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Hispanic/Latino adults are a growing segment of the older U.S. population yet are underrepresented in brain aging research. We aimed to characterize brain aging among diverse Hispanic/Latino individuals. Hispanic/Latino individuals (unweighted n = 2273 ages 35-85 years; 56% female) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) population-based study underwent magnetic resonance imaging (MRI) as part of the SOL- Investigation of Neurocognitive Aging MRI (SOL-INCA-MRI) ancillary study (2018-2022). We performed linear regressions to calculate age associations with brain volumes for each outcome (total (global) brain, hippocampal, lateral ventricle, total white matter hyperintensity (WMH), individual cortical lobar, and total cortical gray matter) and tested modification by sex. Older age was associated with smaller gray matter volumes and larger lateral ventricle and WMH volumes. Age-related differences in global brain volumes and gray matter volumes in specific regions (i.e., the hippocampus and temporal and occipital lobes) were less pronounced among women. Our findings warrant further investigation into sex-specific mechanisms of brain aging using longitudinal studies., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

An individual's pain experiences vary substantially over time. Though variability in pain may be an important metric which usually predicts health consequences, research on the measurement of pain variability estimates is lacking among older adults. We aimed to examine the reliabilities of both intra-individual mean (IIM) and intra-individual variability (IIV) of pain assessed using ecological momentary assessments (EMA) among racially diverse, systematically recruited community dwelling cohort of older adults. Participants (N = 311, age = 70-91) completed a 14-day EMA protocol which included self-reports of pain intensity, pain interference with activities, and pain interference with concentration multiple times a day. Over a 2-week period, we found excellent reliabilities for both pain IIM (.99), and pain IIV (≥.90). We also found that we need 5 to 6 days to achieve good reliability (.8) for pain IIV, suggesting that a shorter protocol may be used to reduce participants' burden among the current sample, although caution is required when using this result to determine EMA study designs among different samples. Future studies are required to examine the associations of various EMA pain metrics with different health outcomes among older adults to facilitate the detection of underlying mechanisms linking pain to health as a prelude to interventions. PERSPECTIVE: Mean levels and variability in pain intensity, pain interference with activities, and pain interference with concentration can be reliably measured to be linked with various health outcomes in older adults. Future studies including these pain metrics will assess the natural history, the consequences, and effects of intervention of pain., (Copyright © 2021 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Despite increased risk of cognitive decline in Hispanics/Latinos, research on early risk markers of Alzheimer's disease in this group is lacking. Subjective cognitive decline (SCD) may be an early risk marker of pathological aging. We investigated associations of SCD with objective cognition among a diverse sample of Hispanics/Latinos living in the United States., Methods: SCD was measured with the Everyday Cognition Short Form (ECog-12) and cognitive performance with a standardized battery in 6125 adults aged ≥ 50 years without mild cognitive impairment or dementia (x̄ age  = 63.2 years, 54.5% women). Regression models interrogated associations of SCD with objective global, memory, and executive function scores., Results: Higher SCD was associated with lower objective global (B = -0.16, SE = 0.01), memory (B = -0.13, SE = 0.02), and executive (B = -0.13, SE = 0.02, p's < .001) function composite scores in fully adjusted models., Discussion: Self-reported SCD, using the ECog-12, may be an indicator of concurrent objective cognition in diverse middle-aged and older community-dwelling Hispanics/Latinos., (© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Emerging evidence suggests that there is significant variability in the progression of frailty in aging. We aimed to identify latent subpopulations of frailty trajectories, and examine their clinical and biological correlates., Methods: We characterized frailty using a 41-item cumulative deficit score at baseline and annual visits up to 12 years in 681 older adults (55% women, mean age 74·6 years). Clinical risk profile and walking while talking performance as a clinical marker of trajectories were examined. Mortality risk associated with trajectories was evaluated using Cox regression adjusted for established survival predictors, and reported as hazard ratios (HR). Proteome-wide analysis was done., Findings: Latent class modeling identified 4 distinct frailty trajectories: relatively stable (34·4%) as well as mild (36·1%), moderate (24·1%) and severely frail (5·4%). Four distinct classes of frailty trajectories were also shown in an independent sample of 515 older adults (60% women, 68% White, 26% Black). The stable group took a median of 31 months to accumulate one additional deficit compared to 20 months in the severely frail group. The worst trajectories were associated with modifiable risk factors such as low education, living alone, obesity, and physical inactivity as well as slower walking while talking speed. In the pooled sample, mild (HR 2·33, 95% CI 1·30-4·18), moderate (HR 2·49, 95% CI 1·33-4·66), and severely frail trajectories (HR 5·28, 95% CI 2·68-10·41) had higher mortality compared to the stable group. Proteomic analysis showed 11 proteins in lipid metabolism and growth factor pathways associated with frailty trajectories., Conclusion: Frailty shows both stable and accelerated patterns in aging, which can be distinguished clinically and biologically., Competing Interests: The authors have declared that no competing interests exist.

Objective: Handgrip strength, an indicator of overall muscle strength, has been found to be associated with slower rate of cognitive decline and decreased risk for cognitive impairment and dementia. However, evaluating the replicability of associations between aging-related changes in physical and cognitive functioning is challenging due to differences in study designs and analytical models. A multiple-study coordinated analysis approach was used to generate new longitudinal results based on comparable construct-level measurements and identical statistical models and to facilitate replication and research synthesis., Methods: We performed coordinated analysis on 9 cohort studies affiliated with the Integrative Analysis of Longitudinal Studies of Aging and Dementia (IALSA) research network. Bivariate linear mixed models were used to examine associations among individual differences in baseline level, rate of change, and occasion-specific variation across grip strength and indicators of cognitive function, including mental status, processing speed, attention and working memory, perceptual reasoning, verbal ability, and learning and memory. Results were summarized using meta-analysis., Results: After adjustment for covariates, we found an overall moderate association between change in grip strength and change in each cognitive domain for both males and females: Average correlation coefficient was 0.55 (95% CI = 0.44-0.56). We also found a high level of heterogeneity in this association across studies., Discussion: Meta-analytic results from nine longitudinal studies showed consistently positive associations between linear rates of change in grip strength and changes in cognitive functioning. Future work will benefit from the examination of individual patterns of change to understand the heterogeneity in rates of aging and health-related changes across physical and cognitive biomarkers., (Published by Oxford University Press on behalf of The Gerontological Society of America 2019.)

Background: The Uniform Data Set, Version 3 Neuropsychological Battery (UDSNB3.0), from the database of the University of Washington's National Alzheimer's Coordinating Center (NACC), is widely used to characterize cognitive performance in clinical and research settings; however, norms for underrepresented community-based samples are scarce., Objective: We compared UDSNB 3.0 test scores between the Einstein Aging Study (EAS), composed of racially/ethnically diverse, community-dwelling older adults aged≥70 and the NACC, and report normative data from the EAS., Methods: Analyses included 225 cognitively normal EAS participants and comparable data from 5,031 NACC database participants. Linear regression models compared performance between the samples, adjusting for demographics (sex, age, education, race/ethnicity), depressive symptoms, and whether English was the first language. Linear regression models to examine demographic factors including age, sex, education and race/ethnicity as predictors for the neuropsychological tests were applied in EAS and NACC separately and were used to create a demographically adjusted z-score calculator., Results: Cognitive performance across all domains was worse in the EAS than in the NACC, adjusting for age, sex, education, race/ethnicity, and depression, and the differences remained in visuo-construction, visuospatial memory, confrontation naming, visual attention/processing speed, and executive functioning after further adjusting for whether English was the first language. In both samples, non-Hispanic Whites outperformed non-Hispanic Blacks and more education was associated with better cognitive performance., Conclusion: Differences observed in demographic, clinical, and cognitive characteristics between the community-based EAS sample and the nationwide NACC sample suggest that separate normative data that more accurately reflect non-clinic, community-based populations should be established.

Background: Methods that can identify subgroups with different trajectories of cognitive decline are crucial for isolating the biologic mechanisms which underlie these groupings., Objective: This study grouped older adults based on their baseline cognitive profiles using a latent variable approach and tested the hypothesis that these groups would differ in their subsequent trajectories of cognitive change., Methods: In this study we applied time-varying effects models (TVEMs) to examine the longitudinal trajectories of cognitive decline across different subgroups of older adults in the Rush Memory and Aging Project., Results: A total of 1,662 individuals (mean age = 79.6 years, SD = 7.4, 75.4%female) participated in the study; these were categorized into five previously identified classes of older adults differing in their baseline cognitive profiles: Superior Cognition (n = 328, 19.7%), Average Cognition (n = 767, 46.1%), Mixed-Domains Impairment (n = 71, 4.3%), Memory-Specific Impairment (n = 274, 16.5%), and Frontal Impairment (n = 222, 13.4%). Differences in the trajectories of cognition for these five classes persisted during 8 years of follow-up. Compared with the Average Cognition class, The Mixed-Domains and Memory-Specific Impairment classes showed steeper rates of decline, while other classes showed moderate declines., Conclusion: Baseline cognitive classes of older adults derived through the use of latent variable methods were associated with distinct longitudinal trajectories of cognitive decline that did not converge during an average of 8 years of follow-up.

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity., (© The Author(s) 2020. 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.)

Objective: Hispanics/Latinos are the largest ethnic/racial group in the U.S., have the highest prevalence of diabetes, and are at increased risk for neurodegenerative disorders. Currently, little is known about the relationship between diabetes and cognitive decline and disorders among diverse Hispanics/Latinos. The purpose of this study is to clarify these relationships in diverse middle-aged and older Hispanics/Latinos., Research Design and Methods: The Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) is an ancillary study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability-sampled (i.e., representative of targeted populations), and prospective cohort study. Between 2016 and 2018, SOL-INCA enrolled diverse Hispanics/Latinos aged ≥50 years ( n = 6,377). Global cognitive decline and mild cognitive impairment (MCI) were the primary outcomes., Results: Prevalent diabetes at visit 1, but not incident diabetes at visit 2, was associated with significantly steeper global cognitive decline (β GC = -0.16 [95% CI -0.25; -0.07]; P < 0.001), domain-specific cognitive decline, and higher odds of MCI (odds ratio 1.74 [95% CI 1.34; 2.26]; P < 0.001) compared with no diabetes in age- and sex-adjusted models., Conclusions: Diabetes was associated with cognitive decline and increased MCI prevalence among diverse Hispanics/Latinos, primarily among those with prevalent diabetes at visit 1. Our findings suggest that significant cognitive decline and MCI may be considered additional disease complications of diabetes among diverse middle-aged and older Hispanics/Latinos., (© 2020 by the American Diabetes Association.)

Background: Conceptualizing cognitive aging as a step-sequential process is useful in identifying particular stages of cognitive function and impairment., Objective: We applied latent transition analysis (LTA) to determine 1) whether the underlying structure of cognitive profiles found at every measurement occasion are uniform across three waves of assessment, 2) whether class-instability is predictive of distal outcomes, and 3) whether class-reversions from impaired to non-impaired using latent modelling is lower than when using clinical criteria of mild cognitive impairment (MCI)., Methods: A mover-stayer LTA model with dementia as a distal outcome was specified to model transitions of ten neuropsychological measures over three annual waves in the Rush Memory and Aging Project (n = 1,661). The predictive validity of the mover-stayer status for incident Alzheimer's disease (AD) was then assessed., Results: We identified a five-class model across the three time-points: Mixed-Domain Impairment, Memory-Specific Impairment, Frontal Impairment, Average, and Superior Cognition. None of the individuals in the Impairment classes reverted to the Average or Superior classes. Conventional MCI classification identified 26.4% and 14.1% at Times 1 and 2 as false-positive cases. "Movers" had 87% increased risk of developing dementia compared to those classified as "Stayers"., Conclusion: Our findings support the use of latent variable modelling that incorporates comprehensive neuropsychological assessment to identify and classify cognitive impairment.

Background: Among older adults, poorer cognitive functioning has been associated with impairments in instrumental activities of daily living (IADLs). However, IADL impairments among older Hispanics/Latinos is poorly understood., Objective: To characterize the relationships between cognition and risk for IADL impairment among diverse Hispanics/Latinos., Methods: Participants included 6,292 community-dwelling adults from the Study of Latinos - Investigation of Neurocognitive Aging, an ancillary study of 45+ year-olds in the Hispanic Community Health Study/Study of Latinos. Cognitive data (learning, memory, executive functioning, processing speed, and a Global cognitive composite) were collected at Visit 1. IADL functioning was self-reported 7 years later, and treated as a categorical (i.e., risk) and continuous (i.e., degree) measures of impairment. Survey two-part models (mixture of logit and generalized linear model with Gaussian distribution) and ordered logistic regression tested the associations of cognitive performance (individual tests and composite z-score) with IADL impairment. Additionally, we investigated the moderating role of age, sex, and Hispanic/Latino background on the association between cognition and IADL impairment., Results: Across all cognitive measures, poorer performance was associated with higher odds of IADL impairment 7 years later. Associations were generally stronger for the oldest group (70+ years) relative to the youngest group (50-59 years). Sex and Hispanic/Latino background did not modify the associations. Across the full sample, lower scores on learning, memory, and the Global cognitive composite were also associated with higher degree of IADL impairment., Conclusion: Across diverse Hispanics/Latinos, cognitive health is an important predictor of everyday functioning 7 years later, especially in older adulthood.

Introduction: We estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle-aged and older diverse Hispanics/Latinos., Methods: Middle-aged and older diverse Hispanics/Latinos enrolled (n = 6377; 50-86 years) in this multisite prospective cohort study were evaluated for MCI using the National Institute on Aging-Alzheimer's Association diagnostic criteria., Results: The overall MCI prevalence was 9.8%, which varied between Hispanic/Latino groups. Older age, high cardiovascular disease (CVD) risk, and elevated depressive symptoms were significant correlates of MCI prevalence. Apolipoprotein E4 (APOE) and APOE2 were not significantly associated with MCI., Discussion: MCI prevalence varied among Hispanic/Latino backgrounds, but not as widely as reported in the previous studies. CVD risk and depressive symptoms were associated with increased MCI, whereas APOE4 was not, suggesting alternative etiologies for MCI among diverse Hispanics/Latinos. Our findings suggest that mitigating CVD risk factors may offer important pathways to understanding and reducing MCI and possibly dementia among diverse Hispanics/Latinos., (Copyright © 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Background: Substantial research is dedicated to understanding the aging-related dynamics among individual differences in level, change, and variation across physical and cognitive abilities. Evaluating replicability and synthesizing these findings has been limited by differences in measurements and samples, and by study design and statistical analyses confounding between-person differences with within-person changes. In this article, we conducted a coordinated analysis and summary meta-analysis of new results on the aging-related dynamics linking pulmonary function and cognitive performance., Methods: We performed coordinated analysis of bivariate growth models in data from 20,586 participants across eight longitudinal studies to examine individual differences in baseline level, rate of change, and occasion-specific variability in pulmonary and cognitive functioning. Results were summarized using meta-analysis., Results: We found consistent but weak baseline and longitudinal associations in levels of pulmonary and cognitive functioning, but no associations in occasion-specific variability., Conclusions: Results provide limited evidence for a consistent link between simultaneous changes in pulmonary and cognitive function in a normal aging population. Further research is required to understand patterns of onset of decline and differences in rates of change within and across physical and cognitive functioning domains, both within-individuals and across countries and birth cohorts. Coordinated analysis provides an efficient and rigorous approach for replicating and comparing results across independent longitudinal studies., (© The Author(s) 2019. 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.)

We aimed to test the hypothesis that the effect of chronic pain on depressive symptoms is mediated through hippocampal volume (HV). Participants were 131 non-demented adults over the age of 70 years from the Einstein Aging Study. Smaller right and left HV were both associated with higher depressive symptoms, but only smaller right HV was associated with chronic pain. In mediation models, right HV was a significant mediator for the effect of chronic pain on depression. Our findings suggest presence of a shared brain substrates between chronic pain and depression as reflected by right HV., (Copyright © 2019. Published by Elsevier B.V.)

Background: In a previous report, we used latent class analysis (LCA) to identify natural subgroups of older adults in the Einstein Aging Study (EAS) based on neuropsychological performance. These subgroups differed in demographics, genetic profile, and prognosis. Herein, we assess the generalizability of these findings to an independent sample, the Rush Memory and Aging Project (MAP), which used an overlapping, but distinct neuropsychological battery., Objective: Our aim was to identify the association of natural subgroups based on neuropsychological performance in the MAP cohort with incident dementia and compare them with the associations identified in the EAS., Methods: MAP is a community-dwelling cohort of older adults living in the northeastern Illinois, Chicago. Latent class models were applied to baseline scores of 10 neuropsychological measures across 1,662 dementia-free MAP participants. Results were compared to prior findings from the EAS., Results: LCA resulted in a 5-class model: Mixed-Domain Impairment (n = 71, 4.3%), Memory-specific-Impairment (n = 274, 16.5%), Average (n = 767, 46.1%), Frontal Impairment (n = 222, 13.4%), and a class of Superior Cognition (n = 328, 19.7%). Similar to the EAS, the Mixed-Domain Impairment, the Memory-Specific Impairment, and the Frontal Impairment classes had higher risk of incident Alzheimer's disease when compared to the Average class. By contrast, the Superior Cognition had a lower risk of Alzheimer's disease when compared to the Average class., Conclusions: Natural cognitive subgroups in MAP are similar to those identified in EAS. These similarities, despite study differences in geography, sampling strategy, and cognitive tests, suggest that LCA is capable of identifying classes that are not limited to a single sample or a set of cognitive tests.

Background: The transition from normal cognition to Alzheimer's disease is considered a continuum, with amnestic mild cognitive impairment (aMCI) an intermediate clinical cognitive state. Although prior work suggests that dementia incidence rates may be declining, there is little information regarding temporal trends in aMCI incidence., Objective: To determine whether age specific rates of aMCI have changed over sequential birth cohorts among individuals included in the population-based Einstein Aging Study (EAS) cohort. A secondary objective was to examine trends in aMCI rates among Blacks and Whites and by sex., Methods: Age specific incidence of aMCI was examined by birth year among 1,233 individuals age 70 years and above enrolled in the population-based EAS cohort between November 1, 1993 and February 22, 2016 and who had at least one annual follow-up assessment (5,321 person years of follow-up). Poisson regression was used to determine whether there has been a change in age specific aMCI rates over sequential years of birth., Results: No significant change in aMCI rates was identified in the overall cohort, among Blacks or Whites, or among males or females born between 1899 and 1946., Conclusions: Despite a trend for decreased dementia incidence in the EAS cohort, rates of incident aMCI have not changed. These apparently conflicting results may indicate a delay or decrease in the rates of transition from aMCI to dementia within the cohort. However, further studies are needed to confirm whether rates of aMCI have changed in other populations, and how aMCI rates are related to secular trends in dementia risk factors.

Background: The relation of pre-dementia stages to mortality has not been fully explored. Previous work examining subjective cognitive decline (SCD) and mortality is limited and mixed regarding methods used and consistency of findings., Objective: To examine SCD and mortality in a longitudinal, community-based cohort, using item response theory (IRT) methodology to form a composite SCD measure. Also, to assess whether this relationship was independent of clinical cognitive status., Methods: The Einstein Aging Study is a diverse longitudinal cohort of adults aged ≥70. SCD items were extracted from baseline CERAD questionnaires and a composite score was formed using IRT methodology. A total of 1,741 participants with complete data were clinically diagnosed as cognitively normal, or as having amnestic mild cognitive impairment (aMCI), nonamnestic mild cognitive impairment (naMCI), or dementia. 645 deaths occurred over a period of 8,912 person-years of follow-up. Cox proportional hazard models predicted time to death adjusting for covariates., Results: A one standard deviation unit increase in level of SCD was associated with >20% higher risk of mortality. However, when models were adjusted for clinical cognitive status, the association was no longer significant. Both dementia and aMCI predicted mortality. Furthermore, when analyses focused only on those without cognitive impairment, SCD level did not predict mortality., Conclusions: The association of SCD with mortality may be due to the association of SCD with clinical cognitive status. Thus, SCD may be used as a community-based screen to initially identify those with cognitive impairment who may be at greatest risk for death.

Background: In this study we investigated the role of hippocampal volume (HV) in visual memory., Methods: Participants were a subsample of older adults (> = 70 years) from the Einstein Aging Study. Visual performance was measured using the Complex Figure (CF) copy and delayed recall tasks from the Repeatable Battery for the Assessment of Neuropsychological Status. Linear regressions were fitted to study associations between HV and visual tasks., Results: Participants' (n = 113, mean age = 78.9 years) average scores on the CF copy and delayed recall were 17.4 and 11.6, respectively. CF delayed recall was associated with total (β = .031, p = 0.001) and left (β = 0.031, p = 0.001) and right HVs (β = 0.24, p = 0.012). CF delayed recall remained significantly associated with left HV even after we also included right HV (β = 0.27, p = 0.025) and the CF copy task (β = 0.30, p = 0.009) in the model. CF copy did not show any significant associations with HV., Conclusion: Our results suggest that left HV contributes in retrieval of visual memory in older adults.

Importance: Trends in dementia incidence rates have important implications for planning and prevention. To better understand incidence trends over time requires separation of age and cohort effects, and few prior studies have used this approach., Objectives: To examine trends in dementia incidence and concomitant trends in cardiovascular comorbidities among individuals aged 70 years or older who were enrolled in the Einstein Aging Study between 1993 and 2015., Design, Setting, and Participants: In this birth cohort analysis of all-cause dementia incidence in persons enrolled in the Einstein Aging Study from October 20, 1993, through November 17, 2015, a systematically recruited, population-based sample of 1348 participants from Bronx County, New York, who were 70 years or older without dementia at enrollment and at least one annual follow-up was studied. Poisson regression was used to model dementia incidence as a function of age, sex, educational level, race, and birth cohort, with profile likelihood used to identify the timing of significant increases or decreases in incidence., Exposures: Birth year and age., Main Outcomes and Measures: Incident dementia defined by consensus case conference based on annual, standardized neuropsychological and neurologic examination findings, using criteria from the DSM-IV., Results: Among 1348 individuals (mean [SD] baseline age, 78.5 [5.4] years; 830 [61.6%] female; 915 [67.9%] non-Hispanic white), 150 incident dementia cases developed during 5932 person-years (mean [SD] follow-up, 4.4 [3.4] years). Dementia incidence decreased in successive birth cohorts. Incidence per 100 person-years was 5.09 in birth cohorts before 1920, 3.11 in the 1920 through 1924 birth cohorts, 1.73 in the 1925 through 1929 birth cohorts, and 0.23 in cohorts born after 1929. Change point analyses identified a significant decrease in dementia incidence among those born after July 1929 (95% CI, June 1929 to January 1930). The relative rate for birth cohorts before July 1929 vs after was 0.13 (95% CI, 0.04-0.41). Prevalence of stroke and myocardial infarction decreased across successive birth cohorts, whereas diabetes prevalence increased. Adjustment for these cardiovascular comorbidities did not explain the decreased dementia incidence rates for more recent birth cohorts., Conclusions and Relevance: Analyses confirm decreasing dementia incidence in this population-based sample. Whether decreasing incidence will contribute to reduced burden of dementia given the aging of the population is not known.

Objective: We aimed to assess reliability and cross-sectional discriminative validity of the Memory Binding Test (MBT) to distinguish persons with amnestic cognitive impairment (aMCI) and dementia from cognitively normal elderly controls., Method: The MBT was administered to 20 participants with dementia, 31 with aMCI and 246 controls, who received the first administration of the MBT from May 2003 to December 2007, as a substudy of the community-based Einstein Aging Study (age range: 70+). The optimal index resulted from comparing the partial area under the receiver operating characteristic curves (ROC AUC) of four major MBT indices for specificities ≥0.70. Optimal cut-score of the optimal index was selected by maximizing the sum of sensitivity and specificity. Age and education effects were assessed using stratified cut-scores and adjusted logistic regression. Reliability was computed as intraclass correlation between scores at baseline and 1-year follow-up for participants who remained cognitively normal., Results: Total number of Items recalled in the Paired condition (TIP) was elected the optimal index. TIP cut-score was ≤22 for differentiating aMCI alone (sensitivity = 0.74, specificity = 0.73) and aMCI and dementia combined (sensitivity = 0.84, specificity = 0.73) from controls. It was ≤17 for differentiating dementia from aMCI and controls (sensitivity = 0.95, specificity = 0.87). Age and education adjustments did not materially improve discriminative validity. The reliability of TIP was 0.77., Conclusions: MBT achieved moderate to good reliability. TIP had superior cross-sectional discriminative validity than the other MBT indices. We recommend using the empirical cut-score of TIP ≤22 for discriminating aMCI and dementia and ≤17 for discriminating dementia alone., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Selective hippocampal (HC) subfield atrophy has been reported in older adults with mild cognitive impairment and Alzheimer's disease. The goal of this study was to investigate the associations between the volume of hippocampal subfields and visual and verbal episodic memory in cognitively normal older adults., Methods: This study was conducted on a subset of 133 participants from the Einstein Aging Study (EAS), a community-based study of non-demented older adults systematically recruited from the Bronx, N.Y. All participants completed comprehensive EAS neuropsychological assessment. Visual episodic memory was assessed using the Complex Figure Delayed Recall subtest from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Verbal episodic memory was assessed using Delayed Recall from the Free and Cued Selective Reminding Test (FCSRT). All participants underwent 3T MRI brain scanning with subsequent automatic measurement of the hemispheric hippocampal subfield volumes (CA1, CA2-CA3, CA4-dente gyrus, presubiculum, and subiculum). We used linear regressions to model the association between hippocampal subfield volumes and visual and verbal episodic memory tests while adjusting for age, sex, education, and total intracranial volume., Results: Participants had a mean age of 78.9 (SD=5.1) and 60.2% were female. Total hippocampal volume was associated with Complex Figure Delayed Recall (β=0.31, p=0.001) and FCSRT Delayed Recall (β=0.27, p=0.007); subiculum volume was associated with Complex Figure Delayed Recall (β=0.27, p=0.002) and FCSRT Delayed Recall (β=0.24, p=0.010); CA1 was associated with Complex Figure Delayed Recall (β=0.26, p<0.002) and FCSRT Delayed Recall (β=0.20, p=0.025)., Conclusions: Our findings confirm previous research on the specific roles of CA1 and subiculum in episodic memory. Our results suggest that hippocampal subfields have sensitive roles in the process of visual and verbal episodic memory., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Among older adults, pain intensity and pain interference are more common in women than men and associated with obesity and inflammatory markers., Objective: We examined whether the obesity and pain relationship is mediated by the high-sensitivity C-reactive protein (hsCRP), a nonspecific marker of systemic inflammation, and whether this relationship differs by sex., Methods: Items from Medical Outcomes Study Short Form-36 were used to measure pain intensity and pain interference in daily life. Ordinal logistic regression was used to assess the cross-sectional association among body mass index (BMI), hsCRP levels, pain intensity and pain interference using gender-stratified models adjusted for demographic variables., Results: Participants included 667 community-residing adults over the age of 70 years, free of dementia, enrolled in the Einstein Aging Study (EAS). In women (n = 410), pain intensity was associated with obesity [BMI ≥30 vs. normal, odds ratio (OR) = 2.29, 95% confidence interval (CI) 1.43-3.68] and higher hsCRP (OR = 1.28, 95% CI 1.08-1.51). In a model with obesity and hsCRP, both remained significant, but the association between hsCRP and pain intensity was somewhat attenuated. Obesity (OR = 3.04, 95% CI 1.81-5.11) and higher hsCRP levels (OR = 1.30, 95% CI 1.08-1.56) were also independently associated with greater pain interference in women. After adjustment for pain intensity and BMI, hsCRP was no longer associated with pain interference in women. Greater pain intensity and being overweight or obese continued to be significantly associated with pain interference in women. In men (n = 257), obesity and hsCRP were not associated with pain intensity or pain interference., Conclusions: In women, the relationship between obesity and higher levels of pain intensity or interference may be accounted for by factors related to hsCRP., Competing Interests: All authors declare that there are no financial, personal, or other potential conflicts of interest to report., (© 2016 S. Karger AG, Basel.)

Background: The Perceived Stress Scale (PSS) is made up of two subscales but is typically used as a single summary measure. However, research has shown that the two subscales may have differential properties in older adults., Objective: To evaluate the internal consistency, test-retest reliability, and the concurrent and predictive validity for development of amnestic mild cognitive impairment (aMCI) of the positively-worded (PSS-PW) and negatively-worded (PSS-NW) subscale scores of the PSS in older adults., Methods: We recruited community residing older adults free of dementia from the Einstein Aging Study. Reliability of the PSS-PW and PSS-NW was assessed using Cronbach's alpha for internal consistency and intraclass correlation for one year test-retest reliability. Concurrent validity was evaluated by examining the relationship between the PSS subscales and depression, anxiety, neuroticism, and positive and negative affect. Predictive validity was assessed using multivariate Cox regression analyses to examine the relationship between baseline PSS-PW and PSS-NW score and subsequent onset of aMCI., Results: Both PSS-PW and PSS-NW showed adequate internal consistency and retest reliabilities. Both the PSS-PW and PSS-NW were associated with depression, neuroticism, and negative affect. The PSS-NW was uniquely associated with anxiety while the PSS-PW was uniquely associated with positive affect. Only the PSS-PW was associated with a statistically significant increased risk of incident aMCI (HR = 1.27; 95% CI: 1.06-1.51 for every 5-point increase in PSS-PW)., Conclusions: Evaluating the separate effects of the two PSS subscales may reveal more information than simply using a single summation score. Future research should investigate the PSS-PW and PSS-NW as separate subscales.

Objective: The relationship between depressive symptoms and subsequent cognitive impairment in older adults is controversial. Sex differences and the differences in the method of categorizing depressive symptoms may contribute to the inconsistencies. The authors examined the effect of severity of baseline depressive symptoms on risk of incident amnestic mild cognitive impairment (aMCI) separately in men and women., Methods: Community-dwelling and cognitively healthy older adults (aged ≥ 70 years) from the Einstein Aging Study completed the 15-item Geriatric Depression Scale (GDS-15) at their baseline visit. Participants were categorized into "no/low symptoms" (GDS-15 score = 0-2), "mild symptoms" (GDS-15 score = 3-5), and "moderate/severe symptoms" (GDS-15 score > 6) groups. Sex-stratified Cox proportional hazards models, adjusted for age, education, and antidepressant medication, estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident aMCI as a function of depressive symptoms group., Results: We followed 572 women (mean age: 78) and 345 men (mean age: 77) for 4.2 years on average (range: 1.0-14.6 years). Ninety women and 64 men developed aMCI during follow-up. Cox models revealed that compared with no/low depressive symptoms, mild symptoms were associated with a two times greater risk of developing aMCI in men (HR: 2.22; 95% CI: 1.26-3.89) but not in women (HR: 1.26; 95% CI: 0.77-2.06). Conversely, moderate/severe depressive symptoms were associated with a two times greater risk of developing aMCI in women (HR: 1.99; 95% CI: 1.05-3.77) but not in men (HR: 0.28; 95% CI: 0.04-2.11), possibly because of low statistical power in this subgroup., Conclusion: Results indicate that mild depressive symptoms in men and moderate/severe symptoms in women may represent a marker for future cognitive impairment., Competing Interests: Dr. Sundermann reports no conflicts of interest., (Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

The hippocampus plays a critical role in verbal and spatial memory, thus any pathological damage to this formation may lead to cognitive impairment. It is suggested that right and left hippocampi are affected differentially in healthy or pathologic aging. The purpose of this study was to test the hypothesis that verbal episodic memory performance is associated with left hippocampal volume (HV) while spatial memory is associated with right HV. 115 non-demented adults over age 70 were drawn from the Einstein Aging Study. Verbal memory was measured using the free recall score from the Free and Cued Selective Reminding Test - immediate recall (FCSRT-IR), logical memory immediate and delayed subtests (LM-I and LM-II) from the Wechsler Memory Scale-Revised (WMS-R). Spatial Memory was measured using a computerized dot memory paradigm that has been validated for use in older adults. All participants underwent 3T MRI with subsequent automatized measurement of the volume of each hippocampus. The sample had a mean age of 78.7 years (SD=5.0); 57% were women, and 52% were white. Participants had a mean of 14.3 years (SD=3.5) of education. In regression models, two tests of verbal memory (FCSRT-IR free recall and LM-II) were positively associated with left HV, but not with right HV. Performance on the spatial memory task was associated with right HV, but not left HV. Our findings support the hypothesis that the left hippocampus plays a critical role in episodic verbal memory, while right hippocampus might be more important for spatial memory processing among non-demented older adults., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844-852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures- approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcomes.

Introduction: While cortical processes play an important role in controlling locomotion, the underlying structural brain changes associated with slowing of gait in aging are not yet fully established. Our study aimed to examine the relationship between cortical gray matter volume (GM), white matter volume (WM), ventricular volume (VV), hippocampal and hippocampal subfield volumes, and gait velocity in older adults free of dementia., Methods: Gait and cognitive performance was tested in 112 community-residing adults, age 70 years and over, participating in the Einstein Aging Study. Gait velocity (cm/s) was obtained using an instrumented walkway. Volumetric MRI measures were estimated using a FreeSurfer software. We examined the cross-sectional relationship of GM, WM, VV, and hippocampal total and subfield volumes and gait velocity using linear regression models. In complementary models, the effect of memory performance on the relationship between gait velocity and regional volumes was evaluated., Results: Slower gait velocity was associated with smaller cortical GM and total hippocampal volumes. There was no association between gait velocity and WM or VV. Among hippocampal subfields, only smaller presubiculum volume was significantly associated with decrease in gait velocity. Addition of the memory performance to the models attenuated the association between gait velocity and all volumetric measures., Conclusions: Our findings indicate that total GM and hippocampal volumes as well as specific hippocampal subfield volumes are inversely associated with locomotor function. These associations are probably affected by cognitive status of study population.

Longitudinal administration of neuropsychological instruments are often used to assess age-related changes in cognition. Informative loss to follow-up may bias the results of these studies. Herein, we use auxiliary data to adjust for informative loss to follow-up. In the Einstein Aging Study, memory was assessed annually in a community sample of adults age 70+, free of dementia at baseline, using the free recall from the Free and Cued Selective Reminding Test, and via telephone using the Memory Impairment Screen for Telephone (the auxiliary data). Joint linear mixed models were used to assess how the effect of the APOE ε4 genotype may be affected by informative missingness in the in-person data. A total of 620 EAS participants contributed 2085 person years of follow-up to the analyses. Memory decline rates estimated in joint models were 19% greater in ε4 negative participants and 27% greater in ε4 positive participants compared to traditional approaches; the effect of APOE ε4 on memory decline was 37% greater. Joint modeling methods can help address bias caused by informative missing data in the estimation of the effect of risk factors on cognitive change, and may be applicable to a broader range of outcomes in longitudinal aging studies.

Background: A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders., Methods/design: Longitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress., Discussion: The challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing.

Objectives: Although apolipoprotein E (APOE) genetic variation may influence risk of gait decline and disability in aging through multiple mechanisms, a systematic examination of this relationship has been lacking. Our objective was to quantify the risk of gait decline and disability associated with the APOE ε4 allele in aging., Methods: We evaluated 627 community-dwelling adults aged 70 and older (white 67.8%) with APOE genotype and quantitative gait measurements participating in the Einstein Aging Study over a median follow-up of 3.0 years. Main outcomes were gait speed decline (cm/s/year) and incident disability., Results: APOE ε4 allele frequency was 24.1%. Presence of APOE ε4 was not significantly associated with gait speed decline overall (p = .37) but was associated with faster gait speed decline in older men (estimate: -1.16, 95% CI: -2.31 to -0.01, p = .04). The interaction between the ε4 allele and male sex predicted gait speed decline (estimate: -1.70, 95% CI: -3.33 to -0.07, p = .04). Presence of the APOE ε4 allele was associated with increased risk of disability in older men (HR 3.72, 95% CI: 1.44-9.59, p = .007). Associations of the ε4 allele with study outcomes remained significant even after accounting for several potential confounders including vascular and cognitive status. The strength of the associations was stronger in the white subgroup., Conclusion: This preliminary report suggests that the APOE ε4 allele is associated with increased risk of gait speed decline and disability in older men.

Objective: to determine the association of high sensitivity C-reactive protein (HsCRP) levels with a risk of mobility disability and decline in older adults with and without vascular disease., Design: prospective cohort., Setting: community-residing population., Subjects: six hundred and twenty-four adults age 70 and older (62% women) with gait and HsCRP assessments., Main Outcome Measures: incident mobility disability (velocity <70 cm/s) and annual rates of decline on gait velocity., Results: elevated HsCRP levels (≥ 3 mg/l) at baseline present in 224 of the 624 eligible subjects was associated with a faster annual decline in gait velocity of 0.91 cm/s (P=0.02). Subjects with elevated HsCRP levels had increased risk of mobility disability (hazard ratio: 1.85, 95% CI: 1.09-3.14). Each one-unit increase in log HsCRP levels in the 406 subjects without prevalent mobility disability was associated with increased risk of mobility disability (hazard ratio: 1.33, 95% CI: 1.05-1.68). The association of baseline HsCRP levels with mobility disability and decline was stronger in the 224 individuals without vascular disease. The associations were not significant in the 400 subjects with vascular disease., Conclusions: HsCRP levels predict mobility disability and accelerated decline in walking speed in older adults. These associations were stronger in those without vascular disease.

This study examined the relationship between cognitive function and sleep onset/maintenance difficulties (SO/MD) in nondemented older adults. We hypothesized that SO/MD negatively impacts cognition and that older adults with lower education would be especially vulnerable to its effects. The sample comprised 549 older adults from the Einstein Aging Study (EAS), a community-based cohort. Participants completed neuropsychological assessment and a sleep questionnaire. Univariate ANCOVAs were performed with cognitive performance as a dependent variable, SO/MD (present or absent) and education (lower: ≤ 12 years; higher: >12 years) as between-subjects factors, and age, ethnicity, gender, depression, and cardiovascular comorbidies as covariates. Participants were an average age of 79.7 ± 5.0 years (range = 71-97 years). Fifty-seven percent (n = 314) of the sample met criteria for SO/MD. Among participants with SO/MD, those with lower education performed more poorly on a test of category fluency than participants with higher education (means: 35.2 vs. 41.0; p < .001); among older adults without SO/MD, educational attainment had no measurable effect on cognition (SO/MD × education interaction (F(1,536) = 14.5; p = .00)). Consistent with the cognitive reserve hypothesis, older adults with lower education appear selectively vulnerable to the negative effects of sleep onset/maintenance difficulties on tests of verbal fluency.

Cognitive reserve is invoked to explain the protective effects of education and cognitively-stimulating activities against all-cause dementia and Alzheimer's disease (AD). For non-native English speakers (n-NES), speaking English may be a cognitive activity associated with lower dementia risk. We hypothesized that n-NES have lower risk of incident dementia/AD and that educational level might modify this relationship. Participants took part in the Einstein Aging Study (Bronx, NY), a longitudinal study of aging and dementia. All (n = 1779) spoke fluent English and self-reported birthplace and whether English was their first language. n-NES additionally reported mother tongue, age of English acquisition, and current percentile-use of a non-English language. Nested Cox proportional hazards models progressively adjusted for gender, race, education, and immigrant and marital status estimated hazard ratios (HR) for incident dementia/AD as a function of n-NES status. 390 (22%) participants were n-NES. 126 incident dementia cases occurred during 4174 person-years of follow-up (median 1.44; range 0-16); 101 individuals met criteria for probable/possible AD. There was no statistically-significant association between n-NES status and incident dementia in the fully-adjusted model (HR 1.26; 95% CI 0.76-2.09; p = 0.36). Results were similar for AD. Stratification of education into three groups revealed increased risk of dementia for n-NES with ≥ 16 years of education (HR 3.97; 95% CI 1.62-9.75; p = 0.003). We conclude that n-NES status does not appear to have an independent protective effect against incident dementia/AD, and that n-NES status may contribute to risk of dementia in an education-dependent manner.

Longitudinal studies of aging often gather repeated observations of cognitive status to describe the development of dementia and to assess the influence of risk factors. Clinical progression to dementia is often conceptualized by a multi-stage model of several transitions that synthesizes time-varying effects. In this study, we assess the influence of risk factors on the transitions among three cognitive status: cognitive stability (normal cognition for age), memory impairment, and clinical dementia. We have developed a shared random effects model that not only links the propensity of transitions and to the probability of informative missingness due to death, but also incorporates heterogeneous transition between subjects. We evaluate four approaches using generalized logit and four using proportional odds models to the first-order Markov transition probabilities as a function of covariates. Random effects were incorporated into these models to account for within-subject correlations. Data from the Einstein Aging Study are used to evaluate the goodness-of-fit of these models using the Akaike information criterion. The best fitting model for each type (generalized logit and proportional odds) is recommended and their results are discussed in more details., (2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Increased inflammatory activity and gait speed decline are common with aging, but the association between the two is not well established. The objective of this study was to determine the influence of inflammatory markers, interleukin-6 (IL-6), and tumor necrosis factor alpha, on gait speed performance and decline in older adults., Methods: We conducted cross-sectional and longitudinal analyses of 333 adults aged 70 and older (61% women) with gait and biomarker assessments identified from participants in the Einstein Aging Study, a community-based aging study. Gait velocity measured at baseline and annual follow-up visits (median follow-up 2.3 years) was the main outcome., Results: At baseline, higher interleukin-6 levels were associated with slower gait velocity (estimate -4.90 cm/s, p = .008). Adjusted for age, gender, education, and medical illnesses, a one-unit increase in baseline log IL-6 levels was associated with a 0.98 cm/s faster gait speed decline per year (p = .002). The results remained significant after adjustments for additional potential confounders such as physical activity levels, body mass index, and medications. Participants in the highest IL-6 quartile had a 1.75 cm/s/year faster decline in gait velocity compared with those in the lowest quartile (p = .002). Tumor necrosis factor alpha was not associated with gait velocity at cross-section or with gait speed decline., Conclusions: IL-6 levels are associated with gait performance in community residing seniors and predicts risk of gait speed decline in aging.

This study examined the relationship between endogenous hormones and cognitive function in nondemented, ethnically-diverse community-dwelling older men enrolled in the Einstein Aging Study (EAS). All eligible participants (185 men, mean age=81 years) received neuropsychological assessment (Free and Cued Selective Reminding Test (FCSRT), Logical Memory (LM), Trail Making Test B (TMTB), block design (BD)) and provided blood samples for hormonal assays (total estradiol, total testosterone, calculated free testosterone index). Linear regression analysis adjusted for age, education, body mass index, and cardiovascular comorbidities indicated that men with high levels of total estradiol demonstrated better FCSRT verbal memory performance (β=0.17, p<0.02) compared to men with lower levels of total estradiol. The results remained unchanged when the model was further adjusted for ethnicity. We did not detect an association between testosterone and cognitive performance. These findings indicate that high levels of total estradiol in older men are associated with better performance on a cue-based, controlled learning test of verbal memory that is a sensitive predictor of dementia., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2, PARK8) are the most commonly identified monogenic etiology of Parkinson disease (PD). Over-represented in the Ashkenazi Jewish population, these mutations are transmitted in an autosomal dominant manner with age-dependent reduced penetrance. The natural history and penetrance of these mutations in the elderly is controversial and inadequately studied. We conducted a nested cohort study in a community-based aging study (the Einstein Aging Study). Six elderly, initially nonmanifesting carriers (NMC) of the LRKK2 G2019S mutation were identified (average age 82.1 ± 7.0, range 72.7-90.8), and five had available longitudinal data. We matched five noncarrier controls to each NMC and followed them for an average of 4.7 years with annual cognitive and motor examinations. PD was identified in one NMC at age 95 and in no control subjects. The remaining carriers did not differ from controls on motor scores at baseline or follow-up. The baseline Unified Parkinson's Disease Rating Scale motor subscore (UPDRS-III) in cases was 6.2 ± 6.9 (range 1-19) and in controls was 4.5 ± 6.6 (1-30), P = 0.6; the mean difference in UPDRS-III slopes over time between cases and controls was 0.1 ± 1.3 and was not statistically significant. Our data, while limited by a small sample size, show that in LRKK2 G2019S mutation carriers, phenoconversion to PD can occur late in life. However, most NMC have motor decline which is indistinguishable from their age mates, suggesting that the larger subset of elderly NMC is not on the motor trajectory to disease., (© 2010 Movement Disorder Society.)

The natural history of life span cognitive performance and its late-life determinants have been studied from an array of perspectives. Significant insights come from psychological disciplines, including cognitive, developmental, and neuropsychology, as well as from medical specialties, such as geriatrics, neurology, psychiatry, neuroradiology, and neuropathology, that contribute to the growing interdisciplinary scientific field: cognitive neuroscience of aging. This survey of longitudinal studies of aging suggests that disease-oriented investigations commonly do not adequately consider normative cognitive changes, whereas developmental studies do not sufficiently measure and model nonnormative cognitive aging. This article argues for an integrative perspective that considers both of these influences on cognitive trajectories and presents a series of methodological concerns that have not been addressed comprehensively. Interdisciplinary methods from longitudinal observational studies should be leveraged to enable translational interventions to promote brain longevity., (© 2010, Copyright the Authors. Journal compilation © 2010, The American Geriatrics Society.)

To estimate the validity of neurological gait evaluations in predicting falls in older adults. We studied 632 adults age 70 and over (mean age 80.6 years, 62% women) enrolled in the Einstein Aging Study whose walking patterns were evaluated by study clinicians using a clinical gait rating scale. Association of neurological gaits and six subtypes (hemiparetic, frontal, Parkinsonian, unsteady, neuropathic, and spastic) with incident falls was studied using generalized estimation equation procedures adjusted for potential confounders, and reported as risk ratio with 95% confidence intervals (CI). Over a mean follow-up of 21 months, 244 (39%) subjects fell. Mean fall rate was 0.47 falls per person year. At baseline, 120 subjects were diagnosed with neurological gaits. Subjects with neurological gaits were at increased risk of falls (risk ratio 1.49, 95% CI 1.11-2.00). Unsteady (risk ratio 1.52, 95% CI 1.04-2.22), and neuropathic gait (risk ratio 1.94, 95% CI 1.07-3.11) were the two gait subtypes that predicted risk of falls. The results remained significant after accounting for disability and cognitive status, and also with injurious falls as the outcome. Neurological gaits and subtypes are independent predictors of falls in older adults. Neurological gait assessments will help clinicians identify and institute preventive measures in older adults at high risk for falls.

The current study provided longitudinal robust norms for individuals age 70 years and older for several neuropsychological tests. We compared baseline neuropsychological test performance in three groups free of dementia at baseline: a robust normative sample free of dementia for at least two post-follow-up assessments, an incident dementia sample which developed new onset dementia during the follow-up and a lost to follow-up (LTF) sample. ANCOVAs showed that the robust sample performed better on all neuropsychological tests compared to the incident dementia and LTF samples. These findings support the argument that individuals in transition to developing dementia may reduce the mean, increase the variability and therefore underestimate cognitive performance in normal aging. We suggest that longitudinal robust norms may help mitigate the limitations inherent in cross-sectional normative samples.

The current study examined the relationship between cognitive function and falls in older people who did not meet criteria for dementia or mild cognitive impairment (N = 172). To address limitations of previous research, the authors controlled for the confounding effects of gait measures and other risk factors by means of associations between cognitive function and falls. A neuropsychological test battery was submitted to factor analysis, yielding 3 orthogonal factors (Verbal IQ, Speed/Executive Attention, Memory). Single and recurrent falls within the last 12 months were evaluated. The authors hypothesized that Speed/Executive Attention would be associated with falls. Additionally, the authors assessed whether associations between different cognitive functions and falls varied depending on whether single or recurrent falls were examined. Multivariate logistic regressions showed that lower scores on Speed/Executive Attention were associated with increased risk of single and recurrent falls. Lower scores on Verbal IQ were related only to increased risk of recurrent falls. Memory was not associated with either single or recurrent falls. These findings are relevant to risk assessment and prevention of falls and point to possible shared neural substrates of cognitive and motor function., ((PsycINFO Database Record (c) 2007 APA, all rights reserved).)

Mutations in leucine-rich repeat kinase 2 gene (LRRK2) have been associated with idiopathic Parkinson's disease (PD), as well as pleomorphic neurodegenerative pathology, including Alzheimer's disease. One specific LRRK2 mutation, G2019S, was reported in 18% of people with PD of Ashkenazi descent, supporting a founder effect in this population. To determine if this mutation is also associated with dementia in the Ashkenazim, we screened 192 elderly Ashkenazi Jewish (AJ) individuals in a longitudinal aging and cognition study, of whom 49 (25.5%) had dementia. Two non-demented individuals harbored the mutation (2/143, 1.4%), but no individuals with dementia. Neither person with the mutation had Parkinson's disease. Therefore, the LRRK2 mutation has a relatively high frequency in the AJ population, is not fully penetrant for parkinsonism in the elderly, and does not appear to be commonly associated with late-onset dementia.

Although evidence suggests that extensive cortical beta-amyloid (Abeta) deposition is essential in Alzheimer disease (AD), it is also detected in nondemented elderly individuals with pathologic aging (PA). Given evidence that neutral endopeptidase (NEP) or neprilysin, a key enzyme for clearance of Abeta, is decreased in AD, the goal of the present study was to determine if NEP was also decreased in PA. We measured NEP immunoreactivity in frontal cortex of 12 AD and six PA cases and compared this with 10 normal (N) elderly individuals. None had any significant other pathology, and they were similar with respect to age, sex, and postmortem delay. In addition, Abeta1-40 and Abeta1-42 were measured by enzyme-linked immunosorbent assay (ELISA), whereas tau, synaptophysin, and alpha-synuclein were measured on Western blots. The AD cases had more neuritic plaques, neurofibrillary tangles, higher Braak stage, and more tau immunoreactivity in frontal cortex than both PA and N. In contrast, both PA and AD had more senile plaques and Abeta1-42 than N. NEP immunoreactivity was decreased in AD but not in PA. The decrease was unlikely the result of neuronal or synaptic loss because NEP immunoreactivity in frontotemporal degeneration with comparable degrees of synaptic loss as the AD cases was not different from control subjects. Although NEP enzyme activity was decreased in approximately half the AD cases, on average, it was not decreased compared with N or PA. The results add further evidence that PA is distinct from AD and indicate that decreased Abeta degradation by NEP is unlikely to contribute significantly to amyloid deposition in PA or, in many cases, of AD.

While aging research has been progressing rapidly recently, the involvement of multiple organs and systems in the aging process has hampered a comprehensive assessment of some of aging's basic features. In response to this problem, the Institute for Aging Research at Einstein did not emerge out of the traditional geriatric programs, but through enhanced collaborations between basic and clinical scientists who had successful careers in the research of a specific organ or system. The strength of the Center derives from three specific programs focused on a specific area of aging research. The programs focus on the Biology of Aging, Genetics of Aging and the Aging Brain. Each programmatic area is characterized by collaboration between basic and clinical scientists. In addition to addressing the traditional questions about the mechanisms of involution, the programs also examine the mechanisms for exceptional and healthy longevity. The mechanisms favoring longevity are being examined in models of caloric restriction (biological nutrient sensing pathways), in human centenarians (longevity genes), and in longitudinal studies identifying humans who maintain excellent cognitive function (protection from Alzheimer's). Each programmatic area is enhanced by common research core laboratory and by the creation of a scientific training program for new investigators. In addition to the investigators involved in the program project, the Institute for Aging Research includes other investigators with funded aging research who participate in journal clubs, seminars, and in specific collaborations. We suggest that this Institute serve as a model that gerontologists at other institutions should consider as they evaluate opportunities for collaborative, multi-disciplinary approaches to enhance aging research.

This longitudinal study examined memory loss in a sample of 391 initially nondemented older adults. Analyses decomposed observed memory loss into decline associated with preclinical dementia, study attrition, terminal decline, and chronological age. Measuring memory as a function of only chronological age failed to provide an adequate representation of cognitive change. Disease progression accounted for virtually all of the memory loss in the 25% of the sample that developed diagnosable dementia. In the remainder of the sample, both chronological age and study attrition contributed to observed memory loss. These results suggest that much of memory loss in aging adults may be attributable to the progression of preclinical dementia and other nonnormative aging processes that are not captured by chronological age.

The Hispanic/Latino population is one of the largest and most diverse ethnoracial groups in the United States at high risk for dementia. We examined cognitive constructs and associations with subsequent hippocampal volume (HV) and white matter hyperintensity volume (WMHV). Participants were from the Hispanic Community Health Study/Study of Latinos-Magnetic Resonance Imaging Study (n = 2029). We examined confirmatory factor analysis and longitudinal invariance using neurocognitive scores at Visits 1 (2008-2011) and 2 (2014-2018) and path analyses. We obtained a longitudinally invariant two-factor episodic memory (EM) and working memory (WM) construct. Lower EM profile at both visits was associated with greater WMHV and smaller HV at Visit 2. Lower WM profile at both visits was associated with larger WMHV and smaller HV at Visit 2. Neurocognitive profiles were associated with subsequent neurodegeneration in a sample of Hispanics/Latinos. Identifying neurocognitive risk profiles may lead to early detection and intervention, and significantly impact the course of neurodegeneration.HighlightsCognitive profiles predict brain integrity up to 10 years later.We observed two-factor latent memory constructs and longitudinal invariance.These findings were observed in a Hispanic/Latino cohort.

ObjectiveHispanic/Latino individuals in the U.S. have the highest prevalence of undiagnosed and untreated diabetes and are at increased risk for cognitive impairment. In this study, we examine glycemic control in relation to cognitive aging and impairment in a large prospective cohort of middle-aged and older Hispanic/Latino individuals of diverse heritages.Research design and methodsStudy of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) is a Hispanic Community Health Study/Study of Latinos (HCHS/SOL) ancillary study. HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability sampled prospective cohort study. SOL-INCA enrolled 6,377 diverse Hispanic/Latino individuals aged 50 years and older (2016-2018). The primary outcomes were cognitive function, 7-year cognitive decline, and mild cognitive impairment (MCI). The primary glycemia exposure variables were measured from fasting blood samples collected at HCHS/SOL visit 1 (2008-2011).ResultsVisit 1 mean age was 56.5 years ± 8.2 SD, and the average glycosylated hemoglobin A1C (HbA1c) was 6.12% (43.5 ± 14.6 mmol/mol). After covariate adjustment, higher HbA1c was associated with accelerated 7-year global (b = -0.045; 95% CI -0.070; -0.021; in z score units) and executive cognitive decline and a higher prevalence of MCI (odds ratio 1.20; 95% CI 1.11; 1.29).ConclusionsElevated HbA1c levels were associated with 7-year executive cognitive decline and increased MCI risk among diverse middle-aged and older Hispanic/Latino individuals. Our findings indicate that poor glycemic control in midlife may pose significant risks for cognitive decline and MCI later in life among Hispanic/Latino individuals of diverse heritages.

IntroductionExecutive functioning and processing speed are crucial elements of neuropsychological assessment. To meet the needs of the Hispanic/Latino population, we aimed to provide normative data for the Digit Symbol Substitution (DSS) test.MethodsThe target population for the Study of Latinos-Investigation of Neurocognitive Aging included six heritage backgrounds (n = 6177). Average age was 63.4 ± 8.3 years, 54.5% were female, and mean education was 11.0 ± 4.7 years. Participants were administered the DSS as part of a larger battery. Heritage-adjusted DSS scores, and percentile cut-points were created using survey-adjusted regression and quantile regression models.ResultsAge, education, sex, heritage, and language preference were associated with DSS scores.DiscussionSignificant correlates of DSS performance should be considered when evaluating cognitive performance. Representative DSS norms for Hispanics/Latinos will advance assessment and accuracy of neurocognitive disorder diagnosis in clinical practice. To facilitate interpretation, we provide norms to reduce test biases and developed an online dashboard.HighlightsNormative data for the Digit Symbol Substitution (DSS) for diverse Hispanic/Latino adults: Results from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) This study is the first to develop norms for the DSS test across four regions of the United States.Factors such as age, education, sex, and Hispanic/Latino heritage and language preference are associated with differences in executive functioning and information processing speed.We created norms and an online dashboard (https://solincalab.shinyapps.io/dsst_shiny/) providing an easily accessible tool to evaluate processing speed and executive functioning in Hispanic/Latino adults.

IntroductionReproductive health history may contribute to cognitive aging and risk for Alzheimer's disease, but this is understudied among Hispanic/Latina women.MethodsParticipants included 2126 Hispanic/Latina postmenopausal women (44 to 75 years) from the Study of Latinos-Investigation of Neurocognitive Aging. Survey linear regressions separately modeled the associations between reproductive health measures (age at menarche, history of oral contraceptive use, number of pregnancies, number of live births, age at menopause, female hormone use at Visit 1, and reproductive span) with cognitive outcomes at Visit 2 (performance, 7-year change, and mild cognitive impairment [MCI] prevalence).ResultsYounger age at menarche, oral contraceptive use, lower pregnancies, lower live births, and older age at menopause were associated with better cognitive performance. Older age at menarche was protective against cognitive change. Hormone use was linked to lower MCI prevalence.DiscussionSeveral aspects of reproductive health appear to impact cognitive aging among Hispanic/Latina women.

BackgroundCardiovascular disease (CVD) risk factors are highly prevalent among Hispanic/Latino adults, while the prevalence of MRI infarcts is not well-documented. We, therefore, sought to examine the relationships between CVD risk factors and infarcts with brain structure among Hispanic/Latino individuals.MethodsParticipants included 1,886 Hispanic/Latino adults (50-85 years) who underwent magnetic resonance imaging (MRI) as part of the Study of Latinos-Investigation of Neurocognitive Aging-MRI (SOL-INCA-MRI) study. CVD risk was measured approximately 10.5 years before MRI using the Framingham cardiovascular risk score, a measure of 10-year CVD risk (low (