence of education, country where education occurred, and monolingual-bilingual (English/Spanish) language usage on late life cognitive trajectories in the Sacramento Area Latino Study on Aging (SALSA), an epidemiological study of health and cognition in Hispanics, mostly of Mexican origin, age 60 and over (N = 1,499). SALSA followed a large cohort of older Latinos for up to 7 assessment waves from 1998 to 2007. Global cognition was assessed by using the Modified Mini Mental State Examination, and the Spanish English Verbal Learning Test was used to measure episodic memory. Education, country of origin, and language usage patterns were collected at the baseline assessment and used as predictors of longitudinal trajectories of cognition. Parallel process mixed effects models were used to examine effects of education and language variables on baseline cognition and rate of cognitive decline. Mixed effects longitudinal models showed that education had strong effects on baseline global cognition and verbal memory but was not related to decline over up to 9 years of longitudinal follow-up. Differences in education effects between subgroups educated in Mexico and in the United States were minor. Monolingual-bilingual language usage was not related to cognitive decline, and bilinguals did not significantly differ from monolingual English speakers on baseline cognitive scores. Hypotheses that higher education and bilingualism protect against late life cognitive decline were not supported and education effects on late-life cognitive trajectories did not substantially differ across U.S.- and Mexico-educated groups. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Prevention of Decline in Cognition after Stroke Trial (PODCAST): a study protocol for a factorial randomised controlled trial of intensive versus guideline lowering of blood pressure and lipids

PubMed Central

2013-01-01

Background Stroke is a common cause of cognitive impairment and dementia. However, effective strategies for reducing the risk of post-stroke dementia remain undefined. Potential strategies include intensive lowering of blood pressure and/or lipids. Methods/Design Design: multi-centre prospective randomised open-label blinded-endpoint controlled partial-factorial phase IV trial in secondary and primary care. Participants: 100 participants from 30 UK Stroke Research Network sites who are post- ischemic stroke or intracerebral haemorrhage by three to seven months. Interventions - all patients (1:1): intensive versus guideline blood pressure lowering (target systolic < 125 mmHg versus < 140 mmHg). Interventions - ischemic stroke (1:1): intensive versus guideline lipid lowering (target low density lipoprotein-cholesterol (LDL-c) < 1.4 mmol/l versus < 3 mmol/l). Hypotheses: does ‘intensive’ blood pressure lowering therapy and/or ‘intensive’ lipid control reduce cognitive decline and dementia in people with ischemic stroke; and does ‘intensive’ blood pressure lowering therapy reduce cognitive decline and dementia in patients with hemorrhagic stroke. Primary outcome: Addenbrooke’s Cognitive Examination-Revised. Secondary outcomes: feasibility of recruitment and retention of participants, tolerability and safety of the interventions, achieving and maintaining the blood pressure and lipid targets, maintaining differences in systolic blood pressure (> 10 mmHg) and low density lipoprotein-cholesterol (> 1 mmol/l) between the treatment groups, and performing clinic and telephone follow-up of cognition measures. Randomisation: using stratification, minimization and simple randomization. Blinding: participants receive open-label management. Cognition is assessed both unblinded (in clinic) and blinded (by telephone) to treatment. Adjudication of events (dementia, vascular, serious adverse events) is blinded to management. Discussion The PODCAST trial is ongoing with 78 patients recruited to date from 22 sites. Outcomes of cognitive impairment and dementia are accruing. Trial registration ISRCTN85562386 PMID:24266960

Long-term cognitive decline in older subjects was not attributable to noncardiac surgery or major illness.

PubMed

Avidan, Michael S; Searleman, Adam C; Storandt, Martha; Barnett, Kara; Vannucci, Andrea; Saager, Leif; Xiong, Chengjie; Grant, Elizabeth A; Kaiser, Dagmar; Morris, John C; Evers, Alex S

2009-11-01

Persistent postoperative cognitive decline is thought to be a public health problem, but its severity may have been overestimated because of limitations in statistical methodology. This study assessed whether long-term cognitive decline occurred after surgery or illness by using an innovative approach and including participants with early Alzheimer disease to overcome some limitations. In this retrospective cohort study, three groups were identified from participants tested annually at the Washington University Alzheimer's Disease Research Center in St. Louis, Missouri: those with noncardiac surgery, illness, or neither. This enabled long-term tracking of cognitive function before and after surgery and illness. The effect of surgery and illness on longitudinal cognitive course was analyzed using a general linear mixed effects model. For participants without initial dementia, time to dementia onset was analyzed using sequential Cox proportional hazards regression. Of the 575 participants, 214 were nondemented and 361 had very mild or mild dementia at enrollment. Cognitive trajectories did not differ among the three groups (surgery, illness, control), although demented participants declined more markedly than nondemented participants. Of the initially nondemented participants, 23% progressed to a clinical dementia rating greater than zero, but this was not more common after surgery or illness. The study did not detect long-term cognitive decline independently attributable to surgery or illness, nor were these events associated with accelerated progression to dementia. The decision to proceed with surgery in elderly people, including those with early Alzheimer disease, may be made without factoring in the specter of persistent cognitive deterioration.

Describing the Sequence of Cognitive Decline in Alzheimer's Disease Patients: Results from an Observational Study.

PubMed

Henneges, Carsten; Reed, Catherine; Chen, Yun-Fei; Dell'Agnello, Grazia; Lebrec, Jeremie

2016-01-01

Improved understanding of the pattern of cognitive decline in Alzheimer's disease (AD) would be useful to assist primary care physicians in explaining AD progression to patients and caregivers. To identify the sequence in which cognitive abilities decline in community-dwelling patients with AD. Baseline data were analyzed from 1,495 patients diagnosed with probable AD and a Mini-Mental State Examination (MMSE) score ≤ 26 enrolled in the 18-month observational GERAS study. Proportional odds logistic regression models were applied to model MMSE subscores (orientation, registration, attention and concentration, recall, language, and drawing) and the corresponding subscores of the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), using MMSE total score as the index of disease progression. Probabilities of impairment start and full impairment were estimated at each MMSE total score level. From the estimated probabilities for each MMSE subscore as a function of the MMSE total score, the first aspect of cognition to start being impaired was recall, followed by orientation in time, attention and concentration, orientation in place, language, drawing, and registration. For full impairment in subscores, the sequence was recall, drawing, attention and concentration, orientation in time, orientation in place, registration, and language. The sequence of cognitive decline for the corresponding ADAS-cog subscores was remarkably consistent with this pattern. The sequence of cognitive decline in AD can be visualized in an animation using probability estimates for key aspects of cognition. This might be useful for clinicians to set expectations on disease progression for patients and caregivers.

Brain-Derived neurotrophic factor levels in late-life depression and comorbid mild cognitive impairment: a longitudinal study

PubMed Central

Diniz, Breno Satler; Reynolds, Charles F.; Begley, Amy; Dew, Mary Amanda; Anderson, Stewart J.; Lotrich, Francis; Erickson, Kirk I.; Lopez, Oscar; Aizenstein, Howard; Sibille, Etienne L.; Butters, Meryl A.

2014-01-01

Changes in brain-derived neurotrophic factor (BDNF) level are implicated in the pathophysiology of cognitive decline in depression and neurodegenerative disorders in older adults. We aimed to evaluate the longitudinal association over two years between BDNF and persistent cognitive decline in individuals with remitted late-life depression and Mild Cognitive Impairment (LLD+MCI) compared to either individuals with remitted LLD and no cognitive decline (LLD+NCD) or never-depressed, cognitively normal, elderly control participants. We additionally evaluated the effect of double-blind, placebo-controlled donepezil treatment on BDNF levels in all of the remitted LLD participants (across the levels of cognitive function). We included 160 elderly participants in this study (72 LLD+NCD, 55 LLD+MCI and 33 never-depressed cognitively normal elderly participants). At the same visits, cognitive assessments were conducted and blood sampling to determine serum BDNF levels were collected at baseline assessment and after one and two years of follow-up. We utilized repeated measure, mixed effect models to assess: (1) the effects of diagnosis (LLD+MCI, LLD+NCD, and controls), time, and their interaction on BDNF levels; and (2) the effects of donepezil treatment (donepezil vs. placebo), time, baseline diagnosis (LLD+MCI vs. LLD+NCD), and interactions between these contrasts on BDNF levels. We found a significant effect of time on BDNF level (p=0.02) and a significant decline in BDNF levels over 2 years of follow-up in participants with LLD+MCI (p=0.004) and controls (p=0.04). We found no effect of donepezil treatment on BDNF level. The present results suggest that aging is an important factor related to decline in BDNF level. PMID:24290367

Cognition and Depression Following Deep Brain Stimulation of the Subthalamic Nucleus and Globus Pallidus Pars Internus in Parkinson's Disease: A Meta-Analysis.

PubMed

Combs, Hannah L; Folley, Bradley S; Berry, David T R; Segerstrom, Suzanne C; Han, Dong Y; Anderson-Mooney, Amelia J; Walls, Brittany D; van Horne, Craig

2015-12-01

Parkinson's disease (PD) is a common, degenerative disorder of the central nervous system. Individuals experience predominantly extrapyramidal symptoms including resting tremor, rigidity, bradykinesia, gait abnormalities, cognitive impairment, depression, and neurobehavioral concerns. Cognitive impairments associated with PD are diverse, including difficulty with attention, processing speed, executive functioning, memory recall, visuospatial functions, word-retrieval, and naming. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is FDA approved and has been shown to be effective in reducing motor symptoms of PD. Studies have found that stimulating STN and GPi are equally effective at improving motor symptoms and dyskinesias; however, there has been discrepancy as to whether the cognitive, behavioral, and mood symptoms are affected differently between the two targets. The present study used random-effects meta-analytic models along with a novel p-curve analytic procedure to compare the potential cognitive and emotional impairments associated with STN-DBS in the current literature to those associated with GPi-DBS. Forty-one articles were reviewed with an aggregated sample size of 1622 patients. Following STN-DBS, small declines were found in psychomotor speed, memory, attention, executive functions, and overall cognition; and moderate declines were found in both semantic and phonemic fluency. However, GPi-DBS resulted in fewer neurocognitive declines than STN-DBS (small declines in attention and small-moderate declines in verbal fluency). With regards to its effect on depression symptomatology, both GPi-DBS and STN-DBS resulted in lower levels of depressive symptoms post-surgery. From a neurocognitive standpoint, both GPi-DBS and STN-DBS produce subtle cognitive declines but appears to be relatively well tolerated.

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

PubMed

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

2018-04-24

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

The effects of healthy aging, amnestic mild cognitive impairment, and Alzheimer's disease on recollection, familiarity and false recognition, estimated by an associative process-dissociation recognition procedure.

PubMed

Pitarque, Alfonso; Meléndez, Juan C; Sales, Alicia; Mayordomo, Teresa; Satorres, Encar; Escudero, Joaquín; Algarabel, Salvador

2016-10-01

Given the uneven experimental results in the literature regarding whether or not familiarity declines with healthy aging and cognitive impairment, we compare four samples (healthy young people, healthy older people, older people with amnestic mild cognitive impairment - aMCI -, and older people with Alzheimer's disease - AD -) on an associative recognition task, which, following the logic of the process-dissociation procedure, allowed us to obtain corrected estimates of recollection, familiarity and false recognition. The results show that familiarity does not decline with healthy aging, but it does with cognitive impairment, whereas false recognition increases with healthy aging, but declines significantly with cognitive impairment. These results support the idea that the deficits detected in recollection, familiarity, or false recognition in older people could be used as early prodromal markers of cognitive impairment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alcohol-impaired speed and accuracy of cognitive functions: a review of acute tolerance and recovery of cognitive performance.

PubMed

Schweizer, Tom A; Vogel-Sprott, Muriel

2008-06-01

Much research on the effects of a dose of alcohol has shown that motor skills recover from impairment as blood alcohol concentrations (BACs) decline and that acute tolerance to alcohol impairment can develop during the course of the dose. Comparable alcohol research on cognitive performance is sparse but has increased with the development of computerized cognitive tasks. This article reviews the results of recent research using these tasks to test the development of acute tolerance in cognitive performance and recovery from impairment during declining BACs. Results show that speed and accuracy do not necessarily agree in detecting cognitive impairment, and this mismatch most frequently occurs during declining BACs. Speed of cognitive performance usually recovers from impairment to drug-free levels during declining BACs, whereas alcohol-increased errors fail to diminish. As a consequence, speed of cognitive processing tends to develop acute tolerance, but no such tendency is shown in accuracy. This "acute protracted error" phenomenon has not previously been documented. The findings pose a challenge to the theory of alcohol tolerance on the basis of physiological adaptation and raise new research questions concerning the independence of speed and accuracy of cognitive processes, as well as hemispheric lateralization of alcohol effects. The occurrence of alcohol-induced protracted cognitive errors long after speed returned to normal is identified as a potential threat to the safety of social drinkers that requires urgent investigation.

Shift work and cognition in the Nurses' Health Study.

PubMed

Devore, Elizabeth E; Grodstein, Francine; Schernhammer, Eva S

2013-10-15

Rotating night-shift work, which can disrupt circadian rhythm, may adversely affect long-term health. Experimental studies indicate that circadian rhythm disruption might specifically accelerate brain aging; thus, we prospectively examined shift-work history at midlife as associated with cognitive function among older women in the Nurses' Health Study. Women reported their history of rotating night-shift work in 1988 and participated in telephone-based cognitive interviews between 1995 and 2001; interviews included 6 cognitive tests that were subsequently repeated 3 times, at 2-year intervals. We focused on shift work through midlife (here, ages 58-68 years) because cognitive decline is thought to begin during this period. Using multivariable-adjusted linear regression, we evaluated mean differences in both "average cognitive status" at older age (averaging cognitive scores from all 4 interviews) and rates of cognitive decline over time across categories of shift-work duration at midlife (none, 1-9, 10-19, or ≥20 years). There was little association between shift work and average cognition in later life or between shift work and cognitive decline. Overall, this study does not clearly support the hypothesis that shift-work history in midlife has long-term effects on cognition in older adults.

Normative Values for the German Version of the Montreal Cognitive Assessment (MoCA)

ClinicalTrials.gov

2018-05-30

Cognitive Impairment; Cognitive Decline; Cognition Disorders; Cognitive Symptom; Cognitive Change; Cognitive Deterioration; Cognitive Abnormality; Cognitive Impairment, Mild; Cognition Disorders in Old Age; Dementia; Dementia Alzheimers; Dementia, Alzheimer Type; Dementia, Mild; Dementia of Alzheimer Type

Effect of educational status on performance of older adults in digital cognitive tasks: A systematic review

PubMed Central

de Carvalho, Lucas Pelegrini Nogueira; Monteiro, Diana Quirino; Orlandi, Fabiana de Souza; Zazzetta, Marisa Silvana; Pavarini, Sofia Cristina Iost

2017-01-01

As people age, cognitive abilities may decline resulting in serious disabilities. Neuropsychological instruments can provide information on the cognitive state of older adults. Researchers worldwide have been using digital cognitive tests to assess cognitive domains. Objective To determine whether educational status affects the performance of older adults on digital cognitive tasks. Methods A systematic review of articles in English, Portuguese, or Spanish published in the last 5 years was conducted. The databases searched were SCOPUS, PubMed, Lilacs, Scielo and PsychInfo. The PRISMA method was used. Results A total of 7,089 articles were initially retrieved. After search and exclusion with justification, seven articles were selected for further review. Conclusion The findings revealed that researchers using digital tasks generally employed paper-based tests to compare results. Also, no association between years of education and test performance was found. Finally, a dearth of studies using digital tests published by Brazilian researchers was evident. PMID:29213502

Over the hill at 24: persistent age-related cognitive-motor decline in reaction times in an ecologically valid video game task begins in early adulthood.

PubMed

Thompson, Joseph J; Blair, Mark R; Henrey, Andrew J

2014-01-01

Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load.

Over the Hill at 24: Persistent Age-Related Cognitive-Motor Decline in Reaction Times in an Ecologically Valid Video Game Task Begins in Early Adulthood

PubMed Central

Thompson, Joseph J.; Blair, Mark R.; Henrey, Andrew J.

2014-01-01

Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load. PMID:24718593

Patients who are near death are frequently unable to self-report dyspnea.

PubMed

Campbell, Margaret L; Templin, Thomas; Walch, Julia

2009-10-01

Standard measures of dyspnea rely on the patient's self-report. Declining consciousness and/or cognitive function and nearness to death may interfere with dyspnea reporting making the patient vulnerable to undertreatment or overtreatment. An observational design was used with 89 consecutive patients referred for inpatient palliative care consultation. Patients were included if they were at risk for dyspnea because of one or more of the following: lung cancer, chronic obstructive pulmonary disease (COPD), heart failure, or pneumonia. Patients were asked "Are you short of breath?" and asked to quantify any distress by pointing to a visual analogue scale (VAS). Other measures included: consciousness, cognitive state, terminal illness severity, and patient demographics. More than half of the patients (54%) were unable to provide a yes or no response. Only 20 of 41 (49%) able to respond with yes or no were able to quantify any distress with the VAS. Ability to self-report was positively associated with consciousness (p < 0.01), cognitive state (p < 0.01), and terminal illness severity (p < 0.01). A significant inverse relationship was found between consciousness and terminal illness severity (p < 0.01). Declines in consciousness and cognitive state were strongly correlated with nearness to death (p < 0.01). Declining consciousness and/or cognitive state are expected when patients are near death. The ability to give even the simplest self-report (yes or no) about dyspnea is lost in the near-death phase of terminal illness, yet the ability to experience distress may persist and may be overlooked and undertreated or overtreated. Other methods for symptom assessment are needed in this context.

[Physical activity diminishes aging-related decline of physical and cognitive performance].

PubMed

Apor, Péter; Babai, László

2014-05-25

Aging-related decline of muscle force, walking speed, locomotor coordination, aerobic capacity and endurance exert prognostic impact on life expectancy. Proper use of training may diminish the aging process and it may improve the quality of life of elderly persons. This paper provides a brief summary on the impact of training on aging-related decline of physical and cognitive functions.

Increased levels of cerebrospinal fluid JNK3 associated with amyloid pathology: links to cognitive decline

PubMed Central

Gourmaud, Sarah; Paquet, Claire; Dumurgier, Julien; Pace, Clarisse; Bouras, Constantin; Gray, Françoise; Laplanche, Jean-Louis; Meurs, Eliane F.; Mouton-Liger, François; Hugon, Jacques

2015-01-01

Background Alzheimer disease is characterized by cognitive decline, senile plaques of β-amyloid (Aβ) peptides, neurofibrillary tangles composed of hyperphosphorylated τ proteins and neuronal loss. Aβ and τ are useful markers in the cerebrospinal fluid (CSF). C-Jun N-terminal kinases (JNKs) are serine-threonine protein kinases activated by phosphorylation and involved in neuronal death. Methods In this study, Western blots, enzyme-linked immunosorbent assay and histological approaches were used to assess the concentrations of Aβ, τ and JNK isoforms in postmortem brain tissue samples (10 Alzheimer disease and 10 control) and in CSF samples from 30 living patients with Alzheimer disease and 27 controls with neurologic disease excluding Alzheimer disease. Patients with Alzheimer disease were followed for 1–3 years and assessed using Mini–Mental State Examination scores. Results The biochemical and morphological results showed a significant increase of JNK3 and phosphorylated JNK levels in patients with Alzheimer disease, and JNK3 levels correlated with Aβ42 levels. Confocal microscopy revealed that JNK3 was associated with Aβ in senile plaques. The JNK3 levels in the CSF were significantly elevated in patients with Alzheimer disease and correlated statistically with the rate of cognitive decline in a mixed linear model. Limitations The study involved different samples grouped into 3 small cohorts. Evaluation of JNK3 in CSF was possible only with immunoblot analysis. Conclusion We found that JNK3 levels are increased in brain tissue and CSF from patients with Alzheimer disease. The finding that increased JNK3 levels in CSF could reflect the rate of cognitive decline is new and merits further investigation. PMID:25455349

The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis.

PubMed

Debette, Stéphanie; Markus, H S

2010-07-26

To review the evidence for an association of white matter hyperintensities with risk of stroke, cognitive decline, dementia, and death. Systematic review and meta-analysis. PubMed from 1966 to 23 November 2009. Prospective longitudinal studies that used magnetic resonance imaging and assessed the impact of white matter hyperintensities on risk of incident stroke, cognitive decline, dementia, and death, and, for the meta-analysis, studies that provided risk estimates for a categorical measure of white matter hyperintensities, assessing the impact of these lesions on risk of stroke, dementia, and death. Population studied, duration of follow-up, method used to measure white matter hyperintensities, definition of the outcome, and measure of the association of white matter hyperintensities with the outcome. 46 longitudinal studies evaluated the association of white matter hyperintensities with risk of stroke (n=12), cognitive decline (n=19), dementia (n=17), and death (n=10). 22 studies could be included in a meta-analysis (nine of stroke, nine of dementia, eight of death). White matter hyperintensities were associated with an increased risk of stroke (hazard ratio 3.3, 95% confidence interval 2.6 to 4.4), dementia (1.9, 1.3 to 2.8), and death (2.0, 1.6 to 2.7). An association of white matter hyperintensities with a faster decline in global cognitive performance, executive function, and processing speed was also suggested. White matter hyperintensities predict an increased risk of stroke, dementia, and death. Therefore white matter hyperintensities indicate an increased risk of cerebrovascular events when identified as part of diagnostic investigations, and support their use as an intermediate marker in a research setting. Their discovery should prompt detailed screening for risk factors of stroke and dementia.

Residents with mild cognitive decline and family members report health students 'enhance capacity of care' and bring 'a new breath of life' in two aged care facilities in Tasmania.

PubMed

Elliott, Kate-Ellen J; Annear, Michael J; Bell, Erica J; Palmer, Andrew J; Robinson, Andrew L

2015-12-01

Care provided by student doctors and nurses is well received by patients in hospital and primary care settings. Whether the same is true for aged care residents of nursing homes with mild cognitive decline and their family members is unknown. To investigate the perspectives of aged care residents with mild cognitive decline and their family members on interdisciplinary student placements in two residential aged care facilities (RACF) in Tasmania. A mixed methods design was employed with both qualitative and quantitative data collected. All participants were interviewed and completed a questionnaire on residents' quality of life, during or after a period of student placements in each facility (October-November, 2012). Qualitative data were coded for themes following a grounded theory approach, and quantitative data were analysed using SPSS. Twenty-one participants (13 residents and 8 family members) were recruited. Four themes were identified from the qualitative data and included (i) increased social interaction and facility vibrancy; (ii) community service and personal development, (iii) vulnerability and sensitivity (learning to care) and (iv) increased capacity and the confidence of enhanced care. Residents' quality of life was reported to be mostly good in the presence of the students, despite their high care needs. Residents with mild cognitive decline and their family members perceive a wide array of benefits of student provided care in RACFs including increased social interaction. Future quantitative research should focus on whether changes in care occur for residents as a result of student involvement. © 2014 The Authors Health Expectations Published by John Wiley & Sons Ltd.

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

PubMed Central

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

2005-01-01

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

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.

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.

Use of spoken and written Japanese did not protect Japanese-American men from cognitive decline in late life.

PubMed

Crane, Paul K; Gruhl, Jonathan C; Erosheva, Elena A; Gibbons, Laura E; McCurry, Susan M; Rhoads, Kristoffer; Nguyen, Viet; Arani, Keerthi; Masaki, Kamal; White, Lon

2010-11-01

Spoken bilingualism may be associated with cognitive reserve. Mastering a complicated written language may be associated with additional reserve. We sought to determine if midlife use of spoken and written Japanese was associated with lower rates of late life cognitive decline. Participants were second-generation Japanese-American men from the Hawaiian island of Oahu, born 1900-1919, free of dementia in 1991, and categorized based on midlife self-reported use of spoken and written Japanese (total n included in primary analysis = 2,520). Cognitive functioning was measured with the Cognitive Abilities Screening Instrument scored using item response theory. We used mixed effects models, controlling for age, income, education, smoking status, apolipoprotein E e4 alleles, and number of study visits. Rates of cognitive decline were not related to use of spoken or written Japanese. This finding was consistent across numerous sensitivity analyses. We did not find evidence to support the hypothesis that multilingualism is associated with cognitive reserve.

Retirement and cognitive development in the Netherlands: Are the retired really inactive?

PubMed

de Grip, Andries; Dupuy, Arnaud; Jolles, Jelle; van Boxtel, Martin

2015-12-01

This paper uses longitudinal data to analyze the relation between retirement and cognitive development in the Netherlands. Controlling for individual fixed effects and lagged cognition, we find that retirees face lower declines in their cognitive flexibility than those who remain employed, which appears to be persistent 6 years after retirement. However, the information processing speed of low-educated retirees declines faster. The magnitude of both changes in cognition is such that retirees appear 5-6 years younger in terms of cognitive flexibility, and older in terms of information processing speed. We show that these relationships between retirement and cognitive development cannot be explained by (1) feeling relieved from routine work, (2) changes in mood, (3) changes in lifestyle, and (4) changes in blood pressure. The decline in information processing speed after retirement particularly holds for the low educated. This could increase the social costs of an aging society. Copyright © 2015 Elsevier B.V. All rights reserved.

Interactive Associations of Vascular Risk and β-Amyloid Burden With Cognitive Decline in Clinically Normal Elderly Individuals: Findings From the Harvard Aging Brain Study.

PubMed

Rabin, Jennifer S; Schultz, Aaron P; Hedden, Trey; Viswanathan, Anand; Marshall, Gad A; Kilpatrick, Emily; Klein, Hannah; Buckley, Rachel F; Yang, Hyun-Sik; Properzi, Michael; Rao, Vaishnavi; Kirn, Dylan R; Papp, Kathryn V; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Chhatwal, Jasmeer P

2018-05-21

Identifying asymptomatic individuals at high risk of impending cognitive decline because of Alzheimer disease is crucial for successful prevention of dementia. Vascular risk and β-amyloid (Aβ) pathology commonly co-occur in older adults and are significant causes of cognitive impairment. To determine whether vascular risk and Aβ burden act additively or synergistically to promote cognitive decline in clinically normal older adults; and, secondarily, to evaluate the unique influence of vascular risk on prospective cognitive decline beyond that of commonly used imaging biomarkers, including Aβ burden, hippocampal volume, fludeoxyglucose F18-labeled (FDG) positron emission tomography (PET), and white matter hyperintensities, a marker of cerebrovascular disease. In this longitudinal observational study, we examined clinically normal older adults from the Harvard Aging Brain Study. Participants were required to have baseline imaging data (FDG-PET, Aβ-PET, and magnetic resonance imaging), baseline medical data to quantify vascular risk, and at least 1 follow-up neuropsychological visit. Data collection began in 2010 and is ongoing. Data analysis was performed on data collected between 2010 and 2017. Vascular risk was quantified using the Framingham Heart Study general cardiovascular disease (FHS-CVD) risk score. We measured Aβ burden with Pittsburgh Compound-B PET. Cognition was measured annually with the Preclinical Alzheimer Cognitive Composite. Models were corrected for baseline age, sex, years of education, and apolipoprotein E ε4 status. Of the 223 participants, 130 (58.3%) were women. The mean (SD) age was 73.7 (6.0) years, and the mean (SD) follow-up time was 3.7 (1.2) years. Faster cognitive decline was associated with both a higher FHS-CVD risk score (β = -0.064; 95% CI, -0.094 to -0.033; P < .001) and higher Aβ burden (β = -0.058; 95% CI, -0.079 to -0.037; P < .001). The interaction of the FHS-CVD risk score and Aβ burden with time was significant (β = -0.040, 95% CI, -0.062 to -0.018; P < .001), suggesting a synergistic effect. The FHS-CVD risk score remained robustly associated with prospective cognitive decline (β = -0.055; 95% CI, -0.086 to -0.024; P < .001), even after adjustment for Aβ burden, hippocampal volume, FDG-PET uptake, and white matter hyperintensities. In this study, vascular risk was associated with prospective cognitive decline in clinically normal older adults, both alone and synergistically with Aβ burden. Vascular risk may complement imaging biomarkers in assessing risk of prospective cognitive decline in preclinical Alzheimer disease.

A longitudinal analysis of the influence of race on cognitive performance.

PubMed

Castora-Binkley, Melissa; Peronto, Carol L; Edwards, Jerri D; Small, Brent J

2015-07-01

Whether there are racial and ethnic disparities in the rate of cognitive decline among older adults is not clear. The purpose of this study was to determine if there are differences in cognitive decline among racial and ethnic older adults. Data were from the Health and Retirement Study, waves 1998-2010. Participants were community dwelling at baseline (n = 9,492), mostly female participants (58.8%), ranged in age from 65 to 105 years (M = 74.41, SD = 6.97), and had education levels that averaged less than high school (M = 11.7, SD = 3.4). Cognition was examined using a combined score from word recall, Serial 7's, backward counting, and naming tasks. To determine changes in cognition across 12 years, we utilized mixed effects models. Results indicated that after adjusting for covariates, race or ethnicity was unrelated to changes in cognitive performance, but there were significant differences in baseline cognition and these differences were more pronounced after adjusting for age, gender, education, poverty, heart disease, diabetes, high blood pressure. It is evident that there are significant differences in baseline cognition, although the rate of cognitive decline across 12 years did not vary significantly by race. These findings support previous assertions that the rate of cognitive decline is not associated with race and suggest that it is likely that baseline cognitive performance is a better indicator of performance over time. © The Author 2013. 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.

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

Long-term association of food and nutrient intakes with cognitive and functional decline: a 13-year follow-up study of elderly French women.

PubMed

Vercambre, Marie-Noël; Boutron-Ruault, Marie-Christine; Ritchie, Karen; Clavel-Chapelon, Françoise; Berr, Claudine

2009-08-01

The objective of the present study was to determine the potential long-term impact of dietary habits on age-related decline among 4809 elderly women (born between 1925 and 1930) in the 'Etude Epidémiologique de Femmes de la Mutuelle Générale de l'Education Nationale' (E3N) study, a French epidemiological cohort. In 1993, an extensive diet history self-administered questionnaire was sent to all participants, and in 2006 another questionnaire on instrumental activities of daily living (IADL) and recent cognitive change was sent to a close relative or friend of each woman. Logistic models adjusted for socio-demographic, lifestyle and health factors were performed to evaluate associations between habitual dietary intakes and two outcomes of interest based on the informant response: recent cognitive decline and IADL impairment. Recent cognitive decline was associated with lower intakes of poultry, fish, and animal fats, as well as higher intakes of dairy desserts and ice-cream. IADL impairment was associated with a lower intake of vegetables. The odds of recent cognitive decline increased significantly with decreasing intake of soluble dietary fibre and n-3 fatty acids but with increasing intake of retinol. The odds of IADL impairment increased significantly with decreasing intakes of vitamins B2, B6 and B12. These results are consistent with a possible long-term neuroprotective effect of dietary fibre, n-3 polyunsaturated fats and B-group vitamins, and support dietary intervention to prevent cognitive decline.

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

PubMed

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

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

Trajectories of social withdrawal and cognitive decline in the schizophrenia prodrome.

PubMed

Cullen, Kathryn; Guimaraes, Angela; Wozniak, Jeffrey; Anjum, Afshan; Schulz, S Charles; White, Tonya

2011-01-01

Schizophrenia is a heterogeneous neurodevelopmental disorder. Patients with high levels of negative symptoms have been identified as a specific subtype, but little is known about how the neurodevelopmental course may differ in this group. This study aimed to characterize developmental trajectories of premorbid social withdrawal and cognitive decline between patients with high versus low levels of negative symptoms in youth with schizophrenia-spectrum disorders. A standardized timeline was used to delineate the emergence of psychosis, social withdrawal, and cognitive decline in 52 subjects aged 8 to 19 with schizophrenia (n=36), schizophreniform (n=6), or schizoaffective disorder (n=10). The sample was divided into subgroups of high- (n=26) versus low- (n=26) negative symptoms, and developmental trajectories of premorbid symptoms were compared between groups. Mean ages for emergence of social withdrawal, cognitive decline, and psychosis were 11.1 years (SD=2.5), 11.9 (SD=4.4) and 13.2 years (SD=1.2), respectively. In the high-negative symptom group, the premorbid developmental trajectory for social withdrawal was more protracted. This group also had more severe cognitive decline at the onset of psychosis, but the premorbid trajectories for cognitive decline did not differ significantly between groups. This work documents a more severe and protracted trajectory of premorbid social withdrawal in patients with high levels of negative symptoms in comparison to those with low-negative symptoms. The findings reported here are supportive of the hypothesis that patients with illness characterized by high levels of negative symptoms may represent a subgroup with distinct neurodevelopmental abnormalities.

Secondary prevention and cognitive function after stroke: a study protocol for a 5-year follow-up of the ASPIRE-S cohort

PubMed Central

Williams, David; Gaynor, Eva; Bennett, Kathleen; Dolan, Eamon; Callaly, Elizabeth; Large, Margaret; Hickey, Anne

2017-01-01

Introduction Cognitive impairment is common following stroke and can increase disability and levels of dependency of patients, potentially leading to greater burden on carers and the healthcare system. Effective cardiovascular risk factor control through secondary preventive medications may reduce the risk of cognitive decline. However, adherence to medications is often poor and can be adversely affected by cognitive deficits. Suboptimal medication adherence negatively impacts secondary prevention targets, increasing the risk of recurrent stroke and further cognitive decline. The aim of this study is to profile cognitive function and secondary prevention, including adherence to secondary preventive medications and healthcare usage, 5 years post-stroke. The prospective associations between cognition, cardiovascular risk factors, adherence to secondary preventive medications, and rates of recurrent stroke or other cardiovascular events will also be explored. Methods and analysis This is a 5-year follow-up of a prospective study of the Action on Secondary Prevention Interventions and Rehabilitation in Stroke (ASPIRE-S) cohort of patients with stroke. This cohort will have a detailed assessment of cognitive function, adherence to secondary preventive medications and cardiovascular risk factor control. Ethics and dissemination Ethical approval for this study was granted by the Research Ethics Committees at Beaumont Hospital, Dublin and Connolly Hospital, Dublin, Mater Misericordiae University Hospital, Dublin, and the Royal College of Surgeons in Ireland. Findings will be disseminated through presentations and peer-reviewed publications. PMID:28348196

Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition

PubMed Central

Pichora-Fuller, M. Kathleen; Mick, Paul; Reed, Marilyn

2015-01-01

Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging. PMID:27516713

Relationship between serum and brain carotenoids, a-tocopherol and retinol concentrations and cognitive performance in the oldest old from the Georgia Centenarian Study

USDA-ARS?s Scientific Manuscript database

Oxidative stress is involved in age-related cognitive decline. The dietary antioxidants, carotenoids, tocopherols and vitamin A may play a role in the prevention or delay in cognitive decline. In this study sera were obtained from 78 octogenarians and 220 centenarians from the Georgia Centenarian St...

Reversal of cognitive decline in Alzheimer's disease

PubMed Central

Bredesen, Dale E.; Amos, Edwin C.; Canick, Jonathan; Ackerley, Mary; Raji, Cyrus; Fiala, Milan; Ahdidan, Jamila

2016-01-01

Alzheimer's disease is one of the most significant healthcare problems nationally and globally. Recently, the first description of the reversal of cognitive decline in patients with early Alzheimer's disease or its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment), was published [1]. The therapeutic approach used was programmatic and personalized rather than monotherapeutic and invariant, and was dubbed metabolic enhancement for neurodegeneration (MEND). Patients who had had to discontinue work were able to return to work, and those struggling at work were able to improve their performance. The patients, their spouses, and their co-workers all reported clear improvements. Here we report the results from quantitative MRI and neuropsychological testing in ten patients with cognitive decline, nine ApoE4+ (five homozygous and four heterozygous) and one ApoE4−, who were treated with the MEND protocol for 5-24 months. The magnitude of the improvement is unprecedented, providing additional objective evidence that this programmatic approach to cognitive decline is highly effective. These results have far-reaching implications for the treatment of Alzheimer's disease, MCI, and SCI; for personalized programs that may enhance pharmaceutical efficacy; and for personal identification of ApoE genotype. PMID:27294343

Cognitive dysfunction in multiple sclerosis: a review of recent developments.

PubMed

Bobholz, Julie A; Rao, Stephen M

2003-06-01

Nearly half of all patients diagnosed with multiple sclerosis will develop cognitive dysfunction, a symptom associated with significant decline in activities of daily living. The purpose of this review is to discuss recent literature investigating issues related to cognitive dysfunction in multiple sclerosis. Recent studies, examined in this review, have provided increased understanding regarding specific cognitive processes affected in multiple sclerosis, as well as a characterization of its natural history. Studies have also continued to emphasize the extent to which cognitive deficits in the condition are associated with decline in daily living skills. Recent concerns regarding driving performance have been documented among cognitively impaired individuals. Studies have also examined correlates of cognitive dysfunction, with particular emphasis on neuroimaging techniques reflecting disease activity or lesion burden. With increased understanding of neurobiological correlates of cognitive deficits, investigators have begun to examine potential treatments for managing cognitive dysfunction. This area of research has suggested that disease modifying medications can have an impact on magnetic resonance imaging disease activity by altering the cerebral demyelinating process resulting in a slower decline in cognitive functions over time and improved activities of daily living for patients with multiple sclerosis.

Characteristic of cognitive decline in Parkinson's disease: a 1-year follow-up.

PubMed

McKinlay, Audrey; Grace, Randolph C

2011-10-01

The aim of this study was to track the evolution of cognitive decline in Parkinson's disease (PD) patients 1 year after baseline testing. Thirty-three PD patients, divided according to three previously determined subgroups based on their initial cognitive performance, and a healthy comparison group were reassessed after a 1-year interval. Participants were assessed in the following five domains: Executive Function, Problem Solving, Working Memory/Attention, Memory, and Visuospatial Ability. The PD groups differed on the domains of Executive Function, Problem Solving, and Working Memory, with the most severe deficits being evident for the group that had previously shown the greatest level of impairment. Increased cognitive problems were also associated with decreased functioning in activities of daily living. The most severely impaired group had evidence of global cognitive decline, possibly reflecting a stage of preclinical dementia.

The hormonal pathway to cognitive impairment in older men.

PubMed

Maggio, M; Dall'Aglio, E; Lauretani, F; Cattabiani, C; Ceresini, G; Caffarra, P; Valenti, G; Volpi, R; Vignali, A; Schiavi, G; Ceda, G P

2012-01-01

In older men there is a multiple hormonal dysregulation with a relative prevalence of catabolic hormones such as thyroid hormones and cortisol and a decline in anabolic hormones such as dehydroepiandrosterone sulphate, testosterone and insulin like growth factor 1 levels. Many studies suggest that this catabolic milieu is an important predictor of frailty and mortality in older persons. There is a close relationship between frailty and cognitive impairment with studies suggesting that development of frailty is consequence of cognitive impairment and others pointing out that physical frailty is a determinant of cognitive decline. Decline in cognitive function, typically memory, is a major symptom of dementia. The "preclinical phase" of cognitive impairment occurs many years before the onset of dementia. The identification of relevant modifiable factors, including the hormonal dysregulation, may lead to therapeutic strategies for preventing the cognitive dysfunction. There are several mechanisms by which anabolic hormones play a role in neuroprotection and neuromodulation. These hormones facilitate recovery after brain injury and attenuate the neuronal loss. In contrast, elevated thyroid hormones may increase oxidative stress and apoptosis, leading to neuronal damage or death. In this mini review we will address the relationship between low levels of anabolic hormones, changes in thyroid hormones and cognitive function in older men. Then, giving the contradictory data of the literature and the multi-factorial origin of dementia, we will introduce the hypothesis of multiple hormonal derangement as a better determinant of cognitive decline in older men.

Non-Pharmacologic Interventions for Older Adults with Subjective Cognitive Decline: Systematic Review, Meta-Analysis, and Preliminary Recommendations.

PubMed

Smart, Colette M; Karr, Justin E; Areshenkoff, Corson N; Rabin, Laura A; Hudon, Carol; Gates, Nicola; Ali, Jordan I; Arenaza-Urquijo, Eider M; Buckley, Rachel F; Chetelat, Gael; Hampel, Harald; Jessen, Frank; Marchant, Natalie L; Sikkes, Sietske A M; Tales, Andrea; van der Flier, Wiesje M; Wesselman, Linda

2017-09-01

In subjective cognitive decline (SCD), older adults present with concerns about self-perceived cognitive decline but are found to have clinically normal function. However, a significant proportion of those adults are subsequently found to develop mild cognitive impairment, Alzheimer's dementia or other neurocognitive disorder. In other cases, SCD may be associated with mood, personality, and physical health concerns. Regardless of etiology, adults with SCD may benefit from interventions that could enhance current function or slow incipient cognitive decline. The objective of this systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, is to examine the benefits of non-pharmacologic intervention (NPI) in persons with SCD. Inclusion criteria were studies of adults aged 55 + with SCD defined using published criteria, receiving NPI or any control condition, with cognitive, behavioural, or psychological outcomes in controlled trails. Published empirical studies were obtained through a standardized search of CINAHL Complete, Cochrane Central Register of Controlled Trials, MEDLINE with Full Text, PsycINFO, and PsycARTICLES, supplemented by a manual retrieval of relevant articles. Study quality and bias was determined using PEDro. Nine studies were included in the review and meta-analysis. A wide range of study quality was observed. Overall, a small effect size was found on cognitive outcomes, greater for cognitive versus other intervention types. The available evidence suggests that NPI may benefit current cognitive function in persons with SCD. Recommendations are provided to improve future trials of NPI in SCD.

Neighbourhood racial/ethnic composition and segregation and trajectories of cognitive decline among US older adults.

PubMed

Kovalchik, Stephanie A; Slaughter, Mary E; Miles, Jeremy; Friedman, Esther M; Shih, Regina A

2015-10-01

The influence of the sociodemographic context of one's environment on cognitive ageing is not well understood. We examined differences in cognitive trajectories according to the racial/ethnic characteristics of the residential environment. On the basis of 63 996 person-years of data from a nationally representative cohort of 6150 adults over the age of 50 years from the Health and Retirement Study, we used multivariate linear mixed models to determine the effect of neighbourhood racial/ethnic composition and county-level segregation on cognitive function and cognitive decline over a 10-year period. In models adjusting for individual demographic and health characteristics, Hispanic composition had a significant positive association with cognitive function (standardised β=0.136, p<0.05) and moderate evidence of an association with greater cognitive decline (standardised β=-0.014, p=0.09). Greater Hispanic-white segregation was associated with statistically significant higher cognitive function at baseline (standardised β=0.099, p<0.001) and greater cognitive decline (standardised β=-0.011, p<0.01). For a 20 percentage-point increase in Hispanic composition and segregation, the observed associations implied 1 and 1.25 additional years of cognitive ageing over 10 years, respectively. These effects did not differ by individual race/ethnicity and were not explained by neighbourhood socioeconomic status or neighbourhood selection. Black composition and black-white segregation did not have a significant influence on cognitive ageing. This study demonstrates disparities in the progression of cognitive ageing according to racial/ethnic characteristics of the neighbourhood environment. 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.

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

PubMed

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

2015-07-01

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

Cognitive Trajectory Changes Over 20 Years Before Dementia Diagnosis: A Large Cohort Study.

PubMed

Li, Ge; Larson, Eric B; Shofer, Jane B; Crane, Paul K; Gibbons, Laura E; McCormick, Wayne; Bowen, James D; Thompson, Mary Lou

2017-12-01

Longitudinal studies have shown an increase in cognitive decline many years before clinical diagnosis of dementia. We sought to estimate changes, relative to "normal" aging, in the trajectory of scores on a global cognitive function test-the Cognitive Abilities Screening Instrument (CASI). A prospective cohort study. Community-dwelling members of a U.S. health maintenance organization. Individuals aged 65 and older who had no dementia diagnosis at baseline and had at least two visits with valid CASI test score (N = 4,315). Average longitudinal trajectories, including changes in trajectory before clinical diagnosis in those who would be diagnosed with dementia, were estimated for CASI item response theory (IRT) scores. The impact of sex, education level, and APOE genotype on cognitive trajectories was assessed. Increased cognitive decline relative to "normal" aging was evident in CASI IRT at least 10 years before clinical diagnosis. Male gender, lower education, and presence of ≥1 APOE ε4 alleles were associated with lower average IRT scores. In those who would be diagnosed with dementia, a trajectory change point was estimated at an average of 3.1 years (95% confidence interval 3.0-3.2) before clinical diagnosis, after which cognitive decline appeared to accelerate. The change point did not differ by sex, education level, or APOE ε4 genotype. There were subtle differences in trajectory slopes by sex and APOE ε4 genotype, but not by education. Decline in average global cognitive function was evident at least 10 years before clinical diagnosis of dementia. The decline accelerated about 3 years before clinical diagnosis. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Age-dependent cognitive impairment in a Drosophila fragile X model and its pharmacological rescue.

PubMed

Choi, Catherine H; McBride, Sean M J; Schoenfeld, Brian P; Liebelt, David A; Ferreiro, David; Ferrick, Neal J; Hinchey, Paul; Kollaros, Maria; Rudominer, Rebecca L; Terlizzi, Allison M; Koenigsberg, Eric; Wang, Yan; Sumida, Ai; Nguyen, Hanh T; Bell, Aaron J; McDonald, Thomas V; Jongens, Thomas A

2010-06-01

Fragile X syndrome afflicts 1 in 2,500 individuals and is the leading heritable cause of mental retardation worldwide. The overriding clinical manifestation of this disease is mild to severe cognitive impairment. Age-dependent cognitive decline has been identified in Fragile X patients, although it has not been fully characterized nor examined in animal models. A Drosophila model of this disease has been shown to display phenotypes bearing similarity to Fragile X symptoms. Most notably, we previously identified naive courtship and memory deficits in young adults with this model that appear to be due to enhanced metabotropic glutamate receptor (mGluR) signaling. Herein we have examined age-related cognitive decline in the Drosophila Fragile X model and found an age-dependent loss of learning during training. We demonstrate that treatment with mGluR antagonists or lithium can prevent this age-dependent cognitive impairment. We also show that treatment with mGluR antagonists or lithium during development alone displays differential efficacy in its ability to rescue naive courtship, learning during training and memory in aged flies. Furthermore, we show that continuous treatment during aging effectively rescues all of these phenotypes. These results indicate that the Drosophila model recapitulates the age-dependent cognitive decline observed in humans. This places Fragile X in a category with several other diseases that result in age-dependent cognitive decline. This demonstrates a role for the Drosophila Fragile X Mental Retardation Protein (dFMR1) in neuronal physiology with regard to cognition during the aging process. Our results indicate that misregulation of mGluR activity may be causative of this age onset decline and strengthens the possibility that mGluR antagonists and lithium may be potential pharmacologic compounds for counteracting several Fragile X symptoms.

Effects of education on the progression of early- versus late-stage mild cognitive impairment.

PubMed

Ye, Byoung Seok; Seo, Sang Won; Cho, Hanna; Kim, Seong Yoon; Lee, Jung-Sun; Kim, Eun-Joo; Lee, Yunhwan; Back, Joung Hwan; Hong, Chang Hyung; Choi, Seong Hye; Park, Kyung Won; Ku, Bon D; Moon, So Young; Kim, Sangyun; Han, Seol-Heui; Lee, Jae-Hong; Cheong, Hae-Kwan; Na, Duk L

2013-04-01

Highly educated participants with normal cognition show lower incidence of Alzheimer's disease (AD) than poorly educated participants, whereas longitudinal studies involving AD have reported that higher education is associated with more rapid cognitive decline. We aimed to evaluate whether highly educated amnestic mild cognitive impairment (aMCI) participants show more rapid cognitive decline than those with lower levels of education. A total of 249 aMCI patients enrolled from 31 memory clinics using the standard assessment and diagnostic processes were followed with neuropsychological evaluation (duration 17.2 ± 8.8 months). According to baseline performances on memory tests, participants were divided into early-stage aMCI (-1.5 to -1.0 standard deviation (SD)) and late-stage aMCI (below -1.5 SD) groups. Risk of AD conversion and changes in neuropsychological performances according to the level of education were evaluated. Sixty-two patients converted to AD over a mean follow-up of 1.43 years. The risk of AD conversion was higher in late-stage aMCI than early-stage aMCI. Cox proportional hazard models showed that aMCI participants, and late-stage aMCI participants in particular, with higher levels of education had a higher risk of AD conversion than those with lower levels of education. Late-stage aMCI participants with higher education showed faster cognitive decline in language, memory, and Clinical Dementia Rating Sum of Boxes (CDR-SOB) scores. On the contrary, early-stage aMCI participants with higher education showed slower cognitive decline in MMSE and CDR-SOB scores. Our findings suggest that the protective effects of education against cognitive decline remain in early-stage aMCI and disappear in late-stage aMCI.

Visual Search Load Effects on Age-Related Cognitive Decline: Evidence From the Yakumo Longitudinal Study.

PubMed

Hatta, Takeshi; Kato, Kimiko; Hotta, Chie; Higashikawa, Mari; Iwahara, Akihiko; Hatta, Taketoshi; Hatta, Junko; Fujiwara, Kazumi; Nagahara, Naoko; Ito, Emi; Hamajima, Nobuyuki

2017-01-01

The validity of Bucur and Madden's (2010) proposal that an age-related decline is particularly pronounced in executive function measures rather than in elementary perceptual speed measures was examined via the Yakumo Study longitudinal database. Their proposal suggests that cognitive load differentially affects cognitive abilities in older adults. To address their proposal, linear regression coefficients of 104 participants were calculated individually for the digit cancellation task 1 (D-CAT1), where participants search for a given single digit, and the D-CAT3, where they search for 3 digits simultaneously. Therefore, it can be conjectured that the D-CAT1 represents primarily elementary perceptual speed and low-visual search load task. whereas the D-CAT3 represents primarily executive function and high-visual search load task. Regression coefficients from age 65 to 75 for the D-CAT3 showed a significantly steeper decline than that for the D-CAT1, and a large number of participants showed this tendency. These results support the proposal by Brcur and Madden (2010) and suggest that the degree of cognitive load affects age-related cognitive decline.

Dementia Risk and Financial Decision Making by Older Households: The Impact of Information

PubMed Central

Hsu, Joanne W.; Willis, Robert

2014-01-01

The knowledge and reasoning ability needed to manage one’s finances is a form of human capital. Alzheimer’s disease and other dementias cause progressive declines in cognition that lead to a complete loss of functional capacities. In this paper we analyze the impact of information about cognitive decline on the choice of household financial decision-maker. Using longitudinal data on older married couples in a novel application of survival analysis, we find that as the financial decision maker’s cognition declines, the management of finances is eventually turned over to his cognitively intact spouse, often well after difficulties handling money have already emerged. However, a memory disease diagnosis increases the hazard of switching the financial respondent by over 200 percent for couples who control their retirement accounts, like 401(k) accounts, relative to those who passively receive retirement income. This finding is consistent with a model of the value of information: households with the most to gain financially from preparation are most responsive to information about cognitive decline. PMID:25525476

Sources of Disconnection in Neurocognitive Aging: Cerebral White Matter Integrity, Resting-state Functional Connectivity, and White Matter Hyperintensity Volume

PubMed Central

Madden, David J.; Parks, Emily L.; Tallman, Catherine W.; Boylan, Maria A.; Hoagey, David A.; Cocjin, Sally B.; Packard, Lauren E.; Johnson, Micah A.; Chou, Ying-hui; Potter, Guy G.; Chen, Nan-kuei; Siciliano, Rachel E.; Monge, Zachary A.; Honig, Jesse A.; Diaz, Michele T.

2017-01-01

Age-related decline in fluid cognition can be characterized as a disconnection among specific brain structures, leading to a decline in functional efficiency. The potential sources of disconnection, however, are unclear. We investigated imaging measures of cerebral white matter integrity, resting-state functional connectivity, and white matter hyperintensity (WMH) volume as mediators of the relation between age and fluid cognition, in 145 healthy, community-dwelling adults 19–79 years of age. At a general level of analysis, with a single composite measure of fluid cognition and single measures of each of the three imaging modalities, age exhibited an independent influence on the cognitive and imaging measures, and the imaging variables did not mediate the age-cognition relation. At a more specific level of analysis, resting-state functional connectivity of sensorimotor networks was a significant mediator of the age-related decline in executive function. These findings suggest that different levels of analysis lead to different models of neurocognitive disconnection, and that resting-state functional connectivity, in particular, may contribute to age-related decline in executive function. PMID:28389085

Amyloid-β--associated clinical decline occurs only in the presence of elevated P-tau.

PubMed

Desikan, Rahul S; McEvoy, Linda K; Thompson, Wesley K; Holland, Dominic; Brewer, James B; Aisen, Paul S; Sperling, Reisa A; Dale, Anders M

2012-06-01

To elucidate the relationship between the 2 hallmark proteins of Alzheimer disease (AD), amyloid-(Aβ) and tau, and clinical decline over time among cognitively normal older individuals. A longitudinal cohort of clinically and cognitively normal older individuals assessed with baseline lumbar puncture and longitudinal clinical assessments. Research centers across the United States and Canada. We examined 107 participants with a Clinical Dementia Rating (CDR) of 0 at baseline examination. Using linear mixed effects models, we investigated the relationship between cerebrospinal fluid (CSF) phospho-tau 181 (p-tau(181p)),CSF Aβ(1-42), and clinical decline as assessed using longitudinal change in global CDR, CDR-Sum of Boxes, and the Alzheimer Disease Assessment Scale-cognitive subscale. We found a significant relationship between decreased CSF Aβ(1-42) and longitudinal change in global CDR,CDR-Sum of Boxes, and Alzheimer Disease Assessment Scale-cognitive subscale in individuals with elevated CSFp-tau(181p). In the absence of CSF p-tau(181p), the effect of CSF Aβ(1-42) on longitudinal clinical decline was not significantly different from 0. In cognitively normal older individuals,A-associated clinical decline during a mean of 3 years may occur only in the presence of ongoing downstream neurodegeneration.

Cognitive decline and survival in Alzheimer's disease according to education level.

PubMed

Bruandet, A; Richard, F; Bombois, S; Maurage, C A; Masse, I; Amouyel, P; Pasquier, F

2008-01-01

We tested the hypothesis that a higher education level is associated with faster cognitive decline and lower survival in a cohort of 670 Alzheimer's disease patients, followed for 3.5 years at the Lille-Bailleul memory centre. The patients were categorized in 3 groups according to educational levels: low (12 years). Cognitive function was measured with the Mini Mental State Examination (MMSE) and the Mattis Dementia Rating Scale (DRS). Survival was analyzed with a Cox model. Analyses were adjusted for age, sex, cholinesterase inhibitor treatment, diabetes, hypertension, visible vascular lesions on MRI, baseline DRS and MMSE. The adjusted mixed random model showed that MMSE declined faster for patients with high and intermediate educational levels compared with those with a low educational level (p < 0.0001). The mean annually adjusted DRS decline was highest for the groups with the most education (p = 0.05). The mortality risk was not higher in the better-educated groups (high vs. low: RR = 0.84; 95% CI = 0.35-1.99, intermediate vs. low: RR = 0.82; 95% CI = 0.41-1.63). In our cohort, highly educated patients had a faster cognitive decline than less educated patients but similar mortality rates. Our findings support the cognitive reserve hypothesis. (c) 2007 S. Karger AG, Basel.

A new approach to the characterization of subtle errors in everyday action: implications for mild cognitive impairment.

PubMed

Seligman, Sarah C; Giovannetti, Tania; Sestito, John; Libon, David J

2014-01-01

Mild functional difficulties have been associated with early cognitive decline in older adults and increased risk for conversion to dementia in mild cognitive impairment, but our understanding of this decline has been limited by a dearth of objective methods. This study evaluated the reliability and validity of a new system to code subtle errors on an established performance-based measure of everyday action and described preliminary findings within the context of a theoretical model of action disruption. Here 45 older adults completed the Naturalistic Action Test (NAT) and neuropsychological measures. NAT performance was coded for overt errors, and subtle action difficulties were scored using a novel coding system. An inter-rater reliability coefficient was calculated. Validity of the coding system was assessed using a repeated-measures ANOVA with NAT task (simple versus complex) and error type (overt versus subtle) as within-group factors. Correlation/regression analyses were conducted among overt NAT errors, subtle NAT errors, and neuropsychological variables. The coding of subtle action errors was reliable and valid, and episodic memory breakdown predicted subtle action disruption. Results suggest that the NAT can be useful in objectively assessing subtle functional decline. Treatments targeting episodic memory may be most effective in addressing early functional impairment in older age.

Cardiovascular risk factors and dementia.

PubMed

Fillit, Howard; Nash, David T; Rundek, Tatjana; Zuckerman, Andrea

2008-06-01

Dementias, such as Alzheimer's disease (AD) and vascular dementia, are disorders of aging populations and represent a significant economic burden. Evidence is accumulating to suggest that cardiovascular disease (CVD) risk factors may be instrumental in the development of dementia. The goal of this review was to discuss the relationship between specific CVD risk factors and dementia and how current treatment strategies for dementia should focus on reducing CVD risks. We conducted a review of the literature for the simultaneous presence of 2 major topics, cardiovascular risk factors and dementia (eg, AD). Special emphasis was placed on clinical outcome studies examining the effects of treatments of pharmacologically modifiable CVD risk factors on dementia and cognitive impairment. Lifestyle risk factors for CVD, such as obesity, lack of exercise, smoking, and certain psychosocial factors, have been associated with an increased risk of cognitive decline and dementia. Some evidence suggests that effectively managing these factors may prevent cognitive decline/dementia. Randomized, placebo-controlled trials of antihypertensive medications have found that such therapy may reduce the risk of cognitive decline, and limited data suggest a benefit for patients with AD. Some small open-label and randomized clinical trials of statins have observed positive effects on cognitive function; larger studies of statins in patients with AD are ongoing. Although more research is needed, current evidence indicates an association between CVD risk factors--such as hypertension, dyslipidemia, and diabetes mellitus--and cognitive decline/dementia. From a clinical perspective, these data further support the rationale for physicians to provide effective management of CVD risk factors and for patients to be compliant with such recommendations to possibly prevent cognitive decline/dementia.

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.

Latent information in fluency lists predicts functional decline in persons at risk for Alzheimer disease.

PubMed

Clark, D G; Kapur, P; Geldmacher, D S; Brockington, J C; Harrell, L; DeRamus, T P; Blanton, P D; Lokken, K; Nicholas, A P; Marson, D C

2014-06-01

We constructed random forest classifiers employing either the traditional method of scoring semantic fluency word lists or new methods. These classifiers were then compared in terms of their ability to diagnose Alzheimer disease (AD) or to prognosticate among individuals along the continuum from cognitively normal (CN) through mild cognitive impairment (MCI) to AD. Semantic fluency lists from 44 cognitively normal elderly individuals, 80 MCI patients, and 41 AD patients were transcribed into electronic text files and scored by four methods: traditional raw scores, clustering and switching scores, "generalized" versions of clustering and switching, and a method based on independent components analysis (ICA). Random forest classifiers based on raw scores were compared to "augmented" classifiers that incorporated newer scoring methods. Outcome variables included AD diagnosis at baseline, MCI conversion, increase in Clinical Dementia Rating-Sum of Boxes (CDR-SOB) score, or decrease in Financial Capacity Instrument (FCI) score. Receiver operating characteristic (ROC) curves were constructed for each classifier and the area under the curve (AUC) was calculated. We compared AUC between raw and augmented classifiers using Delong's test and assessed validity and reliability of the augmented classifier. Augmented classifiers outperformed classifiers based on raw scores for the outcome measures AD diagnosis (AUC .97 vs. .95), MCI conversion (AUC .91 vs. .77), CDR-SOB increase (AUC .90 vs. .79), and FCI decrease (AUC .89 vs. .72). Measures of validity and stability over time support the use of the method. Latent information in semantic fluency word lists is useful for predicting cognitive and functional decline among elderly individuals at increased risk for developing AD. Modern machine learning methods may incorporate latent information to enhance the diagnostic value of semantic fluency raw scores. These methods could yield information valuable for patient care and clinical trial design with a relatively small investment of time and money. Published by Elsevier Ltd.

Terminal decline of episodic memory and perceptual speed in a biracial population.

PubMed

Wilson, Robert S; Rajan, Kumar B; Barnes, Lisa L; Jansen, Willemijn; Amofa, Priscilla; Weuve, Jennifer; Evans, Denis A

2018-05-01

We compared trajectories of terminal cognitive decline in older Black (n = 3372) and White (n = 1756) persons from a defined population who completed tests of episodic memory and perceptual speed at 3-year intervals for up to 18 years. During a mean of 9.9 years of observation, 1608 Black persons and 902 White persons died. Preterminal decline of episodic memory did not differ by race. Terminal episodic memory decline began earlier in Black persons (mean of 4.3 years before death) than in White persons (mean = 3.9 years) and progressed more slowly. By contrast, terminal decline of perceptual speed began earlier in White persons (mean = 5.0 years) than in Black persons (mean = 4.5 years). Rate of perceptual speed decline was more rapid in White persons than in Black persons in both the preterminal and terminal periods. The results indicate that terminal cognitive decline occurs in Black persons but suggest that the rate of cognitive decline during the terminal period is less rapid in Black persons than in White persons.

Commentary on: Subjective cognitive decline is longitudinally associated with lower health-related quality of life.

PubMed

Cooper, Claudia

2017-12-01

Public campaigns to encourage early detection of dementia in the developed world have led to identification of more people with mild cognitive impairment (MCI) or subjective cognitive decline (SCD). Early dementia diagnosis enables earlier information and support, including symptomatic treatments where appropriate. In clinical trials, detection of those with "prodromal dementia," identified from cognitive symptoms and stratified by biomarkers (Schneider, 2010), enables potential disease modifying treatments to be targeted early in the disease process, where success is more likely.

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

PubMed Central

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

2012-01-01

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

Perceived Social Isolation and Cognition

PubMed Central

Cacioppo, John T.; Hawkley, Louise C.

2009-01-01

Social species, from Drosophila melanogaster to Homo sapiens, fare poorly when isolated. Homo sapiens, an irrepressibly meaning-making species, are, in normal circumstances, dramatically affected by perceived social isolation. Research indicates that perceived social isolation (i.e., loneliness) is a risk factor for, and may contribute to, poorer overall cognitive performance, faster cognitive decline, poorer executive functioning, more negativity and depressive cognition, heightened sensitivity to social threats, a confirmatory bias in social cognition that is self-protective and paradoxically self-defeating, heightened anthropomorphism, and contagion that threatens social cohesion. These differences in attention and cognition impact emotions, decisions, behaviors, and interpersonal interactions that may contribute to the association between loneliness and cognitive decline and between loneliness and morbidity more generally. PMID:19726219

Cognitive effects of cancer and its treatments at the intersection of aging: what do we know; what do we need to know?

PubMed

Mandelblatt, Jeanne S; Hurria, Arti; McDonald, Brenna C; Saykin, Andrew J; Stern, Robert A; VanMeter, John W; McGuckin, Meghan; Traina, Tiffani; Denduluri, Neelima; Turner, Scott; Howard, Darlene; Jacobsen, Paul B; Ahles, Tim

2013-12-01

There is a fairly consistent, albeit non-universal body of research documenting cognitive declines after cancer and its treatments. While few of these studies have included subjects aged 65 years and older, it is logical to expect that older patients are at risk of cognitive decline. Here, we use breast cancer as an exemplar disease for inquiry into the intersection of aging and cognitive effects of cancer and its therapies. There are a striking number of common underlying potential biological risks and pathways for the development of cancer, cancer-related cognitive declines, and aging processes, including the development of a frail phenotype. Candidate shared pathways include changes in hormonal milieu, inflammation, oxidative stress, DNA damage and compromised DNA repair, genetic susceptibility, decreased brain blood flow or disruption of the blood-brain barrier, direct neurotoxicity, decreased telomere length, and cell senescence. There also are similar structure and functional changes seen in brain imaging studies of cancer patients and those seen with "normal" aging and Alzheimer's disease. Disentangling the role of these overlapping processes is difficult since they require aged animal models and large samples of older human subjects. From what we do know, frailty and its low cognitive reserve seem to be a clinically useful marker of risk for cognitive decline after cancer and its treatments. This and other results from this review suggest the value of geriatric assessments to identify older patients at the highest risk of cognitive decline. Further research is needed to understand the interactions between aging, genetic predisposition, lifestyle factors, and frailty phenotypes to best identify the subgroups of older patients at greatest risk for decline and to develop behavioral and pharmacological interventions targeting this group. We recommend that basic science and population trials be developed specifically for older hosts with intermediate endpoints of relevance to this group, including cognitive function and trajectories of frailty. Clinicians and their older patients can advance the field by active encouragement of and participation in research designed to improve the care and outcomes of the growing population of older cancer patients. © 2013 Elsevier Inc. All rights reserved.

Cognitive Effects of Cancer and its Treatments at the Intersection of Aging: What do we Know; What do we Need to Know?

PubMed Central

Mandelblatt, Jeanne S.; Hurria, Arti; McDonald, Brenna C.; Saykin, Andrew J.; Stern, Robert A.; VanMeter, John W.; McGuckin, Meghan; Traina, Tiffani; Denduluri, Neelima; Turner, Scott; Howard, Darlene; Jacobsen, Paul B.; Ahles, Tim

2013-01-01

There is a fairly consistent, albeit non-universal body of research documenting cognitive declines after cancer and its treatments. While few of these studies have included those 65 and older, it is logical to expect that older patients are at risk of cognitive decline. In this paper, we use breast cancer as an exemplar disease for inquiry into the intersection of aging and cognitive effects of cancer and its therapies. There are a striking number of common underlying potential biological risks and pathways for the development of cancer, cancer-related cognitive declines, and aging processes, including the development of a frail phenotype. Candidate shared pathways include changes in hormonal milieu, inflammation, oxidative stress, DNA damage and compromised DNA repair, genetic susceptibility, decreased brain blood flow or disruption of the blood-brain barrier, direct neurotoxicity, decreased telomere length, and cell senescence. There are also similar structure and functional changes seen in brain imaging studies of cancer patients and those seen with “normal” aging and Alzheimer’s disease. Disentangling the role of these overlapping processes is difficult since they require aged animal models and large samples of older human subjects. From what we do know, frailty and its low cognitive reserve seem to be a clinically useful marker of risk for cognitive decline after cancer and its treatments. This and other results from this review suggest the value of geriatric assessments to identify older patients at the highest risk of cognitive decline. Further research is needed to understand the interactions between aging, genetic predisposition, lifestyle factors and frailty phenotypes to best identify the sub-groups of older patients at greatest risk for decline and to develop behavioral and pharmacological interventions targeting this group. We recommend that basic science and population trials be developed specifically for older hosts with intermediate endpoints of relevance to this group, including cognitive function and trajectories of frailty. Clinicians and their older patients can advance the field by active encouragement of and participation in research designed to improve the care and outcomes of the growing population of older cancer patients. PMID:24331192

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.

Effortful semantic decision-making boosts memory performance in older adults.

PubMed

Fu, Li; Maes, Joseph H R; Varma, Samarth; Kessels, Roy P C; Daselaar, Sander M

2017-04-01

A major concern in age-related cognitive decline is episodic memory (EM). Previous studies indicate that both resource and binding deficits contribute to EM decline. Environmental support by task manipulations encouraging stronger cognitive effort and deeper levels of processing may facilitate compensation for these two deficits. To clarify factors that can counteract age-related EM decline, we assessed effects of cognitive effort (four levels) and level of processing (LoP, shallow/deep) during encoding on subsequent retrieval. Young (YAs, N = 23) and older (OAs, N = 23) adults performed two incidental encoding tasks, deep/semantic and shallow/perceptual. Cognitive effort was manipulated by varying decision-making demands. EM performance, indexed by d-prime, was later tested using a recognition task. Results showed that regardless of LoP, increased cognitive effort caused higher d-primes in both age groups. Compared to YAs, OAs showed a lower d-prime after shallow encoding across all cognitive effort levels, and after deep encoding with low cognitive effort. Deep encoding with higher levels of cognitive effort completely eliminated these age differences. Our findings support an environmental-compensatory account of cognitive ageing and can have important therapeutic implications.

Development of a subjective cognitive decline questionnaire using item response theory: a pilot study.

PubMed

Gifford, Katherine A; Liu, Dandan; Romano, Raymond; Jones, Richard N; Jefferson, Angela L

2015-12-01

Subjective cognitive decline (SCD) may indicate unhealthy cognitive changes, but no standardized SCD measurement exists. This pilot study aims to identify reliable SCD questions. 112 cognitively normal (NC, 76±8 years, 63% female), 43 mild cognitive impairment (MCI; 77±7 years, 51% female), and 33 diagnostically ambiguous participants (79±9 years, 58% female) were recruited from a research registry and completed 57 self-report SCD questions. Psychometric methods were used for item-reduction. Factor analytic models assessed unidimensionality of the latent trait (SCD); 19 items were removed with extreme response distribution or trait-fit. Item response theory (IRT) provided information about question utility; 17 items with low information were dropped. Post-hoc simulation using computerized adaptive test (CAT) modeling selected the most commonly used items (n=9 of 21 items) that represented the latent trait well (r=0.94) and differentiated NC from MCI participants (F(1,146)=8.9, p=0.003). Item response theory and computerized adaptive test modeling identified nine reliable SCD items. This pilot study is a first step toward refining SCD assessment in older adults. Replication of these findings and validation with Alzheimer's disease biomarkers will be an important next step for the creation of a SCD screener.

Acute Respiratory Distress Syndrome, Sepsis, and Cognitive Decline: A Review and Case Study

PubMed Central

Jackson, James C.; Hopkins, Ramona O.; Miller, Russell R.; Gordon, Sharon M.; Wheeler, Arthur P.; Ely, E. Wesley

2013-01-01

The objective of this investigation is to review existing research pertaining to cognitive impairment and decline following critical illness and describe a case involving a 49-year-old female with sepsis and acute respiratory distress syndrome (ARDS) with no prior neurologic history who, compared to baseline neuropsychological test data, experienced dramatic cognitive decline and brain atrophy following treatment in the medical intensive care unit (ICU) at Vanderbilt University Medical Center. The patient participated in detailed clinical interviews and underwent comprehensive neuropsychological testing and neurological magnetic resonance imaging (MRI) at approximately 8 months and 3.5 years after ICU discharge. Compared to pre-ICU baseline test data, her intellectual function declined approximately 2 standard deviations from 139 to 106 (from the 99th to the 61st percentile) on a standardized intelligence test 8 months post-discharge, with little subsequent improvement. Initial diffusion tensor brain magnetic resonance imaging (DT-MRI) at the end of ICU hospitalization showed diffuse abnormal hyperintense areas involving predominately white matter in both hemispheres and the left cerebellum. A brain MRI nearly 4 years after ICU discharge demonstrated interval development of profound and generalized atrophy with sulcal widening and ventricular enlargement. The magnitude of cognitive decline experienced by ICU survivors is difficult to quantify due to the unavailability of pre-morbid neuropsychological data. The current case, conducted on a patient with baseline neuropsychological data, illustrates the trajectory of decline occurring after critical illness and ICU-associated brain injury with marked atrophy and concomitant cognitive impairments. PMID:19864995

Nutrients and bioactives in green leafy vegetables and cognitive decline: prospective study

USDA-ARS?s Scientific Manuscript database

Objective: To increase understanding of the biological mechanisms underlying this association, we investigated the individual relations to cognitive decline of the primary nutrients and bioactives in green leafy vegetables, including vitamin K (phylloquinone), lutein, beta-carotene, nitrate, folate,...

Alzheimer Disease Cerebrospinal Fluid Biomarkers Moderate Baseline Differences and Predict Longitudinal Change in Attentional Control and Episodic Memory Composites in the Adult Children Study

PubMed Central

Aschenbrenner, Andrew J.; Balota, David A.; Fagan, Anne M.; Duchek, Janet M.; Benzinger, Tammie L.S.; Morris, John C.

2015-01-01

Objective Cognitive measures that are sensitive to biological markers of Alzheimer disease (AD) pathology are needed in order to (a) facilitate preclinical staging, (b) identify individuals who are at the highest risk for developing clinical symptoms and (c) serve as endpoints for evaluating the efficacy of interventions. The present study assesses the utility of two cognitive composite scores of attentional control and episodic memory as markers for preclinical AD pathology in a group of cognitively normal older adults (N = 238), as part of the Adult Children Study. Method All participants were given a baseline cognitive assessment and follow-up assessments every 3 years over an 8-year period, as well as a lumbar puncture within two years of the initial assessment to collect cerebrospinal fluid (CSF) and a PET-PIB scan for amyloid imaging. Results Results indicated that attentional control was correlated with levels of Aβ42 at the initial assessment whereas episodic memory was not. Longitudinally, individuals with high CSF tau exhibited a decline in both attention and episodic memory over the course of the study. Conclusion These results indicate that measures of attentional control and episodic memory can be utilized to evaluate cognitive decline in preclinical AD and provide support that CSF tau may be a key mechanism driving longitudinal cognitive change. PMID:26416094

The assessment of cognitive function in older adult patients with chronic kidney disease: an integrative review.

PubMed

Hannan, Mary; Steffen, Alana; Quinn, Lauretta; Collins, Eileen G; Phillips, Shane A; Bronas, Ulf G

2018-05-25

Chronic kidney disease (CKD) is a common chronic condition in older adults that is associated with cognitive decline. However, the exact prevalence of cognitive impairment in older adults with CKD is unclear likely due to the variety of methods utilized to assess cognitive function. The purpose of this integrative review is to determine how cognitive function is most frequently assessed in older adult patients with CKD. Five electronic databases were searched to explore relevant literature related to cognitive function assessment in older adult patients with CKD. Inclusion and exclusion criteria were created to focus the search to the assessment of cognitive function with standardized cognitive tests in older adults with CKD, not on renal replacement therapy. Through the search methods, 36 articles were found that fulfilled the purpose of the review. There were 36 different types of cognitive tests utilized in the included articles, with each study utilizing between one and 12 tests. The most commonly utilized cognitive test was the Mini Mental State Exam (MMSE), followed by tests of digit symbol substitution and verbal fluency. The most commonly assessed aspect of cognitive function was global cognition. The assessment of cognitive function in older adults with CKD with standardized tests is completed in various ways. Unfortunately, the common methods of assessment of cognitive function may not be fully examining the domains of impairment commonly found in older adults with CKD. Further research is needed to identify the ideal cognitive test to best assess older adults with CKD for cognitive impairment.

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

PubMed

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

2016-08-01

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

The role of cognitive reserve on terminal decline: a cross-cohort analysis from two European studies: OCTO-Twin, Sweden, and Newcastle 85+, UK.

PubMed

Cadar, Dorina; Stephan, Blossom C M; Jagger, Carol; Johansson, Boo; Hofer, Scott M; Piccinin, Andrea M; Muniz-Terrera, Graciela

2016-06-01

Cognitive performance shows a marked deterioration in close proximity to death, as postulated by the terminal decline hypothesis. The effect of education on the rate of terminal decline in the oldest people (i.e. persons 85+ years) has been controversial and not entirely understood. In the current study, we investigated the rate of decline prior to death with a special focus on the role of education and socioeconomic position, in two European longitudinal studies of ageing: the Origins of Variance in the Old-Old: Octogenarian Twins (OCTO-Twin) and the Newcastle 85+ study. A process-based approach was used in which individuals' cognitive scores were aligned according to distance to death. In a coordinated analysis, multilevel models were employed to examine associations between different markers of cognitive reserve (education and socioeconomic position) and terminal decline using the mini-mental state examination (MMSE), controlling for age at baseline, sex, dementia incidence and time to death from the study entry to the time of death within each cohort. The current findings suggest that education was positively associated with higher MMSE scores prior to death in the OCTO-Twin, but not in the Newcastle 85+ study, independent of socioeconomic position and other factors such as baseline age, sex and time to death from the study entry. However, education was not associated with the rate of terminal decline in both of these studies. Our results offer only partial support to the cognitive reserve hypothesis and cognitive performance prior to death. © 2015 The Authors International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.

The role of auditory and cognitive factors in understanding speech in noise by normal-hearing older listeners

PubMed Central

Schoof, Tim; Rosen, Stuart

2014-01-01

Normal-hearing older adults often experience increased difficulties understanding speech in noise. In addition, they benefit less from amplitude fluctuations in the masker. These difficulties may be attributed to an age-related auditory temporal processing deficit. However, a decline in cognitive processing likely also plays an important role. This study examined the relative contribution of declines in both auditory and cognitive processing to the speech in noise performance in older adults. Participants included older (60–72 years) and younger (19–29 years) adults with normal hearing. Speech reception thresholds (SRTs) were measured for sentences in steady-state speech-shaped noise (SS), 10-Hz sinusoidally amplitude-modulated speech-shaped noise (AM), and two-talker babble. In addition, auditory temporal processing abilities were assessed by measuring thresholds for gap, amplitude-modulation, and frequency-modulation detection. Measures of processing speed, attention, working memory, Text Reception Threshold (a visual analog of the SRT), and reading ability were also obtained. Of primary interest was the extent to which the various measures correlate with listeners' abilities to perceive speech in noise. SRTs were significantly worse for older adults in the presence of two-talker babble but not SS and AM noise. In addition, older adults showed some cognitive processing declines (working memory and processing speed) although no declines in auditory temporal processing. However, working memory and processing speed did not correlate significantly with SRTs in babble. Despite declines in cognitive processing, normal-hearing older adults do not necessarily have problems understanding speech in noise as SRTs in SS and AM noise did not differ significantly between the two groups. Moreover, while older adults had higher SRTs in two-talker babble, this could not be explained by age-related cognitive declines in working memory or processing speed. PMID:25429266

Florbetapir F 18 amyloid PET and 36-month cognitive decline: a prospective multicenter study.

PubMed

Doraiswamy, P M; Sperling, R A; Johnson, K; Reiman, E M; Wong, T Z; Sabbagh, M N; Sadowsky, C H; Fleisher, A S; Carpenter, A; Joshi, A D; Lu, M; Grundman, M; Mintun, M A; Skovronsky, D M; Pontecorvo, M J

2014-09-01

This study was designed to evaluate whether subjects with amyloid beta (Aβ) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aβ pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aβ+) or negative (Aβ-), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aβ+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aβ+ MCI subjects demonstrated greater worsening compared with Aβ- subjects on the ADAS-Cog over 36 months (5.66 ± 1.47 vs -0.71 ± 1.09, P = 0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal fluency test (P < 0.05). Similar to MCI subjects, Aβ+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aβ+ AD patients showed greater declines in verbal fluency and the MMSE (P < 0.05). Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aβ+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ- subjects do.

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

PubMed

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

2014-01-01

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

Effects of head circumference and metabolic syndrome on cognitive decline.

PubMed

Lee, Kang Soo; Eom, Jin-Sup; Cheong, Hae-Kwan; Oh, Byoung Hoon; Hong, Chang Hyung

2010-01-01

Brain volume progressively decreases with an increase in atrophy, and the brain becomes more susceptible to degenerative brain diseases such as Alzheimer's disease. Metabolic syndrome has also been associated with an increased risk of cognitive decline in the elderly. In this study, we aimed to examine the effects of head circumference and metabolic syndrome on cognitive decline. This study was part of a longitudinal study conducted on Koreans aged 60 years or older. We analyzed a final sample of 596 Korean participants with complete baseline and 2-year follow-up data. The cognitive function of the subjects was assessed using the Korean version of the Mini Mental State Examination (MMSE). Head circumference was measured from the glabella to the occipital protuberance using a measuring tape. Metabolic syndrome was defined according to the NCEP-ATP III standards. Central obesity was assessed on the basis of waist-circumference values, in accordance with the World Health Organization Western Pacific Region report on Asians. We used a longitudinal factorial design in which the MMSE score was the dependent variable, and head circumference and metabolic syndrome were considered as factors. After adjusting the results for age, gender, education, height, weight, baseline MMSE, and number of follow-up years, we observed that smaller head circumference and the presence of metabolic syndrome were independently associated with rapid cognitive decline. All these findings suggest that smaller head circumference and the presence of metabolic syndrome have additive effects on cognitive decline. Copyright 2009 S. Karger AG, Basel.

Diabetes, impaired fasting glucose, and cognitive decline in a population of elderly community residents.

PubMed

Rouch, Isabelle; Roche, Frédéric; Dauphinot, Virginie; Laurent, Bernard; Antérion, Catherine Thomas; Celle, Sébastien; Krolak-Salmon, Pierre; Barthélémy, Jean-Claude

2012-08-01

Diabetes and impaired fasting glucose, as well as cognitive impairment, are common in the elderly. Although several cross-sectional studies have demonstrated the influence of diabetes on cognitive impairment, only a few longitudinal studies have assessed the relationship between diabetes, impaired fasting glucose and cognitive decline in non-demented elderly community dwellers, by means of extensive neuropsychological batteries. The present study assesses the relationship between baseline diabetes, impaired fasting glucose (IFG) and 2- year evolution of memory, attention and executive performance in a sample of non-demented elderly subjects. Population-based cohort study [(PROgnostic indicator OF cardiovascular and cerebrovascular events (PROOF)]. One hundred and sixty-three community dwellers aged 65 years without dementia at recruitment. Memory, attention and executive performance. A significant association was observed between baseline diabetes mellitus and a higher 2-year decline in the Trial Making Test B and Stroop test exploring attention and executive function. This effect remained significant after adjusting for age, gender, education, anxiety and depressive symptoms, as well as other cardiovascular risk factors (F=2.41; p=0.007). Instead, no relationship was observed between IFG and cognitive decline. Our study showed that, in a sample of elderly non-demented community dwellers, diabetes mellitus (but not IFG) is associated with a higher decline in selective attention and executive functioning. These results emphasize the importance of detecting and man- aging diabetes and impaired fasting glucose, in order to prevent cognitive impairment and dementia.

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

A molecular network of the aging human brain provides insights into the pathology and cognitive decline of Alzheimer's disease.

PubMed

Mostafavi, Sara; Gaiteri, Chris; Sullivan, Sarah E; White, Charles C; Tasaki, Shinya; Xu, Jishu; Taga, Mariko; Klein, Hans-Ulrich; Patrick, Ellis; Komashko, Vitalina; McCabe, Cristin; Smith, Robert; Bradshaw, Elizabeth M; Root, David E; Regev, Aviv; Yu, Lei; Chibnik, Lori B; Schneider, Julie A; Young-Pearse, Tracy L; Bennett, David A; De Jager, Philip L

2018-06-01

There is a need for new therapeutic targets with which to prevent Alzheimer's disease (AD), a major contributor to aging-related cognitive decline. Here we report the construction and validation of a molecular network of the aging human frontal cortex. Using RNA sequence data from 478 individuals, we first build a molecular network using modules of coexpressed genes and then relate these modules to AD and its neuropathologic and cognitive endophenotypes. We confirm these associations in two independent AD datasets. We also illustrate the use of the network in prioritizing amyloid- and cognition-associated genes for in vitro validation in human neurons and astrocytes. These analyses based on unique cohorts enable us to resolve the role of distinct cortical modules that have a direct effect on the accumulation of AD pathology from those that have a direct effect on cognitive decline, exemplifying a network approach to complex diseases.

Human Neural Stem Cell Transplantation Ameliorates Radiation-Induced Cognitive Dysfunction

PubMed Central

Acharya, Munjal M.; Christie, Lori-Ann; Lan, Mary L.; Giedzinski, Erich; Fike, John R.; Rosi, Susanna; Limoli, Charles L.

2012-01-01

Cranial radiotherapy induces progressive and debilitating declines in cognition that may, in part, be caused by the depletion of neural stem cells. The potential of using stem cell replacement as a strategy to combat radiation-induced cognitive decline was addressed by irradiating athymic nude rats followed 2 days later by intrahippocampal transplantation with human neural stem cells (hNSC). Measures of cognitive performance, hNSC survival, and phenotypic fate were assessed at 1 and 4 months after irradiation. Irradiated animals engrafted with hNSCs showed significantly less decline in cognitive function than irradiated, sham-engrafted animals and acted indistinguishably from unirradiated controls. Unbiased stereology revealed that 23% and 12% of the engrafted cells survived 1 and 4 months after transplantation, respectively. Engrafted cells migrated extensively, differentiated along glial and neuronal lineages, and expressed the activity-regulated cytoskeleton-associated protein (Arc), suggesting their capability to functionally integrate into the hippocampus. These data show that hNSCs afford a promising strategy for functionally restoring cognition in irradiated animals. PMID:21757460

Protective Role of Recent and Past Long-Term Physical Activity on Age-Related Cognitive Decline: The Moderating Effect of Sex.

PubMed

Lopez-Fontana, Iréné; Castanier, Carole; Le Scanff, Christine; Perrot, Alexandra

2018-06-13

This study aimed to investigate if the impact of both recent and long-term physical activity on age-related cognitive decline would be modified by sex. One-hundred thirty-five men (N = 67) and women (N = 68) aged 18 to 80 years completed the Modifiable Activity Questionnaire and the Historical Leisure Activity Questionnaire. A composite score of cognitive functions was computed from five experimental tasks. Hierarchical regression analyses performed to test the moderating effect of recent physical activity on age-cognition relationship had not revealed significant result regardless of sex. Conversely, past long-term physical activity was found to slow down the age-related cognitive decline among women (β = 0.22, p = .03), but not men. The findings support a lifecourse approach in identifying determinants of cognitive aging and the importance of taking into account the moderating role of sex. This article presented potential explanations for these moderators and future avenues to explore.

Baseline Neurocognitive Performance and Clearance for Athletes to Return to Contact.

PubMed

Asken, Breton M; Clugston, James R; Snyder, Aliyah R; Bauer, Russell M

2017-01-01

 Computerized neurocognitive assessments are commonly used to manage sport-related concussion. Variations in baseline performance may influence neurocognitive performance after injury as well as the amount of time needed for an athlete to be cleared for return to sport participation.  To investigate the relationship between mean baseline Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) scores and postconcussion reliable decline as well as the association between postconcussion cognitive decline and days missed after injury.  Cross-sectional study.  University concussion databank.  A total of 84 collegiate athletes who sustained a concussion between 2008 and 2015 were studied. For each ImPACT composite score (verbal memory, visual memory, visual motor speed, reaction time), athletes were grouped based on the presence or absence of reliable decline and on the presence of reliable decline in 0, 1, 2, 3, or 4 cognitive domains.  Outcome measures were baseline ImPACT composite scores and days missed due to concussion.  Athletes with a reliable decline in visual memory scored higher on baseline visual memory than did athletes with no decline or an improvement (t 82 = -2.348, P = .021, d = 0.65). When comparing athletes who displayed a reliable decline with those who showed no change or an improvement in any composite score, days missed did not differ. The number of composite scores with a reliable decline demonstrated no main effect on days missed (P = .530).  Athletes who exhibited cognitive decline in most or all of the composite scores did not miss more days after injury than athletes with a decline in fewer or none of the composite scores. Athletes should be educated regarding the lack of association between baseline neurocognitive scores and the presence or absence of a reliable decline after concussion, as well as the fact that, on average, individuals with a reliable decline across multiple domains did not miss more time after concussion.

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

Dual-tasking and gait in people with Mild Cognitive Impairment. The effect of working memory

PubMed Central

Montero-Odasso, Manuel; Bergman, Howard; Phillips, Natalie A; Wong, Chek H; Sourial, Nadia; Chertkow, Howard

2009-01-01

Background Cognition and mobility in older adults are closely associated and they decline together with aging. Studies evaluating associations between cognitive factors and gait performance in people with Mild Cognitive Impairment (MCI) are scarce. In this study, our aim was to determine whether specific cognitive factors have a more identifiable effect on gait velocity during dual-tasking in people with MCI. Methods Fifty-five participants, mean age 77.7 (SD = 5.9), 45% women, with MCI were evaluated for global cognition, working memory, executive function, and attention. Gait Velocity (GV) was measured under a single-task condition (single GV) and under two dual-task conditions: 1) while counting backwards (counting GV), 2) while naming animals (verbal GV). Multivariable linear regression analysis was used to examine associations with an alpha-level of 0.05. Results Participants experienced a reduction in GV while engaging in dual-task challenges (p < 0.005). Low executive function and working memory performances were associated with slow single GV (p = 0.038), slow counting GV (p = 0.017), and slow verbal GV (p = 0.031). After adjustments, working memory was the only cognitive factor which remained significantly associated with a slow GV. Conclusion In older adults with MCI, low working memory performance was associated with slow GV. Dual-task conditions showed the strongest associations with gait slowing. Our findings suggest that cortical control of gait is associated with decline in working memory in people with MCI. PMID:19723315

Initial cognitive decline is associated with cortical thinning in early Parkinson disease

PubMed Central

Svenningsson, Per; Weintraub, Daniel; Brønnick, Kolbjørn; Lebedev, Alexander; Westman, Eric; Aarsland, Dag

2014-01-01

Objectives: Our aim was to assess cortical thickness in a large multicenter cohort of drug-naive patients with early Parkinson disease (PD), with and without mild cognitive impairment (MCI), and explore the cognitive correlates of regional cortical thinning. Methods: One hundred twenty-three newly diagnosed patients with PD and 56 healthy controls with 3-tesla structural MRI scans and complete neuropsychological assessment from the Parkinson's Progression Markers Initiative were included. Modified Movement Disorders Society Task Force level II criteria were applied to diagnose MCI in PD. FreeSurfer image processing and analysis software was used to measure cortical thickness across groups and the association with cognitive domains and tests. Results: In patients with MCI, atrophy was found in temporal, parietal, frontal, and occipital areas compared with controls. Specific regional thinning in the right inferior temporal cortex was also found in cognitively normal patients. Memory, executive, and visuospatial performance was associated with temporoparietal and superior frontal thinning, suggesting a relationship between cognitive impairment and both anterior and posterior cortical atrophy in the whole patient sample. Conclusions: These findings confirm that MCI is associated with widespread cortical atrophy. In addition, they suggest that regional cortical thinning is already present at the time of diagnosis in patients with early, untreated PD who do not meet the criteria for MCI. Together, the results indicate that cortical thinning can serve as a marker for initial cognitive decline in early PD. PMID:24808018

Disrupted white matter structure underlies cognitive deficit in hypertensive patients.

PubMed

Li, Xin; Ma, Chao; Sun, Xuan; Zhang, Junying; Chen, Yaojing; Chen, Kewei; Zhang, Zhanjun

2016-09-01

Hypertension is considered a risk factor of cognitive impairments and could result in white matter changes. Current studies on hypertension-related white matter (WM) changes focus only on regional changes, and the information about global changes in WM structure network is limited. We assessed the cognitive function in 39 hypertensive patients and 37 healthy controls with a battery of neuropsychological tests. The WM structural networks were constructed by utilizing diffusion tensor tractography and calculated topological properties of the networks using a graph theoretical method. The direct and indirect correlations among cognitive impairments, brain WM network disruptions and hypertension were analyzed with structural equation modelling (SEM). Hypertensive patients showed deficits in executive function, memory and attention compared with controls. An aberrant connectivity of WM networks was found in the hypertensive patients (P Eglob = 0.005, P Lp = 0.005), especially in the frontal and parietal regions. Importantly, SEM analysis showed that the decline of executive function resulted from aberrant WM networks in hypertensive patients (p = 0.3788, CFI = 0.99). These results suggest that the cognitive decline in hypertensive patients was due to frontal and parietal WM disconnections. Our findings highlight the importance of brain protection in hypertension patients. • Hypertension has a negative effect on the performance of the cognitive domains • Reduced efficiencies of white matter networks were shown in hypertension • Disrupted white matter networks are responsible for poor cognitive function in hypertension.

The effect of telemedicine on cognitive decline in patients with dementia.

PubMed

Kim, Heeseok; Jhoo, Jin Hyeong; Jang, Jae-Won

2017-01-01

Introduction Telemedicine has the advantage of providing medical resources in rural areas, but few studies have been conducted to investigate its efficacy in dementia care, compared to face-to-face care. This study evaluated the effectiveness of telemedicine in relation to cognitive changes in patients with dementia. Methods We evaluated cognitive changes over time, according to care modality, in 188 patients with dementia who were registered at our university-based dementia clinic. We followed 98 patients using telemedicine services and 90 patients who attended the dementia clinic in person. Patients in the telemedicine group also visited a public health center located in a rural area about 50 km from the dementia clinic. Results Changes in the mean annualized Mini-Mental State Examination (MMSE) score were not significantly different between the telemedicine group and the face-to-face dementia clinic group ( p = 0.291), with changes of 0.60 and 1.03 points, respectively. However, cognitive decline was significantly lower in the telemedicine group for the less severe initial cognitive performance subgroup than more severe cognitive performance subgroup ( p = 0.049), with changes of 0.62 and 1.59 points, respectively. Higher initial Clinical Dementia Rating (CDR) scores, MMSE scores, and age were found to be independent predictive factors of subsequent cognitive changes, as indicated by mean annualized MMSE scores. Discussion These findings suggest that telemedicine may be a useful alternative to face-to-face clinical visits for management of dementia in patients who are located in rural areas.

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

PubMed Central

2013-01-01

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

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

PubMed

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

2014-09-01

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

Cranial Radiation Therapy and Damage to Hippocampal Neurogenesis

ERIC Educational Resources Information Center

Monje, Michelle

2008-01-01

Cranial radiation therapy is associated with a progressive decline in cognitive function, prominently memory function. Impairment of hippocampal neurogenesis is thought to be an important mechanism underlying this cognitive decline. Recent work has elucidated the mechanisms of radiation-induced failure of neurogenesis. Potential therapeutic…

Enhancing Human Cognition with Cocoa Flavonoids

PubMed Central

Socci, Valentina; Tempesta, Daniela; Desideri, Giovambattista; De Gennaro, Luigi; Ferrara, Michele

2017-01-01

Enhancing cognitive abilities has become a fascinating scientific challenge, recently driven by the interest in preventing age-related cognitive decline and sustaining normal cognitive performance in response to cognitively demanding environments. In recent years, cocoa and cocoa-derived products, as a rich source of flavonoids, mainly the flavanols sub-class, have been clearly shown to exert cardiovascular benefits. More recently, neuromodulation and neuroprotective actions have been also suggested. Here, we discuss human studies specifically aimed at investigating the effects of acute and chronic administration of cocoa flavanols on different cognitive domains, such as executive functions, attention and memory. Through a variety of direct and indirect biological actions, in part still speculative, cocoa and cocoa-derived food have been suggested to possess the potential to counteract cognitive decline and sustain cognitive abilities, particularly among patients at risk. Although still at a preliminary stage, research investigating the relations between cocoa and cognition shows dose-dependent improvements in general cognition, attention, processing speed, and working memory. Moreover, cocoa flavanols administration could also enhance normal cognitive functioning and exert a protective role on cognitive performance and cardiovascular function specifically impaired by sleep loss, in healthy subjects. Together, these findings converge at pointing to cocoa as a new interesting nutraceutical tool to protect human cognition and counteract different types of cognitive decline, thus encouraging further investigations. Future research should include complex experimental designs combining neuroimaging techniques with physiological and behavioral measures to better elucidate cocoa neuromodulatory properties and directly compare immediate versus long-lasting cognitive effects. PMID:28560212

Enhancing Human Cognition with Cocoa Flavonoids.

PubMed

Socci, Valentina; Tempesta, Daniela; Desideri, Giovambattista; De Gennaro, Luigi; Ferrara, Michele

2017-01-01

Enhancing cognitive abilities has become a fascinating scientific challenge, recently driven by the interest in preventing age-related cognitive decline and sustaining normal cognitive performance in response to cognitively demanding environments. In recent years, cocoa and cocoa-derived products, as a rich source of flavonoids, mainly the flavanols sub-class, have been clearly shown to exert cardiovascular benefits. More recently, neuromodulation and neuroprotective actions have been also suggested. Here, we discuss human studies specifically aimed at investigating the effects of acute and chronic administration of cocoa flavanols on different cognitive domains, such as executive functions, attention and memory. Through a variety of direct and indirect biological actions, in part still speculative, cocoa and cocoa-derived food have been suggested to possess the potential to counteract cognitive decline and sustain cognitive abilities, particularly among patients at risk. Although still at a preliminary stage, research investigating the relations between cocoa and cognition shows dose-dependent improvements in general cognition, attention, processing speed, and working memory. Moreover, cocoa flavanols administration could also enhance normal cognitive functioning and exert a protective role on cognitive performance and cardiovascular function specifically impaired by sleep loss, in healthy subjects. Together, these findings converge at pointing to cocoa as a new interesting nutraceutical tool to protect human cognition and counteract different types of cognitive decline, thus encouraging further investigations. Future research should include complex experimental designs combining neuroimaging techniques with physiological and behavioral measures to better elucidate cocoa neuromodulatory properties and directly compare immediate versus long-lasting cognitive effects.

Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

DOE PAGES

Leal, Stephanie L.; Landau, Susan M.; Bell, Rachel K.; ...

2017-02-08

The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baselinemore » was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.« less

Accelerated age-related cognitive decline and neurodegeneration, caused by deficient DNA repair.

PubMed

Borgesius, Nils Z; de Waard, Monique C; van der Pluijm, Ingrid; Omrani, Azar; Zondag, Gerben C M; van der Horst, Gijsbertus T J; Melton, David W; Hoeijmakers, Jan H J; Jaarsma, Dick; Elgersma, Ype

2011-08-31

Age-related cognitive decline and neurodegenerative diseases are a growing challenge for our societies with their aging populations. Accumulation of DNA damage has been proposed to contribute to these impairments, but direct proof that DNA damage results in impaired neuronal plasticity and memory is lacking. Here we take advantage of Ercc1(Δ/-) mutant mice, which are impaired in DNA nucleotide excision repair, interstrand crosslink repair, and double-strand break repair. We show that these mice exhibit an age-dependent decrease in neuronal plasticity and progressive neuronal pathology, suggestive of neurodegenerative processes. A similar phenotype is observed in mice where the mutation is restricted to excitatory forebrain neurons. Moreover, these neuron-specific mutants develop a learning impairment. Together, these results suggest a causal relationship between unrepaired, accumulating DNA damage, and age-dependent cognitive decline and neurodegeneration. Hence, accumulated DNA damage could therefore be an important factor in the onset and progression of age-related cognitive decline and neurodegenerative diseases.

Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

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

Leal, Stephanie L.; Landau, Susan M.; Bell, Rachel K.

The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baselinemore » was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.« less

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.

Brain Protection and Cognitive Function: Cocoa Flavonoids as Nutraceuticals.

PubMed

Grassi, Davide; Ferri, Claudio; Desideri, Giovambattista

2016-01-01

Cognitive decline and dementia are major public health social problems, suggesting the specific need to provide research into risk factors for cognitive decline as priority topic. Increasing evidence supports the hypothesis that oxidative stress and neuroinflammation might play a crucial role in the pathophysiology of cognitive decline. Further, cognitive dysfunction and dementia in Alzheimer's disease as well as in vascular dementia seem to be also the consequence of cerebral blood flow decrease and deregulation, also suggesting a putative pathophysiological convergence of mechanisms between atherosclerosis and Alzheimer's disease. In keeping with this, a growing interest has been addressed to flavonoids as potential nutraceuticals with neuroprotective effects. Of interest, cocoa beans have been described as a fundamental source of anti-oxidant flavonoids with the flavan-3-ols and their derivatives being present in high concentrations. Therefore, recent studies specifically focused on the favorable effects of flavonoid-rich cocoa and chocolate on cerebrovascular risk factors and cognitive function. Aim of this review is to summarize new findings concerning the cocoa effects on cognitive function, particularly focusing on some putative mechanisms of vascular and antioxidant action involved in preventing dementia.

Working memory and executive function decline across normal aging, mild cognitive impairment, and Alzheimer's disease.

PubMed

Kirova, Anna-Mariya; Bays, Rebecca B; Lagalwar, Sarita

2015-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease marked by deficits in episodic memory, working memory (WM), and executive function. Examples of executive dysfunction in AD include poor selective and divided attention, failed inhibition of interfering stimuli, and poor manipulation skills. Although episodic deficits during disease progression have been widely studied and are the benchmark of a probable AD diagnosis, more recent research has investigated WM and executive function decline during mild cognitive impairment (MCI), also referred to as the preclinical stage of AD. MCI is a critical period during which cognitive restructuring and neuroplasticity such as compensation still occur; therefore, cognitive therapies could have a beneficial effect on decreasing the likelihood of AD progression during MCI. Monitoring performance on working memory and executive function tasks to track cognitive function may signal progression from normal cognition to MCI to AD. The present review tracks WM decline through normal aging, MCI, and AD to highlight the behavioral and neurological differences that distinguish these three stages in an effort to guide future research on MCI diagnosis, cognitive therapy, and AD prevention.

Complexity and Synchronicity of Resting State BOLD FMRI in Normal Aging and Cognitive Decline

PubMed Central

Liu, Collin Y; Krishnan, Anitha P; Yan, Lirong; Smith, Robert X; Kilroy, Emily; Alger, Jeffery R; Ringman, John M; Wang, Danny JJ

2012-01-01

Purpose To explore the use of approximate entropy (ApEn) as an index of the complexity and the synchronicity of resting state BOLD fMRI in normal aging and cognitive decline associated with familial Alzheimer’s disease (fAD). Materials and Methods Resting state BOLD fMRI data were acquired at 3T from 2 independent cohorts of subjects consisting of healthy young (age 23±2 years, n=8) and aged volunteers (age 66±3 years, n=8), as well as 22 fAD associated subjects (14 mutation carriers, age 41.2±15.8 years; and 8 non-mutation carrying family members, age 28.8±5.9 years). Mean ApEn values were compared between the two age groups, and correlated with cognitive performance in the fAD group. Cross-ApEn (C-ApEn) was further calculated to assess the asynchrony between precuneus and the rest of the brain. Results Complexity of brain activity measured by mean ApEn in gray and white matter decreased with normal aging. In the fAD group, cognitive impairment was associated with decreased mean ApEn in gray matter as well as decreased regional ApEn in right precuneus, right lateral parietal regions, left precentral gyrus, and right paracentral gyrus. A pattern of asynchrony between BOLD fMRI series emerged from C-ApEn analysis, with significant regional anti-correlation with cross-correlation coefficient of functional connectivity analysis. Conclusion ApEn and C-ApEn may be useful for assessing the complexity and synchronicity of brain activity in normal aging and cognitive decline associated with neurodegenerative diseases PMID:23225622

Exercise reduces diet-induced cognitive decline and increases hippocampal brain-derived neurotrophic factor in CA3 neurons

PubMed Central

Noble, Emily E.; Mavanji, Vijayakumar; Little, Morgan R.; Billington, Charles J.; Kotz, Catherine M.; Wang, ChuanFeng

2014-01-01

Background Previous studies have shown that a western diet impairs, whereas physical exercise enhances hippocampus-dependent learning and memory. Both diet and exercise influence expression of hippocampal brain-derived neurotrophic factor (BDNF), which is associated with improved cognition. We hypothesized that exercise reverses diet-induced cognitive decline while increasing hippocampal BDNF. Methods To test the effects of exercise on hippocampal-dependent memory, we compared cognitive scores of Sprague-Dawley rats exercised by voluntary running wheel (RW) access or forced treadmill (TM) to sedentary (Sed) animals. Memory was tested by two-way active avoidance test (TWAA), in which animals are exposed to a brief shock in a specific chamber area. When an animal avoids, escapes or has reduced latency to do either, this is considered a measure of memory. In a second experiment, rats were fed either a high-fat diet or control diet for 16 weeks, then randomly assigned to running wheel access or sedentary condition, and TWAA memory was tested once a week for seven weeks of exercise intervention. Results Both groups of exercised animals had improved memory as indicated by reduced latency to avoid and escape shock, and increased avoid and escape episodes (p<0.05). Exposure to a high-fat diet resulted in poor performance during both the acquisition and retrieval phases of the memory test as compared to controls. Exercise reversed high-fat diet-induced memory impairment, and increased brain-derived neurotrophic factor (BDNF) in neurons of the hippocampal CA3 region. Conclusions These data suggest that exercise improves memory retrieval, particularly with respect to avoiding aversive stimuli, and may be beneficial in protecting against diet induced cognitive decline, likely via elevated BDNF in neurons of the CA3 region. PMID:24755094

Beneath the floor: re-analysis of neurodevelopmental outcomes in untreated Hurler syndrome.

PubMed

Shapiro, Elsa G; Whitley, Chester B; Eisengart, Julie B

2018-05-11

Hurler syndrome (MPS IH), the severe, neurodegenerative form of type one mucopolysaccharidosis, is associated with rapid neurocognitive decline during toddlerhood and multi-system dysfunction. It is now standardly treated with hematopoietic cell transplantation (HCT), which halts accumulating disease pathology and prevents early death. While norm-based data on developmental functioning in untreated children have previously demonstrated neurocognitive decline, advances in methodology for understanding the cognitive functioning of children with neurodegenerative diseases have highlighted that the previous choice of scores to report results was not ideal. Specifically, the lowest possible norm-based score is 50, which obscures the complete range of cognitive functioning at more advanced stages of neurodeterioration. To a set of cognitive data collected on a sample of untreated children, we applied a modern method of score analysis, calculating a developmental quotient based on age equivalent scores, to reveal the full range of cognitive functioning beneath this cutoff of 50, uncovering new information about the rapidity of decline and the profound impairment in these children. Among 39 observations for 32 patients with untreated Hurler syndrome, the full array of cognitive functioning below 50 includes many children in the severely to profoundly impaired range. The loss of skills per time unit was 14 points between age 1 and 2. There was a very large range of developmental quotients corresponding to the norm-based cutoff of 50. This report enables clarification of functioning at levels that extend beneath the floor of 50 in previous work. At the dawn of newborn screening and amidst a proliferation of new therapies for MPS I, these data can provide crucial benchmark information for developing treatments, particularly for areas of the world where transplant may not be available.

Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study.

PubMed

Lipnicki, Darren M; Crawford, John D; Dutta, Rajib; Thalamuthu, Anbupalam; Kochan, Nicole A; Andrews, Gavin; Lima-Costa, M Fernanda; Castro-Costa, Erico; Brayne, Carol; Matthews, Fiona E; Stephan, Blossom C M; Lipton, Richard B; Katz, Mindy J; Ritchie, Karen; Scali, Jacqueline; Ancelin, Marie-Laure; Scarmeas, Nikolaos; Yannakoulia, Mary; Dardiotis, Efthimios; Lam, Linda C W; Wong, Candy H Y; Fung, Ada W T; Guaita, Antonio; Vaccaro, Roberta; Davin, Annalisa; Kim, Ki Woong; Han, Ji Won; Kim, Tae Hui; Anstey, Kaarin J; Cherbuin, Nicolas; Butterworth, Peter; Scazufca, Marcia; Kumagai, Shuzo; Chen, Sanmei; Narazaki, Kenji; Ng, Tze Pin; Gao, Qi; Reppermund, Simone; Brodaty, Henry; Lobo, Antonio; Lopez-Anton, Raúl; Santabárbara, Javier; Sachdev, Perminder S

2017-03-01

The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54-105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2-16 assessment waves (median = 3) and a follow-up duration of 2-15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China. Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data.

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

PubMed

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

1997-05-01

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

Incident lacunes influence cognitive decline: the LADIS study.

PubMed

Jokinen, H; Gouw, A A; Madureira, S; Ylikoski, R; van Straaten, E C W; van der Flier, W M; Barkhof, F; Scheltens, P; Fazekas, F; Schmidt, R; Verdelho, A; Ferro, J M; Pantoni, L; Inzitari, D; Erkinjuntti, T

2011-05-31

In cerebral small vessel disease, the core MRI findings include white matter lesions (WML) and lacunar infarcts. While the clinical significance of WML is better understood, the contribution of lacunes to the rate of cognitive decline has not been established. This study investigated whether incident lacunes on MRI determine longitudinal cognitive change in elderly subjects with WML. Within the Leukoaraiosis and Disability Study (LADIS), 387 subjects were evaluated with repeated MRI and neuropsychological assessment at baseline and after 3 years. Predictors of change in global cognitive function and specific cognitive domains over time were analyzed with multivariate linear regression. After controlling for demographic factors, baseline cognitive performance, baseline lacunar and WML lesion load, and WML progression, the number of new lacunes was related to subtle decrease in compound scores for executive functions (p = 0.021) and speed and motor control (p = 0.045), but not for memory or global cognitive function. Irrespective of lacunes, WML progression was associated with decrease in executive functions score (p = 0.016). Incident lacunes on MRI parallel a steeper rate of decline in executive functions and psychomotor speed. Accordingly, in addition to WML, lacunes determine longitudinal cognitive impairment in small vessel disease. Although the individual contribution of lacunes on cognition was modest, they cannot be considered benign findings, but indicate a risk of progressive cognitive impairment.

Cerebral microbleeds are associated with cognitive decline and dementia: the Rotterdam Study

PubMed Central

Akoudad, Saloua; Wolters, Frank J.; Viswanathan, Anand; de Bruijn, Renée F.; van der Lugt, Aad; Hofman, Albert; Koudstaal, Peter J.; Ikram, M. Arfan; Vernooij, Meike W.

2018-01-01

Importance Cerebral microbleeds are hypothesized downstream markers of brain damage caused by both vascular and amyloid pathological mechanisms. To date, it remains unclear whether their presence if associated with cognitive deterioration in the general population. Objective To determine whether microbleeds, and more specifically microbleed count and location, associate with an increased risk of cognitive impairment and dementia in the general population. Design Prospective population-based Rotterdam Study. Setting General community. Participants In the Rotterdam Study, we assessed presence, number, and location of microbleeds at baseline (2005–2011) on brain MRI of 4,841 participants aged ≥45 years. Participants underwent neuropsychological testing at two time points on average 5.9 years (SD 0.6) apart, and were followed for incident dementia throughout the study period until 2013. The association of microbleeds with cognitive decline and dementia was studied using multiple linear regression, linear mixed effects modeling, and Cox proportional hazards. Exposure cerebral microbleed presence, location, and number. Main outcomes cognitive decline and dementia. Results Microbleed prevalence was 15.3% (median count 1 [1–88]). Presence of >4 microbleeds associated with cognitive decline. Lobar (with or without cerebellar) microbleeds were associated with decline in executive functions, information processing, and memory function, whereas microbleeds in other brain regions were associated with decline in information processing and motor speed. After mean follow-up of 4.8 years (SD 1.4), 72 people developed dementia, of whom 53 had Alzheimer’s disease. Presence of microbleeds was associated with an increased risk of dementia (age, sex, education adjusted HR 2.02, 95%CI 1.25;3.24), including Alzheimer’s dementia (HR 2.10, 95%CI 1.21;3.64). Conclusions and relevance In the general population, a high microbleed count associated with an increased risk of cognitive deterioration and dementia. Microbleeds thus mark the presence of diffuse vascular and neurodegenerative brain damage. PMID:27271785

The NEIL Memory Research Unit: psychosocial, biological, physiological and lifestyle factors associated with healthy ageing: study protocol.

PubMed

Hannigan, Caoimhe; Coen, Robert F; Lawlor, Brian A; Robertson, Ian H; Brennan, Sabina

2015-01-01

Population ageing is a global phenomenon that has characterised demographic trends during the 20th and 21st century. The rapid growth in the proportion of older adults in the population, and resultant increase in the incidence of age-related cognitive decline, dementia and Alzheimer's disease, brings significant social, economic and healthcare challenges. Decline in cognitive abilities represents the most profound threat to active and healthy ageing. Current evidence suggests that a significant proportion of cases of age-related cognitive decline and dementia may be preventable through the modification of risk factors including education, depressive symptomology, physical activity, social engagement and participation in cognitively stimulating activities. The NEIL Memory Research Unit cohort study was established to investigate factors related to brain health and the maintenance of cognitive function. A cohort of 1000 normally ageing adults aged 50 years and over are being recruited to participate in comprehensive assessments at baseline, and at follow-up once every 2 years. The assessment protocol comprises a comprehensive neuropsychological battery, some basic physical measures, psychosocial scales, questionnaire measures related to a range of health, lifestyle and behavioural factors, and a measure of resting state activity using electroencephalography (EEG). The NEIL Memory Research Unit cohort study will address key questions about brain health and cognitive ageing in the population aged 50+, with a particular emphasis on the influence of potentially modifiable factors on cognitive outcomes. Analyses will be conducted with a focus on factors involved in the maintenance of cognitive function among older adults, and therefore will have the potential to contribute significant knowledge related to key questions within the field of cognitive ageing, and to inform the development of public health interventions aimed at preventing cognitive decline and promoting active and healthy ageing.

Role of physical activity in reducing cognitive decline in older Mexican-American adults.

PubMed

Ottenbacher, Allison J; Snih, Soham Al; Bindawas, Saad M; Markides, Kyriakos S; Graham, James E; Samper-Ternent, Rafael; Raji, Mukaila; Ottenbacher, Kenneth J

2014-09-01

The effect of physical activity on cognitive function in older adults from minority and disadvantaged populations is not well understood. This study examined the longitudinal association between physical activity and cognition in older Mexican Americans. The study methodology included a prospective cohort with longitudinal analysis of data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly. General linear mixed models were used to assess the associations and interactions between physical activity and cognitive function over 14 years. Community-based assessments were performed in participants' homes. Physical activity was recorded for 1,669 older Mexican Americans using the Physical Activity Scale for the Elderly. Cognition was measured using the Mini-Mental State Examination (MMSE) and separated into memory and nonmemory components. A statistically significant positive association was observed between levels of physical activity and cognitive function after adjusting for age, sex, marital status, education, and comorbid health conditions. There was a statistically significant difference in MMSE scores over time between participants in the third (β = 0.11, standard error (SE) = 0.05) and fourth (β = 0.10, SE = 0.2) quartiles of physical activity and those in the first. The protective effect of physical activity on cognitive decline was evident for the memory component of the MMSE but not the nonmemory component after adjusting for covariates. Greater physical activity at baseline was associated with less cognitive decline over 14 years in older Mexican Americans. The reduction in cognitive decline appeared to be related to the memory components of cognitive function. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

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

PubMed

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

2016-01-01

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

[Relationship between cognitive function and physical activities: a longitudinal study among community-dwelling elderly].

PubMed

Konagaya, Yoko; Watanabe, Tomoyuki; Ohta, Toshiki

2012-01-01

The purpose of this study was to evaluate whether physical activities reduce the risk of cognitive decline in community-dwelling elderly. We investigated correlations between cognitive functions at baseline and physical activities, correlations between cognitive functions at baseline and cognitive decline over 4 years, as well as correlations between physical activity at baseline and cognitive decline over 4 years. At baseline, 2,431 community-dwelling elderly completed the cognitive screening by telephone (TICS-J), and answered the questionnaires about physical activities. Of these, 1,040 subjects again completed the TICS-J over 4 years. Physical activities contained moving ability, walking frequency, walking speed, the exercise frequency. At baseline, 870 elderly (age 75.87±4.96 (mean±SD) years, duration of education 11.05±2.41) showed normal cognitive functions and 170 (79.19±6.22, 9.61±2.23) showed cognitive impairment. The total TICS-J score was significantly higher in cognitive normal subjects compared with that of cognitive impaired subjects (36.02±1.89, 30.19±2.25, respectively, p<0.001). Logistic regression analyses showed that moving ability significantly reduced the risk of cognitive impairment in an unadjusted model, and walking speed also reduced the risk of cognitive impairment at baseline even in an adjusted model. Cognitive function at baseline might be a predictor of cognitive function over 4 years. The longitudinal study revealed that walking speed and exercise frequency significantly correlate with maintenance of cognitive function over 4 years. This study provides that physical activities, especially walking speed have significant correlation with cognitive function.

Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial.

PubMed

Brown, Paul D; Pugh, Stephanie; Laack, Nadia N; Wefel, Jeffrey S; Khuntia, Deepak; Meyers, Christina; Choucair, Ali; Fox, Sherry; Suh, John H; Roberge, David; Kavadi, Vivek; Bentzen, Soren M; Mehta, Minesh P; Watkins-Bruner, Deborah

2013-10-01

To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT). Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed. Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62-0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks. Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852.

Cognitive decline, mortality, and organophosphorus exposure in aging Mexican Americans.

PubMed

Paul, Kimberly C; Ling, Chenxiao; Lee, Anne; To, Tu My; Cockburn, Myles; Haan, Mary; Ritz, Beate

2018-01-01

Cognitive impairment is a major health concern among older Mexican Americans, associated with significant morbidity and mortality, and may be influenced by environmental exposures. To investigate whether agricultural based ambient organophosphorus (OP) exposure influences 1) the rate of cognitive decline and mortality and 2) whether these associations are mediated through metabolic or inflammatory biomarkers. In a subset of older Mexican Americans from the Sacramento Area Latino Study on Aging (n = 430), who completed modified mini-mental state exams (3MSE) up to 7 times (1998-2007), we examined the relationship between estimated ambient OP exposures and cognitive decline (linear repeated measures model) and time to dementia or being cognitively impaired but not demented (CIND) and time to mortality (cox proportional hazards model). We then explored metabolic and inflammatory biomarkers as potential mediators of these relationships (additive hazards mediation). OP exposures at residential addresses were estimated with a geographic information system (GIS) based exposure assessment tool. Participants with high OP exposure in the five years prior to baseline experienced faster cognitive decline (β = 0.038, p = 0.02) and higher mortality over follow-up (HR = 1.91, 95% CI = 1.12, 3.26). The direct effect of OP exposure was estimated at 241 (95% CI = 27-455) additional deaths per 100,000 person-years, and the proportion mediated through the metabolic hormone adiponectin was estimated to be 4% 1.5-19.2). No other biomarkers were associated with OP exposure. Our study provides support for the involvement of OP pesticides in cognitive decline and mortality among older Mexican Americans, possibly through biologic pathways involving adiponectin. Copyright © 2017 Elsevier Inc. All rights reserved.

The effects of noncoding aquaporin-4 single-nucleotide polymorphisms on cognition and functional progression of Alzheimer's disease.

PubMed

Burfeind, Kevin G; Murchison, Charles F; Westaway, Shawn K; Simon, Matthew J; Erten-Lyons, Deniz; Kaye, Jeffrey A; Quinn, Joseph F; Iliff, Jeffrey J

2017-09-01

The glymphatic system is a brain-wide perivascular network that facilitates clearance of proteins, including amyloid β, from the brain interstitium through the perivascular exchange of cerebrospinal fluid and interstitial fluid. The astrocytic water channel aquaporin-4 (AQP4) is required for glymphatic system function, and impairment of glymphatic function in the aging brain is associated with altered AQP4 expression and localization. In human cortical tissue, alterations in AQP4 expression and localization are associated with Alzheimer's disease (AD) status and pathology. Although this suggests a potential role for AQP4 in the development or progression of AD, the relationship between of naturally occurring variants in the human AQP4 gene and cognitive function has not yet been evaluated. Using data from several longitudinal aging cohorts, we investigated the association between five AQP4 single-nucleotide polymorphisms (SNPs) and the rate of cognitive decline in participants with a diagnosis of AD. None of the five SNPs were associated with different rates of AD diagnosis, age of dementia onset in trial subjects. No association between AQP4 SNPs with histological measures of AD pathology, including Braak stage or neuritic plaque density was observed. However, AQP4 SNPs were associated with altered rates of cognitive decline after AD diagnosis, with two SNPS (rs9951307 and rs3875089) associated with slower cognitive decline and two (rs3763040 and rs3763043) associated with more rapid cognitive decline after AD diagnosis. These results provide the first evidence that variations in the AQP4 gene, whose gene product AQP4 is vital for glymphatic pathway function, may modulate the progression of cognitive decline in AD.

Normal cognitive decline or dementia?

PubMed

Ebmeier, Klaus P

2010-01-01

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

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.

Cognitive rehabilitation therapies for Alzheimer's disease: A review of methods to improve treatment engagement and self-efficacy

PubMed Central

Choi, Jimmy; Twamley, Elizabeth W.

2013-01-01

Cognitive rehabilitation therapies for Alzheimer’s disease (AD) are becoming more readily available to the geriatric population in an attempt to curb the insidious decline in cognitive and functional performance. However, people with AD may have difficulty adhering to these cognitive treatments due to denial of memory deficits, compromised brain systems, cognitive incapacity for self-awareness, general difficulty following through on daily tasks, lack of motivation, hopelessness, and apathy, all of which may be either due to the illness or be secondary to depression. Cognitive rehabilitation training exercises are also labor intensive and, unfortunately, serve as a repeated reminder about the memory impairments and attendant functional consequences. In order for cognitive rehabilitation methods to be effective, patients must be adequately engaged and motivated to not only begin a rehabilitation program but also to remain involved in the intervention until a therapeutic dosage can be attained. We review approaches to cognitive rehabilitation in AD, neuropsychological as well as psychological obstacles to effective treatment in this population, and methods that target adherence to treatment and may therefore be applicable to cognitive rehabilitation therapies for AD. The goal is to stimulate discussion among researchers and clinicians alike on how treatment effects may be mediated by engagement in treatment, and what can be done to enhance patient adherence for cognitive rehabilitation therapies in order to obtain greater cognitive and functional benefits from the treatment itself. PMID:23400790

Pilates and Physical Education: A Natural Fit

ERIC Educational Resources Information Center

Kloubec, June; Banks, Aaron L.

2004-01-01

In a time period characterized by the continual decline of fitness and physical activity among American youths, Pilates can provide physical educators a unique activity that will improve fitness and stimulate the cognitive domain of today's students. Because the Pilates method of exercise encourages the development of strong and flexible muscles…