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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 Lifestyle for brain health and cognitive functioning in midlife to early late-life New Zealanders: Utility of the LIBRA index.(John Wiley and Sons, Inc., 2024-05-01) Röhr S; Stephens C; Alpass FOBJECTIVES: There is enormous potential to improve brain health and reduce the risk of cognitive decline and dementia based on modifiable risk factors. The Lifestyle for Brain Health (LIBRA) index was developed to quantify modifiable dementia risk or room for brain health improvement. The objective of the study was to investigate the utility of the LIBRA index in relation to cognitive functioning in a midlife to early late-life sample of New Zealanders. METHODS: A subsample (n = 1001) of the longitudinal New Zealand Health, Work and Retirement (NZHWR) study completed face-to-face cognitive assessments using the 'Kiwi' Addenbrooke's Cognitive Examination-Revised (ACE-R) in 2010 and again in 2012, in addition to completing biennial NZHWR surveys on socioeconomic, health and wellbeing aspects. The LIBRA index was calculated incorporating information on 8 out of 12 modifiable health and lifestyle factors for dementia. Unadjusted and adjusted regression models and mixed effects models were used to inspect associations of LIBRA with cognitive functioning, cognitive impairment, and cognitive decline. RESULTS: The analytical sample (n = 881 [88.0%], after considering exclusion criteria and missing data) had a mean age of 63.1 (SD = 6.5) years, 53.3% were female, 26.2% were Māori, and 61.7% were highly educated. Higher LIBRA scores (indicating higher modifiable dementia risk) were associated with lower cognitive functioning (B = -0.33, 95% CI = -0.52;-0.15, p < 0.001) and a higher likelihood of cognitive impairment (OR = 1.22, 95% CI = 1.04; 1.42, p = 0.013), but did not predict cognitive decline over 2 years (B = -0.03, 95% CI = -0.22; 0.16, p = 0.766), adjusted for age, age2, gender, education, and ethnicity. CONCLUSIONS: The LIBRA index indicated promising utility for quantifying modifiable dementia risk in midlife and early late-life New Zealanders. For local use, refinement of the LIBRA index should consider cultural differences in health and lifestyle risk factors, and further investigate its utility with a wider range of modifiable factors over a longer observation period.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 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 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 Associations between social connections and cognition: a global collaborative individual participant data meta-analysis(Elsevier B.V, 2022-11) Samtani S; Mahalingam G; 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; Rydberg Sterner T; Scarmeas N; Kim K-W; Riedel-Heller S; Röhr S; Pabst A; Shahar S; Numbers K; Ganguli M; Jacobsen E; Hughes TF; Crowe M; Ng TP; Maddock J; Marseglia A; Mélis R; Szcześniak D; Wiegelmann H; Vernooij-Dassen M; Jeon Y-H; Sachdev PS; Brodaty H; SHARED consortium for the Cohort Studies of Memory in an International Consortium (COSMIC)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 (I2=0·00–15·11%) for all but two of the significant findings (association between slower memory decline and living with others [I2=58·33%] and community group engagement, I2=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.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 — Systematic Review and Meta-Analysis of Randomized Controlled Trials(Springer Nature Switzerland AG, 2023-01) Zülke AE; Riedel-Heller SG; Wittmann F; Pabst A; Röhr S; Luppa MBackground The number of people living with dementia worldwide is increasing rapidly. Preventive approaches constitute a promising strategy to counter the dementia epidemic, and growing numbers of lifestyle interventions are conducted around the globe. Gender differences with respect to modifiable risk factors for dementia have been reported, however, little is known about gender-specific effectiveness of lifestyle trials against cognitive decline and dementia. A systematic review and meta-analysis was conducted to assess evidence on gender-specific design and effectiveness of randomized controlled trials against cognitive decline. Methods Systematic literature searches were conducted in MEDLINE, PsycINFO, Web of Science, Cochrane Central and ALOIS. Studies assessing global and/or domain-specific cognitive function in older adults free from dementia were eligible for the systematic review. We assessed between-group effect sizes using random-effects meta-analysis. Methodological quality of included studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN)-checklist. Results The systematic review and meta-analysis included 34 and 31 studies, respectively. Effects of lifestyle-interventions on global cognition were non-significant overall (g =.27; 95% CI: −.01;.56) and in male subsamples (g = −.05; 95% CI: −.55;.45), and small for female subsamples (g =.38; 95% CI:.05;.72). Small beneficial effects were found for memory (overall: g =.38; 95% CI =.17;.59). Stratified by gender, significant effects were observed only in women (g =.39; 95% CI =.13;.65; men: g =.37; 95% CI:.00;.73). Aspects of gender in study design and conduct were discussed in a small minority of studies. Comparable results were observed for executive function and verbal fluency. Methodological quality was deemed high in 17.6% of studies, acceptable and low quality in 52.9% and 29.4%, respectively. Discussion We found evidence for small differences in the effectiveness of lifestyle interventions on global cognition and memory in favor of women. However, small numbers of trials 1) targeting men and 2) reporting gender-specific results for older adults with mild cognitive impairment warrant further attention. Assessing differences in modifiable risk factors for dementia in men and women and systematically addressing aspects of gender in trial conduction and recruitment in future studies might increase knowledge on gender-specific effectiveness of lifestyle trials against cognitive decline.Item How can urban environments support dementia risk reduction? A qualitative study(John Wiley and Sons Ltd, 2021-12-28) Röhr S; Rodriguez FS; Siemensmeyer R; Müller F; Romero-Ortuno R; Riedel-Heller SGObjective Interventions to reduce the risk of cognitive decline and dementia largely focus on individual-level strategies. To maximize risk reduction, it is also necessary to consider the environment. With the majority of older people living in cities, we explored how urban environments could support risk reduction. Materials and Methods In our qualitative study, we conducted semi-structured interviews with community members aged ≥65 years and stakeholders, all living in Leipzig, Germany. Interview guides were informed by the framework on modifiable risk factors for dementia of the Lancet Commission on Dementia Prevention, Intervention, and Care. Interviews were audio-recorded, verbatim-transcribed, and thematically analysed. Results Community members (n = 10) were M = 73.7 (SD = 6.0) years old and 50% were women. Stakeholders (n = 10) were aged 39–72 years, and 70% were women. Stakeholders' fields included architecture, cultural/arts education, environmental sciences, geriatrics, health policy, information and technology, philosophy, psychology, public health, and urban sociology. Across interviews with both older individuals and stakeholders, three main themes were identified: (i) social participation and inclusion (emphasizing social contacts, social housing, intergenerationality, neighbourhood assistance, information and orientation, digital and technological literacy, lifelong learning, co-creation/co-design), (ii) proximity and accessibility (emphasizing proximity and reachability, mobility, affordability, access to health care, access to cultural events, public toilets), (iii) local recreation and wellbeing (emphasizing safety in traffic, security, cleanliness and environmental protection, urban greenery, climate change and heat waves, outdoor physical activity). Discussion The design of urban environments holds large potential to create favourable conditions for community-dwelling individuals to practice lifestyles that promote brain health. Public policy should involve community members in co-creating such environments.