Perceived but not objective measures of neighborhood safety and food environments are associated with longitudinal changes in processing speed among urban older adults.

BACKGROUND: Although a growing body of literature documents the importance of neighborhood effects on late-life cognition, little is known about the relative strength of objective and subjective neighborhood measures on late-life cognitive changes. This study examined effects of objective and subjective neighborhood measures in three neighborhood domains (neighborhood safety, physical disorder, food environments) on longitudinal changes in processing speed, an early marker of cognitive aging and impairment. METHODS: The analysis sample included 306 community-dwelling older adults enrolled in the Einstein Aging Study (mean age = 77, age range = 70 to 91; female = 67.7%; non-Hispanic White: 45.1%, non-Hispanic Black: 40.9%). Objective and subjective measures of neighborhood included three neighborhood domains (i.e., neighborhood safety, physical disorder, food environments). Processing speed was assessed using a brief Symbol Match task (unit: second), administered on a smartphone device six times a day for 16 days and repeated annually for up to five years. Years from baseline was used as the within-person time index. RESULTS: Results from mixed effects models showed that subjective neighborhood safety (ß= -0.028) and subjective availability of healthy foods (ß= -0.028) were significantly associated with less cognitive slowing over time. When objective and subjective neighborhood measures were simultaneously examined, subjective availability of healthy foods remained significant (ß= -0.028) after controlling for objective availability of healthy foods. Associations of objective neighborhood crime and physical disorder with processing speed seemed to be confounded by individual-level race and socioeconomic status; after controlling for these confounders, none of objective neighborhood measures showed significant associations with processing speed. CONCLUSION: Subjective neighborhood safety and subjective availability of healthy foods, rather than objective measures, were associated with less cognitive slowing over time over a five-year period. Perception of one's neighborhood may be a more proximal predictor of cognitive health outcomes as it may reflect one's experiences in the environment. It would be important to improve our understanding of both objective and subjective neighborhood factors to improve cognitive health among older adults.

Personality predictors of dementia diagnosis and neuropathological burden: An individual participant data meta-analysis.

INTRODUCTION: The extent to which the Big Five personality traits and subjective well-being (SWB) are discriminatory predictors of clinical manifestation of dementia versus dementia-related neuropathology is unclear. METHODS: Using data from eight independent studies (Ntotal = 44,531; Ndementia = 1703; baseline Mage = 49 to 81 years, 26 to 61% female; Mfollow-up range = 3.53 to 21.00 years), Bayesian multilevel models tested whether personality traits and SWB differentially predicted neuropsychological and neuropathological characteristics of dementia. RESULTS: Synthesized and individual study results indicate that high neuroticism and negative affect and low conscientiousness, extraversion, and positive affect were associated with increased risk of long-term dementia diagnosis. There were no consistent associations with neuropathology. DISCUSSION: This multistudy project provides robust, conceptually replicated and extended evidence that psychosocial factors are strong predictors of dementia diagnosis but not consistently associated with neuropathology at autopsy. HIGHLIGHTS: N(+), C(-), E(-), PA(-), and NA(+) were associated with incident diagnosis. Results were consistent despite self-report versus clinical diagnosis of dementia. Psychological factors were not associated with neuropathology at autopsy. Individuals with higher conscientiousness and no diagnosis had less neuropathology. High C individuals may withstand neuropathology for longer before death.

Lifestyle and incident dementia: A COSMIC individual participant data meta­analysis.

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

Availability of healthy foods, fruit and vegetable consumption, and cognition among urban older adults.

BACKGROUND: . Although prior studies have examined the associations between neighborhood characteristics and cognitive health, little is known about whether local food environments, which are critical for individuals' daily living, are associated with late-life cognition. Further, little is known about how local environments may shape individuals' health-related behaviors and impact cognitive health. The aim of this study is to examine whether objective and subjective measures of healthy food availability are associated with ambulatory cognitive performance and whether behavioral and cardiovascular factors mediate these associations among urban older adults. METHODS: . The sample consisted of systematically recruited, community-dwelling older adults (N = 315, mean age = 77.5, range = 70-91) from the Einstein Aging Study. Objective availability of healthy foods was defined as density of healthy food stores. Subjective availability of healthy foods and fruit/vegetable consumption were assessed using self-reported questionnaires. Cognitive performance was assessed using smartphone-administered cognitive tasks that measured processing speed, short-term memory binding, and spatial working memory performance 6 times a day for 14 days. RESULTS: . Results from multilevel models showed that subjective availability of healthy foods, but not objective food environments, was associated with better processing speed (estimate= -0.176, p = .003) and more accurate memory binding performance (estimate = 0.042, p = .012). Further, 14~16% of the effects of subjective availability of healthy foods on cognition were mediated through fruit and vegetable consumption. CONCLUSIONS: . Local food environments seem to be important for individuals' dietary behavior and cognitive health. Specifically, subjective measures of food environments may better reflect individuals' experiences regarding their local food environments not captured by objective measures. Future policy and intervention strategies will need to include both objective and subjective food environment measures in identifying impactful target for intervention and evaluating effectiveness of policy changes.

Dose-response relationship between late-life physical activity and incident dementia: A pooled analysis of 10 cohort studies of memory in an international consortium.

INTRODUCTION: Though consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear. METHODS: We harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incident dementia among older adults. RESULTS: Using no physical activity as a reference, dementia risk decreased with duration of physical activity up to 3.1 to 6.0 hours/week (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.67 to 1.15 for 0.1 to 3.0 hours/week; HR 0.68, 95% CI 0.52 to 0.89 for 3.1 to 6.0 hours/week), but plateaued with higher duration. For the amount of physical activity, a similar pattern of dose-response curve was observed, with an inflection point of 9.1 to 18.0 metabolic equivalent value (MET)-hours/week (HR 0.92, 95% CI 0.70 to 1.22 for 0.1 to 9.0 MET-hours/week; HR 0.70, 95% CI 0.53 to 0.93 for 9.1 to 18.0 MET-hours/week). DISCUSSION: This cross-national analysis suggests that performing 3.1 to 6.0 hours of physical activity and expending 9.1 to 18.0/MET-hours of energy per week may reduce dementia risk.

Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium.

INTRODUCTION: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. METHODS: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. RESULTS: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. DISCUSSION: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.

Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.

BACKGROUND: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. METHODS AND FINDINGS: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. CONCLUSIONS: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

Health-related Quality of Life, Cognitive Performance, and Incident Dementia in a Community-based Elderly Cohort.

BACKGROUND: We hypothesized that higher quality of life would be associated with better cognitive function and a reduced risk of incident all cause dementia and Alzheimer disease (AD) in older adults. MATERIALS AND METHODS: Participants included 1183 older adults with an average age of 78.2 (SD=5.3) from Einstein Aging Study. The 36-Item Short-Form Health Survey was used to measure health-related quality of life (HRQoL). We investigated baseline associations between the cognitive domains of memory, executive function, and general fluid ability with 8 subscales of the 36-Item Short-Form Health Survey (physical functioning, role limitations due to physical problems, bodily pain, general health perceptions, social functioning, role limitations due to emotional problems, vitality, and general mental health) and the 2 component summary scores of physical component summary (PCS) and mental component summary (MCS). Next, we used Cox proportional hazard models to assess the predictive validity of HRQoL subscales for the onset of incident dementia and incident AD. RESULTS: At baseline, higher scores (better HRQoL) on MCS and its 4 subscales (social functioning, role limitations due to emotional problems, vitality, and general mental health) were associated with higher performance on both memory and executive function domains. Higher scores in role limitation due to physical problems, role limitation due to emotional problems, and general mental health subscales were associated with reduced risk of incident dementia. Higher MCS, but not PCS, predicted a reduced incident of all-cause dementia and AD. CONCLUSIONS: These findings suggest that diminution of HRQoL precedes the onset of diagnosable dementia and may be useful in the prediction of dementia onset.

Depressive Symptoms Predict Incident Dementia in a Community Sample of Older Adults: Results From the Einstein Aging Study.

BACKGROUND:: There is increasing evidence that depressive symptoms are associated with increased risk of cognitive impairment and dementia in older adults. In current study, we aimed to investigate the effect of depressive symptoms on incident Alzheimer disease and all-cause dementia in a community sample of older adults. METHODS:: Participants were 1219 older adults from the Einstein Aging Study, a longitudinal cohort study of community-dwelling older adults in Bronx County, New York. The Geriatric Depression Scale (GDS, 15-item) was used as a measure of depressive symptoms. The primary outcome was incident dementia diagnosed using the Diagnostic and Statistical Manual, Fourth Edition, criteria. Cox proportional hazard models were used to estimate the risk of incident dementia as a function of GDS score for the whole population and also for 2 different time intervals, <3 years and ≥3 years after baseline assessment. RESULTS:: Among participants, 132 individuals developed dementia over an average 4.5 years (standard deviation [SD] = 3.5) of follow-up. Participants had an average age of 78.3 (SD = 5.4) at baseline, and 62% were women. Among all participants, after controlling for demographic variables and medical comorbidities, a 1-point increase in GDS was associated with higher incidence of dementia (hazard ratio [HR] = 1.11, P = .007). After up to 3 years of follow-up, depressive symptoms were not significantly associated with dementia incidence (HR = 1.09; P = .070). However, after more than 3 years, GDS score was a significant predictor of incident dementia (HR = 1.13, P = .028). CONCLUSIONS:: Our results suggest that depressive symptoms are associated with an increased risk of incident dementia in older adults.

Visual memory tests enhance the identification of amnestic MCI cases at greater risk of Alzheimer's disease.

OBJECTIVES: To investigate whether amnestic mild cognitive impairment (aMCI) identified with visual memory tests conveys an increased risk of Alzheimer's disease (risk-AD) and if the risk-AD differs from that associated with aMCI based on verbal memory tests. PARTICIPANTS: 4,771 participants aged 70.76 (SD = 6.74, 45.4% females) from five community-based studies, each a member of the international COSMIC consortium and from a different country, were classified as having normal cognition (NC) or one of visual, verbal, or combined (visual and verbal) aMCI using international criteria and followed for an average of 2.48 years. Hazard ratios (HR) and individual patient data (IPD) meta-analysis analyzed the risk-AD with age, sex, education, single/multiple domain aMCI, and Mini-Mental State Examination (MMSE) scores as covariates. RESULTS: All aMCI groups (n = 760) had a greater risk-AD than NC (n = 4,011; HR range = 3.66 - 9.25). The risk-AD was not different between visual (n = 208, 17 converters) and verbal aMCI (n = 449, 29 converters, HR = 1.70, 95%CI: 0.88, 3.27, p = 0.111). Combined aMCI (n = 103, 12 converters, HR = 2.34, 95%CI: 1.13, 4.84, p = 0.023) had a higher risk-AD than verbal aMCI. Age and MMSE scores were related to the risk-AD. The IPD meta-analyses replicated these results, though with slightly lower HR estimates (HR range = 3.68, 7.43) for aMCI vs. NC. CONCLUSIONS: Although verbal aMCI was most common, a significant proportion of participants had visual-only or combined visual and verbal aMCI. Compared with verbal aMCI, the risk-AD was the same for visual aMCI and higher for combined aMCI. Our results highlight the importance of including both verbal and visual memory tests in neuropsychological assessments to more reliably identify aMCI.

Motoric cognitive risk syndrome and predictors of transition to dementia: A multicenter study.

INTRODUCTION: To report clinical predictors of transition to dementia in motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait. METHODS: We examined if cognitive or motoric impairments predicted transition to dementia in 610 older adults with MCR from three cohorts. Association of cognitive (logical memory, clinical dementia rating, cognitive complaint severity, and Mini-Mental State Examination) and motoric factors (gait velocity) with dementia risk was computed using Cox models. RESULTS: There were 156 incident dementias (134 Alzheimer's disease). In the pooled sample, logical memory (adjusted hazard ratio [aHR] 0.91), cognitive complaint severity (aHR 1.53), and Mini-Mental State Examination (aHR 0.75) predicted transition of MCR to dementia. Clinical dementia rating score ≥0.5 predicted dementia (aHR 3.18) in one cohort. Gait velocity did not predict dementia. DISCUSSION: While MCR is a motoric-based predementia syndrome, severity of cognitive but not motoric impairments predicts conversion to dementia.

Neuropsychological latent classes at enrollment and postmortem neuropathology.

INTRODUCTION: We classified individuals based on their baseline performance on cognitive measures and investigated the association between cognitive classifications and neuropathological findings ∼7 years later, as an external validator. METHODS: Brain autopsies of 779 decedents were examined. Baseline latent class analysis on 10 neuropsychological measures was previously assigned: mixed-domains impairment (n = 39, 5%), memory-specific impairment (n = 210, 27%), frontal impairment (n = 113, 14.5%), average cognition (n = 360, 46.2%), and superior cognition (n = 57, 7.3%). Linear regressions and risks ratios were used to examine the relation of latent class assignment at enrollment with neuropathological indices. RESULTS: Amyloid ß, tau, and transactive response DNA-binding protein 43 were associated with mixed-domains impairment and memory-specific impairment classes ∼7 years before death. Moderate arteriolosclerosis was associated with membership in the frontal impairment class. DISCUSSION: Our findings support the use of latent class models that incorporate more comprehensive neuropsychological measures to classify cognitive impairment.

Negative and positive affect as predictors of inflammation: Timing matters.

Very little research has assessed how measures of negative and positive affect (NA and PA) derived from assessments at multiple time points per day (e.g., via ecological momentary assessment [EMA]), as opposed to questionnaires that rely on recall over a longer period, are related to levels of peripheral inflammation. We examined how different indicators of NA and PA predicted concentrations of C-reactive protein (CRP) and seven peripheral inflammatory cytokines (IL-1ß, IL-6, TNF-α, IL-8, IL-4, IL-10, and IFN-γ) that were examined in the form of an inflammatory composite. A community-based sample of 220 adults (62% Black/African-American and 25% Hispanic/Latino; aged 25-65; 65% female) completed questionnaires at baseline (including recalled affect "over the past month") and then provided EMA reports 5x/day for 14 days. Blood was drawn from each participant after completion of EMA and used to determine plasma levels of CRP and cytokines. Analyses examined if indicators of affect predicted inflammation, controlling for age, gender, body mass index, education, health conditions, and statin use. Neither recalled NA or PA nor momentary NA or PA (aggregated across the 14 days of EMA) were significantly associated with the cytokine composite or CRP. Negative mood more proximal to the blood draw (i.e., aggregated momentary NA in week 2 of EMA) was associated with the cytokine composite but not CRP. Exploratory moderation analyses revealed that the cytokine composite was also associated with PA in week 2 for men only, and with recalled NA for those with lower education. Exploratory analyses around temporal dynamics suggested that the timing of NA measurement relative to the blood draw mattered: Specifically, there were stronger trends of association between momentary NA and inflammatory cytokines when NA was assessed closer in time to blood collection. Future investigation of the relevance of temporal proximity and other measurement details may improve understanding of how affect relates to inflammation.

Identification of Heterogeneous Cognitive Subgroups in Community-Dwelling Older Adults: A Latent Class Analysis of the Einstein Aging Study.

OBJECTIVES: The aim of this study was to identify natural subgroups of older adults based on cognitive performance, and to establish each subgroup's characteristics based on demographic factors, physical function, psychosocial well-being, and comorbidity. METHODS: We applied latent class (LC) modeling to identify subgroups in baseline assessments of 1345 Einstein Aging Study (EAS) participants free of dementia. The EAS is a community-dwelling cohort study of 70+ year-old adults living in the Bronx, NY. We used 10 neurocognitive tests and 3 covariates (age, sex, education) to identify latent subgroups. We used goodness-of-fit statistics to identify the optimal class solution and assess model adequacy. We also validated our model using two-fold split-half cross-validation. RESULTS: The sample had a mean age of 78.0 (SD=5.4) and a mean of 13.6 years of education (SD=3.5). A 9-class solution based on cognitive performance at baseline was the best-fitting model. We characterized the 9 identified classes as (i) disadvantaged, (ii) poor language, (iii) poor episodic memory and fluency, (iv) poor processing speed and executive function, (v) low average, (vi) high average, (vii) average, (viii) poor executive and poor working memory, (ix) elite. The cross validation indicated stable class assignment with the exception of the average and high average classes. CONCLUSIONS: LC modeling in a community sample of older adults revealed 9 cognitive subgroups. Assignment of subgroups was reliable and associated with external validators. Future work will test the predictive validity of these groups for outcomes such as Alzheimer's disease, vascular dementia and death, as well as markers of biological pathways that contribute to cognitive decline. (JINS, 2018, 24, 511-523).

Recalled early life adversity and pain: the role of mood, sleep, optimism, and control.

Early life adversity (ELA) has been associated with pain symptomatology in adulthood, but mechanisms and moderators of these associations are unclear. Using recall based and concurrently assessed self-report data, we examined associations between ELA, mood, sleep, and recent pain intensity and interference, and whether optimism and perceived control weakened these associations in a midlife community sample of diverse adults reporting some ELA. Controlling for demographic variables and BMI, higher levels of ELA were associated with more pain intensity and interference; greater sleep disturbance and negative mood accounted for these associations. When moderation was examined, only the path from sleep disturbance to pain interference was significantly attenuated for those with higher optimism and higher perceived control. These findings suggest that higher levels of ELA may link with pain in adulthood through poorer mood and sleep, and that resilience resources such as optimism and control may buffer some of these pathways.

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

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

Sex Differences in the Relationship between Depressive Symptoms and Risk of Amnestic Mild Cognitive Impairment.

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.

Pain Intensity and Pain Interference in Older Adults: Role of Gender, Obesity and High-Sensitivity C-Reactive Protein.

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.

Cognitive Impairment and Dementia in Older Adults With Chronic Kidney Disease: A Review.

Individuals with chronic kidney disease (CKD), especially older adults, are at more risk of experiencing cognitive impairment, possibly leading to mild cognitive impairment and/or dementia. Studies report associations between CKD and cognitive impairment; although unclear, there seems to be a graded association between stage of CKD and affected cognitive domains, with executive function being affected earlier in the process than episodic memory and global ability. In CKD, dysexecutive mild cognitive impairment and vascular dementia are also more prominent than other subtypes. Explanations are directed toward traditional and nontraditional vascular factors, which may also explain or mediate the association between CKD and type of cognitive impairment. Future research is urged to focus on the longitudinal association between specific domains of cognitive function, including executive function and memory and CKD; to develop screening tools fit for every CKD stage in elderly individuals, and lastly, to use imaging methods that may help clarify the underlying mechanisms connecting the kidney and the brain.

Influence of Perceived Stress on Incident Amnestic Mild Cognitive Impairment: Results From the Einstein Aging Study.

Stress is a potentially remediable risk factor for amnestic mild cognitive impairment (aMCI). Our objective is to determine whether perceived stress predicts incident aMCI and to determine if the influence of stress on aMCI is independent of known aMCI risk factors, particularly demographic variables, depression, and apolipoprotein genotype. The Einstein Aging Study is a longitudinal community-based study of older adults. The Perceived Stress Scale (PSS) was administered annually in the Einstein Aging Study to participants (N=507; 71 developed incident aMCI; mean follow-up time=3.6 y, SD=2.0) who were aged 70 years and older, free of aMCI and dementia at baseline PSS administration, and had at least 1 subsequent annual follow-up. Cox hazard models were used to examine time to aMCI onset adjusting for covariates. High levels of perceived stress are associated with a 30% greater risk of incident aMCI (per 5-point increase in PSS: hazard ratio=1.30; 95% confidence interval, 1.08-1.58) independent of covariates. The consistency of results after covariate adjustment and the lack of evidence for reverse causation in longitudinal analyses suggest that these findings are robust. Understanding of the effect of perceived stress on cognition may lead to intervention strategies that prevent the onset of aMCI and Alzheimer dementia.