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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 A multidomain intervention against cognitive decline in an at-risk-population in Germany: Results from the cluster-randomized AgeWell.de trial.(John Wiley and Sons, Inc., 2024-01-01) Zülke AE; Pabst A; Luppa M; Roehr S; Seidling H; Oey A; Cardona MI; Blotenberg I; Bauer A; Weise S; Zöllinger I; Sanftenberg L; Brettschneider C; Döhring J; Lunden L; Czock D; Haefeli WE; Wiese B; Hoffmann W; Frese T; Gensichen J; König H-H; Kaduszkiewicz H; Thyrian JR; Riedel-Heller SGINTRODUCTION: We investigated the effectiveness of a multidomain intervention to preserve cognitive function in older adults at risk for dementia in Germany in a cluster-randomized trial. METHODS: Individuals with a Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk score ≥ 9 aged 60 to 77 years were recruited. After randomization of their general practitioner (GP), patients received a multidomain intervention (including optimization of nutrition and medication, and physical, social, and cognitive activity) or general health advice and GP treatment as usual over 24 months. Primary outcome was global cognitive performance (composite z score, based on domain-specific neuropsychological tests). RESULTS: Of 1030 participants at baseline, n = 819 completed the 24-month follow-up assessment. No differences regarding global cognitive performance (average marginal effect = 0.010, 95% confidence interval: -0.113, 0.133) were found between groups at follow-up. Perceived restrictions in intervention conduct by the COVID-19 pandemic did not impact intervention effectiveness. DISCUSSION: The intervention did not improve global cognitive performance. HIGHLIGHTS: Overall, no intervention effects on global cognitive performance were detected. The multidomain intervention improved health-related quality of life in the total sample. In women, the multidomain intervention reduced depressive symptoms. The intervention was completed during the COVID-19 pandemic.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 Depression and Anxiety in Old Age during the COVID-19 Pandemic: A Comparative Study of Individuals at Cardiovascular Risk and the General Population.(MDPI (Basel, Switzerland), 2023-02-08) Gerhards SK; Luppa M; Röhr S; Pabst A; Bauer A; Frankhänel T; Döhring J; Escales C; Zöllinger IR; Oey A; Brettschneider C; Wiese B; Hoffmann W; Gensichen J; König H-H; Frese T; Thyrian JR; Kaduszkiewicz H; Riedel-Heller SG; Miettunen JOur study aims to examine the associations of sociodemographic factors, social support, resilience, and perceptions of the COVID-19 pandemic with late-life depression and anxiety symptoms in a cardiovascular risk group and a matched sample from the German general population during the beginning of the pandemic and draw a comparison regarding psychosocial characteristics. Data of n = 1236 participants (aged 64-81 years) were analyzed, with n = 618 participants showing a cardiovascular risk profile, and n = 618 participants from the general population. The cardiovascular risk sample had slightly higher levels of depressive symptoms and felt more threatened by the virus due to pre-existing conditions. In the cardiovascular risk group, social support was associated with less depressive and anxiety symptoms. In the general population, high social support was associated with less depressive symptoms. Experiencing high levels of worries due to COVID-19 was associated with more anxiety in the general population. Resilience was associated with less depressive and anxiety symptoms in both groups. Compared to the general population, the cardiovascular risk group showed slightly higher levels of depressive symptomatology even at the beginning of the pandemic and may be supported by addressing perceived social support and resilience in prevention programs targeting mental health.Item Beneficial and Impeding Factors for the Implementation of Health-Promoting Lifestyle Interventions-A Gender-Specific Focus Group Study.(MDPI (Basel, Switzerland), 2023-02-16) Wittmann FG; Zülke A; Schultz A; Claus M; Röhr S; Luppa M; Riedel-Heller SG; Tchounwou PB(1) Background: The prevalence of dementia increases and so does the number of interventions that address modifiable risk factors for dementia. Recent evidence suggests that there are gender differences in the prevalence of those lifestyle factors as well as in the effectiveness of interventions. This study aims to identify differences in factors that benefit or hinder the effectiveness of interventions since a target group's perspective gets more relevant. (2) Methods: Two focus groups, a female (n = 11) and a male (n = 8) group, were interviewed, audio recorded and transcribed. Qualitative analyses were performed and main- and subcategories were identified. (3) Results: Main differences were observed including aspects of lifestyle changes (e.g., respective diet and importance of an active lifestyle) and gender-typical behavior and perception by relevant healthcare actors. (4) Conclusions: Identified differences might help to address and raise the efficiency of lifestyle interventions. Further, the importance of social aspects and retirement as an auspicious moment to start interventions were identified as relevant by study participants.Item Social Isolation and Incident Dementia in the Oldest-Old—A Competing Risk Analysis(Frontiers Media S.A, 2022-06) Grothe J; Röhr S; Luppa M; Pabst A; Kleineidam L; Heser K; Fuchs A; Pentzek M; Oey A; Wiese B; Lühmann D; van den Bussche H; Weyerer S; Werle J; Weeg D; Bickel H; Scherer M; König H-H; Hajek A; Wagner M; Riedel-Heller SGPurpose: Social isolation is considered a risk factor for dementia. However, less is known about social isolation and dementia with respect to competing risk of death, particularly in the oldest-old, who are at highest risk for social isolation, dementia and mortality. Therefore, we aimed to examine these associations in a sample of oldest-old individuals. Methods: Analyses were based on follow-up (FU) 5–9 of the longitudinal German study AgeCoDe/AgeQualiDe. Social isolation was assessed using the short form of the Lubben Social Network Scale (LSNS-6), with a score ≤ 12 indicating social isolation. Structured interviews were used to identify dementia cases. Competing risk analysis based on the Fine-Gray model was conducted to test the association between social isolation and incident dementia. Results: Excluding participants with prevalent dementia, n = 1,161 individuals were included. Their mean age was 86.6 (SD = 3.1) years and 67.0% were female. The prevalence of social isolation was 34.7% at FU 5, 9.7% developed dementia and 36.0% died during a mean FU time of 4.3 (SD = 0.4) years. Adjusting for covariates and cumulative mortality risk, social isolation was not significantly associated with incident dementia; neither in the total sample (sHR: 1.07, 95%CI 0.65-1.76, p = 0.80), nor if stratified by sex (men: sHR: 0.71, 95%CI 0.28-1.83, p = 0.48; women: sHR: 1.39, 95%CI 0.77-2.51, p = 0.27). Conclusion: In contrast to the findings of previous studies, we did not find an association between social isolation and incident dementia in the oldest-old. However, our analysis took into account the competing risk of death and the FU period was rather short. Future studies, especially with longer FU periods and more comprehensive assessment of qualitative social network characteristics (e.g., loneliness and satisfaction with social relationships) may be useful for clarification.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 Social determinants and lifestyle factors for brain health: implications for risk reduction of cognitive decline and dementia(Springer Nature Limited, 2022-07-28) Röhr S; Pabst A; Baber R; Engel C; Glaesmer H; Hinz A; Schroeter ML; Witte AV; Zeynalova S; Villringer A; Löffler M; Riedel-Heller SGSubstantial evidence indicates a huge potential for risk reduction of cognitive decline and dementia based on modifiable health and lifestyle factors. To maximize the chances for risk reduction, it is useful to investigate associations of social determinants and lifestyle for brain health. We computed the “LIfestyle for BRAin health” (LIBRA) score for baseline participants of the Leipzig Research Centre for Civilization Diseases (LIFE) Adult Study, a population-based urban cohort in Germany. LIBRA predicts dementia in midlife and early late life populations, comprising 12 modifiable risk factors (heart disease, kidney disease, diabetes, obesity, hypertension, hypercholesterolemia, alcohol consumption, smoking, physical inactivity, diet, depression, cognitive inactivity). Associations of social determinants (living situation, marital status, social isolation, education, net equivalence income, occupational status, socioeconomic status/SES, employment) with LIBRA were inspected using age- and sex-adjusted multivariable linear regression analysis. Z-standardization and sampling weights were applied. Participants (n = 6203) were M = 57.4 (SD = 10.6, range 40–79) years old and without dementia, 53.0% were women. Except for marital status, all considered social determinants were significantly associated with LIBRA. Beta coefficients for the association with higher LIBRA scores were most pronounced for low SES (β = 0.80, 95% CI [0.72–0.88]; p < 0.001) and middle SES (β = 0.55, 95% CI [0.47–0.62]; p < 0.001). Social determinants, particularly socioeconomic factors, are associated with lifestyle for brain health, and should thus be addressed in risk reduction strategies for cognitive decline and dementia. A social-ecological public health perspective on risk reduction might be more effective and equitable than focusing on individual lifestyle behaviors alone.Item Gender-specific design and effectiveness of non-pharmacological interventions against cognitive decline and dementia–protocol for a systematic review and meta-analysis(Public Library of Science (PLoS), 2021-08-27) Zuelke AE; Riedel-Heller SG; Wittmann F; Pabst A; Roehr S; Luppa MIntroduction Dementia is a public health priority with projected increases in the number of people living with dementia worldwide. Prevention constitutes a promising strategy to counter the dementia epidemic, and an increasing number of lifestyle interventions has been launched aiming at reducing risk of cognitive decline and dementia. Gender differences regarding various modifiable risk factors for dementia have been reported, however, evidence on gender-specific design and effectiveness of lifestyle trials is lacking. Therefore, we aim to systematically review evidence on gender-specific design and effectiveness of trials targeting cognitive decline and dementia. Methods and analysis We will conduct a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases MEDLINE (PubMed interface), PsycINFO, Web of Science Core Collection, Cochrane Central Register of Controlled Trials (CENTRAL) and ALOIS will be searched for eligible studies using a predefined strategy, complemented by searches in clinical trials registers and Google for grey literature. Studies assessing cognitive function (overall measure or specific subdomains) as outcome in dementia-free adults will be included, with analyses stratified by level of cognitive functioning at baseline: a) cognitively healthy b) subjective cognitive decline 3) mild cognitive impairment. Two reviewers will independently evaluate eligible studies, extract data and determine methodological quality using the Scottish Intercollegiate Guidelines Network (SIGN)-criteria. If sufficient data with regards to quality and quantity are available, a meta-analysis will be conducted. Ethics and dissemination No ethical approval will be required as no primary data will be collected. PROSPERO registration number CRD42021235281.