Cognitive Activity Is Associated with Cognitive Function over Time in a Diverse Group of Older Adults, Independent of Baseline Biomarkers.

BACKGROUND: More frequent engagement in cognitive activity is associated with better cognitive function in older adults, but the mechanism of action is not fully understood. Debate remains whether increased cognitive activity provides a meaningful benefit for cognitive health or if decreased cognitive activity represents a prodrome of cognitive impairment. Neurological biomarkers provide a novel way to examine this relationship in the context of cognitive aging. METHODS: We examined the association of self-reported cognitive activity, cognitive function, and concentrations of three biomarkers in community-dwelling participants of a longitudinal, population-based study. Cognitive activity was measured at baseline by asking participants to rate the frequency of 7 activities: (1) viewing television, (2) listening to the radio, (3) visiting a museum, (4) playing games, such as cards, checkers, crosswords, or other puzzles or games, (5) reading books, (6) reading magazines, and (7) reading newspapers. Cognitive function was measured with a battery of four tests (Mini-Mental State Examination, Digit Symbol Test, and the immediate and delayed recall of the East Boston Test) averaged into a composite score. At baseline, we evaluated the concentration of total tau (tau), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). RESULTS: The study sample comprised 1,168 older participants, primarily non-Hispanic Blacks (60%) and women (63%). At baseline, they were an average of 77 years old with 12.6 years of education. Mixed-effects models showed that cognitive activity was associated with better cognitive functioning at baseline and over time. These relationships remained after each biomarker was added to the model. Over an average of 6.4 years of follow-up, cognitive activity was associated with cognitive decline in the model with tau (estimate = 0.0123; p value = 0.03) and was mildly attenuated in the models with NfL (estimate = 0.0110; p value = 0.06) and GFAP (estimate = 0.0111; p value = 0.06). Biomarkers did not modify the association between cognitive activity and cognitive function over time. CONCLUSION: The benefits of cognitive activity on cognition appear to be independent of biomarkers: tau, NfL, and GFAP, measured at baseline. More frequent cognitive activity may benefit the cognitive health of older adults with a wide range of potential disease risk and presentations.

Neuroticism, physical activity, and cognitive functioning in a population-based cohort of older adults.

BACKGROUND: Little is known about how physical activity influences the relationship between neuroticism and cognitive function and cognitive decline. METHODS: Data from the Chicago Health and Aging Project (CHAP) was utilized to conduct this study. CHAP is a population-based cohort study of chronic conditions in older adults. Participants completed in-home interviews cycles of three years from 1993-2012. Mixed effects regression models were conducted to test the associations between physical activity, neuroticism, and the interaction between neuroticism and physical activity on outcomes: global cognitive function, global cognitive decline, episodic memory, decline in episodic memory, perceptual speed, and decline in perceptual speed. Stratified mixed effects regression models by physical activity level were conducted to test the associations between neuroticism and global cognitive function and global cognitive decline. RESULTS: A total of 7,685 participants were eligible for this study. Participants were 62% female and 64% African American. We found statistically significant associations for the interaction of high physical activity and neuroticism on baseline global cognitive function (ß = 0.017 (SE = 0.007), p = .010) and on the interaction of neuroticism and high physical activity on baseline episodic memory (ß = 0.020 (SE = .009), p = .021) and on decline in episodic memory over time (ß = -0.003 (SE = .001), p = .039). CONCLUSION: Higher physical activity lessened the association between higher neuroticism and poor cognitive outcomes.

Prevalence of Alzheimer's disease dementia in the 50 US states and 3142 counties: A population estimate using the 2020 bridged-race postcensal from the National Center for Health Statistics.

INTRODUCTION: This study estimates the prevalence and number of people living with Alzheimer's disease (AD) dementia in 50 US states and 3142 counties. METHODS: We used cognitive data from the Chicago Health and Aging Project, a population-based study, and combined it with the National Center for Health Statistics 2020 bridged-race population estimates to determine the prevalence of AD in adults ≥65 years. RESULTS: A higher prevalence of AD was estimated in the east and southeastern regions of the United States, with the highest in Maryland (12.9%), New York (12.7%), and Mississippi (12.5%). US states with the highest number of people with AD were California, Florida, and Texas. Among larger counties, those with the highest prevalence of AD were Miami-Dade County in Florida, Baltimore city in Maryland, and Bronx County in New York. DISCUSSION: The state- and county-specific estimates could help public health officials develop region-specific strategies for caring for people with AD.

The "cognitive clock": A novel indicator of brain health.

INTRODUCTION: We identified a "cognitive clock," a novel indicator of brain health that provides person-specific estimates of cognitive age, and tested the hypothesis that cognitive age is a better predictor of brain health than chronological age in two independent datasets. METHODS: The initial analyses were based on 1057 participants from the Rush Memory and Aging Project and the Religious Orders Study who began without impairment and underwent cognitive assessments up to 24 years. A shape invariant model characterized the latent pattern of cognitive decline, conceptualized here as the "cognitive clock," and yielded person-specific estimates of cognitive age. Survival analyses examined cognitive versus chronological age for predicting Alzheimer's disease dementia, mild cognitive impairment and mortality, and regression analyses examined associations of cognitive versus chronological age with neuropathology and brain atrophy. Finally, we applied the cognitive clock to an independent validation sample of 2592 participants from the Chicago Health and Aging Project, a biracial population-based study, to confirm the predictive utility of cognitive age. RESULTS: The "cognitive clock" showed that cognition remained stable until a cognitive age of about 80, then declined moderately until 90, then declined precipitously. In the initial dataset, cognitive age was a better predictor of dementia, mild cognitive impairment and mortality than chronological age, and was more strongly associated with neuropathology and brain atrophy. Application of the cognitive clock to the independent validation sample provided further support for the utility of cognitive age as a strong prognostic indicator of adverse outcomes. DISCUSSION: Cognitive age is a robust prognostic indicator of adverse health outcomes and may serve as a useful biomarker in aging research.

Long-term community noise exposure in relation to dementia, cognition, and cognitive decline in older adults.

INTRODUCTION: Exposure to noise might influence risk of Alzheimer's disease (AD) dementia. METHODS: Participants of the Chicago Health and Aging Project (≥65 years) underwent triennial cognitive assessments. For the 5 years preceding each assessment, we estimated 5227 participants' residential level of noise from the community using a spatial prediction model, and estimated associations of noise level with prevalent mild cognitive impairment (MCI) and AD, cognitive performance, and rate of cognitive decline. RESULTS: Among these participants, an increment of 10 A-weighted decibels (dBA) in noise corresponded to 36% and 29% higher odds of prevalent MCI (odds ratio [OR] = 1.36; 95% confidence interval [CI], 1.15 to 1.62) and AD (OR = 1.29, 95% CI, 1.08 to 1.55). Noise level was associated with worse global cognitive performance, principally in perceptual speed (-0.09 standard deviation per 10 dBA, 95% CI: -0.16 to -0.03), but not consistently associated with cognitive decline. DISCUSSION: These results join emerging evidence suggesting that noise may influence late-life cognition and risk of dementia.

Cognitive Aging in Black and White Americans: Cognition, Cognitive Decline, and Incidence of Alzheimer Disease Dementia.

BACKGROUND: US-based studies have reported that older blacks perform worse than older whites on cognitive tests and have higher risk of Alzheimer disease dementia (AD). It is unclear whether these findings reflect differences in cognitive decline. METHODS: The Chicago Health and Aging Project followed individuals, 65+ years old (64% black, 36% white), for up to 18 years. Participants underwent triennial cognitive assessments; stratified randomized samples underwent assessments for AD. We compared black and white participants' cognitive performance, cognitive decline rate (N = 7,735), and AD incidence (N = 2,144), adjusting for age and sex. RESULTS: Black participants performed worse than white participants on the cognitive tests; 441 participants developed AD. Black participants' incident AD risk was twice that of whites (RR = 1.9; 95% CI, 1.4, 2.7), with 58 excess cases/1,000 occurring among blacks (95% CI, 28, 88). Among noncarriers of APOE ε4, blacks had 2.3 times the AD risk (95% CI, 1.5, 3.6), but among carriers, race was not associated with risk (RR = 1.1; 95% CI, 0.6, 2.0; Pinteraction = 0.05). However, cognitive decline was not faster among blacks: the black-white difference in 5-year change in global cognitive score was 0.007 standard unit (95% CI, -0.034, 0.047). Years of education accounted for a sizable portion of racial disparities in cognitive level and AD risk, in analyses using a counterfactual approach. CONCLUSIONS: The higher risk of AD among blacks may stem from lower level of cognitive test performance persisting throughout the observation period rather than faster rate of late-life cognitive decline. Disparities in educational attainment may contribute to these performance disparities. See video abstract at, http://links.lww.com/EDE/B299.

Perceived stress and change in cognitive function among adults 65 years and older.

OBJECTIVE: Exposure to acute and chronic stress can affect learning and memory, but most evidence comes from animal studies or clinical observations. Almost no population-based studies have investigated the relation of stress to cognition or changes in cognition over time. We examined whether higher levels of perceived stress were associated with accelerated decline in cognitive function in older blacks and whites from a community-based population sample. METHODS: Participants included 6207 black and white adults (65.7% black, 63.3% women) from the Chicago Health and Aging Project. Two to five in-home assessments were completed over an average of 6.8 years of follow-up and included sociodemographics, health behaviors, psychosocial measures, cognitive function tests, and health history. Perceived stress was measured by a six-item scale, and a composite measure of four tests of cognition was used to determine cognitive function at each assessment. RESULTS: Mixed-effects regression models showed that increasing levels of perceived stress were related to lower initial cognitive scores (B = -0.0379, standard error = 0.0025, p < .001) and a faster rate of cognitive decline (stress × time interaction: B = -0.0015, standard error = 0.0004, p < .001). Results were similar after adjusting for demographic variables, smoking, systolic blood pressure, body mass index, chronic medical conditions, and psychosocial factors and did not vary by race, sex, age, or education. CONCLUSIONS: Increasing levels of stress are independently associated with accelerated declines in cognitive function in black and white adults 65 years and older.

Decline in cognitive function and elder mistreatment: findings from the Chicago Health and Aging Project.

OBJECTIVE: This study aimed to examine the longitudinal association between decline in cognitive function and elder mistreatment (EM). METHODS: Chicago Health and Aging Project (CHAP) is an epidemiologic study conducted in a geographically defined community (N = 6,159). We identified 143 CHAP participants who had longitudinal cognitive data and EM reported to social services agency. The primary predictor was cognitive function, which was assessed using the Mini-Mental State Examination (MMSE), the Symbol Digit Modalities Test (Perceptual Speed), and both 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. Logistic regression models were used to assess the association of cognitive function domains and risk for EM. RESULTS: After adjusting for potential confounders, every one-point decline in global cognitive function (odds ratio [OR]: 1.57 [1.21-2.03]), MMSE (OR: 1.07 [1.03-1.10]), Episodic Memory (OR: 1.46 [1.14-1.86]), and Perceptual Speed (OR: 1.05 [1.02-1.07]) scores were associated with increased risk for EM. Lowest tertiles in global cognitive function (OR: 2.71 [1.49-4.88]), MMSE (OR: 2.02 [1.07-3.80]), Episodic Memory (OR: 2.70 [1.41-5.16]), and Perceptual Speed (OR: 4.41 [2.22-8.76]) scores were associated with increased risk for EM. CONCLUSION: Decline in global cognitive function, MMSE, and Perceptual Speed scores were associated with increased risk for EM.

Perceived stress is associated with subclinical cerebrovascular disease in older adults.

OBJECTIVE: To examine the association of perceived stress with magnetic resonance imaging (MRI) markers of subclinical cerebrovascular disease in an elderly cohort. METHODS: Using a cross-sectional study of a community-based cohort in Chicago, 571 adults (57% women; 58.1% African American; 41.9% non-Hispanic white; mean [SD] age: 79.8 [5.9] years) from the Chicago Health and Aging Project, an epidemiologic study of aging, completed questionnaires on perceived stress, medical history, and demographics as part of an in-home assessment and 5 years later underwent a clinical neurologic examination and MRI of the brain. Outcome measures were volumetric MRI assessments of white matter hyperintensity volume (WMHV), total brain volume (TBV), and cerebral infarction. RESULTS: Stress was measured with six items from the Perceived Stress Scale (PSS); item responses, ranging from never (0) to often (3), were summed to create an overall stress score (mean [SD]: 4.9 [3.3]; range: 0-18). Most participants had some evidence of vascular disease on MRI, with 153 participants (26.8%) having infarctions. In separate linear and logistic regression models adjusted for age, sex, education, race, and time between stress assessment and MRI, each one-point increase in PSS score was associated with significantly lower TBV (coefficient = -0.111, SE = 0.049, t[563] = -2.28, p = 0.023) and 7% greater odds of infarction (odds ratio: 1.07; 95% confidence interval: 1.01, 1.13; Wald χ(2)[1] = 4.90; p = 0.027). PSS scores were unrelated to WMHV. Results were unchanged with further adjustment for smoking, body mass index, physical activity, history of heart disease, stroke, diabetes, hypertension, depressive symptoms, and dementia. CONCLUSIONS: Greater perceived stress was significantly and independently associated with cerebral infarction and lower brain volume assessed 5 years later in this elderly cohort.

Serum total tau, neurofilament light, and glial fibrillary acidic protein are associated with mortality in a population study.

BACKGROUND: Total tau (t-tau), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) are neuronal cytoskeletal biomarkers that may indicate greater risk of poor outcomes in age-related conditions, including mortality. Health disparities experienced by some racial minority subgroups may influence biomarker expression and effects on longevity. We aimed to examine (a) associations of serum t-tau, NfL, and GFAP with overall and cardiovascular mortality and (b) differences in associations by racial background. METHODS: Data came from 1327 older participants from the Chicago Health and Aging Project (CHAP), a longitudinal population-based study. Cox proportional hazards regression models were used to examine associations between concentrations of serum t-tau, NfL, and GFAP biomarker(s) and mortality (overall/cardiovascular mortality based on age at death). Interaction terms were used to examine differences between African-American and European-American participants. Models were adjusted for age, sex, education, the APOE-ε4 allele, body mass index, chronic health conditions, and cognitive and physical functioning. RESULTS: Models showed that fivefold higher concentrations of t-tau (HR = 1.46, 95% CI: 1.27, 1.68), NfL (HR = 2.13, 95% CI: 1.76, 2.58), and GFAP (HR = 1.43, 95% CI: 1.08, 1.90) were separately associated with increased risk of overall mortality, with higher risk in African Americans in t-tau or NfL. In models with all biomarkers, NfL (HR = 2.17, 95% CI: 1.65, 2.85) was associated with risk of overall mortality, with racial differences in t-tau. Higher concentrations of t-tau (HR = 1.32, 95% CI: 1.02, 1.70), NfL (HR = 1.95, 95% CI: 1.40, 2.72), and GFAP (HR = 1.87, 95% CI: 1.18, 2.98) were separately associated with risk of cardiovascular mortality, with racial differences in t-tau, NfL, or GFAP. In combined models, NfL (HR = 1.73, 95% CI: 1.08, 2.78) was associated with cardiovascular mortality. CONCLUSIONS: Serum t-tau, NfL, and GFAP may be early indicators for mortality outcomes among older adults, with racial differences among associations.

Dietary fats and the APOE-e4 risk allele in relation to cognitive decline: a longitudinal investigation in a biracial population sample.

BACKGROUND: APOE-e4 is the strongest genetic risk factor for Alzheimer's disease. However, the influence of APOE-e4 on dietary fat intake and cognition has not been investigated. OBJECTIVE: We aim to examine the association of types of dietary fat and their association to cognitive decline among those with and without the APOE-e4 allele. METHODS: The study included 3,360 Chicago Health and Aging Project (CHAP) participants from four Southside Chicago communities. Global cognition was assessed using a composite score of episodic memory, perceptual speed, MMSE, and diet using a 144-item food frequency questionnaire. APOE genotype was assessed by the hME Sequenom mass-array platform. Longitudinal mixed-effect regression models were used to examine the association of dietary fat and the APOE-e4 allele with cognitive decline, adjusted for age, sex, education, smoking status, and calorie intake. RESULTS: The present study involved 3,360 participants with a mean age of 74 at baseline, 62% African Americans, 63% females, and a mean follow-up of 7.8 years. Among participants with the APOE-e4 risk allele, higher intakes of total and saturated fat (SFA) were associated with a faster decline in global cognition. Among individuals with the APOE-e4 risk allele, a 5% increase in calories from SFA was associated with a 21% faster decline (ß = -0.0197, P = 0.0038). In contrast, a higher intake of long-chain n-3 polyunsaturated fatty acids (LC-n3 PUFA) was associated with a slower rate of decline in global cognition among APOE-e4 carriers. Specifically, for every 1% energy increment from LC-n3 PUFA, the annual rate of global cognitive decline was slower by 0.024 standardized unit (SD 0.010, P = 0.023), about 30.4% slower annual cognitive decline. Higher SFA or other types of dietary fat were not associated with cognitive decline among APOE-e4 non-carriers. CONCLUSIONS: Our study found a significant association between SFA and faster cognitive decline, LC-n3 PUFA and slower cognitive decline among those with the APOE-e4 allele. Our findings suggested that higher intake of SFA might contribute faster cognitive decline in combination with APOE-e4 whereas LC-n3 PUFA might compensate the adverse effects of APOE-e4. The interaction between intakes of different types of dietary fat and APOE-e4 on cognitive function warrants further research.

Psychosocial distress and stroke risk in older adults.

BACKGROUND AND PURPOSE: To investigate the association of psychosocial distress with risk of stroke mortality and incident stroke in older adults. METHODS: Data were from the Chicago Health and Aging Project, a longitudinal population-based study conducted in 3 contiguous neighborhoods on the south side of Chicago, IL. Participants were community-dwelling black and non-Hispanic white adults, aged 65 years and older (n=4120 for stroke mortality; n=2649 for incident stroke). Psychosocial distress was an analytically derived composite measure of depressive symptoms, perceived stress, neuroticism, and life dissatisfaction. Cox proportional hazards models examined the association of distress with stroke mortality and incident stroke over 6 years of follow-up. RESULTS: Stroke deaths (151) and 452 incident strokes were identified. Adjusting for age, race, and sex, the hazard ratio (HR) for each 1-SD increase in distress was 1.47 (95% confidence interval [CI]=1.28-1.70) for stroke mortality and 1.18 (95% CI=1.07-1.30) for incident stroke. Associations were reduced after adjustment for stroke risk factors and remained significant for stroke mortality (HR=1.29; 95% CI=1.10-1.52) but not for incident stroke (HR=1.09; 95% CI=0.98-1.21). Secondary analyses of stroke subtypes showed that distress was strongly related to incident hemorrhagic strokes (HR=1.70; 95% CI=1.28-2.25) but not ischemic strokes (HR=1.02; 95% CI=0.91-1.15) in fully adjusted models. CONCLUSIONS: Increasing levels of psychosocial distress are related to excess risk of both fatal and nonfatal stroke in older black and white adults. Additional research is needed to examine pathways linking psychosocial distress to cerebrovascular disease risk.

Advanced adenoma detection rate is independent of nonadvanced adenoma detection rate.

OBJECTIVES: Adenoma detection rate (ADR) is the accepted rate marker in colonoscopy quality. Advanced adenomas detected at index colonoscopy, while less frequent than nonadvanced adenomas, carry greater risk for future advanced neoplasia during surveillance colonoscopy. This study aimed to determine the effect of the colonoscopist and other factors on advanced ADR and to define the correlation of advanced and nonadvanced ADRs among colonoscopists. METHODS: An observational study of a cohort of patients undergoing first-time colorectal cancer screening colonoscopy was conducted. Patient characteristics and colonoscopic findings were collected. Adenoma, advanced adenoma, and nonadvanced ADRs were calculated. Logistic regression was used to determine variable effects on advanced adenoma detection, and Spearman's rank-order correlation was used to evaluate the relationship between advanced and nonadvanced ADRs. RESULTS: A total of 1,944 patients had first-time screening colonoscopies by 14 colonoscopists. All colonoscopists had adequate (>20%) ADRs. The variability in the colonoscopist ranges of detection was 22.22 to 44.66% for adenomas and 2.00 to 18.18% for advanced adenomas. Logistic regression showed that increasing patient age (odds ratio (OR) 1.16 per 5-year increase, 95% confidence interval (CI) 1.05-1.28, P=0.008) and male gender (OR 2.15, 95% CI 1.51-3.06, P<0.0001) were variables associated with advanced adenoma detection. Colonoscopists were significantly different in detecting advanced adenomas by random effects model (P=0.002), adjusting for patient age, gender, race, year of colonoscopy, gastroenterology fellow participation during colonoscopy, and nonadvanced adenomas. Spearman's rank-order correlation coefficient of -0.42 (95% CI -0.77 to 0.14, P=0.13) was not significant and showed no correlation between advanced and nonadvanced adenoma detection by the group of colonoscopists. CONCLUSIONS: Advanced ADR is variable among colonoscopists with acceptable ADRs. Colonoscopists' advanced ADRs are independent of their nonadvanced ADRs.

Neuroticism, Physical Activity, and Cognitive Functioning in a Population-Based Cohort of Older Adults.

Background: Little is known about how physical activity influences the relationship between neuroticism and cognitive function and cognitive decline. Methods: Data from the Chicago Health and Aging Project (CHAP) was utilized to conduct this study. CHAP is a population-based cohort study of chronic conditions in older adults. Participants completed in-home interviews cycles of three years from 1993-2012. Mixed effects regression models were conducted to test the associations between physical activity, neuroticism, and the interaction between neuroticism and global cognitive function and global cognitive decline. Stratified mixed effects regression models by physical activity level were conducted to test the associations between neuroticism and global cognitive function and global cognitive decline. Results: A total of 7,685 participants were eligible for this study. Participants were 62% female and 64% African American. We found statistically significant associations for the interaction of medium physical and neuroticism (ß = 0.014 (SE = 0.007), p = .037) and the interaction of high physical activity and neuroticism (ß = 0.021 (SE = 0.007), p = .003) on global cognitive function at baseline but not for decline over time. Stratified analysis showed that among participants with high physical activity levels, the association between neuroticism and global cognitive decline was statistically significant (ß=-0.002 (SE = 0.001), p = .023). Conclusion: Increasing physical activity level benefits the cognitive functioning of individuals with high neuroticism. Interventions should incorporate health behavior change approaches which aim to reduce characteristics of neuroticism.

Association of Vitamin E and Cognitive Decline in Older Adults with and without the APOEɛ4 Allele: A Biracial Population-Based Community Study.

BACKGROUND: The association of different types of tocopherols (vitamin E) with cognition might vary by the APOEɛ4 allele status. OBJECTIVE: We examined the association of dietary tocopherols with cognitive decline among participants with and without the APOEɛ4 allele over a median of 12 years. METHODS: 2,193 participants from the Chicago Health and Aging Project were included in the analyses. Global cognition was assessed in three-year cycles. We used a 144-item FFQ to assess dietary intakes of tocopherols and hME Sequenom mass-array platform to assess APOE genotype. We used linear mixed effects models to examine the relationship between tocopherol from food sources and global cognitive decline. RESULTS: The mean baseline age was 74.1 (SD = 5.9) years. Among APOEɛ4 carriers, participants in the highest quintile of intakes of dietary vitamin E had a slower cognitive decline of 0.022 SDU (95% CI: 0.000, 0.043) compared to those in the lowest quintile. A higher intake of dietary α-tocopherol from food sources only was associated with slower cognitive decline in APOEɛ4 carriers (p for trend 0.002) but not among the non-carriers (p for trend 0.937). Among APOEɛ4 carriers, those in the highest quintile of intake of α-tocopherol had a 16.4% slower rate of decline of global cognition compared to those in the lowest quintile (ß= 0.034, 95% CI: 0.013, 0.054). CONCLUSIONS: Individuals consuming high α-tocopherol from food sources had slower cognitive decline among APOEɛ4 carriers. In older adults, different forms of vitamin E might moderate the relationship of APOEɛ4 with global cognition.

Dietary Sugar Intake Associated with a Higher Risk of Dementia in Community-Dwelling Older Adults.

BACKGROUND: We have limited evidence for the relationship of high sugar intake with dementia risk. OBJECTIVE: To determine whether high sugar intake is associated with an increased risk of dementia in community-dwelling older adultsMethods:This study included 789 participants of the Rush Memory and Aging Project (community-based longitudinal cohort study of older adults free of known dementia at enrollment), with annual clinical assessments and complete nutrient data (obtained by validated food frequency questionnaire). Clinical diagnosis of dementia is based on the criteria of the joint working group of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. We used Cox proportional hazard models. RESULTS: 118 participants developed dementia during 7.3±3.8 years of follow-up. Those in the highest quintile of total sugar intake were twice as likely to develop dementia than those in the lowest quintile (Q5 versus Q1:HR=2.10 (95% CI: 1.05, 4.19) when adjusted for age, sex, education, APOEɛ4 allele, calories from sources other than sugar, physical activity, and diet score. Higher percent calories from sugar were positively associated with dementia risk (ß=0.042, p = 0.0009). In exploratory analyses, the highest versus lowest quintile of fructose and sucrose in the diet had higher dementia risk by 2.8 (95% CI: 1.38, 5.67) and 1.93 (95% CI: 1.05, 3.54) times, respectively. CONCLUSIONS: A higher intake of total sugar or total calories from sugar is associated with increased dementia risk in older adults. Among simple sugars, fructose (e.g., sweetened beverages, snacks, packaged desserts) and sucrose (table sugar in juices, desserts, candies, and commercial cereals) are associated with higher dementia risk.

Association of Whole Grain Consumption and Cognitive Decline: An Investigation From a Community-Based Biracial Cohort of Older Adults.

BACKGROUND AND OBJECTIVES: To examine the association of whole grain consumption and longitudinal change in global cognition, perceptual speed, and episodic memory by different race/ethnicity. METHODS: We included 3,326 participants from the Chicago Health and Aging Project who responded to a Food Frequency Questionnaire (FFQ), with 2 or more cognitive assessments. Global cognition was assessed using a composite score of episodic memory, perceptual speed, and the Mini Mental State Examination (MMSE). Diet was assessed by a 144-item FFQ. Linear mixed-effects models were used to estimate the association of intakes of whole grains and cognitive decline. RESULTS: This study involved 3,326 participants (60.1% African American [AA], 63.7% female) with a mean age of 75 years at baseline and a mean follow-up of 6.1 years. Higher consumption of whole grains was associated with a slower rate of global cognitive decline. Among AA participants, those in the highest quintile of whole grain consumption had a slower rate of decline in global cognition (ß = 0.024, 95% CI [0.008-0.039], p = 0.004), perceptual speed (ß = 0.023, 95% CI [0.007-0.040], p = 0.005), and episodic memory (ß = 0.028, 95% CI [0.005-0.050], p = 0.01) compared with those on the lowest quintile. Regarding the amount consumed, in AA participants, those who consumed >3 servings/d vs those who consumed <1 serving/d had a slower rate of decline in global cognition (ß = 0.021, 95% CI [0.005-0.036], p = 0.0093). In White participants, with >3 servings/d, we found a suggestive association of whole grains with global cognitive decline when compared with those who consumed <1 serving/d (ß = 0.025, 95% CI [-0.003 to 0.053], p = 0.08). DISCUSSION: Among AA participants, individuals with higher consumption of whole grains and more frequent consumption of whole grain had slower decline in global cognition, perceptual speed, and episodic memory. We did not see a similar trend in White adults.

Accounting for bias due to selective attrition: the example of smoking and cognitive decline.

BACKGROUND: Selective attrition may introduce bias into analyses of the determinants of cognitive decline. This is a concern especially for risk factors, such as smoking, that strongly influence mortality and dropout. Using inverse-probability-of-attrition weights, we examined the influence of selective attrition on the estimated association of current smoking (vs. never smoking) with cognitive decline. METHODS: Chicago Health and Aging Project participants (n = 3713), aged 65-109 years, who were current smokers or never- smokers, underwent cognitive assessments up to 5 times at 3-year interval. We used pooled logistic regression to fit predictive models of attrition due to death or study dropout across the follow-up waves. With these models, we computed inverse-probability-of-attrition weights for each observation. We fit unweighted and weighted, multivariable-adjusted generalized-estimating-equation models, contrasting rates of change in cognitive scores in current versus never-smokers. Estimates are expressed as rates of change in z score per decade. RESULTS: During the 12 years of follow-up, smokers had higher mortality than never-smokers (hazard ratio = 1.93 [95% confidence interval = 1.67 to 2.23]). Higher previous cognitive score was associated with increased likelihood of survival and continued participation. In unweighted analyses, current smokers' cognitive scores declined 0.11 standard units per decade more rapidly than never-smokers' (95% CI = -0.20 to -0.02). Weighting to account for attrition yielded estimates that were 56% to 86% larger, with smokers' estimated 10-year rate of decline up to 0.20 units faster than never-smokers' (95% CI = -0.36 to -0.04). CONCLUSIONS: Estimates of smoking's effects on cognitive decline may be underestimated due to differential attrition. Analyses that weight for the inverse probability of attrition help compensate for this attrition.

Characteristics of MR infarcts associated with dementia and cognitive function in the elderly.

BACKGROUND: Little information exists on the simultaneous effects of magnetic resonance (MR) infarct characteristics, that may increase the likelihood of dementia or lower cognitive function in community populations. METHODS: Participants were 580 community-dwelling individuals from the Chicago Health and Aging Project (CHAP) who underwent detailed clinical evaluation and MR imaging. The association of MR infarct characteristics (region, number, side, and size) with dementia, global cognition and cognition in five separate cognitive domains was examined using logistic and linear regression analyses controlling for age, sex, race, education and time elapsed between clinical evaluation and MRI. RESULTS: A total of 156 persons had MR infarcts: 108 with 1 infarct and 48 with multiple. Poorer cognitive function and, in particular, slower perceptual speed, were associated with infarcts characterized as cortical, multiple, bilateral or large (all p < 0.05). Multiple infarcts in multiple regions were associated with poor performance in all cognitive domains except visuospatial ability (p < 0.05). Race did not modify any of these associations. CONCLUSIONS: In this community sample, cortical and multiple infarcts in multiple regions were associated with dementia; cortical, multiple, large and bilateral infarcts were associated with lower cognition, particularly lower memory function and perceptual speed. These effects were not modified by race.

Association of Neurofilament Light With the Development and Severity of Parkinson Disease.

BACKGROUND AND OBJECTIVES: Blood biomarkers may allow earlier identification of Parkinson disease (PD), parkinsonism, and poor PD-related outcomes, such as physical functioning. Neurofilament light (NfL), a neuronal cytoplasmic protein, is a biomarker of neurodegeneration measurable in biofluids. Our objective was to examine the association of serum NfL at baseline with clinically diagnosed PD, parkinsonian signs, and physical functioning change over 16 years in a population-based sample of older adults. METHODS: Data came from 1,327 older participants from the Chicago Health and Aging Project, a longitudinal population-based study. Clinical evaluations included assessing parkinsonian signs in 4 domains-bradykinesia, parkinsonian gait, rigidity, and tremors-using a structured version of the Unified Parkinson's Disease Rating Scale. Board-certified neurologists diagnosed PD. Physical functioning was assessed using chair stands, tandem walk, and timed walk. An ultrasensitive immunoassay was used to measure the concentration of NfL in blood. RESULTS: Of the 1,254 participants examined for clinical PD, 77 (6.1%) developed clinical PD and parkinsonian signs were on average 9.5 (range 0-66.0). After adjusting for demographic characteristics, APOE ε4 allele, and global cognition, a 2-fold higher concentration of serum NfL was associated with incident clinical PD (odds ratio [OR] 2.54, 95% CI 1.70, 3.81) and global parkinsonian signs (OR 2.44, 95% CI 1.94, 2.94). This association was significant >5 years before diagnosis. Compared with participants with levels below 18.5 pg/mL of serum NfL at baseline, participants with levels between 18.5 and 25.4 pg/mL, between 25.4 and 37.3 pg/mL, and above 37.3 pg/mL had a higher OR of clinical PD at all time intervals from the time of diagnosis to >5 years before diagnosis. A higher concentration of serum NfL was associated with a faster rate of physical functioning decline. In participants with 2-fold higher concentrations of serum NfL, the annual rate of decline in physical functioning increased by 0.15 units (95% CI 0.21, 0.08). DICUSSION: Serum NfL was associated with incident clinical PD, parkinsonian signs, and physical functioning decline in a population-based sample. Our findings suggest that NfL may serve as a potential biomarker for neurodegeneration, including PD outcomes. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that serum NfL levels are associated with incident PD, parkinsonian signs, and physical functioning decline.