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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.

Background: Recent studies suggest a decline in the age-specific incidence and prevalence of dementia. However, results are mixed regarding trends among octogenarians. We investigated time trends in the prevalence and incidence of dementia in 3 population-based cohorts of 85–90-year olds. We also examined if there were different time trends for men and women. Methods: We examined population-based birth cohorts within the Gothenburg H70 Birth Cohort Studies born 1901–02, 1923–24, and 1930, at ages 85 (N = 1481) and 88 (N = 840) years. The first 2 cohorts were also examined at age 90 (N = 450). The incidence was examined in 1 109 individuals free from dementia at baseline using information from the examination at age 88 or register data. All 3 cohorts were examined with identical methods. Results: The prevalence of dementia decreased from 29.8% in 1986–87 to 21.5% in 2008–10 and 24.5% in 2015–16 among 85-year olds, and from 41.9% in 1989–90 to 28.0% in 2011–12 to 21.7% in 2018–19 among 88-year olds, and from 41.5% in 1991–92 to 37.2% in 2013–14 among 90-year olds. The decline was most accentuated among women. The incidence of dementia per 1 000 risk-years from ages 85 to 89 declined from 48.8 among those born 1901–02 to 37.9 in those born 1923–24 to 22.5 among those born 1930. Conclusions: The prevalence and incidence of dementia decreased substantially over 3 decades among octogenarians. This might slow down the projected increase in cases of dementia expected by the increasing number of octogenarians during the following decades.

Introduction: There are few studies investigating genetic factors related to suicidal ideation or behavior in older adult populations. Our aim was to test associations between passive and active suicidal ideation and polygenic risk scores (PRSs) for suicidality and other traits of relevance for suicidality in old age (i.e. depression, neuroticism, loneliness, Alzheimer's disease, cognitive performance, educational attainment, and several specified vascular diseases) in a population-based sample aged 70 years and older. Methods: Participants in the prospective H70 study in Gothenburg, Sweden, took part in a psychiatric examination that included the Paykel questions on active and passive suicidal ideation. Genotyping was performed with the Neurochip (Illumina). After quality control of the genetic data the sample included 3467 participants. PRSs for suicidality and other related traits were calculated based on summary statistics from recent GWASs of relevance. Exclusion of persons with dementia or incomplete data on suicidal ideation yielded 3019 participants, age range 70-101 years. Associations between past year suicidal ideation (any level) and selected PRSs were analysed using general estimation equation (GEE) models, adjusted for sex and age. Results: We observed associations between passive/active suicidal ideation and PRSs for depression (three versions), neuroticism, and general cognitive performance. After excluding individuals with current major depressive disorder (MDD), similar associations were seen with PRS for neuroticism, general cognitive performance and two PRSs for depression. No associations were found between suicidal ideation and PRSs for suicidality, loneliness, Alzheimer's disease, educational attainment, or vascular disease. Discussion: Our results could indicate which types of genetic susceptibility that are of importance for suicidality in old age, and these findings can help to shed light on potential mechanisms that may be involved in pass

Healthy metabolic measures in humans are associated with longevity. Dysregulation leads to metabolic syndrome (MetS) and negative health outcomes. Recent exceptional longevity (EL) genome wide association studies have facilitated estimation of an individual’s polygenic risk score (PRS) for EL. We tested the hypothesis that individuals with high ELPRS have a low prevalence of MetS. Participants were from five cohorts of middle-aged to older adults. The primary analyses were performed in the UK Biobank (UKBB) (n = 407,800, 40–69 years). Replication analyses were undertaken using three Australian studies: Hunter Community Study (n = 2122, 55–85 years), Older Australian Twins Study (n = 539, 65–90 years) and Sydney Memory and Ageing Study (n = 925, 70–90 years), as well as the Swedish Gothenburg H70 Birth Cohort Studies (n = 2273, 70–93 years). MetS was defined using established criteria. Regressions and meta-analyses were performed with the ELPRS and MetS and its components. Generally, MetS prevalence (22–30%) was higher in the older cohorts. In the UKBB, high EL polygenic risk was associated with lower MetS prevalence (OR = 0.94, p = 1.84 × 10–42) and its components (p < 2.30 × 10–8). Meta-analyses of the replication cohorts showed nominal associations with MetS (p = 0.028) and 3 MetS components (p < 0.05). This work suggests individuals with a high polygenic risk for EL have a healthy metabolic profile promoting longevity.

Övriga forskningsfinaniserärer & strategiska forskningsprojekt:Open access funding provided by University of Gothenburg. SK was fnanced by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-81392, ALF GBG-771071). [...] HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (2018-02532), the European Research Council (681712), Swedish State Support for Clinical Research (ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (201809-2016862), the AD Strategic Fund and the Alzheimer’s Association (ADSF-21-831376-C, ADSF-21-831381-C and ADSF-21-831377-C), [...] the Erling-Persson Family Foundation, [...] the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), and the UK Dementia Research Institute at UCL. IS was fnanced by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALF 716681), Stena Foundation, Swedish Research Council (11267, 2005-8460, 2007-7462, 2012-5041, 2015-02830, 2019-01096, 2013-8717, NEAR 2017-00639), [...] The Alzheimer’s Association Zenith Award (ZEN-01-3151), The Alzheimer's Association Stephanie B. Overstreet Scholars (IIRG-00-2159), The Bank of Sweden Tercentenary Foundation, Stiftelsen Söderström-Königska Sjukhemmet, [...] KB is supported by the Swedish Research Council (2017-00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (RDAPB-201809-2016615), the Swedish Alzheimer Foundation (AF-742881), [...] the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (ALFGBG-715986), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), and the National Institute of Health (NIH), USA (grant 1R01AG068398-01). AZ was supported by the Swedish Alzheimer Foundation (AF-930582, AF-6

Introduction: Studies examining the effect of polygenic risk scores (PRS) for Alzheimer’s disease (AD) and apolipoprotein E (APOE) genotype on incident dementia in very old individuals are lacking. Methods: A population-based sample of 2052 individuals ages 70 to 111, from Swe-den, was followed in relation to dementia. AD-PRSs including 39, 57, 1333, and 13,942 single nucleotide polymorphisms (SNPs) were used. Results: AD-PRSs (including 39 or 57 SNPs) were associated with dementia (57-SNPs AD-PRS: hazard ratio 1.09, confidence interval 1.01–1.19, P = .03), particularly in APOE ɛ4 non-carriers (57-SNPs AD-PRS: 1.15, 1.05–1.27, P = 4 × 10–3, 39-SNPs AD-PRS: 1.22, 1.10–1.35, P = 2 × 10–4 ). No association was found with the other AD-PRSs. Further, APOE ɛ4 was associated with increased risk of dementia (1.60, 1.35–1.92, P = 1 × 10–7 ). In those aged ≥95 years, the results were similar for the AD-PRSs, while APOE ɛ4 only predicted dementia in the low-risk tertile of AD-PRSs. Discussion: These results provide information to identify individuals at increased risk of dementia. © 2021 The Authors.