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Item Trajectory of Cognitive Decline Before and After Stroke in 14 Population Cohorts(American Medical Association, 2024-10-02) Lo JW; Crawford JD; Lipnicki DM; Lipton RB; Katz MJ; Preux P-M; Guerchet M; d'Orsi E; Quialheiro A; Rech CR; Ritchie K; Skoog I; Najar J; Sterner TR; Rolandi E; Davin A; Rossi M; Riedel-Heller SG; Pabst A; Röhr S; Ganguli M; Jacobsen E; Snitz BE; Anstey KJ; Aiello AE; Brodaty H; Kochan NA; Chen Y-C; Chen J-H; Sanchez-Juan P; Del Ser T; Valentí M; Lobo A; De-la-Cámara C; Lobo E; Sachdev PSIMPORTANCE: Poststroke cognitive impairment is common, but the cognitive trajectory following a first stroke, relative to prestroke cognitive function, remains unclear. OBJECTIVE: To map the trajectory of cognitive function before any stroke and after stroke in global cognition and in 4 cognitive domains, as well as to compare the cognitive trajectory prestroke in stroke survivors with the trajectory of individuals without incident stroke over follow-up. DESIGN, SETTING, AND PARTICIPANTS: The study used harmonized and pooled data from 14 population-based cohort studies included in the Cohort Studies of Memory in an International Consortium collaboration. These studies were conducted from 1993 to 2019 across 11 countries among community-dwelling older adults without a history of stroke or dementia. For this study, linear mixed-effects models were used to estimate trajectories of cognitive function poststroke relative to a stroke-free cognitive trajectory. The full model adjusted for demographic and vascular risk factors. Data were analyzed from July 2022 to March 2024. EXPOSURE: Incident stroke. MAIN OUTCOMES AND MEASURES: The primary outcome was global cognition, defined as the standardized average of 4 cognitive domains (language, memory, processing speed, and executive function). Cognitive domain scores were formed by selecting the most commonly administered test within each domain and standardizing the scores. RESULTS: The study included 20 860 participants (12 261 [58.8%] female) with a mean (SD) age of 72.9 (8.0) years and follow-up of 7.51 (4.2) years. Incident stroke was associated with a substantial acute decline in global cognition (-0.25 SD; 95% CI, -0.33 to -0.17 SD), the Mini-Mental State Examination, and all cognitive domains (ranging from -0.17 SD to -0.22 SD), as well as accelerated decline in global cognition (-0.038 SD per year; 95% CI, -0.057 to -0.019 SD per year) and all domains except memory (ranging from -0.020 to -0.055 SD per year), relative to a stroke-free cognitive trajectory. There was no significant difference in prestroke slope in stroke survivors compared with the rate of decline in individuals without stroke in all cognitive measures. The mean rate of decline without a previous stroke was -0.049 SD per year (95% CI, -0.051 to -0.047 SD) in global cognition. CONCLUSIONS AND RELEVANCE: In this cohort study using pooled data from 14 cohorts, incident stroke was associated with acute and accelerated long-term cognitive decline in older stroke survivors.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 Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium.(John Wiley and Sons, Inc., 2023-08-01) Gong J; Harris K; Lipnicki DM; Castro-Costa E; Lima-Costa MF; Diniz BS; Xiao S; Lipton RB; Katz MJ; Wang C; Preux P-M; Guerchet M; Gbessemehlan A; Ritchie K; Ancelin M-L; Skoog I; Najar J; Sterner TR; Scarmeas N; Yannakoulia M; Kosmidis MH; Guaita A; Rolandi E; Davin A; Gureje O; Trompet S; Gussekloo J; Riedel-Heller S; Pabst A; Röhr S; Shahar S; Singh DKA; Rivan NFM; Boxtel MV; Köhler S; Ganguli M; Chang C-C; Jacobsen E; Haan M; Ding D; Zhao Q; Narazaki K; Chen T; Chen S; Ng TP; Gwee X; Numbers K; Mather KA; Scazufca M; Lobo A; De-la-Cámara C; Lobo E; Sachdev PS; Brodaty H; Hackett ML; Peters SAE; Woodward MINTRODUCTION: 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.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 Does parity matter in women’s risk of dementia? A COSMIC collaboration cohort study(BMC, 2020-08-05) 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; Llibre-Rodriguez JJ; Llibre-Guerra JJ; Valhuerdi-Cepero AJ; Ritchie K; Ancelin M-L; Carriere I; Skoog I; Najar J; Sterner TR; Scarmeas N; Yannakoulia M; Dardiotis E; Meguro K; Kasai M; Nakamura K; Riedel-Heller S; Roehr S; Pabst A; van Boxtel M; Köhler S; Ding D; Zhao Q; Liang X; Scazufca M; Lobo A; De-la-Cámara C; Lobo E; Kim KW; for Cohort Studies of Memory in an International Consortium (COSMIC)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.