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Introduction: Low vitamin D intake and low vitamin D circulating levels have been associated with increased risk for dementia. We aimed to examine the association between vitamin D intake and dementia in a multiethnic cohort., Methods: A longitudinal study of 1759 non-demented older (≥65 years) participants of the Washington Heights-Inwood Columbia Aging Project with follow-up visits and completed a food frequency questionnaire. Dementia was diagnosed by consensus using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Cox hazard regression was performed., Results: During a mean follow-up of 5.8 years, 329 participants developed dementia. Participants with the highest tertile of vitamin D intake from food sources had decreased risk (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.54-0.97, P = .030) for dementia compared with those with the lowest tertile, adjusting for age, sex, race/ethnicity, education, apolipoprotein E (APOE)-ε4, physical activity, Mediterranean diet (MeDI) score, income, depression, hypertension, diabetes, cardiovascular disease, and smoking., Discussion: Higher vitamin D intake is associated with decreased risk of dementia in a multiethnic cohort., (© 2020 the Alzheimer's Association.)

Objective: To evaluate the association between long-term exposure to ambient air pollution and cognitive decline in older adults residing in an urban area., Methods: Data for this study were obtained from 2 prospective cohorts of residents in the northern Manhattan area of New York City: the Washington Heights-Inwood Community Aging Project (WHICAP) and the Northern Manhattan Study (NOMAS). Participants of both cohorts received in-depth neuropsychological testing at enrollment and during follow-up. In each cohort, we used inverse probability weighted linear mixed models to evaluate the cross-sectional and longitudinal associations between markers of average residential ambient air pollution (nitrogen dioxide [NO 2 ], fine particulate matter [PM 2.5 ], and respirable particulate matter [PM 10 ]) levels in the year prior to enrollment and measures of global and domain-specific cognition, adjusting for sociodemographic factors, temporal trends, and censoring., Results: Among 5,330 participants in WHICAP, an increase in NO 2 was associated with a 0.22 SD lower global cognitive score at enrollment (95% confidence interval [CI], -0.30, -0.14) and 0.06 SD (95% CI, -0.08, -0.04) more rapid decline in cognitive scores between visits. Results were similar for PM 2.5 and PM 10 and across functional cognitive domains. We found no evidence of an association between pollution and cognitive function in NOMAS., Conclusion: WHICAP participants living in areas with higher levels of ambient air pollutants have lower cognitive scores at enrollment and more rapid rates of cognitive decline over time. In NOMAS, a smaller cohort with fewer repeat measurements, we found no statistically significant associations. These results add to the evidence regarding the adverse effect of air pollution on cognitive aging and brain health., (© 2020 American Academy of Neurology.)

Introduction: The present study sought to determine whether cognitive trajectories differ between men and women across and within racial/ethnic groups., Methods: Participants were 5258 non-Hispanic White (NHW), Black, and Hispanic men and women in the Washington/Hamilton Heights-Inwood Columbia Aging Project who were administered neuropsychological tests of memory, language, and visuospatial abilities at 18- to 24-month intervals for up to 25 years. Multiple-group latent growth curve modeling examined trajectories across sex/gender by race/ethnicity., Results: After adjusting for age and education, the largest baseline differences were between NHW men and Hispanic women on visuospatial and language, and between NHW women and Black men on memory. Memory and visuospatial decline was steeper for Black women compared with Hispanic men and NHW women, respectively., Discussion: This study takes an important first step in understanding interactions between race/ethnicity and sex/gender on cognitive trajectories by demonstrating variability in sex/gender differences across race/ethnicity., (Copyright © 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Introduction: The associations between self-reported current and past leisure time physical activity (LTPA) and Alzheimer's disease (AD) incidence were determined using data from the multiethnic Washington/Hamilton Heights-Inwood Columbia Aging Project (WHICAP) study., Methods: The metabolic equivalent of LTPA energy expenditure was calculated for self-reported current and past LTPA for 1345 older adults. A Cox proportional hazard model was conducted to estimate the association between LTPA (low, middle, and high) and incident AD risk., Results: Comparing high to low level, current and past LTPA were both associated with reduced AD risk, with hazard ratio (95% confidence interval) = 0.39 (0.20-0.75) and 0.37 (0.18-0.75), respectively. Compared with "always low," "increased" and "always high" LTPA throughout life were associated with reduced AD risk, with hazard ratio (95% confidence interval) = 0.60 (0.36-0.99) and 0.28 (0.08-0.94), respectively. Light- and moderate-intensity LTPA were associated with lower AD risk., Discussion: LTPA both throughout life and later in life are associated with lower risk of AD., (Copyright © 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Objectives: Low educational attainment is a risk factor for more rapid cognitive aging, but there is substantial variability in cognitive trajectories within educational groups. The aim of this study was to determine the factors that confer resilience to memory decline within educational strata., Methods: We selected 2573 initially nondemented White, African American, and Hispanic participants from the longitudinal community-based Washington Heights/Inwood Columbia Aging Project who had at least two visits. We estimated initial memory (intercept) and the rate of memory decline (slope) using up to five occasions of measurement. We classified groups according to the educational attainment groups as low (≤5 years), medium (6-11 years), and high (≥12 years). We used a multiple-group latent growth model to identify the baseline predictors of initial memory performance and rate of memory decline across groups. The model specification considered the influence of demographic, socioeconomic, biomedical, and cognitive variables on the intercept and the slope of memory trajectory., Results: Our results indicated that the three educational groups do not benefit from the same factors. When allowed to differ across groups, the predictors were related to cognitive outcomes in the highly educated group, but we found no unique predictor of cognition for the low educated older adults., Conclusions: These findings highlight that memory-protective factors may differ across older adults with distinct educational backgrounds, and the need to evaluate a broader range of potential resilience factors for older adults with few years of school.

Background: This study aimed to examine the association between self-reported sleep disordered breathing (SDB) ("awaken short of breath or with a headache") and mortality in a large and ethnically diverse group of community-dwelling elderly people., Methods: A total of 1288 participants, 65 years and older, were examined longitudinally. Sleep problems were estimated using the Medical Outcomes Study Sleep Scale examining sleep disturbance, snoring, awaken short of breath or with a headache, sleep adequacy, and sleep somnolence. Cox regression analysis was used to examine the association between sleep problems and mortality. Age, gender, education, ethnicity, and body mass index were included as covariates. In further analyses we included hypertension, diabetes, heart disease, and stroke as additional covariates., Results: The participants were followed for up to 6 years (mean = 2.9, standard deviation = 1.1), and 239 (18.6%) participants died during the follow-up. In unadjusted models, SDB at the initial visit was associated with mortality (hazard ratio [HR] = 1.37; 95% confidence interval [CI] 1.21-1.55; P < .0001). After adjusting for all the covariates, the relationship between SDB and mortality remained significant (HR = 1.48; 95% CI 1.29-1.70; P < .0001). Participants with Caribbean-Hispanic ancestry have higher risk for mortality., Conclusions: Our results suggest that SDB is a risk factor for mortality in a large and ethnically diverse group of older adults, independent of demographic and clinical factors. Further research is needed to examine the underlying mechanisms of this association., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The trajectory, or slope, of cognitive decline may provide differentiation of older adults with and without incipient neurodegenerative disease. Cognitive aging phenotypes based on memory trajectories could be used as outcome measures for clinical trials or observational studies of risk and protective factors for dementia. This study used growth mixture modeling (GMM) to identify trajectory groups based on age- and education-corrected composite memory scores derived from immediate, delayed and recognition trials of the Selective Reminding Test. Participants included 2593 participants initially without dementia (mean age at entry = 76) in a community-based study of aging and dementia in northern Manhattan. Trajectory groups were compared on consensus diagnoses of dementia and structural MRI measures of hippocampal volume and entorhinal cortical thickness. Heterogeneity in memory trajectories allowed us to identify four groups: Stable-High (43.5 %), Stable-Low (17.1 %), Decliner (26.8 %), and Rapid Decliner (12.5 %). Decliners had more brain atrophy and higher rates of conversion to dementia. This study highlights the heterogeneity in cognitive aging and provides evidence that most elderly maintain memory function as they age. Associations with dementia and imaging measures validate subgroups of older adults identified with GMM based on their memory trajectories. Future research should use these memory trajectory phenotypes to determine whether dementia risk and protective factors differ for individuals following different memory trajectories.

Background: Structural magnetic resonance imaging (MRI) provides key biomarkers to predict onset and track progression of Alzheimer's disease (AD). However, most published reports of relationships between MRI variables and cognition in older adults include racially, ethnically, and socioeconomically homogenous samples. Racial/ethnic differences in MRI variables and cognitive performance, as well as health, socioeconomic status and psychological factors, raise the possibility that brain-behavior relationships may be stronger or weaker in different groups. The current study tested whether MRI predictors of cognition differ in African Americans and Hispanics, compared with non-Hispanic Whites., Methods: Participants were 638 non-demented older adults (29% non-Hispanic White, 36% African American, 35% Hispanic) in the Washington Heights-Inwood Columbia Aging Project. Composite scores of memory, language, speed/executive functioning, and visuospatial function were derived from a neuropsychological battery. Hippocampal volume, regional cortical thickness, infarcts, and white matter hyperintensity (WMH) volumes were quantified with FreeSurfer and in-house developed procedures. Multiple-group regression analysis, in which each cognitive composite score was regressed onto MRI variables, demographics, and cardiovascular health, tested which paths differed across groups., Results: Larger WMH volume was associated with worse language and speed/executive functioning among African Americans, but not among non-Hispanic Whites. Larger hippocampal volume was more strongly associated with better memory among non-Hispanic Whites compared with Hispanics. Cortical thickness and infarcts were similarly associated with cognition across groups., Conclusion: The main finding of this study was that certain MRI predictors of cognition differed across racial/ethnic groups. These results highlight the critical need for more diverse samples in the study of cognitive aging, as the type and relation of neurobiological substrates of cognitive functioning may be different for different groups.

The evidence relating obesity measured with body mass index (BMI) in the elderly to late-onset Alzheimer disease (LOAD) is conflicting. Central obesity in middle age is related to a higher risk of LOAD, but data in the elderly are lacking. We explored whether measures of central obesity, waist circumference, and waist to hip ratio (WHR) were better predictors of LOAD compared with BMI in the elderly. Participants were 1459 persons aged 65 years and older without dementia at baseline, with follow-up, and with anthropometric data from a longitudinal study of aging in New York City. Proportional hazards regression was used for multivariable analyses relating BMI, waist circumference, and WHR to LOAD. There were 145 cases of Alzheimer disease in 5734 person-years of follow-up. Only WHR was related to higher LOAD risk (hazard ratio of the fourth quartile compared with the first=2.5; 95% confidence interval=1.3, 4.7) after adjustment for age, sex, education, ethnic group, Apolipoprotein E-ε4, type 2 diabetes, hypertension, non-high-density lipoprotein-cholesterol, high-density lipoprotein cholesterol, and stroke. Our results support the notion that central obesity is related to a higher risk of LOAD.

Objective: To develop a simple summary risk score for the prediction of Alzheimer disease in elderly persons based on their vascular risk profiles., Design: A longitudinal, community-based study., Setting: New York, New York. Patients One thousand fifty-one Medicare recipients aged 65 years or older and residing in New York who were free of dementia or cognitive impairment at baseline., Main Outcome Measures: We separately explored the associations of several vascular risk factors with late-onset Alzheimer disease (LOAD) using Cox proportional hazards models to identify factors that would contribute to the risk score. Then we estimated the score values of each factor based on their beta coefficients and created the LOAD vascular risk score by summing these individual scores., Results: Risk factors contributing to the risk score were age, sex, education, ethnicity, APOE epsilon4 genotype, history of diabetes, hypertension or smoking, high-density lipoprotein levels, and waist to hip ratio. The resulting risk score predicted dementia well. According to the vascular risk score quintiles, the risk to develop probable LOAD was 1.0 for persons with a score of 0 to 14 and increased 3.7-fold for persons with a score of 15 to 18, 3.6-fold for persons with a score of 19 to 22, 12.6-fold for persons with a score of 23 to 28, and 20.5-fold for persons with a score higher than 28., Conclusions: While additional studies in other populations are needed to validate and further develop the score, our study suggests that this vascular risk score could be a valuable tool to identify elderly individuals who might be at risk of LOAD. This risk score could be used to identify persons at risk of LOAD, but can also be used to adjust for confounders in epidemiologic studies.

Background: The importance of subclinical cerebrovascular disease in the elderly is increasingly recognized, but its determinants have not been fully explicated. Elevated blood pressure (BP) and fluctuation in BP may lead to cerebrovascular disease through ischemic changes and compromised cerebral autoregulation., Objective: To determine the association of BP and long-term fluctuation in BP with cerebrovascular disease., Design: A community-based epidemiological study of older adults from northern Manhattan., Setting: The Washington Heights-Inwood Columbia Aging Project., Participants: A total of 686 nondemented older adults who had BP measurements during 3 study visits at 24-month intervals and underwent structural magnetic resonance imaging (corresponding temporally with the third assessment). We derived the mean (SD) of the mean BP for each participant during the 3 intervals and divided the participants into 4 groups defined as below or above the group median (96.48 mm Hg) and further subdivided them as below or above the median SD (7.21 mm Hg). This scheme yielded 4 groups representing the full range of BPs and fluctuations in BP., Main Outcome Measures: Differences in white matter hyperintensity (WMH) volume and presence of brain infarctions across groups., Results: White matter hyperintensity volume increased across the 4 groups in a linear manner, with the lowest WMH volume in the lowest mean/lowest SD group and the highest WMH volume in the highest mean/highest SD group (F(3,610) = 3.52, P = .02). Frequency of infarction also increased monotonically across groups (from 22% to 41%, P for trend = .004)., Conclusions: Compared with individuals with low BP and low fluctuations in BP, the risk of cerebrovascular disease increased with higher BP and BP fluctuations. Given that cerebrovascular disease is associated with disability, these findings suggest that interventions should focus on long-term fluctuating BP and elevated BP.

There is some evidence that mild parkinsonian signs (MPSs) are associated with increased risk of dementia, suggesting that MPS could be an early biomarker for dementia. Our aims, in a new cohort, were to determine whether (1) baseline MPS are a predictor of incident dementia and (2) there is an interaction between MPS and other baseline risk factors for dementia (i.e., the presence of both together greatly elevates the risk of dementia) was the objective. In a prospective, longitudinal study of community-dwelling elders in northern Manhattan, NY, Parkinsonian signs were rated with an abbreviated Unified Parkinson's Disease Rating Scale. Risk of incident dementia was assessed using Cox proportional hazards models. There were 1,851 participants (mean follow-up = 3.7 years). Participants with baseline MPS were twice as likely to develop dementia as participants without MPS: 16.3% versus 7.7%, unadjusted hazards ratio (HR) = 2.24 (P< 0.001), adjusted HR = 1.98 (P < 0.001). MPS were divided into three subtypes: adjusted HR(axial dysfunction) = 2.45 (P < 0.001), adjusted HR(tremor) = 2.38 (P = 0.006), and adjusted HR(rigidity) = 1.16 (P = 0.58). When MPS were treated as a continuous variable, the adjusted HR = 1.15 (P = 0.001). There were no interactions between MPS and other baseline risk factors for dementia, including gender, education, race, family history of dementia, stroke, and apolipoprotein E-e4. Baseline MPS seems to be a predictor of incident dementia. These motor signs might, therefore, serve as a useful biomarker for emerging dementia., ((c) 2010 Movement Disorder Society.)

Background: Mild cognitive deficits, mainly in frontal-executive function and memory, have been reported in patients with essential tremor (ET). Furthermore, an association between ET and dementia has been reported in a single population-based study in Spain. This has not been confirmed elsewhere., Objective: To determine whether baseline ET is associated with prevalent and incident dementia in an ethnically diverse, community-based sample of elders., Methods: Community-dwelling elders in northern Manhattan were enrolled in a prospective cohort study. Baseline ET diagnoses were assigned from handwriting samples. Dementia was diagnosed at baseline and follow-up using DSM-III-R criteria., Results: In cross-sectional analyses, 31/124 (25.0%) ET cases had prevalent dementia vs 198/2,161 (9.2%) controls (odds ratio [OR](unadjusted) = 3.31, 95% confidence interval [CI] = 2.15-5.09, p < 0.001; OR(adjusted) = 1.84, 95% CI = 1.13-2.98, p = 0.01). In prospective analyses, 17/93 (18.3%) ET cases vs 171/1,963 (8.7%) controls developed incident dementia (hazard ratio [HR](unadjusted) = 2.78, 95% CI = 1.69-4.57, p < 0.001; HR(adjusted) = 1.64, 95% CI = 0.99-2.72, p = 0.055)., Conclusions: In a second population-based study of elders, essential tremor (ET) was associated with both increased odds of prevalent dementia and increased risk of incident dementia. Presence of dementia, therefore, appeared to be greater than that expected for age (i.e., a disease-associated feature). Rather than attributing cognitive complaints in patients with ET to old age, assessment and possible treatment of dementia should be routinely incorporated into the treatment plan.

Context: Both higher adherence to a Mediterranean-type diet and more physical activity have been independently associated with lower Alzheimer disease (AD) risk but their combined association has not been investigated., Objective: To investigate the combined association of diet and physical activity with AD risk., Design, Setting, and Patients: Prospective cohort study of 2 cohorts comprising 1880 community-dwelling elders without dementia living in New York, New York, with both diet and physical activity information available. Standardized neurological and neuropsychological measures were administered approximately every 1.5 years from 1992 through 2006. Adherence to a Mediterranean-type diet (scale of 0-9; trichotomized into low, middle, or high; and dichotomized into low or high) and physical activity (sum of weekly participation in various physical activities, weighted by the type of physical activity [light, moderate, vigorous]; trichotomized into no physical activity, some, or much; and dichotomized into low or high), separately and combined, were the main predictors in Cox models. Models were adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, body mass index, smoking status, depression, leisure activities, a comorbidity index, and baseline Clinical Dementia Rating score., Main Outcome Measure: Time to incident AD., Results: A total of 282 incident AD cases occurred during a mean (SD) of 5.4 (3.3) years of follow-up. When considered simultaneously, both Mediterranean-type diet adherence (compared with low diet score, hazard ratio [HR] for middle diet score was 0.98 [95% confidence interval {CI}, 0.72-1.33]; the HR for high diet score was 0.60 [95% CI, 0.42-0.87]; P = .008 for trend) and physical activity (compared with no physical activity, the HR for some physical activity was 0.75 [95% CI, 0.54-1.04]; the HR for much physical activity was 0.67 [95% CI, 0.47-0.95]; P = .03 for trend) were associated with lower AD risk. Compared with individuals neither adhering to the diet nor participating in physical activity (low diet score and no physical activity; absolute AD risk of 19%), those both adhering to the diet and participating in physical activity (high diet score and high physical activity) had a lower risk of AD (absolute risk, 12%; HR, 0.65 [95% CI, 0.44-0.96]; P = .03 for trend)., Conclusion: In this study, both higher Mediterranean-type diet adherence and higher physical activity were independently associated with reduced risk for AD.

Background: Aging is accompanied by a decrease in brain volume and by an increase in cerebrovascular disease., Objective: To examine the effects of age, sex, race/ethnicity, and vascular disease history on measures of brain morphology, including relative brain volume, ventricular volume, hippocampus and entorhinal cortex volumes, and white matter hyperintensity (WMH) burden, in a large community-based cohort of racially/ethnically diverse older adults without dementia., Design: The associations of age, sex, race/ethnicity, and self-reported vascular disease history with brain morphology were examined in a cross-sectional study using multiple linear regression analyses. Sex x race/ethnicity interactions were also considered., Setting: The Washington Heights-Inwood Columbia Aging Project, a community-based epidemiological study of older adults from 3 racial/ethnic groups (white, Hispanic, and African American) from northern Manhattan., Participants: Beginning in 2003, high-resolution quantitative magnetic resonance (MR) images were acquired in 769 participants without dementia., Main Outcome Measures: Relative brain volume (total brain volume/intracranial volume), ventricular volume, and hippocampus and entorhinal cortex volumes were derived manually on high-resolution MR images. White matter hyperintensities were quantified semiautomatically on fluid-attenuated inversion recovery-T2-weighted MR images., Results: Older age was associated with decreased relative brain volume and with increased ventricular and WMH volumes. Hispanic and African American participants had larger relative brain volumes and more severe WMH burden than white participants, but the associations of these variables with age were similar across racial/ethnic groups. Compared with men, women had larger relative brain volumes. Vascular disease was associated with smaller relative brain volume and with higher WMH burden, particularly among African Americans., Conclusions: Older age and vascular disease, particularly among African Americans, are associated with increased brain atrophy and WMH burden. African American and Hispanic subjects have larger relative brain volumes and more WMH than white subjects. Racial/ethnic group differences in WMH severity seem to be partially attributable to differences in vascular disease. Future work will focus on the determinants and cognitive correlates of these differences.

Objectives: to investigate the relation of plasma lipids to all-cause mortality in a multi-ethnic cohort of non-demented elderly., Setting: community-based sample of Medicare recipients, 65 years and older, residing in Northern Manhattan., Participants: about two thousand five hundred and fifty-six non-demented elderly, 65-103 years. Among participants, 66.1% were women, 27.6% were White/non-Hispanic, 31.2% were African-American and 41.2% were Hispanic., Methods: a standardised assessment, including functional ability, medical history, physical and neurological examination and a neuropsychological battery was conducted. Vital status was ascertained through the National Death Index (NDI). We used survival analyses stratified by race and ethnicity to examine the relation of plasma lipids to subsequent all-cause mortality., Results: hispanics had the best overall survival, followed by African-Americans and Whites. Whites and African-Americans in the lowest quartiles of total cholesterol, non-HDL cholesterol and low-density lipoprotein cholesterol (LDL cholesterol) were approximately twice as likely to die as those in the highest quartile (White HR: 2.2, for lowest total cholesterol quartile; HR: 2.3, for lowest non-HDL cholesterol quartile; and HR: 1.8, for lowest LDL cholesterol quartile. African-American HR: 1.9, for lowest total cholesterol, HR: 2.0, for lowest non-HDL cholesterol and HR: 1.9, for lowest LDL cholesterol). In contrast, plasma lipid levels were not related to mortality risk among Hispanics., Conclusions: hispanic ethnicity modifies the associations between lipid levels and all-cause mortality in the elderly.

Background/aims: The metabolic syndrome (MeSy) may be related to Alzheimer's disease (AD). Our aims were to investigate the association of the MeSy with incident dementia in a multiethnic elderly cohort in the United States., Methods: We conducted cross-sectional and prospective analyses in 2,476 men and women aged 65 years and older and with data available on the MeSy and dementia diagnosis in Northern New York City. MeSy was defined by the National Cholesterol Education Program Adult Treatment Program III and the European Group for the Study of Insulin Resistance criteria. Dementia was diagnosed using standard criteria., Results: No association was found between MeSy and prevalent dementia. After 4.4 years of follow-up, 236 individuals of the 1,833 without prevalent dementia developed dementia. MeSy was not associated with incident dementia. Of the components of the MeSy, diabetes and hyperinsulinemia were associated with an increased risk of incident AD [hazard ratio 1.4 (95% CI 1.0-2.1), and hazard ratio 1.4 (95% CI 0.9-2.7), respectively] and dementia associated with stroke [hazard ratio 1.9 (95% CI 1.1-3.1), and hazard ratio 2.3 (95% CI 1.1-4.7), respectively]., Conclusions: The MeSy was not associated with an increased dementia risk in a multiethnic elderly cohort, but diabetes and hyperinsulinemia were. In the elderly, examining diabetes and hyperinsulinemia separately may be preferable to using the MeSy as a risk factor., (2007 S. Karger AG, Basel)

Objective: Reduced telomere length may be a marker of biological aging. We hypothesized that telomere length might thus relate to increased risk for dementia and mortality., Methods: This nested case-control study used stored leukocyte DNA from 257 individuals (mean age, 81.4 +/- 7.9 years; 64.6% female; 44.7% Hispanic, 33.5% non-Hispanic black, and 21.8% non-Hispanic white). Our assay used real-time polymerase chain reaction, with two separate reactions amplifying telomere sequence and reference single copy gene (ribosomal-protein-P0), providing a calculated telomere-to-single copy gene (T/S) ratio., Results: Mean telomere length was shorter among subjects dying during follow-up than in those surviving (0.453 +/- 0.211 vs 0.525 +/- 0.226 [+/- standard deviation]; p < 0.009). It was also shorter in those with Alzheimer's disease compared with control subjects (0.458 +/- 0.207 vs 0.516 +/- 0.229; p < 0.03). For participants with Alzheimer's disease, compared with those with the longest telomeres, the mortality odds ratio (OR) was 4.8 (95% confidence interval [CI], 1.7-13.8) in those with intermediate-length telomeres and 7.3 (95% CI, 2.4-22.0) in those with the shortest telomeres. The presence of an epsilon4 allele also increased the mortality OR, with an OR of 5.8 (95% CI, 1.3-26.4) for intermediate-length telomeres and an OR of 9.0 (95% CI, 1.9-41) for the shortest telomeres., Interpretation: Our findings suggest that leukocyte telomere length is related to both dementia and mortality and may be a marker of biological aging.

Researchers on genetic and environmental influences on risk for Alzheimer's disease must be prepared for the growing ethnic and racial diversity of our participants. Within the investigation, years of education has typically served as a proxy for cognitive reserve, which may be one factor in influencing risk of cognitive decline among aging people. However, among ethnic minorities, years of education is a poor reflection of the value of educational experience and native ability. This study was conducted among 1002 ethnically diverse English-speaking residents of Northern Manhattan who were cognitively and functionally normal at a baseline evaluation. We found that literacy level was a better predictor of decline in memory, executive function, and language skills than was years of education. The results of this study suggest that in an ethnically diverse cohort, literacy level should be considered as a mediator of the interactions of biological and environmental factors on cognitive decline.

Objectives: To investigate the relationship between plasma lipids and risk of death from all causes in nondemented elderly., Design: Prospective cohort study., Setting: Community-based sample of Medicare recipients, aged 65 years and older, residing in northern Manhattan., Participants: Two thousand two hundred seventy-seven nondemented elderly, aged 65 to 98; 672 (29.5%) white/non-Hispanic, 699 (30.7%) black/non-Hispanic, 876 (38.5%) Hispanic, and 30 (1.3%) other., Measurements: Anthropometric measures: fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and non-HDL-C, body mass index, and apolipoprotein E (APOE) genotype. clinical measures: neuropsychological, neurological, medical, and functional assessments; medical history of diabetes mellitus, heart disease, hypertension, stroke, and treatment with lipid-lowering drugs. Vital status measure: National Death Index date of death. Survival methods were used to examine the relationship between plasma lipids and subsequent mortality in younger and older nondemented elderly, adjusting for potential confounders., Results: Nondemented elderly with levels of total cholesterol, non-HDL-C, and LDL-C in the lowest quartile were approximately twice as likely to die as those in the highest quartile (rate ratio (RR)=1.8, 95% confidence interval (CI)=1.3-2.4). These results did not vary when analyses were adjusted for body mass index, APOE genotype, diabetes mellitus, heart disease, hypertension, stroke, diagnosis of cancer, current smoking status, or demographic variables. The association between lipid levels and risk of death was attenuated when subjects with less than 1 year of follow-up were excluded (RR=1.4, 95% CI=1.0-2.1). The relationship between total cholesterol, non-HDL-C, HDL-C, and triglycerides and risk of death did not differ for older (>or=75) and younger participants (>75), whereas the relationship between LDL-C and risk of death was stronger in younger than older participants (RR=2.4, 95% CI=1.2-4.9 vs RR=1.6, 95% CI=1.02-2.6, respectively). Overall, women had higher mean lipid levels than men and lower mortality risk, but the risk of death was comparable for men and women with comparable low lipid levels., Conclusion: Low cholesterol level is a robust predictor of mortality in the nondemented elderly and may be a surrogate of frailty or subclinical disease. More research is needed to understand these associations.

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.