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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. [ABSTRACT FROM AUTHOR]

Human longevity is moderately heritable and is hence influenced by both genetic and environmental factors. However, there remains considerable uncertainty regarding its relationship with brain aging. Here, we used a discovery sample (N = 19 136, aged 45-81 years) from the UK Biobank and a replication sample (N = 809, aged 66-93 years) from the Sydney Memory and Ageing Study and the Older Australian Twins Study to investigate the associations between both parental life span (parental age at death) and polygenic risk score (PRS) for longevity (longevity-PRS) and structural magnetic resonance imaging brain metrics, which are considered to reflect the brain aging process, namely white matter hyperintensities (WMHs), total gray matter, and cortical volumes. We found lower volumes of WMHs to be significantly associated with longer parental life span in the discovery (whole WMH, β = -0.0323, padj = .0002) and replication samples (whole WMH, β = -0.0871, padj = .0208) and higher longevity-PRS in the discovery sample (whole WMH, β = -0.0331, padj = .0015) and a similar trend in the replication sample (significant before multiple comparison adjustment). The association of longevity-PRS with WMH remained significant after removing the influence of the apolipoprotein E locus (whole WMH, β = -0.0297, padj = .0048). While total gray matter and cortical volumes were related to parental life span in the discovery sample, they were not significantly associated with longevity-PRS. Additionally, the effects of longevity-PRS on the association were more prominent in males. Our findings suggest that enrichment of longevity-related alleles may provide some protection against WMH burden and highlight the important aspect of genetic relationship between longevity and WMH. [ABSTRACT FROM AUTHOR]

Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

The Australian Government has commenced a two-year pilot of consumer-directed care (CDC) across 500 home and community aged care packages. This policy paper discusses the model being trialled in Australia in light of the UK's Individual Budgets' Pilot Programme and the USA's Cash and Counselling Demonstration. The results of these randomised controlled studies suggest that older people vary in their preferences for consumer direction and that many find the administrative tasks of implementing CDC programs difficult. The relatively restricted model of CDC that the Australian Government is trialling may minimise the problems encountered in the overseas programs, but does not allow consumers to hire family or friends which they preferred to do overseas. [ABSTRACT FROM AUTHOR]

Background: Various models of intervention for caregivers of patients with dementia have been described. There has been little direct comparison of cultural differences between countries and the effect any differences may exert on the outcome of caregiver interventions. Aims: The aims of the three-country study (USA, Australia and the UK) were to assess whether caregiver interventions can still be successful when anti-dementia drugs are provided to patients, and whether a caregiver intervention can be successfully implemented using the same methods in three different English-speaking countries. In this paper, the cultural differences and similarities between the three countries are examined. Method: Randomised, controlled trial involving 158 patients and their caregivers (divided equally across three centres, New York, Sydney and Manchester) with all the patients receiving donepezil and the caregivers randomised to a caregiver intervention or treatment as usual. Results: There were few differences between countries in the main outcome measures, and no differences between the treatment-as-usual group and the intervention, but interesting cultural nuances were observed between groups. Despite these differences, the caregiver intervention was associated with positive results on caregiver depression across all the countries. Conclusions: This first multinational carer intervention study has emphasised the similarities between the three countries whilst highlighting crucial differences which may be important when planning cross-cultural studies in the future. The positive results achieved on caregiver depression were replicated across the three centres. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

• We developed a new DWI measure called DDF to characterize the white matter integrity. • DDF explained more variance of the changes related to age and cognition than other existing DWI measures. • Our findings have been replicated in an independent healthy ageing cohort and CSVD patients. Diffusion weighted imaging (DWI) is a widely recognized neuroimaging technique to evaluate the microstructure of brain white matter. The objective of this study is to establish an improved automated DWI marker for estimating white matter integrity and investigating ageing related cognitive decline. The concept of Wasserstein distance was introduced to help establish a new measure: difference in distribution functions (DDF), which captures the difference of reshaping one's mean diffusivity (MD) distribution to a reference MD distribution. This new DWI measure was developed using a population-based cohort (n =19,369) from the UK Biobank. Validation was conducted using the data drawn from two independent cohorts: the Sydney Memory and Ageing Study, a community-dwelling sample (n =402), and the Renji Cerebral Small Vessel Disease Cohort Study (RCCS), which consisted of cerebral small vessel disease (CSVD) patients (n =171) and cognitively normal controls (NC) (n =43). DDF was associated with age across all three samples and better explained the variance of changes than other established DWI measures, such as fractional anisotropy, mean diffusivity and peak width of skeletonized mean diffusivity (PSMD). Significant correlations between DDF and cognition were found in the UK Biobank cohort and the MAS cohort. Binary logistic analysis and receiver operator characteristic curve analysis of RCCS demonstrated that DDF had higher sensitivity in distinguishing CSVD patients from NC than the other DWI measures. To demonstrate the flexibility of DDF, we calculated regional DDF which also showed significant correlation with age and cognition. DDF can be used as a marker for monitoring the white matter microstructural changes and ageing related cognitive decline in the elderly. [ABSTRACT FROM AUTHOR]

Objectives: The study aims to describe people with dementia and informal caregivers' respective experiences of support after diagnosis and compares these experiences. Additionally, we determine how people with dementia and informal caregivers who are satisfied with support differ from those dissatisfied., Methods: A cross-sectional survey study in Australia, Canada, the Netherlands, Poland, and United Kingdom was carried out to examine people with dementia and informal caregivers experience with support (satisfaction with information, access to care, health literacy, and confidence in ability to live well with dementia). The separate surveys contained closed questions. Analysis consisted of descriptive statistics and Chi-square tests., Results: Ninety people with dementia and 300 informal caregivers participated, and 69% of people with dementia and 67% of informal caregivers said support after diagnosis helped them deal more efficiently with their concerns. Up to one-third of people with dementia and informal caregivers were dissatisfied with information about management, prognosis, and strategies for living positively. Few people with dementia (22%) and informal caregivers (35%) received a care plan. People with dementia were more often satisfied with information, had more often confidence in their ability to live well with dementia, and were less often satisfied with access to care compared to informal caregivers. Informal caregivers who were satisfied with support were more satisfied with information and access to care compared to informal caregivers not satisfied with support., Conclusions: Experience of dementia support can be improved and people with dementia and informal caregiver differ in their experiences of support., (© 2023 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)