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Background: The influence of socio-economic conditions on covariates of depression has received little attention. Aims: Examine whether prevalence and covariates of depressive symptoms are affected by socio-economic circumstances. Methods: Participants were 1,499 (86%) residents in Bambui city, Brazil, aged ->- 60 years. Depressive symptoms were assessed by the GHQ-12 questionnaire and exploratory variables included demographic characteristics, life events, social support, health conditions and health service use. The analysis was stratified by family income (< US$240.00 [lowest tertile] vs. ->- US$240.00). Results: The prevalence of depressive symptoms was higher in those with lower income (43.9%) in comparison with the better off (27.7%). Dissatisfaction with relationships, worse self-rated health and insomnia were independently associated with depressive symptoms in both income groups (OR from 2.00 to 4.74; p < 0.05). Depressive symptoms were associated with number of chronic diseases, functional disability and hospitalizations among the poorer (OR from 1.73 to 2.37; p < 0.05), while old age (OR 2.08) and female gender (OR 2.03) were associated with depressive symptoms among the better off. Conclusion: This study provides evidence that the prevalence of depressive symptoms and their covariates are influenced by socio-economic conditions in a population with slight income differences. Key words: Brazil, depressive symptoms, elderly, General Health Questionnaire (GHQ-12), socio-economic influence

OBJECTIVES: To investigate the validity of previously suggested dimensions underlying the Mini-Mental State Examination (MMSE) and differences in associations of these dimensions with sociodemographic and health characteristics in an older Latin-American community sample with low levels of education. DESIGN: Secondary analysis of baseline data from a population-based cohort study. SETTING: Bambuí, Brazil. PARTICIPANTS: Of 1,742 total residents aged 60 years or older, 1,558 (89.4%) participated at this study. MEASUREMENTS: A standard Brazilian version of the MMSE. RESULTS: A five-factor solution (Concentration, Language/Praxis, Orientation, Attention, and Memory) for the MMSE was generated from Principal Components Analysis, and the five-factor solutions proposed in previous studies of developed nation samples were tested in this sample by Confirmatory Factor Analysis. In the adjusted linear regression models, MMSE factors varied in their correlates: for example, female gender was associated with higher concentration, orientation, and attention but lower Language/Praxis; increased age was inversely associated only with language and attention; and activity of daily living impairment was principally associated with lower Language/Praxis. CONCLUSION: This study provides support for the cross-sectional equivalence of the MMSE, suggesting that most of the items and underlying constructs remain meaningful after alteration and translation in a low-education sample with lower overall distribution of scores. [ABSTRACT FROM AUTHOR]

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., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: To investigate whether having a higher number of depressive symptoms is associated with negative self-rated health (SRH) even in the absence of illness., Methods: This is a secondary analysis of baseline data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), conducted in 2015-2016, using a national sample of 9,412 people aged 50 or over. SRH was dichotomized into poor or very poor and very good or excellent, good, or average. Depressive symptoms were assessed through the eight-item Center for Epidemiologic Studies Depression Scale (CES-D8). Sociodemographic variables, information about unhealthy behaviors, and the number of chronic conditions were also analyzed., Results: Having depressive symptoms was strongly associated with poor or very poor SRH both in the unadjusted and adjusted analyses. The magnitude of the association was reduced when the number of chronic illnesses was included in the multivariate analysis, along with the other sociodemographic variables and unhealthy behaviors (OR 1.35, 95%CI 1.31-1.39)., Conclusion: Having depressive symptoms may contribute towards having a poorer perception of health, even in the absence of health conditions. SRH is a multidimensional construct that can accurately reflect a person's state of general mental health., Competing Interests: The authors report no conflicts of interest.

Introduction: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers., Methods: We used individual participant data (N = 39271, M age  = 70.67 (40-102), 58.86% female, M education  = 8.43 years, M follow-up  = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes., Results: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality., Discussion: Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally., Highlights: Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: This study aims to investigate handgrip strength and dynapenia prevalence among older adults stratified by Brazilian macroregions. Additionally, we aim to evaluate the overlap between dynapenia and Instrumental Activities of Daily Living (IADL) disability, depression, and executive dysfunction on a national basis and by each Brazilian macroregion., Methods: This cross-sectional analysis was based on data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil). A multistage cluster sample design was used, with a representative population-based study of non-institutionalized community-dwelling Brazilians aged ≥ 50 years from 70 municipalities across all five macroregions of the country. The outcome variable was dynapenia. Covariables were IADL disability, depression, and executive dysfunction. The Brazilian macroregions were used for stratification. In addition, the following additional variables were included: age group, gender, education level, macroregions (North, Northeast, Southeast, South, and Midwest), self-reported health, multimorbidity, and falls., Results: A total of 8,849 (94%) of the sample provided complete information for the handgrip strength assessment and were included in this analysis. Dynapenia prevalence was higher in North and Northeast regions (28.5% and 35.1%, respectively). We identified statistically significant differences between different macroregions for dynapenia, IADL disability, and verbal fluency, with worse values in the North and Northeast regions. In the North and Northeast macroregions, nearly half of the subjects that presented executive dysfunction and IADL disability also had dynapenia. There was a more significant overlap in the prevalence of all four conditions in the North and Northeast regions (4.8% and 5.5%, respectively), whereas the overlap was smaller in the South (2.3%). There was also a smaller overlap in the prevalence of dynapenia and depression in the South (5.8%) compared with other macroregions., Conclusions: Macroregions in Brazil exhibit marked differences in the prevalence of dynapenia and in its overlap with IADL disability, depression, and executive dysfunction.

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., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Approximately 77% of older adults with dementia in Brazil have not been diagnosed, indicating a major public health issue. Previous epidemiological dementia studies in Brazil were based on data from 1 geopolitical region., Methods: We aimed to estimate the general and subgroup-specific (age, education, and sex) prevalence of dementia and cognitive impairment no dementia (CIND) classification using data from 5 249 participants aged 60 years and older from the ELSI-Brazil, a large nationally representative sample. Participants were classified as having normal cognitive function, CIND, or dementia based on a combination of the individual's cognitive and functional status., Results: We found a general prevalence of 5.8% (95% CI = 4.7-7.2) for dementia and 8.1% (95% CI = 6.8-9.5) for CIND. Dementia prevalence ranged from 3.2% (60-64 years old) to 42.8% (≥90 years old) by age, and from 2.1% (college level or higher) to 16.5% (illiterates) by education. Females had a higher dementia prevalence (6.8%) than males (4.6%). CIND prevalence was similar across age, sex, and education., Conclusions: The estimated dementia prevalence is lower than that in previous Brazilian epidemiological studies, but is in line with other Latin American studies. Only 1.2% of the ELSI-Brazil participants reported having a previous diagnosis of dementia, revealing that underdiagnosis is rampant and a common reality. Based on our results and national statistics projections, we estimate that in 2019, there were 1 757 480 people aged 60 years and older living with dementia in Brazil and, at least, another 2 271 314 having to deal with some form of cognitive impairment., (© The Author(s) 2023. 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.)

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.)

Background: Poor social connections (eg, small networks, infrequent interactions, and loneliness) are modifiable risk factors for cognitive decline. Existing meta-analyses are limited by reporting aggregate responses, a focus on global cognition, and combining social measures into single constructs. We aimed to investigate the association between social connection markers and the rate of annual change in cognition (ie, global and domain-specific), as well as sex differences, using an individual participant data meta-analysis., Methods: We harmonised data from 13 longitudinal cohort studies of ageing in North America, South America, Europe, Africa, Asia, and Australia. Studies were eligible for inclusion if they had baseline data for social connection markers and at least two waves of cognitive scores. Follow-up periods ranged from 0 years to 15 years across cohorts. We included participants with cognitive data for at least two waves and social connection data for at least one wave. We then identified and excluded people with dementia at baseline. Primary outcomes were annual rates of change in global cognition and cognitive domain scores over time until final follow-up within each cohort study analysed by use of an individual participant data meta-analysis. Linear mixed models within cohorts used baseline social connection markers as predictors of the primary outcomes. Effects were pooled in two stages using random-effects meta-analyses. We assessed the primary outcomes in the main (partially adjusted) and fully adjusted models. Partially adjusted models controlled for age, sex, and education; fully adjusted models additionally controlled for diabetes, hypertension, smoking, cardiovascular risk, and depression., Findings: Of the 40 006 participants in the 13 cohort studies, we excluded 1392 people with dementia at baseline. 38 614 individual participants were included in our analyses. For the main models, being in a relationship or married predicted slower global cognitive decline (b=0·010, 95% CI 0·000-0·019) than did being single or never married; living with others predicted slower global cognitive (b=0·007, 0·002-0·012), memory (b=0·017, 0·006-0·028), and language (b=0·008, 0·000-0·015) decline than did living alone; and weekly interactions with family and friends (b=0·016, 0·006-0·026) and weekly community group engagement (b=0·030, 0·007-0·052) predicted slower memory decline than did no interactions and no engagement. Never feeling lonely predicted slower global cognitive (b=0·047, 95% CI 0·018-0·075) and executive function (b=0·047, 0·017-0·077) decline than did often feeling lonely. Degree of social support, having a confidante, and relationship satisfaction did not predict cognitive decline across global cognition or cognitive domains. Heterogeneity was low (I 2 =0·00-15·11%) for all but two of the significant findings (association between slower memory decline and living with others [I 2 =58·33%] and community group engagement, I 2 =37·54-72·19%), suggesting robust results across studies., Interpretation: Good social connections (ie, living with others, weekly community group engagement, interacting weekly with family and friends, and never feeling lonely) are associated with slower cognitive decline., Funding: EU Joint Programme-Neurodegenerative Disease Research grant, funded by the National Health and Medical Research Council Australia, and the US National Institute on Aging of the US National Institutes of Health., Competing Interests: Declaration of interests HB declares consulting fees from Biogen; advisory board fees from Nutricia, Roche, Skin2Neuron, and Cranbrook Care; and grant funding through the EU Joint Programme–Neurodegenerative Disease Research (JPND) from the National Health and Medical Research Council Australia. DML declares funding to their institution by the US National Institute on Aging–National Institutes of Health (NIA–NIH) award (number RF1AG05753 1RF1AG057531–01). RM declares funding from the JPND. HW declares a research grant from the JPND for the SHARED project (grant number HESOCARE-329–109). PSS declares payments for advisory board meetings for Biogen Australia and Roche Australia, and funding to the university for another cohort study (OATS), unrelated to the submitted work. SSa declares payments for lectures from New York University Sydney and University of Sydney; grant funding from the Dementia Australia Research Foundation, unrelated to the submitted work; and grant funding from the JPND and National Health and Medical Research Council Australia. NS declares that they are the chair of the data safety monitoring board for a study funded by the NIH at Albert Einstein College of Medicine. DS declares funding under the aegis of the JPND (National Center for Research and Development in Poland, project number JPND/06/2020). JM declares funding as part of the SHARED consortium, a JPND that is supported by the Alzheimer's Society (reference 469) in the UK. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To examine the prevalence of psychiatric symptoms and associated factors in the adult population of Brumadinho (MG), after the dam collapse., Methods: We included 2,740 participants with information about symptoms of post-traumatic stress disorder (PTSD), depression, anxiety, thoughts of death/self-harm, and poor sleep quality collected in 2021. Prevalence values of all conditions were estimated to compare the prevalence of psychiatric symptoms with the participants' sociodemographic characteristics and place of residence. Pearson's c2 test was used, with Rao Scott's correction. Crude and adjusted logistic regressions estimated odds ratios and 95% confidence intervals to assess the association between psychiatric symptoms and participants' characteristics., Results: The most common condition was depressive symptoms (29.3%), followed by post-traumatic stress symptoms (22.9%) and anxious symptoms (18.9%). Regarding the association between participants' characteristics in the adjusted analysis, being a female and living in a mining area was positively associated with symptoms of PTSD, depression, anxiety, thoughts of death/self-harm, and poor sleep quality. A positive association was also found between high school education and post-traumatic stress symptoms. In contrast a negative association was found between being aged ≥60 years and symptoms of PTSD, depression, and anxiety., Conclusion: High prevalence values were found for all psychiatric symptoms after the dam failure in Brumadinho. Being a female, living in the mining area, being ≥60 years old, and having an educational level were all associated with the psychiatric symptoms investigated.

Background: Cognitive impairment and physical frailty are common among older adults and associated with a higher likelihood of adverse health outcomes. These two conditions frequently coexist in the same individual as cognitive frailty, yet few studies have examined the impact of such comorbidity on clinical outcomes or underlying biological mechanisms., Methods: A total of 1,340 older adults (age ≥60 years old) from the Bambui Cohort Study of Ageing, with a total follow-up of 10 years, were included in this study. Frailty was defined by the accumulation of deficit framework and cognitive impairment based on scores on the MMSE less than 22. In addition, serum IL-6 levels were measured by cytometric bead array assay., Results: Individuals classified with cognitive frailty had significantly higher serum IL-6 levels compared to the robust, cognitively unimpaired group. Those with cognitive frailty (aOR = 1.97 [1.18-3.27] and prefrailty and cognitive impairment (aOR = 1.83 [1.24-2.69]) had the highest mortality risk over 10 years of follow-up. Higher IL-6 levels were also independently associated with a higher mortality rate (aOR = 1.37 [1.23-1.54])., Conclusion: Our study shows that cognitive Frailty indicates a vulnerability state and of increasing mortality risk. Our findings also suggested that proinflammatory abnormalities can be viewed as a central phenomenon underlying common age-related problems (e.g., cognitive impairment and Frailty) and outcomes (e.g., mortality)., (Copyright © 2022 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objectives: This study estimates the national prevalence of drinking patterns (current, heavy, and binge) and the associated factors, among older Brazilians., Design: Cross-sectional study using survey data from ELSI-Brazil (2015-2016)., Setting/participants: A total of 7839 adults aged 50 years or older., Measurements: Respondents were asked about alcohol drinking. Alcohol consumption status was categorized as current drinkers (last month), heavy drinkers (≥7 drinks/week for females and ≥14 drinks/week for males), and binge drinkers (≥4 drinks on one occasion for females and ≥5 drinks on one occasion for males). Covariates included sociodemographic characteristics, tobacco smoking, depression, and number of chronic diseases., Results: Of the 7839 participants, 29.4% were current drinkers, 5.1% were heavy drinkers, and 10.3% reported binge drinking. In the ≥60 years old age group, the prevalence of current drinking was 23.8%, 3.9% were heavy drinkers, and 6.7% reported binge drinking. All drinking patterns had similar associated factors: being male, being younger, having higher education, tobacco smoking, and falls. In addition, the greater the number of chronic conditions, the lower the prevalence of current drinking and binge drinking., Conclusion: Heavy drinking and binge drinking are often reported by older Brazilians, particularly among males, those with higher education and in the younger age groups. These behaviors can negatively affect the health of older adults. It is, therefore, important to identify the problems related to alcohol consumption among older adults to minimize the risks and harms., (© 2021 John Wiley & Sons Ltd.)

Background: Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment. However, most of the evidence has been based on self-reported T2DM, and undiagnosed diabetes has not been considered as a separate category. We aimed to examine the extent to which undiagnosed diabetes modifies the association between diabetes and cognitive impairment in a representative sample of Brazilian adults aged 50 years and older., Methods: We analyzed baseline data from 1944 participants of the Brazilian Longitudinal Study of Aging (ELSI-Brazil) conducted from 2015 to 2016. Diabetes was evaluated based on self-reported doctor diagnosis and glycosylated hemoglobin levels. Participants were classified as diabetics (D), undiagnosed diabetics (UDD), or nondiabetics (ND). Cognitive function was assessed by word list learning and verbal fluency tests. Three multiple logistic regression models were used to evaluate the changes in the strength of the associations., Results: Participants with diabetes had 49% greater odds of exhibiting impaired memory than nondiabetics (odds ratio [OR] = 1.49; 95% CI: 1.01-2.20). By combining UDD and ND, the association between diabetes and impaired memory was attenuated by 2.0%, losing its statistical significance (OR = 1.46; 95% CI: 0.98-2.17). By combining UDD and D, the association was attenuated by 7.4% (OR = 1.38; 95% CI: 1.01-1.90). No significant association was found between T2DM and impaired verbal fluency., Conclusion: This study found an association between T2DM and impaired memory but not with impaired verbal fluency. When UDD individuals are considered diabetics, this association is attenuated; when UDD individuals are considered as ND, this association is attenuated to the extent that it loses its statistical significance, affecting thus the clinical interpretation., (© 2020 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

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.)

Objective: To compare mortality in older adults with and without mild or moderate cognitive impairment over 15 years of follow-up in a middle-income country, where little information on this subject is available., Methods: A total of 1,281 community-dwelling older adults were followed-up for a median of 13.3 years. We evaluated their cognitive impairment using the Mini-Mental State Examination, categorizing it as none (1.0 SD above cutoff means), mild (1.0 SD below cutoff means) or moderate (2.0 SD below cutoff means). The date of death was determined by reviewing death certificates. Cox's proportional hazards models were used to evaluate the risk of mortality in participants with cognitive impairment., Results: Participants with mild or moderate cognitive impairment had a higher mortality risk than those without it in the unadjusted model, but these associations did not remain in the final model. After sex stratification, only men with moderate cognitive impairment had a higher mortality risk in the final model., Conclusion: The findings suggest an association between moderate cognitive impairment and all-cause mortality in men in a large Brazilian cohort of older adults.

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.)

Age-related cognitive decline (ACD) is the gradual process of decreasing of cognitive function over age. Most genetic risk factors for ACD have been identified in European populations and there are no reports in admixed Latin American individuals. We performed admixture mapping, genome-wide association analysis (GWAS), and fine-mapping to examine genetic factors associated with 15-year cognitive trajectory in 1,407 Brazilian older adults, comprising 14,956 Mini-Mental State Examination measures. Participants were enrolled as part of the Bambuí-Epigen Cohort Study of Aging. Our admixture mapping analysis identified a genomic region (3p24.2) in which increased Native American ancestry was significantly associated with faster ACD. Fine-mapping of this region identified a single nucleotide polymorphism (SNP) rs142380904 (β = -0.044, SE = 0.01, p = 7.5 × 10 -5 ) associated with ACD. In addition, our GWAS identified 24 associated SNPs, most in genes previously reported to influence cognitive function. The top six associated SNPs accounted for 18.5% of the ACD variance in our data. Furthermore, our longitudinal study replicated previous GWAS hits for cognitive decline and Alzheimer's disease. Our 15-year longitudinal study identified both ancestry-specific and cosmopolitan genetic variants associated with ACD in Brazilians, highlighting the need for more trans-ancestry genomic studies, especially in underrepresented ethnic groups.

Background: Both diabetes and depression increase the mortality risk in the elderly. In this study, we evaluated mortality risk associated with the comorbidity between depression and diabetes. We also assessed the moderating role of inflammation in the mortality risk in this population., Methods: We included a total of 1,183 community-dwelling older adults, divided into four groups: "neither diabetes nor depression"; "diabetes only"; "depression only," and "both diabetes and depression," and followed-up for a median of 13.5 years. We evaluated the inflammatory status by the high-sensitivity C-reactive protein (hs-CRP) levels. Date of death was computed by reviewing death certificates. We used Cox's proportional hazards models and additive interactions to evaluate the risk of mortality in the subject groups and the moderating effect of hs-CRP., Results: Participants with both diabetes and depression had higher death risk (hazard ratio [HR]: 2.33; 95% confidence interval [CI]: 1.59-3.42) than those with each condition alone (HR diabetes: 2.08 95% CI: 1.56-2.76 HR depression: 1.26; 95% CI: 1.03-1.54). High level of hs-CRP, indicative of high inflammatory status, significantly moderated the risk of mortality in subjects with both diabetes and depression (Bonferroni-adjusted p = 0.0116)., Conclusions: The coexistence of diabetes and depression symptoms is associated with the highest death risk in this population. This risk is moderated by inflammatory status., (© 2019 Wiley Periodicals, Inc.)

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., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: AEA is a consultant for Kinsa Inc. and has received an unrestricted gift from Gojo Inc. CB is a member of the Editorial Board of PLOS Medicine. HB is on the Advisory Board of Nutricia Australia. MG was on Biogen Inc’s “Patient Journey Advisory Group” in 2016 and 2017. NS reports personal fees from Merck Consumer Health and the NIH outside the submitted work. RBL 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. PSS received grant funding from the NIH/NIA (USA) and the NHMRC (Australia), as well as philanthropic funding through The Dementia Momentum. He is on the Australian Advisory Board of Biogen Pharmaceuticals. All other authors have declared that no competing interests exist.

Objective: To investigate macroregional variations in cognitive function in a national sample representative of the Brazilian population aged 50 years and older., Methods: Data from the baseline of the Longitudinal Study of Brazilian Elderly (ELSI-Brazil), collected between 2015 and 2016, were used. Memory was measured by means of a 10-word list and executive function, by semantic verbal fluency, based on the naming of animals. Gender, age, education, and rural or urban residence were potentially confounding., Results: Among the 9,412 ELSI-Brazil participants, 9,085 were included in the analysis; 53.9% were women and the average age was 63.0 (0.42) years. After adjusting for potential confounding variables, average scores for memory and verbal fluency were lower in the Northeast region and higher in the Midwest and Southeast, respectively. In the South region, higher scores were found for immediate and combined memory. In all regions, older participants and those with lower schooling had worse scores for memory and verbal fluency., Conclusions: There are differences in cognitive function among older adults in the different macroregions, independent of age, gender, schooling, and rural or urban residence.

Objectives: To investigate the association between African and Native American genomic ancestry and long-term cognitive trajectories in admixed Brazilians., Design: Population-based longitudinal study., Setting: Bambui-Epigen (Brazil) cohort study., Participants: Adults aged 60 and older (N=1,215) MEASUREMENTS: Participants were followed from January 1997 to December 2011. Cognitive function was assessed annually using the Mini-Mental State Examination (MMSE), totaling 12,208 measurements. We used linear mixed-effects pattern models to assess MMSE score trajectories. Ancestry was assessed using a genome-wide approach., Results: After adjustments for covariates, the highest quintile of African ancestry was associated with poorer baseline cognitive performance (β=-0.73, 95% confidence interval (CI)=-1.36 to -0.11) but not with cognitive trajectory. Educational level modified the baseline association between highest African ancestry and cognitive performance in that the association was observed only in those with very low (<4 years) education (β=-1.13, 95% CI=-2.02 to -0.23). No association was found between Native American ancestry and baseline cognitive function or its trajectory., Conclusion: Genomic African and Native American ancestry levels had no prognostic value for age-related cognitive decline in this admixed population., (© 2018, Copyright the Author Journal compilation © 2018, The American Geriatrics Society.)

Psychosocial factors appear to be associated with increased risk of disability in later life. However, there is a lack of evidence based on long-term longitudinal data from Western low-middle income countries. We investigated whether psychosocial factors at baseline predict new-onset disability in long term in a population-based cohort of older Brazilians adults. We used 15-year follow-up data from 1,014 participants aged 60 years and older of the Bambuí (Brazil) Cohort Study of Aging. Limitations on activities of daily living (ADL) were measured annually, comprising 9,252 measures. Psychosocial factors included depressive symptoms, social support and social network. Potential covariates included sociodemographic characteristics, lifestyle, cognitive function and a physical health score based on 10 self-reported and objectively measured medical conditions. Statistical analysis was based on competitive-risk framework, having death as the competing risk event. Baseline depressive symptoms and emotional support from the closest person were both associated with future ADL disability, independently of potential covariates wide range. The findings showed a clear graded association, in that the risk gradually increased from low emotional support alone (sub-hazard ratio - SHR = 1.11; 95%CI: 1.01; 1.45) to depressive symptoms alone (SHR = 1.52; 95%CI: 1.13; 2.01) and then to both factors combined (SHR = 1.61; 95%CI: 1.18; 2.18). Marital status and social network size were not associated with incident disability. In a population of older Brazilian adults, lower emotional support and depressive symptoms have independent predictive value for subsequent disability in very long term.

Brazil is experiencing among the world's fastest demographic aging worldwide. This demographic transition is occurring in a context of few resources and great social inequalities. The Brazilian Longitudinal Study of Aging (ELSI-Brazil) is a nationally representative study of 9,412 people aged 50 years or older, residing in 70 municipalities across the 5 Brazilian regions. ELSI-Brazil allows investigations of the aging process, its health, psychosocial and economic determinants, and societal consequences. The baseline examination (2015-2016) included detailed household and individual interviews and physical measurements (blood pressure, anthropometry, grip strength, and timed walk and balance tests). Blood tests and sample storage were performed in a subsample of study participants. Subsequent waves are planned for every 3 years. The study adopts a conceptual framework common to other large-scale longitudinal studies of aging in the world, such as the Health and Retirement Study, allowing cross-national comparisons. The goal of ELSI-Brazil is not only to build an understanding of aging in a large, Western, middle-income country in a rapid demographic transition but also to provide scientific data to support and study policy changes that may affect older adults. We describe the methodology of the study and some descriptive results of the baseline survey.

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.