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Item Lifestyle and incident dementia: A COSMIC individual participant data meta-analysis(Wiley Periodicals LLC on behalf of Alzheimer's Association, 2024-06-16) Van Asbroeck S; Köhler S; van Boxtel MPJ; Lipnicki DM; Crawford JD; Castro-Costa E; Lima-Costa MF; Blay SL; Shifu X; Wang T; Yue L; Lipton RB; Katz MJ; Derby CA; Guerchet M; Preux P-M; Mbelesso P; Norton J; Ritchie K; Skoog I; Najar J; Sterner TR; Scarmeas N; Yannakoulia M; Dardiotis T; Rolandi E; Davin A; Rossi M; Gureje O; Ojagbemi A; Bello T; Kim KW; Han JW; Oh DJ; Trompet S; Gussekloo J; Riedel-Heller SG; Röhr S; Pabst A; Shahar S; Rivan NFM; Singh DKA; Jacobsen E; Ganguli M; Hughes T; Haan M; Aiello AE; Ding D; Zhao Q; Xiao Z; Narazaki K; Chen T; Chen S; Ng TP; Gwee X; Gao Q; Brodaty H; Trollor J; Kochan N; Lobo A; Santabárbara J; Gracia-Garcia P; Sachdev PS; Deckers K; for Cohort Studies of Memory in an International Consortium (COSMIC)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.Item Use of Antihypertensives, Blood Pressure, and Estimated Risk of Dementia in Late Life: An Individual Participant Data Meta-Analysis.(American Medical Association, 2023-09-12) Lennon MJ; Lam BCP; Lipnicki DM; Crawford JD; Peters R; Schutte AE; Brodaty H; Thalamuthu A; Rydberg-Sterner T; Najar J; Skoog I; Riedel-Heller SG; Röhr S; Pabst A; Lobo A; De-la-Cámara C; Lobo E; Bello T; Gureje O; Ojagbemi A; Lipton RB; Katz MJ; Derby CA; Kim KW; Han JW; Oh DJ; Rolandi E; Davin A; Rossi M; Scarmeas N; Yannakoulia M; Dardiotis T; Hendrie HC; Gao S; Carrière I; Ritchie K; Anstey KJ; Cherbuin N; Xiao S; Yue L; Li W; Guerchet MM; Preux P-M; Aboyans V; Haan MN; Aiello AE; Ng TP; Nyunt MSZ; Gao Q; Scazufca M; Sachdev PSSIMPORTANCE: 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.Item Social connections and risk of incident mild cognitive impairment, dementia, and mortality in 13 longitudinal cohort studies of ageing.(Wiley Periodicals LLC on behalf of Alzheimer’s Association., 2023-11) Mahalingam G; Samtani S; Lam BCP; Lipnicki DM; Lima-Costa MF; Blay SL; Castro-Costa E; Shifu X; Guerchet M; Preux P-M; Gbessemehlan A; Skoog I; Najar J; Sterner TR; Scarmeas N; Yannakoulia M; Dardiotis T; Kim K-W; Riedel-Heller S; Röhr S; Pabst A; Shahar S; Numbers K; Ganguli M; Hughes TF; Chang C-CH; Crowe M; Ng TP; Gwee X; Chua DQL; Rymaszewska J; Wolf-Ostermann K; Welmer A-K; Stafford J; Mélis R; Vernooij-Dassen M; Jeon Y-H; Sachdev PS; Brodaty H; SHARED consortium for the Cohort Studies of Memory in an International Consortium (COSMIC)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, Mage = 70.67 (40-102), 58.86% female, Meducation = 8.43 years, Mfollow-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. 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.Item Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study(Public Library of Science (PLoS), 2019-07) Lipnicki DM; Makkar SR; Crawford JD; Thalamuthu A; Kochan NA; Lima-Costa MF; Castro-Costa E; Ferri CP; Brayne C; Stephan B; Llibre-Rodriguez JJ; Llibre-Guerra JJ; Valhuerdi-Cepero AJ; Lipton RB; Katz MJ; Derby CA; Ritchie K; Ancelin M-L; Carrière I; Scarmeas N; Yannakoulia M; Hadjigeorgiou GM; Lam L; Chan W-C; Fung A; Guaita A; Vaccaro R; Davin A; Kim KW; Han JW; Suh SW; Riedel-Heller SG; Roehr S; Pabst A; van Boxtel M; Köhler S; Deckers K; Ganguli M; Jacobsen EP; Hughes TF; Anstey KJ; Cherbuin N; Haan MN; Aiello AE; Dang K; Kumagai S; Chen T; Narazaki K; Ng TP; Gao Q; Nyunt MSZ; Scazufca M; Brodaty H; Numbers K; Trollor JN; Meguro K; Yamaguchi S; Ishii H; Lobo A; Lopez-Anton R; Santabárbara J; Leung Y; Lo JW; Popovic G; Sachdev PS; for Cohort Studies of Memory in an International Consortium (COSMIC)Background With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. Methods and findings We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54–105 (mean = 72.7) years and without dementia at baseline. Studies had 2–15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = −0.1, SE = 0.01), APOE*4 carriage (B = −0.31, SE = 0.11), depression (B = −0.11, SE = 0.06), diabetes (B = −0.23, SE = 0.10), current smoking (B = −0.20, SE = 0.08), and history of stroke (B = −0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = −0.07, SE = 0.01), APOE*4 carriage (B = −0.41, SE = 0.18), and diabetes (B = −0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = −0.24, SE = 0.12), and between diabetes and cognitive decline (B = −0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. Conclusions These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.Item Parity and the risk of incident dementia: a COSMIC study(Cambridge University Press, 2020-10-20) Bae JB; Lipnicki DM; Han JW; Sachdev PS; Kim TH; Kwak KP; Kim BJ; Kim SG; Kim JL; Moon SW; Park JH; Ryu S-H; Youn JC; Lee DY; Lee DW; Lee SB; Lee JJ; Jhoo JH; Skoog I; Najar J; Sterner TR; Scarmeas N; Yannakoulia M; Dardiotis E; Riedel-Heller S; Roehr S; Pabst A; Ding D; Zhao Q; Liang X; Lobo A; De-la-Cámara C; Lobo E; Kim KW; for Cohort Studies of Memory in an International Consortium (COSMIC)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.Item Subjective cognitive decline and rates of incident Alzheimer's disease and non–Alzheimer's disease dementia.(John Wiley and Sons Inc on behalf of The Alzheimer's Association, 2019-03) Slot RER; Sikkes SAM; Berkhof J; Brodaty H; Buckley R; Cavedo E; Dardiotis E; Guillo-Benarous F; Hampel H; Kochan NA; Lista S; Luck T; Maruff P; Molinuevo JL; Kornhuber J; Reisberg B; Riedel-Heller SG; Risacher SL; Roehr S; Sachdev PS; Scarmeas N; Scheltens P; Shulman MB; Saykin AJ; Verfaillie SCJ; Visser PJ; Vos SJB; Wagner M; Wolfsgruber S; Jessen F; Alzheimer's Disease Neuroimaging Initiative; DESCRIPA working group; INSIGHT-preAD study group; SCD-I working group; van der Flier WMIntroduction In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia. Methods Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models. Results In SCD, incidence of dementia was 17.7 (95% Poisson confidence interval 15.2-20.3)/1000 person-years (AD: 11.5 [9.6-13.7], non-AD: 6.1 [4.7-7.7]), compared with 14.2 (11.3-17.6) in controls (AD: 10.1 [7.7-13.0], non-AD: 4.1 [2.6-6.0]). The risk of dementia was strongly increased in SCD in a memory clinic setting but less so in a community-based setting. In addition, higher age (hazard ratio 1.1 [95% confidence interval 1.1-1.1]), lower Mini–Mental State Examination (0.7 [0.66-0.8]), and apolipoprotein E ε4 (1.8 [1.3-2.5]) increased the risk of dementia. Discussion SCD can precede both AD and non-AD dementia. Despite their younger age, individuals with SCD in a memory clinic setting have a higher risk of dementia than those in community-based cohorts.