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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 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 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 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.Item Effects of APOE e4-allele and mental work demands on cognitive decline in old age: Results from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe)(John Wiley and Sons Ltd, 2021-01) Rodriguez FS; Roehr S; Pabst A; Kleineidam L; Fuchs A; Wiese B; Lühmann D; Brettschneider C; Wolfsgruber S; Pentzek M; van den Bussche H; König H-H; Weyerer S; Werle J; Bickel H; Weeg D; Maier W; Scherer M; Wagner M; Riedel-Heller SGObjectives Previous studies have observed protective effects of high mental demands at work on cognitive functioning and dementia risk. However, it is unclear what types of demands drive this effect and whether this effect is subject to a person's genetic risk. We investigated to what extent eight different types of mental demands at work together with the APOE e4 allele, a major risk gene for late-onset Alzheimer's disease, affect cognitive functioning in late life. Methods/Design The population-based German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe, n = 2 154) followed cognitively healthy individuals aged 75 years and older in seven assessment waves. Cognitive functioning was assessed via the mini-mental status examination. Results Mixed-effects modeling (adjusted for education, gender, marital status, stroke, depression, and diabetes) indicated that participants who had an occupational history of working in jobs with high compared to low demands in “Language & Knowledge”, “Pattern detection”, “Information processing”, and “Service” had a slower cognitive decline. APOE e4-allele carriers had an accelerated cognitive decline, but this decline was significantly smaller if they had a medium compared to a low level of demands in contrast to non-carriers. Conclusions Our longitudinal observations suggest that cognitive decline could be slowed by an intellectually enriched lifestyle even in risk gene carriers. Fostering intellectual engagement throughout the life-course could be a key prevention initiative to promote better cognitive health in old age.Item Estimating prevalence of subjective cognitive decline in and across international cohort studies of aging: a COSMIC study(BioMed Central Ltd, 2020-12-18) Röhr S; Pabst A; Riedel-Heller SG; Jessen F; Turana Y; Handajani YS; Brayne C; Matthews FE; Stephan BCM; Lipton RB; Katz MJ; Wang C; Guerchet M; Preux P-M; Mbelesso P; Ritchie K; Ancelin M-L; Carrière I; Guaita A; Davin A; Vaccaro R; Kim KW; Han JW; Suh SW; Shahar S; Din NC; Vanoh D; van Boxtel M; Köhler S; Ganguli M; Jacobsen EP; Snitz BE; Anstey KJ; Cherbuin N; Kumagai S; Chen S; Narazaki K; Ng TP; Gao Q; Gwee X; Brodaty H; Kochan NA; Trollor J; Lobo A; López-Antón R; Santabárbara J; Crawford JD; Lipnicki DM; Sachdev PS; for Cohort Studies of Memory in an International Consortium (COSMIC)Background Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer’s disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. Methods We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence. Results The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3–24.4%) and IRT (25.6%, 95%CI = 25.1–26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1–7.0%, to 52.7%, 95%CI = 47.4–58.0%; IRT: 7.8%, 95%CI = 6.8–8.9%, to 52.7%, 95%CI = 47.4–58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades. Conclusions SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.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 AgeWell.de – study protocol of a pragmatic multi-center cluster-randomized controlled prevention trial against cognitive decline in older primary care patients(BioMed Central Ltd, 2019-08-01) Zülke A; Luck T; Pabst A; Hoffmann W; Thyrian JR; Gensichen J; Kaduszkiewicz H; König H-H; Haefeli WE; Czock D; Wiese B; Frese T; Röhr S; Riedel-Heller SGBackground In the absence of treatment options, the WHO emphasizes the identification of effective prevention strategies as a key element to counteract the dementia epidemic. Regarding the complex nature of dementia, trials simultaneously targeting multiple risk factors should be particularly effective for prevention. So far, however, only few such multi-component trials have been launched, but yielding promising results. In Germany, comparable initiatives are lacking, and translation of these complex interventions into routine care was not yet done. Therefore, AgeWell.de will be conducted as the first multi-component prevention trial in Germany which is closely linked to the primary care setting. Methods AgeWell.de will be designed as a multi-centric, cluster-randomized controlled multi-component prevention trial. Participants will be older community-dwelling general practitioner (GP) patients (60–77 years; n = 1,152) with increased dementia risk according to CAIDE (Cardiovascular Risk Factors, Aging, and Incidence of Dementia) Dementia Risk Score. Recruitment will take place at 5 study sites across Germany. GP practices will be randomized to either intervention A (advanced) or B (basic). GPs will be blinded to their respective group assignment, as will be the statistician conducting the randomization. The multi-component intervention (A) includes nutritional counseling, physical activity, cognitive training, optimization of medication, management of vascular risk factors, social activity, and, if necessary, further specific interventions targeting grief and depression. Intervention B includes general health advice on the intervention components and GP treatment as usual. We hypothesize that over the 2-year follow-up period the intervention group A will benefit significantly from the intervention program in terms of preserved cognitive function/delayed cognitive decline (primary outcome), and other relevant (secondary) outcomes (e.g. quality of life, social activities, depressive symptomatology, cost-effectiveness). Discussion AgeWell.de will be the first multi-component trial targeting risk of cognitive decline in older adults in Germany. Compared to previous trials, AgeWell.de covers an even broader set of interventions suggested to be beneficial for the intended outcomes. The findings will add substantial knowledge on modifiable lifestyle factors to prevent or delay cognitive decline. Trial registration German Clinical Trials Register (reference number: DRKS00013555).