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AIM: To synthesise international findings on the alcohol-dementia relationship, including representation from low- and middle-income countries. METHODS: Individual participant data meta-analysis of 15 prospective epidemiological cohort studies from countries situated in six continents. Cox regression investigated the dementia risk associated with alcohol use in older adults aged over 60 years. Additional analyses assessed the alcohol-dementia relationship in the sample stratified by sex and by continent. Participants included 24,478 community dwelling individuals without a history of dementia at baseline and at least one follow-up dementia assessment. The main outcome measure was all-cause dementia as determined by clinical interview. RESULTS: At baseline, the mean age across studies was 71.8 (standard deviation 7.5, range 60-102 years), 14,260 (58.3%) were female, and 13,269 (54.2%) were current drinkers. During 151,636 person-years of follow-up, there were 2,124 incident cases of dementia (14.0 per 1,000 person-years). When compared with abstainers, the risk for dementia was lower in occasional (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.68-0.89), light-moderate (HR: 0.78; 95% CI: 0.70-0.87) and moderate-heavy drinkers (HR: 0.62; 95% CI: 0.51-0.77). There was no evidence of differences between lifetime abstainers and former drinkers in terms of dementia risk (HR: 0.98; 95% CI: 0.81-1.18). In dose-response analyses, moderate drinking up to 40g/day was associated with a lower risk of dementia when compared with lifetime abstaining. Among current drinkers, there was no consistent evidence for differences in terms of dementia risk. Results were similar when the sample was stratified by sex. When analysed at the continent level, there was considerable heterogeneity in the alcohol-dementia relationship. CONCLUSIONS: Abstinence from alcohol appears to be associated with an increased risk for all-cause dementia. Among current drinkers, there appears to be no consistent evidence to suggest that the amount of alcohol consumed in later life is associated with dementia risk.

BackgroundRecent 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.MethodsWe 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.ResultsThe 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.ConclusionsThe 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.

To describe representativeness in the Gothenburg H70 1930 Birth Cohort Study.Repeated cross-sectional examinations of a population-based study.Gothenburg, Sweden.All residents of Gothenburg, Sweden, born on specific birth dates in 1930 were invited to a comprehensive health examination at ages 70, 75, 79, 85 and 88. The number of participants at each examination was 524 at age 70, 767 at age 75, 580 at age 79, 416 at age 85, and 258 at age 88.We compared register data on sociodemographic characteristics and hospital discharge diagnoses between participants and (1) refusals, (2) all same-aged individuals in Gothenburg and (3) all same-aged individuals in Sweden. We also compared mortality rates between participants and refusals.Refusal rate increased with age. At two or more examination waves, participants compared with refusals had higher educational level, more often had osteoarthritis, had lower mortality rates, had lower prevalence of neuropsychiatric, alcohol-related and cardiovascular disorders, and were more often married. At two examination waves, participants compared with same-aged individuals in Gothenburg had higher education and were more often born in Sweden. At two examination waves or more, participants compared with same-aged individuals in Sweden had higher education, had higher average income, less often had ischaemic heart disease, were less often born in Sweden and were more often divorced.Participants were more similar to the target population in Gothenburg than to refusals and same-aged individuals in Sweden. Our study shows the importance of having different comparison groups when assessing representativeness of population studies, which is important in evaluating generalisability of results. The study also contributes unique and up-to-date knowledge about participation bias in these high age groups.

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.

The effect of Alzheimer’s disease (AD) polygenic risk scores (PRS) on amyloid and tau pathophysiology and neurodegeneration in cognitively unimpaired older adults is not known in detail. This study aims to investigate non-APOE AD-PRS and APOE ε4 in relation to AD pathophysiology evaluated by cerebrospinal fluid (CSF) biomarkers in a population-based sample of 70-year olds. A total of 303 dementia-free individuals from the Gothenburg H70 Birth Cohort Studies were included. Genotyping was performed using the NeuroChip, and AD-PRS were calculated. CSF levels of amyloid-β (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), neurogranin (Ng), and neurofilament light (NfL) were measured with enzyme-linked immunosorbent assay. Associations were found between non-APOE PRS and both NfL (p = .001) and Aβ42 (p = .02), and between APOE ε4 and Aβ42 (p = 1e−10), t-tau (p = 5e−4), and p-tau (p = .002). Similar results were observed when only including individuals with CDR = 0, except for no evidence of an association between non-APOE PRS and Aβ42. There was an interaction between non-APOE PRS and Aβ42 pathology status in relation to NfL (p = .005); association was only present in individuals without Aβ42 pathology (p = 3e-4). In relation to Aβ42, there was a borderline interaction (p = .06) between non-APOE PRS and APOE ε4; association was present in ε4 carriers only (p = .03). Similar results were observed in individuals with CDR = 0 (n = 246). In conclusion, among cognitively healthy 70-year olds from the general population, genetic risk of AD beyond the APOE locus was associated with NfL in individuals without Aβ42 pathology, and with Aβ42 in APOE ε4 carriers, suggesting these associations are driven by different mechanisms.

Healthy metabolic measures in humans are associated with longevity. Dysregulation leads to metabolic syndrome (MetS) and negative health outcomes. Recent exceptional longevity (EL) genome wide association studies have facilitated estimation of an individual’s polygenic risk score (PRS) for EL. We tested the hypothesis that individuals with high ELPRS have a low prevalence of MetS. Participants were from five cohorts of middle-aged to older adults. The primary analyses were performed in the UK Biobank (UKBB) (n = 407,800, 40–69 years). Replication analyses were undertaken using three Australian studies: Hunter Community Study (n = 2122, 55–85 years), Older Australian Twins Study (n = 539, 65–90 years) and Sydney Memory and Ageing Study (n = 925, 70–90 years), as well as the Swedish Gothenburg H70 Birth Cohort Studies (n = 2273, 70–93 years). MetS was defined using established criteria. Regressions and meta-analyses were performed with the ELPRS and MetS and its components. Generally, MetS prevalence (22–30%) was higher in the older cohorts. In the UKBB, high EL polygenic risk was associated with lower MetS prevalence (OR = 0.94, p = 1.84 × 10–42) and its components (p –8). Meta-analyses of the replication cohorts showed nominal associations with MetS (p = 0.028) and 3 MetS components (p

Contains fulltext : 287762.pdf (Publisher’s version ) (Open Access) 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.

Objective: To synthesise international findings on the alcohol-dementia relationship and provide a cross-national comparison of the alcohol-dementia relationship with critical evidence for the relationship between alcohol use and dementia in under-studied populations. Design and setting: Individual participant data meta-analysis of 15 prospective epidemiological cohort studies from countries situated in five continents. Cox regression investigated the dementia risk associated with alcohol use. Sensitivity analyses compared lifetime abstainers with former drinkers, adjusted extensively for demographic and clinical characteristics, and assessed the competing risk of death. Participants: 24,472 community-dwelling individuals without a history of dementia at baseline and at least one follow-up dementia assessment. Main outcome measure: All-cause dementia as determined by clinical interview. Results: During 151,574 person-years of follow-up, there were 2,137 incident cases of dementia (14.1 per 1,000 person-years). In the combined sample, when compared with occasional drinkers (

The aim of the study was to examine the association between reproductive period, as an indicator of endogenous estrogen, and levels of cerebrospinal fluid (CSF) biomarkers for Alzheimer disease (AD).A population-based sample of women from Gothenburg, Sweden was followed from 1968 to 1994 (N = 75). All women had natural menopause and were free from dementia. Information on reproductive period (age at menarche to age at menopause) was obtained from interviews from 1968 to 1980. Lumbar puncture was performed from 1992 to 1994 and CSF levels of Aβ42, Aβ40, P-tau, and T-tau were measured with immunochemical methods. Linear regression models adjusted for potential confounders were used to analyze the relationship between reproductive period and CSF biomarkers for AD.Longer reproductive period was associated with lower levels of Aβ42 (β = -19.2, P = 0.01), higher levels of P-tau (β = 0.03, P = 0.01), and lower ratio of Aβ42/Aβ40 (β = -0.02, P = 0.01), while no association was observed for T-tau (β = 0.01, P = 0.46). In separate analyses, examining the different components of reproductive period, earlier age at menarche was associated higher levels of P-tau (β = -0.07, P = 0.031) and lower ratio of Aβ42/Aβ40 (β = 0.05, P = 0.021), whereas no association was observed with Aβ42 (β = 31.1, P = 0.11) and T-tau (β = -0.001, P = 0.98). Furthermore, no association was observed between age at menopause and CSF biomarkers for AD.Our findings suggest that longer exposure to endogenous estrogen may be associated with increased levels of AD biomarkers in the preclinical phase of AD. These findings, however, need to be confirmed in larger samples.Video Summary:http://links.lww.com/MENO/A804.

PURPOSE: To investigate potential interactions between dietary patterns and genetic factors modulating risk for Alzheimer's disease (AD) in relation to incident dementia. METHODS: Data were derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden, including 602 dementia-free 70-year-olds (examined 1992-93, or 2000-02; 64% women) followed for incident dementia until 2016. Two factors from a reduced rank regression analysis were translated into dietary patterns, one healthy (e.g., vegetables, fruit, and fish) and one western (e.g., red meat, refined cereals, and full-fat dairy products). Genetic risk was determined by APOE ε4 status and non-APOE AD-polygenic risk scores (AD-PRSs). Gene-diet interactions in relation to incident dementia were analysed with Cox regression models. The interaction p value threshold was, Övriga forskningsfinaniserärer & strategiska forskningsprojekt:Open access funding provided by University of Gothenburg. SK was fnanced by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-81392, ALF GBG-771071). [...] HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (2018-02532), the European Research Council (681712), Swedish State Support for Clinical Research (ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (201809-2016862), the AD Strategic Fund and the Alzheimer’s Association (ADSF-21-831376-C, ADSF-21-831381-C and ADSF-21-831377-C), [...] the Erling-Persson Family Foundation, [...] the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), and the UK Dementia Research Institute at UCL. IS was fnanced by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALF 716681), Stena Foundation, Swedish Research Council (11267, 2005-8460, 2007-7462, 2012-5041, 2015-02830, 2019-01096, 2013-8717, NEAR 2017-00639), [...] The Alzheimer’s Association Zenith Award (ZEN-01-3151), The Alzheimer's Association Stephanie B. Overstreet Scholars (IIRG-00-2159), The Bank of Sweden Tercentenary Foundation, Stiftelsen Söderström-Königska Sjukhemmet, [...] KB is supported by the Swedish Research Council (2017-00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (RDAPB-201809-2016615), the Swedish Alzheimer Foundation (AF-742881), [...] the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (ALFGBG-715986), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), and the National Institute of Health (NIH), USA (grant 1R01AG068398-01). AZ was supported by the Swedish Alzheimer Foundation (AF-930582, AF-646061, AF-741361, AF-939988) [...].

Introduction: Studies examining the effect of polygenic risk scores (PRS) for Alzheimer's disease (AD) and apolipoprotein E (APOE) genotype on incident dementia in very old individuals are lacking. / Methods: A population‐based sample of 2052 individuals ages 70 to 111, from Sweden, was followed in relation to dementia. AD‐PRSs including 39, 57, 1333, and 13,942 single nucleotide polymorphisms (SNPs) were used. / Results: AD‐PRSs (including 39 or 57 SNPs) were associated with dementia (57‐SNPs AD‐PRS: hazard ratio 1.09, confidence interval 1.01–1.19, P = .03), particularly in APOE ɛ4 non‐carriers (57‐SNPs AD‐PRS: 1.15, 1.05–1.27, P = 4 × 10–3, 39‐SNPs AD‐PRS: 1.22, 1.10–1.35, P = 2 × 10–4). No association was found with the other AD‐PRSs. Further, APOE ɛ4 was associated with increased risk of dementia (1.60, 1.35–1.92, P = 1 × 10–7). In those aged ≥95 years, the results were similar for the AD‐PRSs, while APOE ɛ4 only predicted dementia in the low‐risk tertile of AD‐PRSs. / Discussion: These results provide information to identify individuals at increased risk of dementia.

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.

Aims To investigate the association between parity and the risk of incident dementia in women. Methods We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)). Results Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity. Conclusions Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.

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. Supplementary Information The online version contains supplementary material available at 10.1007/s10654-021-00745-5.

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.