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  1. Wu W, Ding D, Zhao Q, Xiao Z, Luo J, Ganguli M, et al.
    Alzheimers Dement, 2023 Jan;19(1):107-122.
    PMID: 35290713 DOI: 10.1002/alz.12628
    INTRODUCTION: Though consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear.

    METHODS: We harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incident dementia among older adults.

    RESULTS: Using no physical activity as a reference, dementia risk decreased with duration of physical activity up to 3.1 to 6.0 hours/week (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.67 to 1.15 for 0.1 to 3.0 hours/week; HR 0.68, 95% CI 0.52 to 0.89 for 3.1 to 6.0 hours/week), but plateaued with higher duration. For the amount of physical activity, a similar pattern of dose-response curve was observed, with an inflection point of 9.1 to 18.0 metabolic equivalent value (MET)-hours/week (HR 0.92, 95% CI 0.70 to 1.22 for 0.1 to 9.0 MET-hours/week; HR 0.70, 95% CI 0.53 to 0.93 for 9.1 to 18.0 MET-hours/week).

    DISCUSSION: This cross-national analysis suggests that performing 3.1 to 6.0 hours of physical activity and expending 9.1 to 18.0/MET-hours of energy per week may reduce dementia risk.

  2. Kobayashi LC, O'Shea BQ, Wixom C, Jones RN, Langa KM, Weir D, et al.
    Alzheimers Dement, 2024 Mar;20(3):1933-1943.
    PMID: 38159252 DOI: 10.1002/alz.13665
    INTRODUCTION: We conducted a cross-national comparison of the association between main lifetime occupational skills and later-life cognitive function across four economically and socially distinct countries.

    METHODS: Data were from population-based studies of aging and their Harmonized Cognitive Assessment Protocols (HCAPs) in the US, South Africa, India, and Mexico (N = 10,037; Age range: 50 to 105 years; 2016 to 2020). Main lifetime occupational skill was classified according to the International Standard Classification of Occupations. Weighted, adjusted regression models estimated pooled and country-specific associations between main lifetime occupational skill and later-life general cognitive function in men and women.

    RESULTS: We observed positive gradients between occupational skill and later-life cognitive function for men and women in the US and Mexico, a positive gradient for women but not men in India, and no association for men or women in South Africa.

    DISCUSSION: Main lifetime occupations may be a source of later-life cognitive reserve, with cross-national heterogeneity in this association.

    HIGHLIGHTS: No studies have examined cross-national differences in the association of occupational skill with cognition. We used data from Harmonized Cognitive Assessment Protocols in the US, Mexico, India, and South Africa. The association of occupational skill with cognitive function varies by country and gender.

  3. Mahalingam G, Samtani S, Lam BCP, Lipnicki DM, Lima-Costa MF, Blay SL, et al.
    Alzheimers Dement, 2023 Nov;19(11):5114-5128.
    PMID: 37102417 DOI: 10.1002/alz.13072
    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.

  4. Gong J, Harris K, Lipnicki DM, Castro-Costa E, Lima-Costa MF, Diniz BS, et al.
    Alzheimers Dement, 2023 Aug;19(8):3365-3378.
    PMID: 36790027 DOI: 10.1002/alz.12962
    INTRODUCTION: 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.

  5. Van Asbroeck S, Köhler S, van Boxtel MPJ, Lipnicki DM, Crawford JD, Castro-Costa E, et al.
    Alzheimers Dement, 2024 Apr 27.
    PMID: 38676366 DOI: 10.1002/alz.13846
    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.

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