Search

OBJECTIVE: Although patients with type 2 diabetes have double the risk of dementia, potential racial/ethnic differences in dementia risk have not been explored in this population. We evaluated racial/ethnic differences in dementia and potential explanatory

OBJECTIVE-Type 2 diabetes has been linked with increased risk of dementia and cognitive impairment among older adults and with premature mortality in young and middleaged adults. No studies have evaluated the association between diabetes and dementia among

Background:Persistent pathogens have been proposed as risk factors for stroke; however, the evidence remains inconclusive. Mexican Americans have an increased risk of stroke especially at younger ages, as well as a higher prevalence of infections caused by

Background: There is a need for more Comparative Effectiveness Research (CER) to strengthen the evidence base for clinical and policy decision-making. Effectiveness Guidance Documents (EGD) are targeted to clinical researchers. The aim of this EGD is to pr

Background/objectivesA common polymorphism, C776G, in the plasma B12 transport protein transcobalamin (TC), encodes for either proline or arginine at codon 259. This polymorphism may affect the affinity of TC for B12 and subsequent delivery of B12 to tissues.Subjects/methodsTC genotype and its associations with indicators of B12 status, including total B12, holotranscobalamin (holoTC), methylmalonic acid and homocysteine, were evaluated in a cohort of elderly Latinos (N=554, age 60-93 years) from the Sacramento Area Latino Study on Aging (SALSA).ResultsThe distribution of TC genotypes was 41.3% homozygous reference (776CC) and 11.6% homozygous variant (776GG). No differences between the homozygous genotypes were observed in total B12, holoTC, methylmalonic acid or homocysteine. The holoTC/total B12 ratio was lower in the 776GG group compared with the 776CC group (P=0.04). Significant interactions of TC genotype with total B12 (P=0.04) and with holoTC (P< or =0.03) were observed such that mean homocysteine concentrations and the odds ratios for hyperhomocysteinemia (>13 micromol/l) were higher in the 776CC subjects compared with all carriers of the G allele (776CG and 776GG combined) when total B12 (

Background: Although the apolipoprotein (APOE)-epsilon4 allele has been shown to determine the outcome of several infections, its relationship with cytomegalovirus (CMV) has not been explored. We examine whether APOE determines CMV and herpes simplex virus type 1 (HSV-1) antibody levels and assess whether C-reactive protein (CRP) mediates any observed relationships.Methods: We conducted a cross-sectional analysis of a randomly selected subset (n = 1561/1789) of participants aged 60-101 in the Sacramento Area Latino Study on Aging. Blood samples were tested for APOE genotype, CRP, and immunoglobulin G antibodies to CMV and HSV-1. Multivariate logistic regression was used to examine the association between epsilon4 and CMV and HSV antibody levels. We also assessed whether CRP mediates the effects of any observed associations between epsilon4 and viral antibody levels.Results: CMV antibody and CRP levels varied significantly by APOE genotype. The association between CRP and CMV antibody was strengthened in the presence of epsilon4. In contrast, this effect was not observed in HSV-1. We found that APOE-epsilon4 carriers had significantly lower levels of CRP yet significantly higher levels of CMV antibodies, suggesting a mediating pathway.Conclusions: APOE-epsilon4 carriers may experience immunological aberrations that lead to lower levels of CRP and correspondingly higher CMV antibody levels. [ABSTRACT FROM AUTHOR]

Objective: We sought to examine demographic, socioeconomic, and biological predictors of all-cause, cardiovascular, and noncardiovascular mortality in patients with diabetes.Research Design and Methods: Survey, medical record, and administrative data were obtained from 8,733 participants in the Translating Research Into Action for Diabetes Study, a multicenter, prospective, observational study of diabetes care in managed care. Data on deaths (n = 791) and cause of death were obtained from the National Death Index after 4 years. Predictors examined included age, sex, race, education, income, duration, and treatment of diabetes, BMI, smoking, microvascular and macrovascular complications, and comorbidities.Results: Predictors of adjusted all-cause mortality included older age (hazard ratio [HR] 1.04 [95% CI 1.03-1.05]), male sex (1.57 [1.35-1.83]), lower income (< $15,000 vs. > $75,000, HR 1.82 [1.30-2.54]; $15,000-$40,000 vs. > $75,000, HR 1.58 [1.15-2.17]), longer duration of diabetes (> or = 9 years vs. < 9 years, HR 1.20 [1.02-1.41]), lower BMI (< 26 vs. 26-30 kg/m2, HR 1.43 [1.13-1.69]), smoking (1.44 [1.20-1.74]), nephropathy (1.46 [1.23-2.73]), macrovascular disease (1.46 [1.23-1.74]), and greater Charlson index (> or = 2-3 vs. < 1, HR 2.01 [1.04-3.90]; > or = 3 vs. < 1, HR 4.38 [2.26-8.47]). The predictors of cardiovascular and noncardiovascular mortality were different. Macrovascular disease predicted cardiovascular but not noncardiovascular mortality.Conclusions: Among people with diabetes and access to medical care, older age, male sex, smoking, and renal disease are important predictors of mortality. Even within an insured population, socioeconomic circumstance is an important independent predictor of health. [ABSTRACT FROM AUTHOR]

Purpose: The current study was designed to evaluate the utility of antidiabetic medications in affecting changes in physical and cognitive functioning among older Mexican Americans with diabetes over a 2-year period.Methods: A longitudinal analysis with repeated measurements between 1999 and 2001 was performed in a cohort of Mexican Americans, 60 or older, in the SALSA Project. Statistical analysis was conducted using a generalized estimating equation.Results: For subjects with diagnosed diabetes Conclusions: Antidiabetic drugs appear to be useful in alleviating the decline in physical and cognitive functioning among older Mexican Americans with diabetes, especially for those with a longer duration of the disease. [ABSTRACT FROM AUTHOR]

Objective: Epidemiological studies have demonstrated that older Mexican Americans are at high risk for type 2 diabetes and its complications. Type 2 diabetes leads to a more rapid decline in functional status among older Mexican Americans with diabetes. This study was designed to examine the impact of diabetes on change in self-reported functional status over a 2-year period among older Mexican Americans with diabetes.Research Design and Methods: We performed a longitudinal analysis with repeated measurements of functional limitations in a cohort of Mexican Americans aged > or =60 years in the Sacramento Area Latino Study on Aging (SALSA). Diabetes was diagnosed on the basis of self-report of physician diagnosis, medication use, and fasting plasma glucose. Functional status was measured by assessment of activities of daily living (ADL) and instrumental activities of daily living (IADL) at baseline and 1 and 2 years.Results: Of 1,789 SALSA participants, 585 (33%) had diabetes at baseline. Diabetic subjects reported 74% more limitations than nondiabetic subjects in ADL (summary score for number of limitations, 0.99 vs. 0.57; P = 0.002) and 50% more limitations in IADL (summary score for number of limitations, 7.83 vs. 5.25; P < 0.0001). The annual rate of increase in limitations of ADL and IADL was 0.046 and 0.033 (log scale) on each scale among diabetic subjects compared with 0.013 and 0.003 (log scale) among nondiabetic subjects (P < 0.0005). Complications of diabetes were found to increase ADL and IADL limitations among diabetic subjects. Longer duration of diabetes was also associated with an increase in ADL and IADL limitations.Conclusions: There was lower baseline functional status and a more rapid decline in functional status among older Mexican Americans with diabetes versus those without diabetes. [ABSTRACT FROM AUTHOR]

Background: This study examined the secular trends of life expectancy without dementia among elderly American members of a health maintenance organization, and observed if an increased life expectancy is accompanied by an increase in the duration of life with dementia.Methods: The data derived from two chronological 9-year prospective cohort studies of members of the Kaiser Permanente Medical Care Program of Northern California. The first and second cohorts included 2,702 and 2,926 people aged > or =65 years free from dementia at baseline. Life expectancy without dementia or dementia-free life expectancy (DemFLE) is defined as the average number of years a person is expected to live without dementia. Total life expectancy is equal to the sum of DemFLE and life expectancy with dementia. Estimations of DemFLE were based on mortality data and incidence of dementia, using double-decrement life tables.Results: Between the first and second cohorts, all-cause mortality rates declined, while the incidence of dementia remained constant in both men and women. Among the males, total life expectancy increased at a higher rate than DemFLE. Consequently, the duration of life with dementia was extended in the second cohort. Conversely, among the females DemFLE increased at a higher rate than total life expectancy, thus the duration of life with dementia decreased in the second cohort. The median age of dementia onset was postponed by 2-3 years in the second cohort for females, and did not show any specific difference between the two cohorts in males.Conclusion: The trends of health expectancies suggest an extension of the duration of life with dementia for males and a compression of dementia for females. A decreased incidence of risk factors for dementia among females in the second cohort such as stroke may explain these trends. [ABSTRACT FROM AUTHOR]

OBJECTIVES: this study examined the association between medically recognized urinary incontinence and risk of several disease conditions, hospitalization, nursing home admission and mortality. DESIGN: review and abstraction of medical records and computerized data bases from 5986 members, aged 65 years and older, of a large health maintenance organization in northern California. RESULTS: there was an increased risk of newly recognized urinary incontinence following a diagnosis of Parkinson's disease, dementia, stroke, depression and congestive heart failure in both men and women, after adjustment for age and cohort. The risk of hospitalization was 30% higher in women following the diagnosis of incontinence [relative risk (RR) = 1.3, 95% confidence interval (CI) = 1.2-1.5] and 50% higher in men (RR = 1.5, 95% CI = 1.3-1.6) after adjustment for age, cohort and co-morbid conditions. The adjusted risk of admission to a nursing facility was 2.0 times greater for incontinent women (95% CI = 1.7-2.4) and 3.2 times greater for incontinent men (95% CI = 2.7-3.8). In contrast, the adjusted risk of mortality was only slightly greater for women (RR = 1.1; 95% CI = 0.99-1.3) and men (RR= 1.2; 95% CI= 1.1-1.4). CONCLUSIONS: urinary incontinence increases the risk of hospitalization and substantially increases the risk of admission to a nursing home, independently of age, gender and the presence of other disease conditions, but has little effect on total mortality. [ABSTRACT FROM AUTHOR]

Background and Objectives: Previous randomized controlled trials and longitudinal studies have indicated that ongoing antihypertensive use in late life reduces all-cause dementia risk, but the specific impact on Alzheimer dementia (AD) and non-AD risk remains unclear. This study investigates whether previous hypertension or antihypertensive use modifies AD or non-AD risk in late life and the ideal blood pressure (BP) for risk reduction in a diverse consortium of cohort studies., Methods: This individual participant data meta-analysis included community-based longitudinal studies of aging from a preexisting consortium. The main outcomes were risk of developing AD and non-AD. The main exposures were hypertension history/antihypertensive use and baseline systolic BP/diastolic BP. Mixed-effects Cox proportional hazards models were used to assess risk and natural splines were applied to model the relationship between BP and the dementia outcomes. The main model controlled for age, age 2 , sex, education, ethnoracial group, and study cohort. Supplementary analyses included a fully adjusted model, an analysis restricting to those with >5 years of follow-up and models that examined the moderating effect of age, sex, and ethnoracial group., Results: There were 31,250 participants from 14 nations in the analysis (41% male) with a mean baseline age of 72 (SD 7.5, range 60-110) years. Participants with untreated hypertension had a 36% (hazard ratio [HR] 1.36, 95% CI 1.01-1.83, p = 0.0406) and 42% (HR 1.42, 95% CI 1.08-1.87, p = 0.0135) increased risk of AD compared with "healthy controls" and those with treated hypertension, respectively. Compared with "healthy controls" both those with treated (HR 1.29, 95% CI 1.03-1.60, p = 0.0267) and untreated hypertension (HR 1.69, 95% CI 1.19-2.40, p = 0.0032) had greater non-AD risk, but there was no difference between the treated and untreated groups. Baseline diastolic BP had a significant U-shaped relationship ( p = 0.0227) with non-AD risk in an analysis restricted to those with 5-year follow-up, but otherwise there was no significant relationship between baseline BP and either AD or non-AD risk., Discussion: Antihypertensive use was associated with decreased AD but not non-AD risk throughout late life. This suggests that treating hypertension throughout late life continues to be crucial in AD risk mitigation. A single measure of BP was not associated with AD risk, but DBP may have a U-shaped relationship with non-AD risk over longer periods in late life.

Importance: The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested., Objectives: To assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age >60 years) with dementia and the moderating factors of age, sex, and racial group., Data Source and Study Selection: Longitudinal, population-based studies of aging participating in the Cohort Studies of Memory in an International Consortium (COSMIC) group were included. Participants were individuals without dementia at baseline aged 60 to 110 years and were based in 15 different countries (US, Brazil, Australia, China, Korea, Singapore, Central African Republic, Republic of Congo, Nigeria, Germany, Spain, Italy, France, Sweden, and Greece)., Data Extraction and Synthesis: Participants were grouped in 3 categories based on previous diagnosis of hypertension and baseline antihypertensive use: healthy controls, treated hypertension, and untreated hypertension. Baseline systolic BP (SBP) and diastolic BP (DBP) were treated as continuous variables. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data reporting guidelines., Main Outcomes and Measures: The key outcome was all-cause dementia. Mixed-effects Cox proportional hazards models were used to assess the associations between the exposures and the key outcome variable. The association between dementia and baseline BP was modeled using nonlinear natural splines. The main analysis was a partially adjusted Cox proportional hazards model controlling for age, age squared, sex, education, racial group, and a random effect for study. Sensitivity analyses included a fully adjusted analysis, a restricted analysis of those individuals with more than 5 years of follow-up data, and models examining the moderating factors of age, sex, and racial group., Results: The analysis included 17 studies with 34 519 community dwelling older adults (20 160 [58.4%] female) with a mean (SD) age of 72.5 (7.5) years and a mean (SD) follow-up of 4.3 (4.3) years. In the main, partially adjusted analysis including 14 studies, individuals with untreated hypertension had a 42% increased risk of dementia compared with healthy controls (hazard ratio [HR], 1.42; 95% CI 1.15-1.76; P = .001) and 26% increased risk compared with individuals with treated hypertension (HR, 1.26; 95% CI, 1.03-1.53; P = .02). Individuals with treated hypertension had no significant increased dementia risk compared with healthy controls (HR, 1.13; 95% CI, 0.99-1.28; P = .07). The association of antihypertensive use or hypertension status with dementia did not vary with baseline BP. There was no significant association of baseline SBP or DBP with dementia risk in any of the analyses. There were no significant interactions with age, sex, or racial group for any of the analyses., Conclusions and Relevance: This individual patient data meta-analysis of longitudinal cohort studies found that antihypertensive use was associated with decreased dementia risk compared with individuals with untreated hypertension through all ages in late life. Individuals with treated hypertension had no increased risk of dementia compared with healthy controls.

Purpose: We tested whether dietary modification (DM) altered the risk for incident primary open-angle glaucoma (POAG)., Design: Secondary analysis of a randomized intervention trial., Participants: We linked Medicare claims data to 45 203 women in the Women's Health Initiative Dietary Modification Trial, of which 23 776 participants were enrolled in fee-for-service Medicare Part B and had physician claims., Methods: Women were randomized to follow either DM (a low-fat diet, with increased vegetable, fruit, and grain intake) or their usual diet without modification. Nine thousand three hundred forty women were randomized to the DM intervention, whereas 13 877 women were randomized to the control group. Our analyses were based on an intention-to-treat design, with a follow-up to the end of continuous Medicare coverage, death, or the last claims date (12/31/2018), whichever occurred first. Primary open-angle glaucoma was defined as the first claim with the International Classification of Diseases, Ninth or Tenth Revision, codes. Dietary data were assessed using a food frequency questionnaire., Main Outcome Measures: We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of POAG. Subgroup analyses were performed with P values for interaction., Results: After exclusion of women with Medicare-derived glaucoma before randomization, the final analysis included 23 217 women (mean age, 64.4 ± 5.8 years). Baseline characteristics were balanced between the intervention and control groups. Primary open-angle glaucoma incidence was 11.1 per 1000 woman-years (mean follow-up, 11.6 ± 7.4 years; mean DM duration, 5.2 ± 3.2 years). We found no overall benefit of DM in reducing incident POAG (HR, 1.04; 95% CI, 0.96-1.12). Race and participant age did not modify this relation (P = 0.08 and P = 0.24 for interaction, respectively). In further analysis of baseline nutrient and food intake stratified by quartile groups, risk of open-angle glaucoma (OAG) in DM participants in the lowest quartile group for percentage calories (kilocalories) from total fat (33.8 or lower) was increased (HR, 1.22; 95% CI, 1.05-1.41; P = 0.007 for interaction)., Conclusions: Analysis suggests that DM in participants in the lowest quartile group for percentage calories from total fat at baseline increased the risk of incident OAG among women regardless of age or race., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the relationships between optic nerve cupping and total and regional brain volumes., Design: Secondary analysis of randomized clinical trial data., Methods: Women 65 to 79 years of age without glaucoma with cup-to-disc ratio (CDR) measurements from the Women's Health Initiative (WHI) Sight Examination study and magnetic resonance imaging (MRI)-based total and regional brain volumes from the WHI Memory Study MRI-1 were included. Large CDR was defined as 0.6 or greater in either eye. Generalized estimating equation models were used to account for intra-brain correlations between the right and left sides. The final analysis was adjusted for demographic and clinical characteristics and for total brain volume (for regional analyses)., Results: Final analyses included 471 women, with the mean age ± SD was 69.2 ± 3.6 years; 92.8% of the subjects were white. Of 471 women, 34 (7.2%) had large CDR. Controlling for total brain volume and for demographic and clinical characteristics, lateral ventricle volume was 3.01 cc larger for subjects with large CDR compared to those without large CDR (95% CI = 0.02 to 5.99; P = .048). Furthermore, frontal lobe volume was 4.78 cc lower for subjects with large CDR compared to those without (95% CI = -8.71, -0.84; P = 0.02), and occipital lobe volume was 1.86 cc lower for those with large CDR compared to those without (95% CI = -3.39, -0.3; P =.02)., Conclusions: Our analysis suggests that in women aged 65 years or more, large CDR is associated with lower relative total brain volume and absolute regional volume in the frontal and occipital lobes. Enlarged CDR in individuals without glaucoma may represent a sign of optic nerve and brain aging, although more longitudinal data are needed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (© 2022 the Alzheimer's Association.)

Purpose: To investigate if accounting for a cup-to-disc ratio (CDR) genetic risk score (GRS) modified the association between large CDR and cognitive function among women., Design: This was a retrospective study using data from the Women's Health Initiative., Methods: Patients with glaucoma or ocular hypertension were excluded. Large CDR was defined as ≥ 0.6 in either eye. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used the combined effects from 13 single nucleotide polymorphisms (SNPs) to formulate the GRS for CDR. We used logistic regression to investigate associations between weighted GRS and large CDR, then a linear regression to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for demographic and clinical characteristics., Results: Final analyses included 1,196 White women with mean age of 69.60 ± 3.62 years and 7.27% with large CDR. Mean GRS in women with and without large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, respectively (p = 0.004). The odds of large CDR for a one unit increase in GRS was 2.30 (95% CI: (1.22, 4.36), p = 0.011). Adding the CDR GRS in the model with CDR and 3MSE, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.84 (p = 0.007)., Conclusions: Independent of the CDR GRS, women with large CDR had a lower cognitive function., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To evaluate the relationship between red blood cell (RBC) polyunsaturated fatty acid (PUFA) levels, and dietary PUFA and fish intake, with prevalent and incident age-related macular degeneration (AMD) in a US cohort of postmenopausal women., Methods: This analysis included 1456 postmenopausal women from the Women's Health Initiative (WHI) Clinical Trials. RBC PUFAs were measured from fasting serum samples collected at WHI baseline. Dietary PUFAs and fish intake were assessed via food frequency questionnaires at baseline. There were 240 women who had prevalent AMD and 138 who self-reported AMD development over 9.5 years. Adjusted odds ratios and 95% confidence intervals were estimated for prevalent AMD by RBC PUFA levels, dietary PUFA intake, and frequency of fish consumption. Adjusted hazard ratios and 95% confidence intervals were estimated for incident AMD. A p-for-trend was estimated for continuous measures of dietary PUFA and fish intake., Results: No significant association was found between prevalent or incident AMD and RBC docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), EPA, DHA, alpha-linolenic acid (ALA), linoleic acid (LA), or arachidonic acid (AA). A positive association was found between dietary intake of AA and odds of prevalent AMD (p-for-trend for continuous AA intake = 0.02) and between intake of LA/ALA and incident AMD (p-for-trend for continuous ratio of LA/ALA intake = 0.03). No statistically significant associations were found between AMD and dietary intake of PUFAs or fish., Conclusions: RBC PUFAs were not associated with AMD in this cohort. Overall, dietary analyses of PUFAs supported this, excepting dietary AA intake and intake of LA in proportion to ALA of which there were trends of increased risk., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: United States (US) Latinos have the lowest educational attainment of any US racial/ethnic group, which may contribute to their disparate burden of Type 2 Diabetes. Herein, we aimed to examine the association between intergenerational educational mobility and Type 2 Diabetes among US Latino adults., Methods: We used data from the Niños Lifestyle and Diabetes Study (2013-2014) and the Sacramento Area Latino Study on Aging (1998-1999) to link 616 adult Latino children to their parents. Model-based standardization and robust Poisson regression were used to estimate the prevalence of prediabetes, Type 2 Diabetes, treatment and glycemic control, and describe their associations with intergenerational educational mobility., Results: Adult children with stable high intergenerational educational attainment had a higher prevalence of prediabetes (Prevalence Ratio, PR=1.58; 95% Confidence Interval, CI=1.08, 2.34) and lower prevalence of Type 2 Diabetes (PR=0.64, CI=0.41, 0.99), as compared to those who experienced low educational attainment across generations. Downward mobility was associated with a higher prevalence of prediabetes (PR=1.54, CI=1.06, 2.23) and worse glycemic control (PR=2.20, CI=1.13, 4.30), and upward mobility was associated with a lower prevalence of Type 2 Diabetes (PR=0.39, CI=0.22, 0.70)., Conclusions: Our findings from a predominantly Mexican-heritage community suggest that higher education across generations may buffer individuals from glycemic dysregulation. As such, higher education may be a promising public health target to address the rising burden of Type 2 Diabetes in the US., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Migrating from Mexico to the U.S. is a major, stressful life event with potentially profound influences on mental health. However, estimating the health effects of migration is challenging because of differential selection into migration and time-varying confounder mediators of migration effects on health., Methods: We pooled data from the Mexican Health and Aging Study (N = 17,771) and Mexican-born U.S. Health and Retirement Study (N = 898) participants to evaluate the effects of migration to the U.S. (at any age and in models for migration in childhood or adulthood) on depressive symptom-count, measured with a modified Centers for Epidemiologic Studies-Depression scale. We modeled probability of migrating in each year of life from birth to either age at initial migration to the U.S. or enrollment and used these models to calculate inverse probability of migration weights. We applied the weights to covariate-adjusted negative binomial GEE models, estimating the ratio of average symptom-count associated with migration., Results: Mexico to U.S. migration was unrelated to depressive symptoms among men (ratio of average symptom-count= 0.98 [95% CI: 0.89, 1.08]) and women (ratio of average symptom-count = 1.00 [95% CI: 0.92, 1.09]). Results were similar for migration in childhood, early adulthood, or later adulthood., Conclusions: In this sample of older Mexican-born adults, migration to the U.S. was unrelated to depressive symptoms., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: This study aimed to estimate the association between cycles of poverty, measured by intergenerational educational attainment (IEA), and the burden of obesity and metabolic dysfunction among Hispanic/Latino individuals in the United States., Methods: This is a cross-sectional study utilizing data from 392 adults linked to 286 biologic parents from the Niños Lifestyle and Diabetes Study and the Sacramento Area Latino Study on Aging. The educational attainment of parents and offspring was dichotomized in order to categorize IEA. Outcomes included obesity and metabolic syndrome (MetS). Model-based standardization with population weights was used to compare obesity and MetS across generations, and Poisson regression was used to estimate prevalence ratios by IEA., Results: A higher prevalence of obesity and MetS was observed in offspring (54% and 69%, respectively) compared with their parents (48% and 42%, respectively). Compared with stable-low IEA, any category with high offspring education was associated with lower obesity and MetS prevalence. The upwardly mobile group saw the greatest benefit; they were 38% (95% CI: 10%-57%) and 46% (95% CI: 21%-63%) less likely to have obesity or MetS., Conclusions: IEA strongly patterns cardiometabolic health among Hispanic/Latino individuals living in the United States, suggesting that promotion of higher education is associated with reductions in obesity and MetS, potentially benefitting future generations of this population., (© 2021 The Obesity Society.)

US Latinos, a growing, aging population, are disproportionately burdened by cognitive decline and dementia. Identification of modifiable risk factors is needed for interventions aimed at reducing risk. Broad sociocultural context may illuminate complex etiology among culturally diverse Latinos. Among 1,418 older (≥60 years), low-socioeconomic position (SEP) Latinos (predominantly of Mexican descent) in Sacramento, California, we examined whether US acculturation was associated with cognitive performance, cognitive decline, and dementia/ cognitive impairment without dementia over a 10-year period and whether education modified the associations (Sacramento Area Latino Study on Aging, 1998-2008). Analyses used linear mixed models, competing-risk regression, and inverse probability of censoring weights for attrition. Participants with high US acculturation had better cognitive performance (0.21 fewer cognitive errors at grand-mean-centered age 70 years) than those with low acculturation after adjustment for sociodemographic factors, practice effects, and survey language. Results may have been driven by cultural language use rather than identity factors (e.g., ethnic identity, interactions). Rate of cognitive decline and risk of dementia/cognitive impairment without dementia did not differ by acculturation, regardless of education (β = 0.00 (standard error, 0.00) and hazard ratio = 0.81 (95% confidence interval: 0.49, 1.35), respectively). High US acculturation was associated with better cognitive performance among these older, low-SEP Latinos. Acculturation may benefit cognition when SEP is low. Future studies should incorporate extended longitudinal assessments among more diverse groups., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Depression commonly accompanies Alzheimer's disease, but the nature of this association remains uncertain., Methods: Longitudinal data from the COSMIC consortium were harmonized for eight population-based cohorts from four continents. Incident dementia was diagnosed in 646 participants, with a median follow-up time of 5.6 years to diagnosis. The association between years to dementia diagnosis and successive depressive states was assessed using a mixed effect logistic regression model. A generic inverse variance method was used to group study results, construct forest plots, and generate heterogeneity statistics., Results: A common trajectory was observed showing an increase in the incidence of depression as the time to dementia diagnosis decreased despite cross-national variability in depression rates., Discussion: The results support the hypothesis that depression occurring in the preclinical phases of dementia is more likely to be attributable to dementia-related brain changes than environment or reverse causality., (© 2020 the Alzheimer's Association.)

Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4)., Methods: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School., Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers., Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study., Competing Interests: Declaration of Competing Interest Richard B. Lipton Is the Edwin S. Lowe Professor of Neurology at the Albert Einstein College of Medicine in New York. He receives research support from the NIH: 2PO1 AG003949 (mPI), 5U10 NS077308 (PI), RO1 NS082432 (Investigator), 1RF1 AG057531 (Site PI), RF1 AG054548 (Investigator), 1RO1 AG048642 (Investigator), R56 AG057548 (Investigator), K23 NS09610 (Mentor), K23AG049466 (Mentor), 1K01AG054700 (Mentor). He also receives support from the Migraine Research Foundation and the National Headache Foundation. He serves on the editorial board of Neurology, senior advisor to Headache, and associate editor to Cephalalgia. He has reviewed for the NIA and NINDS, holds stock options in eNeura Therapeutics and Biohaven Holdings; serves as consultant, advisory board member, or has received honoraria from: American Academy of Neurology, Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, Vedanta. He receives royalties from Wolff’s Headache 7th and 8th Edition, Oxford Press University, 2009, Wiley and Informa. Henry Brodaty is on the Advisory Committee for Nutricia Australia; Clinincal Advisory Committee, Montefiore Home; Medical Advisory Committee, Cranbrook Care. Nikolaos Scarmeas reports personal fees from Merck Consumer Health and the NIH outside the submitted work. Mary Ganguli was on Biogen Inc.’s “Patient Journey Advisory Group” in 2016 and 2017. Allison E. Aiello is a consultant for Kinsa Inc. and has received an unrestricted gift from Gojo Inc. Henry Brodaty is on the Advisory Board of Nutricia Australia., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.)

Low- and middle-income countries (LMICs) are experiencing rapid aging, a growing dementia burden, and relatively high rates of out-migration among working-age adults. Family member migration status may be a unique societal determinant of cognitive aging in LMIC settings. We aimed to evaluate the association between adult child US migration status and change in cognitive performance scores using data from the Mexican Health and Aging Study, a population-based, national-level cohort study of Mexico adults aged ≥50 years at baseline (2001), with 2-, 12-, and 14-year follow-up waves (2003, 2012, and 2015). Cognitive performance assessments were completed by 5,972 and 4,939 respondents at 11 years and 14 years of follow-up, respectively. For women, having an adult child in the United States was associated with steeper decline in verbal memory scores (e.g., for 9-year change in immediate verbal recall z score, marginal risk difference (RD) = -0.09 (95% confidence interval (CI): -0.16, -0.03); for delayed verbal recall z score, RD = -0.10 (95% CI: -0.17, -0.03)) and overall cognitive performance (for overall cognitive performance z score, RD = -0.04, 95% CI: -0.07, -0.00). There were mostly null associations for men. To our knowledge, this is the first study to have evaluated the association between family member migration status and cognitive decline; future work should be extended to other LMICs facing population aging., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To assess whether unhealthy behaviors moderated the relationship between allostatic load (AL) and future significant depressive symptoms (SDSs) among 1,789 older Latinos. Method: Longitudinal data included baseline AL, three unhealthy behaviors (UBs), and 2-year follow-up SDS. Multivariable logistic regression analyses, stratified by birthplace (U.S. vs. foreign born), modeled the effects of AL, UB count (range = 0-3), and their interaction on follow-up SDS. Results: Compared with U.S.-born, foreign-born participants engaged in fewer UBs (0.52 vs. 0.60 behaviors, p = .01) and had higher baseline SDS (31% vs. 20%, p < .001). Among foreign-born participants, the effect of AL on future SDS (adjusted odds ratios [aORs]; 95% confidence interval [CI]) significantly increased across UB counts of 0 to 3: 1.06 [0.83, 1.35], 1.46 [1.14, 1.87], 2.00 [1.18, 3.41], and 2.75 [1.18, 6.44], respectively. Discussion: Among foreign-born Latinos, these results were most pronounced for women and adults above age 80, which may represent higher risk groups requiring more intensive screening for depression.

Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5-22.4 kg/m 2 ), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m 2 ) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative., (© 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background and Objectives: Globally, obesity influences the risk of many major chronic diseases. Our study examines the association between individual nativity and neighborhood level concentration of immigrants with 10-year changes in weight, body mass index (BMI), and waist circumference (WC) among older Latinos., Research Design and Methods: The Sacramento Area Latino Study on Aging (SALSA) is a population-based prospective study of community-dwelling older adults of Mexican origin (baseline ages 58-101 years). The primary outcome was repeated measures of weight over a 10-year period for 1,628 respondents. Nativity was defined by participants' reported place of birth (US-born or Latin American foreign born). Neighborhood immigrant concentration was measured as the percentage of foreign born at census tract level (2000 US Census). We used linear mixed models with repeated measures of weight, height, BMI, and WC as dependent variables (level 1), clustered within individuals (level 2) and neighborhood migrant concentration (level 3)., Results: Foreign born (FB) respondents had lower baseline weight than the US-born (mean, 160 vs. 171 lbs, p < .0001). Over time, weight differences between the FB and the US-born decreased by 1.7 lbs/5 years as US-born weight decreased more rapidly. We observed a significant interaction between individual nativity and neighborhood immigrant concentration (p = .012). We found similar patterns for BMI, but did not find statistically significant differences in WC trajectories., Discussion and Implications: Our study observed significant differences by foreign born vs. US nativity in baseline weight/BMI and in their trajectories over time. Additionally, we found weight/BMI differences in neighborhood immigrant concentration for the FB, but not for the US-born., (© 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.)

Background: Besides physical activity as a target for dementia prevention, sedentary behaviour is hypothesized to be a potential target in its own right. The rising number of persons with dementia and lack of any effective treatment highlight the urgency to better understand these modifiable risk factors. Therefore, we aimed to investigate whether higher levels of sedentary behaviour are associated with reduced global cognitive functioning and slower cognitive decline in older persons without dementia., Methods: We used five population cohorts from Greece, Australia, USA, Japan, and Singapore (HELIAD, PATH, SALSA, SGS, and SLAS2) from the Cohort Studies of Memory in an International Consortium. In a coordinated analysis, we assessed the relationship between sedentary behaviour and global cognitive function with the use of linear mixed growth model analysis (mean follow-up range of 2.0-8.1 years)., Results: Baseline datasets combined 10,450 older adults without dementia with a mean age range between cohorts of 66.7-75.1 years. After adjusting for multiple covariates, no cross-sectional association between sedentary behaviour and cognition was found in four studies. One association was detected where more sedentary behaviour was cross-sectionally linked to higher cognition levels (SLAS2, B = 0.118 (0.075; 0.160), P < 0.001). Longitudinally, there were no associations between baseline sedentary behaviour and cognitive decline (P > 0.05)., Conclusions: Overall, these results do not suggest an association between total sedentary time and lower global cognition in older persons without dementia at baseline or over time. We hypothesize that specific types of sedentary behaviour may differentially influence cognition which should be investigated further. For now, it is, however, too early to establish undifferentiated sedentary time as a potential effective target for minimizing cognitive decline in older adults without dementia.

Heterogeneous exposure associations (HEAs) can be defined as differences in the association of an exposure with an outcome among subgroups that differ by a set of characteristics. In this article, we intend to foster discussion of HEAs in the epidemiologic literature and present a variant of the random forest algorithm that can be used to identify HEAs. We demonstrate the use of this algorithm in the setting of the association between systolic blood pressure and death in older adults. The training set included pooled data from the baseline examination of the Cardiovascular Health Study (1989-1993), the Health, Aging, and Body Composition Study (1997-1998), and the Sacramento Area Latino Study on Aging (1998-1999). The test set included data from the National Health and Nutrition Examination Survey (1999-2002). The hazard ratios ranged from 1.25 (95% confidence interval: 1.13, 1.37) per 10-mm Hg increase in systolic blood pressure among men aged ≤67 years with diastolic blood pressure greater than 80 mm Hg to 1.00 (95% confidence interval: 0.96, 1.03) among women with creatinine concentration ≤0.7 mg/dL and a history of hypertension. HEAs have the potential to improve our understanding of disease mechanisms in diverse populations and guide the design of randomized controlled trials to control exposures in heterogeneous populations., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A higher level of physical activity (PA) is associated with decreased risk of mortality, dementia, and depression, yet the mechanisms involved are not well understood, and little evidence exists for Mexican Americans. With data from the Sacramento Area Latino Study on Aging (1998-2007), we used Cox proportional hazards regression to separately evaluate associations of baseline PA level with mortality, dementia/cognitive impairment without dementia (CIND), and depressive symptoms, and we estimated the mediating effects of inflammatory markers in additive hazard models. A low level of PA (<35 metabolic equivalent of task-hours/week) was associated with increased mortality (hazard ratio (HR) = 1.50, 95% confidence interval (CI): 1.20, 1.88), dementia/CIND (HR = 1.37, 95% CI: 0.96, 1.96), and depressive symptoms (HR = 1.23, 95% CI: 1.00, 1.52). A low PA level added 512 (95% CI: -34, 1,058) cases of dementia/CIND per 100,000 person-years at risk (direct effect), while, through a mediating path, interleukin 6 (IL-6) added another 49 (95% CI: 5, 94) cases, or 9% of the total effect. For mortality, 8%-10% of the PA total effect was mediated through IL-6, tumor necrosis factor α (TNF-α), or TNF-α receptors. None of the inflammatory markers mediated the association between PA and depressive symptoms. Our results suggest that antiinflammation (especially as assessed by IL-6 and TNF-α levels) may partly explain how PA protects against dementia/CIND and mortality., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)