Lifestyle and incident dementia: A COSMIC individual participant data meta­analysis.

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.

Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: The COSMIC consortium.

INTRODUCTION: White matter hyperintensities (WMHs) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well documented in populations of different ethnicities and/or from different geographical regions. METHODS: We investigated how WMHs were associated with vascular risk factors and cognition in both Whites and Asians, using data from five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1946). WMH volumes (whole brain, periventricular, and deep) were quantified with UBO Detector and harmonized using the ComBat model. We also harmonized various vascular risk factors and scores for global cognition and individual cognitive domains. RESULTS: Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake, and insufficient physical activity. Hypertension and stroke had stronger associations with WMH volumes in Whites than in Asians. No associations between WMH volumes and cognitive performance were found after correction for multiple testing. CONCLUSION: The current study highlights ethnic differences in the contributions of vascular risk factors to WMHs.

Associations between fruit and vegetable intakes and incident depression in middle-aged and older adults from 10 diverse international longitudinal cohorts.

BACKGROUND: Emerging observational evidence supports a role for higher fruit and vegetable intake in protecting against the development of depression. However, there is a scarcity of research in older adults or in low- to middle-income countries (LMICs). METHODS: Participants were 7801 community-based adults (mean age 68.6 ± 8.0 years, 55.8 % female) without depression, from 10 diverse cohorts, including four cohorts from LMICs. Fruit and vegetable intake was self-reported via comprehensive food frequency questionnaire, short food questionnaire or diet history. Depressive symptoms were assessed using validated measures, and depression defined applying validated cut-offs. The associations between baseline fruit and vegetable intakes and incident depression over a follow-up period of three to nine years were examined using Cox regression. Analyses were performed by cohort with results meta-analysed. RESULTS: There were 1630 cases of incident depression (21 % of participants) over 40,258 person-years of follow-up. Higher intake of fruit was associated with a lower risk of incident depression (HR 0.87, 95%CI [0.77, 0.99], I2 = 4 %). No association was found between vegetable intake and incident depression (HR 0.93, 95%CI [0.84, 1.04], I2 = 0 %). LIMITATIONS: Diverse measures used across the different cohorts and the modest sample size of our study compared with prior studies may have prevented an association being detected for vegetable intake. CONCLUSIONS: Our study supports a role for fruit, but not vegetable intake in protecting against depression. Research investigating different types of fruits and vegetables using standardised measures in larger cohorts of older adults from low- and middle-income countries is warranted.

Blood Pressure, Antihypertensive Use, and Late-Life Alzheimer and Non-Alzheimer Dementia Risk: An Individual Participant Data Meta-Analysis.

BACKGROUND AND OBJECTIVES: Previous randomized controlled trials and longitudinal studies have indicated that ongoing antihypertensive use in late life reduces all-cause dementia risk, but the specific impact on Alzheimer dementia (AD) and non-AD risk remains unclear. This study investigates whether previous hypertension or antihypertensive use modifies AD or non-AD risk in late life and the ideal blood pressure (BP) for risk reduction in a diverse consortium of cohort studies. METHODS: This individual participant data meta-analysis included community-based longitudinal studies of aging from a preexisting consortium. The main outcomes were risk of developing AD and non-AD. The main exposures were hypertension history/antihypertensive use and baseline systolic BP/diastolic BP. Mixed-effects Cox proportional hazards models were used to assess risk and natural splines were applied to model the relationship between BP and the dementia outcomes. The main model controlled for age, age2, sex, education, ethnoracial group, and study cohort. Supplementary analyses included a fully adjusted model, an analysis restricting to those with >5 years of follow-up and models that examined the moderating effect of age, sex, and ethnoracial group. RESULTS: There were 31,250 participants from 14 nations in the analysis (41% male) with a mean baseline age of 72 (SD 7.5, range 60-110) years. Participants with untreated hypertension had a 36% (hazard ratio [HR] 1.36, 95% CI 1.01-1.83, p = 0.0406) and 42% (HR 1.42, 95% CI 1.08-1.87, p = 0.0135) increased risk of AD compared with "healthy controls" and those with treated hypertension, respectively. Compared with "healthy controls" both those with treated (HR 1.29, 95% CI 1.03-1.60, p = 0.0267) and untreated hypertension (HR 1.69, 95% CI 1.19-2.40, p = 0.0032) had greater non-AD risk, but there was no difference between the treated and untreated groups. Baseline diastolic BP had a significant U-shaped relationship (p = 0.0227) with non-AD risk in an analysis restricted to those with 5-year follow-up, but otherwise there was no significant relationship between baseline BP and either AD or non-AD risk. DISCUSSION: Antihypertensive use was associated with decreased AD but not non-AD risk throughout late life. This suggests that treating hypertension throughout late life continues to be crucial in AD risk mitigation. A single measure of BP was not associated with AD risk, but DBP may have a U-shaped relationship with non-AD risk over longer periods in late life.