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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.

Backgrounds: Cognitive problems are common symptoms among individuals with stress-related exhaustion. It is still unknown whether these individuals are at a higher risk of developing dementia later. This study aims to examine the relationship between midlife stress-related exhaustion and dementia incidence., Methods: A population sample of 777 women (aged 38, 46, 50 and 54 years) without dementia at baseline was followed over 50 years, from 1968 to 2019. Stress-related exhaustion was based on information from the psychiatric examination in 1968/69. Information on dementia incidence between 1968 and 2019 was obtained from neuropsychiatric examinations, key-informant interviews, and hospital registry. Dementia was diagnosed according to the DSM-III-R criteria. A subgroup of non-demented women (n = 284) was examined for cognitive functions by the Gottfries-Bråne-Steen scale 24 years after baseline., Results: Stress-related exhaustion in midlife was associated with higher risk for development of dementia before age 75 (Hazard ratio and 95% confidence interval: 2.95 and 1.35-6.44). The association remained after adjustment for age, major depression, and anxiety disorder. Mean age of dementia onset was younger for women with stress-related exhaustion than women without stress (mean ± SD, 76 ± 9 vs. 82 ± 8 . p = 0.009). Women with stress-related exhaustion in midlife still showed more cognitive impairments 24 years later compared with women without stress (Odds ratio and 95% confidence interval: 2.64 and 1.15-6.06)., Conclusions: We found that women with stress-related exhaustion in midlife were at a higher risk to develop dementia at relatively younger age. These women showed persistently lower cognitive functions over years even without dementia. Present study results need to be interpreted with caution due to small sample size and should be confirmed in future studies with larger sample size. Our study findings may imply the importance of long-term follow-up regarding cognitive function among individuals with stress-related exhaustion., (© 2024. The Author(s).)

Background: Some cohort studies have reported a decline in dementia prevalence and incidence over time, although these findings have not been consistent across studies. We reviewed evidence on changes in dementia prevalence and incidence over time using published population-based cohort studies that had used consistent methods with each wave and aimed to quantify associated changes in risk factors over time using population attributable fractions (PAFs)., Methods: We searched for systematic reviews of cohort studies examining changes in dementia prevalence or incidence over time. We searched PubMed for publications from database inception up to Jan 12, 2023, using the search terms "systematic review" AND "dementia" AND ("prevalence" OR "incidence"), with no language restrictions. We repeated this search on March 28, 2024. From eligible systematic reviews, we searched the references and selected peer-reviewed publications about cohort studies where dementia prevalence or incidence was measured in the same geographical location, at a minimum of two timepoints, and that reported age-standardised prevalence or incidence of dementia. Additionally, data had to be from population-based samples, in which participants' cognitive status was assessed and where validated criteria were used to diagnose dementia. We extracted summary-level data from each paper about dementia risk factors, contacting authors when such data were not available in the published paper, and calculated PAFs for each risk factor at all available timepoints. Where possible, we linked changes in dementia prevalence or incidence with changes in the prevalence of risk factors., Findings: We identified 1925 records in our initial search, of which five eligible systematic reviews were identified. Within these systematic reviews, we identified 71 potentially eligible primary papers, of which 27 were included in our analysis. 13 (48%) of 27 primary papers reported change in prevalence of dementia, ten (37%) reported change in incidence of dementia, and four (15%) reported change in both incidence and prevalence of dementia. Studies reporting change in dementia incidence over time in Europe (n=5) and the USA (n=5) consistently reported a declining incidence in dementia. One study from Japan reported an increase in dementia prevalence and incidence and a stable incidence was reported in one study from Nigeria. Overall, across studies, the PAFs for less education or smoking, or both, generally declined over time, whereas PAFs for obesity, hypertension, and diabetes generally increased. The decrease in PAFs for less education and smoking was associated with a decline in the incidence of dementia in the Framingham study (Framingham, MA, USA, 1997-2013), the only study with sufficient data to allow analysis., Interpretation: Our findings suggest that lifestyle interventions such as compulsory education and reducing rates of smoking through country-level policy changes could be associated with an observed reduction, and therefore future reduction, in the incidence of dementia. More studies are needed in low-income and middle-income countries, where the burden of dementia is highest, and continues to increase., Funding: National Institute for Health and Care Research Three Schools' Dementia Research Programme., Competing Interests: Declaration of interests GL and NM are supported by University College London Hospitals’ National Institute for Health Research (NIHR) Biomedical Research Centre. GL is also supported by North Thames NIHR Applied Research Collaboration and as an NIHR Senior Investigator and has grants from NIHR PGfAR, Alzheimer's Association, Norwegian Research Council, and Wellcome. All other authors declare no competing interests., (Copyright © 2024 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.)

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.)

Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objectives: To examine how the use of different diagnostic criteria (Diagnostic and Statistical Manual of Mental Disorders third revised, fourth, and fifth editions [DSM-III-R, DSM-IV, and DSM-5], and the 10th and 11th editions of the International Classification of Diseases [ICD-10 and ICD-11] influences the reported prevalence of dementia., Methods: Two cross-sectional population-based studies of systematically selected 85-year-olds in Gothenburg, Sweden, (N = 774), were examined in comprehensive health examinations including comprehensive neurocognitive examinations. Five algorithms based on the diagnostic criteria in the DSM-III-R, DSM-IV, DSM-5, ICD-10, and ICD-11 were created, including 105 different variables that were operationalized in different ways to match the criteria of each classification system., Results: ICD-11 yielded the highest prevalence of dementia (36.4%), followed by DSM-5 (32.9%), DSM-IV (30.7%), the clinical consensus DSM-III-R diagnosis (26.7%), DSM-III-R (21.4%), and ICD-10 (20.5%). The agreement between the DSM-5 and the ICD-11 was κ = 0.9. All other kappa values ranged between 0.6 and 0.9., Conclusions: The choice of diagnostic criteria has a large effect on the estimated prevalence of dementia. We found that the recent editions, the DSM-5 and ICD-11, gave a higher prevalence of dementia than older editions. We also show that the attempts to harmonize DSM and ICD have in part been successful, however, there are still differences between the systems., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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.)

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.

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: Recent studies suggest a decline in the age-specific incidence and prevalence of dementia. However, results are mixed regarding trends among octogenarians. We investigated time trends in the prevalence and incidence of dementia in 3 population-based cohorts of 85-90-year olds. We also examined if there were different time trends for men and women., Methods: We examined population-based birth cohorts within the Gothenburg H70 Birth Cohort Studies born 1901-02, 1923-24, and 1930, at ages 85 (N = 1481) and 88 (N = 840) years. The first 2 cohorts were also examined at age 90 (N = 450). The incidence was examined in 1 109 individuals free from dementia at baseline using information from the examination at age 88 or register data. All 3 cohorts were examined with identical methods., Results: The prevalence of dementia decreased from 29.8% in 1986-87 to 21.5% in 2008-10 and 24.5% in 2015-16 among 85-year olds, and from 41.9% in 1989-90 to 28.0% in 2011-12 to 21.7% in 2018-19 among 88-year olds, and from 41.5% in 1991-92 to 37.2% in 2013-14 among 90-year olds. The decline was most accentuated among women. The incidence of dementia per 1 000 risk-years from ages 85 to 89 declined from 48.8 among those born 1901-02 to 37.9 in those born 1923-24 to 22.5 among those born 1930., Conclusions: The prevalence and incidence of dementia decreased substantially over 3 decades among octogenarians. This might slow down the projected increase in cases of dementia expected by the increasing number of octogenarians during the following decades., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

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.)

Importance: The optimal systolic blood pressure (SBP) to minimize the risk of dementia in older age is unknown., Objective: To investigate whether the association between SBP and dementia risk is U-shaped and whether age and comorbidity play a role in this association., Design, Setting, and Participants: This cohort study used an individual participant data approach to analyze 7 prospective, observational, population-based cohort studies that were designed to evaluate incident dementia in older adults. These studies started between 1987 and 2006 in Europe and the US. Participants had no dementia diagnosis and had SBP and/or diastolic blood pressure (BP) data at baseline and incident dementia status during follow-up. Data analysis was conducted from November 7, 2019, to October 3, 2021., Exposures: Baseline systolic BP., Main Outcomes and Measures: All-cause dementia (defined using Diagnostic and Statistical Manual of Mental Disorders [Third Edition Revised] or Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition] and established at follow-up measurements or in clinical practice), mortality, and combined dementia and mortality were the outcomes. Covariates included baseline antihypertensive medication use, sex, educational level, body mass index, smoking status, diabetes, stroke history, myocardial infarction history, and polypharmacy. Cox proportional hazards regression models were used, and nonlinear associations were explored using natural splines., Results: The study analyzed 7 cohort studies with a total of 17 286 participants, among whom 10 393 were women (60.1%) and the mean (SD) baseline age was 74.5 (7.3) years. Overall, dementia risk was lower for individuals with higher SBP, with the lowest risk associated with an SBP of approximately 185 mm Hg (95% CI, 161-230 mm Hg; P = .001). Stratified by overlapping 10-year baseline age groups, the lowest dementia risk was observed at somewhat lower systolic BP levels in those older than 75 years (158 [95% CI, 152-178] mm Hg to 170 [95% CI, 160-260] mm Hg). For mortality, there was a clear U-shaped association, with the lowest risk at 160 mm Hg (95% CI, 154-181 mm Hg; P < .001). This U-shape occurred across all age groups, with the lowest dementia risk associated with an SBP of 134 mm Hg (95% CI, 102-149 mm Hg; P = .03) in those aged 60 to 70 years and increasing to between 155 mm Hg (95% CI, 150-166 mm Hg; P < .001) and 166 mm Hg (95% CI, 154-260 mm Hg; P = .02) for age groups between 70 and 95 years. Combined dementia and mortality risk curves closely resembled those for mortality. Associations of diastolic BP with dementia risk were generally similar but were less distinct., Conclusions and Relevance: This cohort study found that dementia risk was lower for older individuals with higher SBP levels and that more distinctly U-shaped associations appeared for those older than 75 years, but these associations cannot be explained by SBP-associated changes in mortality risk. The findings may warrant future trials on tailored BP management in older age groups that take life expectancy and health context into consideration.

Background: Individual conditions of metabolic syndrome (MetS) have been related to dementia; however, their combined impact on the preclinical stage is unknown. We investigated the associations between MetS and domain-specific cognitive function as well as the role of sociodemographic, cardiovascular, and genetic factors., Methods: Within the Gothenburg H70 Birth Cohort Study-Birth cohort 1944, 1131 dementia-free participants (aged 70 years) were examined during 2014-2016. MetS (central obesity plus at least 2 factors [reduced HDL-cholesterol, elevated triglycerides, blood pressure, or blood glucose]) was identified according to the International Diabetes Federation criteria. Five cognitive domains (memory, attention/perceptual speed, executive function, verbal fluency, visuospatial abilities) were generated after z-standardizing raw scores from 10 neuropsychological tests. Education, heart disease, claudication (indicating peripheral atherosclerosis), and apolipoprotein genotype were ascertained by trained staff. Data were analyzed with linear regression models., Results: Overall, 618 participants (55%) had MetS. In multiadjusted linear regressions, MetS was related to poorer performance in attention/perceptual speed (β -0.14 [95% CI -0.25, -0.02]), executive function (β -0.12 [95% CI -0.23, -0.01]), and verbal fluency (β -0.19 [95% CI -0.30, -0.08]). These associations were present only among individuals who did not carry any APOE-ε4 allele or were highly educated. However, among those with MetS, high education was related to better cognitive performance. MetS together with comorbid heart disease or claudication was associated with even worse cognitive performance than each alone., Conclusions: MetS is associated with poor attention/perceptual speed, executive function, and verbal fluency performance. Education, apolipoprotein E-ε4 allele, and comorbid cardiovascular disease influenced the observed associations., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objectives: Blood pressure has decreased in the general population. We aimed to examine whether this is true also among the very old, and among persons with and without dementia. Further, we aimed to investigate how common undetected and untreated hypertension is in the very old, both among people with and without dementia., Method: Blood pressure was measured in representative population samples of 85-year-olds living in Gothenburg, Sweden, examined 1986-1987 (n = 484) and 2008-2010 (n = 571). Dementia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, edition 3 revised, by the same medical doctor at both examinations., Results: Both systolic and diastolic blood pressure were lower in 85-year-olds examined 2008-2010 than in those examined 1986-1987, both among those with and without dementia. Participants with dementia had lower systolic blood pressure than those without dementia in both cohorts, and blood pressure levels related to dementia severity. Despite this, hypertension (≥140/90 mmHg) was found in almost half (46.5%) of those with dementia in 2008-2010., Conclusion: Our findings show that time-trends of lower blood pressure in western populations also applies to the very old, and that individuals with dementia continue to have lower blood pressure compared to the rest of the population. The latter finding suggests that the pathophysiological processes in dementia affect blood pressure regulating regions in the brain independent of time trends. Still, hypertension is common in dementia and needs to be detected and treated., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Evidence on sex differences in the risk for dementia has been mixed. The goal was to assess sex differences in the development of dementia, and in the effects of a lifestyle intervention., Methods: Two strategies were adopted, one using combined data from three large Nordic population-based cohort studies (n = 2289), adopting dementia as outcome, and 2-year multidomain lifestyle intervention (n = 1260), adopting cognitive change as outcome., Results: There was higher risk for dementia after age 80 years in women. The positive effects of the lifestyle intervention on cognition did not significantly differ between men and women. Sex-specific analyses suggested that different vascular, lifestyle, and psychosocial risk factors are important for women and men in mid- and late-life., Conclusion: Women had higher risk for dementia among the oldest individuals. Lifestyle interventions may be effectively implemented among older men and women., (© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: We examined the long-term risk of dementia after coronary artery bypass grafting (CABG) in relation to age and sex., Methods: All CABG patients in Sweden 1992-2015 (n = 111,335), and matched controls (n = 222,396) were included in a population-based study. Adjusted hazard ratios (aHR) for all-cause dementia, vascular dementia, and Alzheimer's disease were calculated., Results: There was no difference in the risk for all-cause dementia between CABG patients and control subjects (aHR 0.98 [95% confidence interval 0.95 to 1.02]). CABG patients <65 years and 65 to 74 years had higher risk (aHR 1.29 [1.17-1.42] and 1.08 [1.02-1.13], respectively), and patients ≥75 years had lower risk (aHR 0.76 [0.71-0.81]). The highest risk was observed in women <65 years (aHR 1.64 [1.31-2.05])., Discussion: Overall, the long-term risk for all-cause dementia does not differ between CABG patients and the general population. Younger patients have a higher risk, while older patients have a lower risk, compared to controls., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Dementia is the major predictor of death in old age. The aim of this paper was to determine whether 8-year mortality among 85-year olds with and without dementia, and if the contribution of dementia to mortality relative to other common diseases has changed. We used two population-based cohorts of 85-year-olds (N = 1065), born in 1901-02 and 1923-24, which were examined with identical methods in 1986-87 and 2008-2010 and followed for 8-year mortality according to data from the Swedish Tax Agency. Dementia was diagnosed according to DSM-III-R. Other diseases were diagnosed based on self-reports, close informant interviews, somatic examinations, and the Swedish National In-patient Register. Compared to cohort 1901-02, cohort 1923-24 had a lower 8-year mortality both among those with (HR 0.7; 95% CI 0.5-0.99) and without dementia (HR 0.7; 95% CI 0.5-0.9). Dementia was associated with increased mortality in both cohorts (cohort 1901-02, HR 2.6; 95% CI 2.0-3.2, cohort 1923-24, HR 2.8; 95% CI 2.3-3.5), and remained the major predictor of death, with a population attributable risk of 31.7% in 1986-87 and 27.7% in 2008-10. Dementia remained the most important predictor of death in both cohorts. The relative risk for mortality with dementia did not change between cohorts, despite a decreased mortality rate in the population.

Background: The modifying effect of sex on the relation between marital status and dementia has yet to be determined., Objective: To examine if sex modifies the association between marital status and incident dementia., Methods: Population-based samples from the Mayo Clinic Study of Aging (MCSA, N = 3,471) and the Gothenburg H70 Birth Cohort Study (H70-study, N = 913) were used. A multiplicative interaction term was used to analyze the modifying effect of sex on the relation between marital status (married versus not married) and incident dementia using Cox regression models. Further, risk of dementia by marital status was also evaluated in models separated by sex., Results: In the MCSA, there was an interaction between marital status and sex in relation to dementia (p = 0.015). In contrast, in the H70-study, no significant interaction was observed (p = 0.28). Nevertheless, in both studies, not married men had increased risk of dementia compared to married men in models adjusted for age, education, and number of children (H70-study: 1.99; 1.06-3.76, MCSA: 1.43; 1.08-1.89). Associations remained similar after additional adjustment for depression, BMI, hypertension, dyslipidemia, and diabetes mellitus (H70-study: 2.00; 1.05-3.82, MCSA: 1.32; 0.99-1.76). Further, no significant association was observed between marital status and dementia in women (H70-study: 1.24; 0.82-1.89, MCSA: 0.82; 0.64-1.04)., Conclusion: Sex had a modifying effect on the association between marital status and incident dementia. In analyses separated by sex, not married men had an increased risk of dementia compared to married men, while no significant association was observed between marital status and risk of dementia in women.

We have provided an overview on the profound impact of COVID-19 upon older people with Alzheimer's disease and other dementias and the challenges encountered in our management of dementia in different health-care settings, including hospital, out-patient, care homes, and the community during the COVID-19 pandemic. We have also proposed a conceptual framework and practical suggestions for health-care providers in tackling these challenges, which can also apply to the care of older people in general, with or without other neurological diseases, such as stroke or parkinsonism. We believe this review will provide strategic directions and set standards for health-care leaders in dementia, including governmental bodies around the world in coordinating emergency response plans for protecting and caring for older people with dementia amid the COIVD-19 outbreak, which is likely to continue at varying severity in different regions around the world in the medium term., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Old-age dementias are known to disproportionally affect women as well as individuals with low educational attainment. The higher lifetime risk of dementia among women is usually attributed to their longer life expectancy. However, the impact of sex, and subsequent gender inequity, is likely to be more multifaceted than this explanation implies. Not least because of historical inequities in access to education between the sexes and the gender and socio-economic gradients in risk factors such as stress, depression and social isolation. Consequently, the present study sought to test whether differences in educational attainment and experiences of general psychological distress mediate the association between female sex and dementia., Methods: The study utilizes data obtained through the Gothenburg H70 Birth Cohort Study and the Prospective Populations Study on Women (n = 892). Data were analysed using Confirmatory Factor Analysis (CFA) and Structural Equation Modelling (SEM) with Weighted Least Squares Means and Variance adjusted (WLSMV) estimation. General psychological distress was indicated by a latent variable and constructed from five manifest items (previous depression, stress, self-esteem, chronic loneliness and satisfaction with social situation) that were all measured at baseline., Results: While the results could not corroborate that education directly mediates the effect of sex on dementia, level of distress was predicted by both female sex (0.607, p < .001) and education (- 0.166, p < .01) and, in turn, shown to be significantly associated with dementia (0.167, p < .05), also after controlling for confounders. When time from baseline to diagnosis was increased through sequential exclusion of dementia cases, the effect of distress on dementia was no longer significant., Conclusion: The overall findings suggest that social (dis) advantage predicts general psychological distress, which thereby constitutes a potential, and rarely acknowledged, pathway between female sex, education, and dementia. They further underline the importance of attending to both education and distress as 'gendered' phenomena when considering the nature of their associations with dementia. However, the possibility of reverse causality bias must be acknowledged and the need for longitudinal studies with longer follow-up stressed.

Background: Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied., Methods: We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype., Results: Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10-1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38-6.47) and Latin America (OR = 1.49, 95% CI = 1.04-2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33-3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81-26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07-3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44-8.35) in Asia., Conclusion: Parity is associated with women's risk of dementia, though this is not uniform across regions and dementia subtypes.

Objective: To determine changes in the incidence of dementia between 1988 and 2015., Methods: This analysis was performed in aggregated data from individuals >65 years of age in 7 population-based cohort studies in the United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause dementia, and then defined nonoverlapping 5-year epochs within each study to determine trends in incidence. Estimates of change per 10-year interval were pooled and results are presented combined and stratified by sex., Results: Of 49,202 individuals, 4,253 (8.6%) developed dementia. The incidence rate of dementia increased with age, similarly for women and men, ranging from about 4 per 1,000 person-years in individuals aged 65-69 years to 65 per 1,000 person-years for those aged 85-89 years. The incidence rate of dementia declined by 13% per calendar decade (95% confidence interval [CI], 7%-19%), consistently across studies, and somewhat more pronouncedly in men than in women (24% [95% CI 14%-32%] vs 8% [0%-15%])., Conclusion: The incidence rate of dementia in Europe and North America has declined by 13% per decade over the past 25 years, consistently across studies. Incidence is similar for men and women, although declines were somewhat more profound in men. These observations call for sustained efforts to finding the causes for this decline, as well as determining their validity in geographically and ethnically diverse populations., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction: Longitudinal studies examining the effect of endogenous estrogens on dementia risk are needed to understand why women have higher dementia incidence than men after age 85., Methods: A population-based sample of women with natural menopause (N = 1364) from Gothenburg, Sweden, was followed from 1968-2012. Information on endogenous estrogens (age at menarche and menopause, number of pregnancies, and months of breastfeeding) was obtained from interviews in 1968-1992. Dementia was diagnosed according to established criteria based on information from neuropsychiatric examinations and close informant interviews., Results: We found that longer reproductive period was associated with increased risk of dementia (hazard ratio [HR] per year 1.06, 95% confidence interval [CI] 1.03-1.20) and Alzheimer's disease (AD) (1.06, 1.02-1.11), particularly for those with dementia (1.10, 1.04-1.17) and AD (1.15, 1.06-1.26) onset after age 85., Discussion: These results may explain why women have higher dementia incidence compared to men after age 85, the age with the highest number of dementia cases., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objectives: Emerging evidence suggests that social networks may protect against the development of dementia among older adults. In this study we analysed the association between social networks, the apolipoprotein E ( APOE ) ε4 allele, and dementia. We also investigated whether there were gender-specific patterns in this respect. Method: The analyses used population-based longitudinal data from Gothenburg, Sweden: the H70 Birth Cohort Study and the Prospective Population Study on Women (PPSW). A total of 580 individuals born in 1930 underwent semi-structured neuropsychiatric examinations in 2000-2001. Follow-up examinations were carried out in 2005-2006 and 2009-2010. The timing of dementia onset was analysed using Cox proportional hazards regression. Results: The presence of the APOE ε4 allele affected the risk of developing dementia in both genders. Among women, distant social networks had a protective effect on dementia, while among men the significant associations between close social networks and dementia did not remain after controlling for covariates. Significant interactions between social networks and the APOE ε4 allele were not found. Conclusion: Strong social networks do not seem to moderate the increased risk of dementia implied by the APOE ε4 allele. Nevertheless, our results underline the importance of strong social networks in postponing dementia onset and indicate that their impact may differ among men and women.

Objective: High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data., Methods: To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data., Results: Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age., Conclusion: Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals., Clinical Trials Registration: The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454., (© 2019 American Academy of Neurology.)

In recent years, a rapidly increasing collection of investigative methods in addition to changes in diagnostic criteria for dementia have followed "high-tech" trends in medicine, with the aim to better define the dementia syndrome and its biological substrates, mainly in order to predict risk prior to clinical expression. These approaches are not without challenge. A set of guidelines have been developed by a group of European experts in population-based cohort research through a series of workshops, funded by the Joint Program for Neurodegenerative Disorders (JPND). The aims of the guidelines are to assist policy makers and researchers to understand (1) What population studies for ageing populations should encompass and (2) How to interpret the findings from population studies. Such studies are essential to provide evidence relevant to the understanding of healthy and frail brain ageing, including the dementia syndrome for contemporary and future societies by drawing on the past., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.

Objective: To investigate whether cognitive and physical activities in midlife are associated with reduced risk of dementia and dementia subtypes in women followed for 44 years., Methods: A population-based sample of 800 women aged 38-54 years (mean age 47 years) was followed from 1968 to 2012. Cognitive (artistic, intellectual, manual, religious, and club) and physical activity were assessed at baseline. During follow-up, dementia (n = 194), Alzheimer disease (n = 102), vascular dementia (n = 27), mixed dementia (n = 41), and dementia with cerebrovascular disease (n = 81) were diagnosed according to established criteria based on information from neuropsychiatric examinations, informant interviews, hospital records, and registry data. Cox regression models were used with adjustment for age, education, socioeconomic status, hypertension, body mass index, cigarette smoking, diabetes mellitus, angina pectoris, stress, and major depression., Results: We found that cognitive activity in midlife was associated with a reduced risk of total dementia (hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.49-0.89) and Alzheimer disease (HR 0.54; 95% CI 0.36-0.82) during follow-up. Physical activity in midlife was associated with a reduced risk of mixed dementia (HR 0.43; 95% CI 0.22-0.86) and dementia with cerebrovascular disease (HR 0.47; 95% CI 0.28-0.78). The results were similar after excluding those who developed dementia before 1990 (n = 21), except that physical activity was then also associated with reduced risk of total dementia (HR 0.67; 95% CI 0.46-0.99)., Conclusion: Our findings suggests that midlife cognitive and physical activities are independently associated with reduced risk of dementia and dementia subtypes. The results indicate that these midlife activities may have a role in preserving cognitive health in old age., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction: Longitudinal studies are needed to understand the long-term associations between stroke and dementia., Methods: A population sample of 1460 women without stroke or dementia at baseline was followed over 44 years, from 1968 to 2012. Information on stroke and dementia was obtained from neuropsychiatric examinations, key-informant interviews, hospital registry, and medical records., Results: During 44 years follow-up, 362 women developed stroke and 325, dementia. The age-specific incidence of the two disorders was similar. The incidence of dementia was higher in those with stroke than among those without (33.7% vs. 18.5%; age-adjusted hazard ratio 1.44, 95% confidence interval 1.15-1.81). The increased risk of dementia started already 5 years before stroke, was highest 1 year after stroke, and continued more than 11 years after stroke., Discussion: There is an increased risk for dementia both before and after stroke. This has implications for understanding the relation between the two disorders and for prevention of dementia and stroke., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Few longitudinal studies assessed whether sleep disturbances are associated with dementia risk., Methods: Sleep disturbances were assessed in three population-based studies (H70 study and Kungsholmen Project [Sweden]; Cardiovascular Risk Factors, Aging and Dementia study [Finland]). Late-life baseline analyses (3-10 years follow-up) used all three studies (N = 1446). Baseline ages ≈ 70 years (Cardiovascular Risk Factors, Aging and Dementia, H70), and ≈84 years (Kungsholmen Project). Midlife baseline (age ≈ 50 years) analyses used Cardiovascular Risk Factors, Aging and Dementia (21 and 32 years follow-up) (N = 1407)., Results: Midlife insomnia (fully adjusted hazard ratio = 1.24, 95% confidence interval = 1.02-1.50) and late-life terminal insomnia (fully adjusted odds ratio = 1.94, 95% confidence interval = 1.08-3.49) were associated with a higher dementia risk. Late-life long sleep duration (>9 hours) was also associated with an increased dementia risk (adjusted odds ratio = 3.98, 95% confidence interval = 1.87-8.48)., Discussion: Midlife insomnia and late-life terminal insomnia or long sleep duration were associated with a higher late-life dementia risk., (Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Objective: In a representative population of women followed over 34 years, we investigated the prospective association between fasting serum insulin and dementia, taking into account the incidence of diabetes mellitus., Methods: Fasting values for serum insulin and blood glucose were obtained in 1,212 nondiabetic women 38 to 60 years of age at the 1968 baseline. Risk of dementia was assessed by Cox proportional hazard regression with adjustment for insulin, glucose, and other covariates and, in a second model, after censoring for incident cases of diabetes mellitus. Incident diabetes mellitus was considered as a third endpoint for comparison with dementia., Results: Over 34 years, we observed 142 incident cases of dementia. The low tertile of insulin displayed excess risk for dementia (hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.52-3.58) compared to the medium tertile, but the high tertile of insulin did not (HR 1.28, 95% CI 0.81-2.03). These associations were also seen for dementia without diabetes comorbidity. In contrast, high but not low insulin predicted incident diabetes mellitus (115 cases) (HR 1.70, 95% CI 1.08-2.68 and HR 0.76, 95% CI 0.43-1.37, respectively)., Conclusion: A previous study reported a U-shaped association between fasting insulin and dementia in a 5-year follow-up of elderly men. Our results confirmed a nonlinear association in a female population, with high risk at low insulin values that was not attributable to preclinical dementia or impaired insulin secretion. This condition suggests a new pathway to dementia, which differs from the metabolic pathway involving diabetes mellitus., (Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To investigate whether greater cardiovascular fitness in midlife is associated with decreased dementia risk in women followed up for 44 years., Methods: A population-based sample of 1,462 women 38 to 60 years of age was examined in 1968. Of these, a systematic subsample comprising 191 women completed a stepwise-increased maximal ergometer cycling test to evaluate cardiovascular fitness. Subsequent examinations of dementia incidence were done in 1974, 1980, 1992, 2000, 2005, and 2009. Dementia was diagnosed according to DSM-III-R criteria on the basis of information from neuropsychiatric examinations, informant interviews, hospital records, and registry data up to 2012. Cox regressions were performed with adjustment for socioeconomic, lifestyle, and medical confounders., Results: Compared with medium fitness, the adjusted hazard ratio for all-cause dementia during the 44-year follow-up was 0.12 (95% confidence interval [CI] 0.03-0.54) among those with high fitness and 1.41 (95% CI 0.72-2.79) among those with low fitness. High fitness delayed age at dementia onset by 9.5 years and time to dementia onset by 5 years compared to medium fitness., Conclusions: Among Swedish women, a high cardiovascular fitness in midlife was associated with a decreased risk of subsequent dementia. Promotion of a high cardiovascular fitness may be included in strategies to mitigate or prevent dementia. Findings are not causal, and future research needs to focus on whether improved fitness could have positive effects on dementia risk and when during the life course a high cardiovascular fitness is most important., (Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction: This study examines the role of educational attainment, an indicator of cognitive reserve, on transitions in later life between cognitive states (normal Mini-Mental State Examination (MMSE), mild MMSE impairment, and severe MMSE impairment) and death., Methods: Analysis of six international longitudinal studies was performed using a coordinated approach. Multistate survival models were used to estimate the transition patterns via different cognitive states. Life expectancies were estimated., Results: Across most studies, a higher level of education was associated with a lower risk of transitioning from normal MMSE to mild MMSE impairment but was not associated with other transitions. Those with higher levels of education and socioeconomic status had longer nonimpaired life expectancies., Discussion: This study highlights the importance of education in later life and that early life experiences can delay later compromised cognitive health. This study also demonstrates the feasibility and benefit in conducting coordinated analysis across multiple studies to validate findings., (Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Over recent decades, epidemiology has made significant contributions to our understanding of dementia, translating scientific discoveries into population health. Here, we propose reframing dementia epidemiology as "population neuroscience," blending techniques and models from contemporary neuroscience with those of epidemiology and biostatistics. On the basis of emerging evidence and newer paradigms and methods, population neuroscience will minimize the bias typical of traditional clinical research, identify the relatively homogenous subgroups that comprise the general population, and investigate broader and denser phenotypes of dementia and cognitive impairment. Long-term follow-up of sufficiently large study cohorts will allow the identification of cohort effects and critical windows of exposure. Molecular epidemiology and omics will allow us to unravel the key distinctions within and among subgroups and better understand individuals' risk profiles. Interventional epidemiology will allow us to identify the different subgroups that respond to different treatment/prevention strategies. These strategies will inform precision medicine. In addition, insights into interactions between disease biology, personal and environmental factors, and social determinants of health will allow us to measure and track disease in communities and improve population health. By placing neuroscience within a real-world context, population neuroscience can fulfill its potential to serve both precision medicine and population health.

Background: Adiposity measured in mid- or late-life and estimated using anthropometric measures such as body mass index (BMI) and waist-to-hip ratio (WHR), or metabolic markers such as blood leptin and adiponectin levels, is associated with late-onset dementia risk. However, during later life, this association may reverse and aging- and dementia-related processes may differentially affect adiposity measures., Objective: We explored associations of concurrent BMI, WHR, and blood leptin and high molecular weight adiponectin levels with dementia occurrence., Methods: 924 Swedish community-dwelling elderly without dementia, aged 70 years and older, systematically-sampled by birth day and birth year population-based in the Gothenburg city region of Sweden. The Gothenburg Birth Cohort Studies are designed for evaluating risk and protective factors for dementia. All dementias diagnosed after age 70 for 10 years were identified. Multivariable logistic regression models were used to predict dementia occurrence between 2000-2005, 2005-2010, and 2000-2010 after excluding prevalent baseline (year 2000) dementias. Baseline levels of BMI, WHR, leptin, and adiponectin were used., Results: Within 5 years of baseline, low BMI (<20 kg/m2) was associated with higher odds of dementia compared to those in the healthy BMI category (≥ 20-24.9 kg/m2). Compared to the lowest quartile, leptin levels in the second quartile were associated with lower odds of dementia in women (p < 0.05)., Conclusion: In late-life, anthropometric and metabolic adiposity measures appear to be differentially associated with dementia risk. While BMI and leptin levels are highly positively correlated, our results show that their association with dementia at age ≥70 years, is asynchronous. These data suggest that with aging, the complexity of the adiposity exposure may increase and suggests metabolic dysregulation. Additional studies are needed to better understand this complexity.

Background: Low cerebrospinal fluid (CSF) levels of Aβ42 may be the earliest manifestation of Alzheimer's disease (AD). Knowledge on how CSF Aβ interacts with different brain pathologies early in the disease process is limited. We examined how CSF Aβ markers relate to brain atrophy and white matter lesions (WMLs) in octogenarians with and without dementia to explore the earliest pathogenetic pathways of AD in the oldest old., Objective: To study CSF amyloid biomarkers in relation to brain atrophy and WMLs in 85-year-olds with and without dementia., Methods: 53 octogenarians took part in neuropsychiatric examinations and underwent both a lumbar puncture and a brain CT scan. CSF levels of Aβ42 and Aβ40 were examined in relation to cerebral atrophy and WMLs. Dementia was diagnosed., Results: In 85-year-olds without dementia, lower levels of both CSF Aβ42 and CSF Aβ40 were associated with WMLs. CSF Aβ42 also correlated with measures of central atrophy, but not with cortical atrophy. In participants with dementia, lower CSF levels of Aβ42 were related to frontal, temporal, and parietal cortical atrophy but not to WMLs., Conclusions: Our findings may suggest that there is an interrelationship between Aβ and subcortical WMLs in older persons without dementia. After onset of dementia, low CSF Aβ42, probably representing amyloid deposition in plaques, is associated with cortical atrophy. WMLs may be an earlier manifestation of Aβ deposition than cortical degeneration.

Background: Subjective cognitive decline (SCD) has low predictive value for incident dementia., Objectives: We examined whether CT detectable brain changes add predictive value to SCD in a population sample with high scores on the Mini-Mental State Examination., Methods: Subjective reports of memory and executive function were gathered in a non-demented population sample ≥70 years (n = 921). CT-brain was performed at baseline (n = 626). Brain atrophy, infarcts, and white matter lesions (WMLs) were classified using visual ratings. Dementia incidence was evaluated periodically during 12 years., Results: The prevalence of SCD was 32.5% among individuals without dementia. During follow-up, 151 individuals (16.4%) developed dementia. The risk of dementia was increased in SCD, and increased further with WMLs and cortical atrophy present. However, the positive predictive values for incident dementia were low, 25% in SCD and 41% in SCD with WMLs and cortical atrophy., Conclusion: Our observations add clinical value to the use of SCD and CT to select relevant populations for interventions against dementia, but more stringent screening methods are necessary to reach individuals at risk.

Background: empirical evidence from high-income countries suggests that self-rated health (SRH) is useful as a brief and simple outcome measure in public health research. However, in many low- and middle-income countries (LMIC) there is a lack of evaluation and the cross-cultural validity of SRH remains largely untested. This study aims to explore the prevalence of SRH and its association with mortality in older adults in LMIC in order to cross-culturally validate the construct of SRH., Methods: population-based cohort studies including 16,940 persons aged ≥65 years in China, India, Cuba, Dominican Republic, Peru, Venezuela, Mexico and Puerto Rico in 2003. SRH was assessed by asking 'how do you rate your overall health in the past 30 days' with responses ranging from excellent to poor. Covariates included socio-demographic characteristics, use of health services and health factors. Mortality was ascertained through a screening of all respondents until 2007., Results: the prevalence of good SRH was higher in urban compared to rural sites, except in China. Men reported higher SRH than women, and depression had the largest negative impact on SRH in all sites. Without adjustment, those with poor SRH showed a 142% increase risk of dying within 4 years compared to those with moderate SRH. After adjusting for all covariates, those with poor SRH still showed a 43% increased risk., Conclusion: our findings support the use of SRH as a simple measure in survey settings to identify vulnerable groups and evaluate health interventions in resource-scares settings., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Several studies have reported a decline in incidence of dementia which may have large implications for the projected burden of disease, and provide important guidance to preventive efforts. However, reports are conflicting or inconclusive with regard to the impact of gender and education with underlying causes of a presumed declining trend remaining largely unidentified. The Alzheimer Cohorts Consortium aggregates data from nine international population-based cohorts to determine changes in the incidence of dementia since 1990. We will employ Poisson regression models to calculate incidence rates in each cohort and Cox proportional hazard regression to compare 5-year cumulative hazards across study-specific epochs. Finally, we will meta-analyse changes per decade across cohorts, and repeat all analysis stratified by sex, education and APOE genotype. In all cohorts combined, there are data on almost 69,000 people at risk of dementia with the range of follow-up years between 2 and 27. The average age at baseline is similar across cohorts ranging between 72 and 77. Uniting a wide range of disease-specific and methodological expertise in research teams, the first analyses within the Alzheimer Cohorts Consortium are underway to tackle outstanding challenges in the assessment of time-trends in dementia occurrence.

Introduction: We examined mortality, dementia, and progression of hydrocephalic symptoms among untreated individuals with idiopathic normal-pressure hydrocephalus (iNPH) in a population-based sample., Methods: A total of 1235 persons were examined between 1986 and 2012. Shunted individuals were excluded. We examined 53 persons with hydrocephalic ventricular enlargement (probable iNPH: n = 24, asymptomatic or possible iNPH: n = 29). Comparisons were made with individuals without hydrocephalic ventricular enlargement., Results: The 5-year mortality was 87.5% among those with probable iNPH. The hazard ratio (HR) for death was 3.8 (95% confidence interval [CI]: 2.5-6.0) for probable iNPH. Those with possible iNPH and asymptomatic hydrocephalic ventricular enlargement had increased risk of developing dementia, HR 2.8 (95% CI: 1.5-5.2). Only two individuals with hydrocephalic ventricular enlargement remained asymptomatic., Discussion: In the present sample, persons with clinical and imaging signs of iNPH had excess mortality and an increased risk of dementia. The data also suggest that radiological signs of iNPH might be more important than previously supposed., (Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Dementia is an increasing focus for policymakers, civil organizations and multidisciplinary researchers. The most recent descriptive epidemiological research into dementia is enabling investigation into how the prevalence and incidence are changing over time. To establish clear trends, such comparisons need to be founded on population-based studies that use similar diagnostic and research methods consistently over time. This narrative Review synthesizes the findings from 14 studies that investigated trends in dementia prevalence (nine studies) and incidence (five studies) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study, these studies indicate stable or declining prevalence and incidence of dementia, and some provide evidence of sex-specific changes. No single risk or protective factor has been identified that fully explains the observed trends, but major societal changes and improvements in living conditions, education and healthcare might have favourably influenced physical, mental and cognitive health throughout an individual's life course, and could be responsible for a reduced risk of dementia in later life. Analytical epidemiological approaches combined with translational neuroscientific research could provide a unique opportunity to explore the neuropathology that underlies changing occurrence of dementia in the general population.

Objectives: To examine level of and change in cognitive status using the Mini-Mental State Examination (MMSE) in relation to dementia, mortality, education, and sex in late nonagenarians., Design: Three-year longitudinal study with examinations at ages 97, 99, and 100., Setting: Trained psychiatric research nurses examined participants at their place of living., Participants: A representative population-based sample of 97-year-old Swedes (N = 591; 107 men, 484 women) living in Gothenburg, Sweden., Measurements: A Swedish version of the MMSE was used to measure cognitive status. Geriatric psychiatrists diagnosed dementia according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised. Mixed models were fitted to the data to model the longitudinal relationship between MMSE score and explanatory variables., Results: Individuals with dementia between age 97 and 100 had lower mean MMSE scores than those without dementia. Those who died during the 3-year follow-up had lower MMSE scores than those who survived. MMSE scores at baseline did not differ between those without dementia and those who developed dementia during the 3-year follow-up. Participants with more education had higher MMSE scores, but there was no association between education and linear change., Conclusion: MMSE score is associated with dementia and subsequent mortality even in very old individuals, although the preclinical phase of dementia may be short in older age. Level of education is positively associated with MMSE score but not rate of decline in individuals approaching age 100., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

Objective: Depression and dementia in the elderly have been suggested to share similar risk factors and pathogenetic background, and recently the authors reported that the APOEɛ4 allele is a risk factor for both disorders in the general population. The aim of the present study was to examine the influence of the well-known polymorphisms rs1799752 in the angiotensin-converting enzyme (ACE) and rs5186 in the angiotensin receptor II type 1 (AGTR1) on late-life depression and dementia in a population-based Swedish cohort of older individuals followed over 12 years., Methods: In 2000-2001, 900 individuals underwent neuropsychiatric and neuropsychological examinations. Follow-up evaluations were performed in 2005-2006 and 2009-2010, and register data on dementia to 2012 were included. Cross-sectional associations between genotypes/alleles and depression and dementia at baseline and between genotypes/alleles and depression on at least one occasion during the study period and dementia onset to 2012 were investigated., Results: As previously found for rs1799752 in ACE, rs5186 in AGTR1 was associated with dementia at baseline (OR: 3.25 [CI: 1.42-7.06], z = 2.90, p = 0.004). These associations became substantially weaker, or disappeared, when dementia onset to 2012 was included. For rs1799752 this could be explained by a significant association with age at onset (mean: 79.5 [SD: 6.45] years for risk-genotype carriers and 81.7 [SD: 7.12] years for carriers of other genotypes, b = -2.43, t = -2.38, df = 192, p = 0.02). When individuals with major depression on at least one occasion were analyzed, a significant association (OR: 2.14 [95% CI: 1.13-4.20], z = 2.28, p = 0.02), remaining after exclusion of dementia, with rs1799752 in ACE was found., Conclusion: In this population-based sample of older individuals, genetic variations in ACE seem to be important both for late-life major depression and dementia., (Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Recently, the LIfestyle for BRAin health (LIBRA) index was developed to assess an individual's prevention potential for dementia., Objective: We investigated the predictive validity of the LIBRA index for incident dementia in midlife, late life, and the oldest-old., Methods: 9,387 non-demented individuals were recruited from the European population-based DESCRIPA study. An individual's LIBRA index was calculated solely based on modifiable risk factors: depression, diabetes, physical activity, hypertension, obesity, smoking, hypercholesterolemia, coronary heart disease, and mild/moderate alcohol use. Cox regression was used to test the predictive validity of LIBRA for dementia at follow-up (mean 7.2 y, range 1-16)., Results: In midlife (55-69 y, n = 3,256) and late life (70-79 y, n = 4,320), the risk for dementia increased with higher LIBRA scores. Individuals in the intermediate- and high-risk groups had a higher risk of dementia than those in the low-risk group. In the oldest-old (80-97 y, n = 1,811), higher LIBRA scores did not increase the risk for dementia., Conclusion: LIBRA might be a useful tool to identify individuals for primary prevention interventions of dementia in midlife, and maybe in late life, but not in the oldest-old.

Objective: To determine whether calcium supplementation is associated with the development of dementia in women after a 5-year follow-up., Methods: This was a longitudinal population-based study. The sample was derived from the Prospective Population Study of Women and H70 Birth Cohort Study in Gothenburg, Sweden, and included 700 dementia-free women aged 70-92 years. At baseline in 2000-2001, and at follow-up in 2005-2006, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Dementia was diagnosed according to DSM-III-R criteria., Results: Women treated with calcium supplements (n = 98) were at a higher risk of developing dementia (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.01-4.37, p = 0.046) and the subtype stroke-related dementia (vascular dementia and mixed dementia) (OR 4.40, 95% CI 1.54-12.61, p = 0.006) than women not given supplementation (n = 602). In stratified analyses, calcium supplementation was associated with the development of dementia in groups with a history of stroke (OR 6.77, 95% CI 1.36-33.75, p = 0.020) or presence of white matter lesions (OR 2.99, 95% CI 1.28-6.96, p = 0.011), but not in groups without these conditions., Conclusions: Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease. Because our sample was relatively small and the study was observational, these findings need to be confirmed., (© 2016 American Academy of Neurology.)