Publications by authors named "Karen Mather"

Beneficial associations between higher fruit and vegetable intakes and risk of depression appear to exist but few studies have focused on adults aged 45 + years and the potential that associations are due to residual confounding has not been tested. This longitudinal study of twins (n = 3483, age 45-90 years) from Australia, Denmark, Sweden and USA, assessed the associations between baseline fruit/vegetable intake and depressive symptoms over 5-11 years using linear mixed effects models. Intakes from food frequency questionnaires were trichotomized.

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  • Subcortical brain structures play a crucial role in various developmental and psychiatric disorders, and a study analyzed brain volumes in 74,898 individuals, identifying 254 genetic loci linked to these volumes, which accounted for up to 35% of variation.
  • The research included exploring gene expression in specific neural cell types, focusing on genes involved in intracellular signaling and processes related to brain aging.
  • The findings suggest that certain genetic variants not only influence brain volume but also have potential causal links to conditions like Parkinson’s disease and ADHD, highlighting the genetic basis for risks associated with neuropsychiatric disorders.
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  • Subcortical brain structures play a crucial role in various disorders, and a study analyzed the genetic basis of brain volumes in nearly 75,000 individuals of European ancestry, revealing 254 loci linked to these volumes.
  • The research identified significant gene expression in neural cells, relating to brain aging and signaling, and found that polygenic scores could predict brain volumes across different ancestries.
  • The study highlights genetic connections between brain volumes and conditions like Parkinson's disease and ADHD, suggesting specific gene expression patterns could be involved in neuropsychiatric disorders.
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  • The study investigated how individuals with mild cognitive impairment (MCI) and dementia perform on social cognition tests, comparing these results to those without cognitive impairment.
  • It involved a cross-sectional analysis of 321 older adults aged 80 and above, utilizing various social cognitive assessment tools and screening for levels of apathy and neurocognitive function.
  • Findings indicated that participants with dementia showed notably worse social cognitive abilities compared to those with MCI and no cognitive impairment, particularly in emotional recognition and perspective-taking tasks.
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Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression.

Methods: Participants will be recruited from six study centres across Australia for an observational study of CADASIL.

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  • A study involving 7,801 older adults examined the connection between fruit and vegetable consumption and the development of depression, finding that higher fruit intake was linked to a lower risk of depression.
  • Over a follow-up period of 3 to 9 years, 21% of participants developed depression, with fruit intake showing a significant protective effect, while vegetable intake did not show a notable association.
  • The authors noted limitations due to varied measurement methods and the relatively modest sample size, suggesting further research is needed on fruit and vegetable consumption in larger, more standardized studies among older adults in low- and middle-income countries.
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  • Individual sensitivity to environmental exposures is influenced by genetics, showing that different genetic makeups can lead to varying reactions to the same environment.
  • A large meta-analysis was conducted using data from nearly 22,000 monozygotic twins to explore genetic influences on seven psychiatric and neurodevelopmental traits.
  • The study found 13 significant genetic associations related to factors like stress-reactivity, growth factors, and catecholamine uptake, highlighting the potential role of genetics in understanding environmental sensitivity.
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  • - The study explored how genetic variation and the environment affect gene expression in older adults, focusing on a community sample of 246 individuals (mostly female twins).
  • - Researchers found that about 24% of the analyzed genes showed heritability in blood gene expression, with 5269 significant probes identified, particularly linked to immune response and aging.
  • - Comparisons with other studies revealed that only a small fraction of heritable genes were common, underscoring the necessity of studying gene expression specifically in older populations.
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  • This study explored how the structure of the brain changes with age, specifically looking at the thickness of the cortex and the volume of subcortical areas, using data from over 42,000 participants aged 45-83.
  • Researchers found significant changes in the way brain regions are interconnected as people age, noting increased variability and decreased complexity in these connections.
  • Notably, specific trends in brain region correlations were observed, particularly in the occipital lobe, and older individuals demonstrated distinct structural covariance patterns, with many correlations being associated with cognitive decline that opposed age-related changes.
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Background: Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D pathogenesis and progression.

Methods: We profiled DNA methylation in 248 blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites.

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  • Research on verbal declarative memory (VDM) aims to understand the genetic factors that influence memory decline and dementia in older adults to develop potential interventions.
  • The study analyzed data from over 29,000 older, non-demented Europeans to explore relationships between genetic variants, gene expression, and brain tissues, finding significant associations across various pathways.
  • Results indicated that genetic variations linked to VDM are regulated by genes, transcription factors, and immune-related pathways, highlighting their importance in cognitive performance among older individuals.
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  • Long-term improvements in physical inactivity and behavioral risk factors are crucial for reducing dementia risk, but sustained behavior changes are difficult due to conditions like apathy, depression, and fatigue.
  • Research on 1,037 older adults (70-90 years) found that apathy negatively impacted physical activity and alcohol consumption, while depression and fatigue showed no consistent effects on health behaviors.
  • The study suggests that understanding and addressing apathy is essential for promoting healthier behaviors in older adults, especially in the context of dementia prevention strategies.
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As disease-specific interventions for dementia are being developed, the ability to identify the underlying pathology and dementia subtypes is increasingly important. Vascular cognitive impairment and dementia (VCID) is the second most common cause of dementia after Alzheimer disease, but progress in identifying molecular biomarkers for accurate diagnosis of VCID has been relatively limited. In this Review, we examine the roles of large and small vessel disease in VCID, considering the underlying pathophysiological processes that lead to vascular brain injury, including atherosclerosis, arteriolosclerosis, ischaemic injury, haemorrhage, hypoperfusion, endothelial dysfunction, blood-brain barrier breakdown, inflammation, oxidative stress, hypoxia, and neuronal and glial degeneration.

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  • Carriers of specific genetic variants (1q21.1 distal and 15q11.2 BP1-BP2) show both regional and global brain structure differences compared to noncarriers, but analyzing these differences can be complicated.
  • The study used MRI data from various groups (carriers and noncarriers) to assess how regional brain characteristics diverge from overall brain structure differences.
  • Findings revealed that certain brain regions in carriers exhibited distinct patterns of cortical surface area and thickness that deviated from the global average, suggesting more complex effects of these genetic variants on brain development.
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Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.

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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.

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  • Study investigates how genetics and environment affect fruit and vegetable consumption in older adults, with an aim to link diet to depression reduction.
  • * Analysis involved 374 twins aged 65 and older, using dietary questionnaires and depression assessments to estimate influences on their consumption habits.
  • * Results showed that vegetable intake is moderately heritable, especially for certain types, while fruit intake is solely influenced by environmental factors, with no genetic link to depressive symptoms found.
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  • This study compares three methods of assessing cognitive and affective empathy (behavioral, informant-report, and self-report) in a large adult sample (n=371) and finds that cognitive empathy measures show less agreement than affective ones.
  • While self-reports on affective empathy align with behavioral and informant-reports, cognitive empathy measures do not correlate with each other, highlighting issues with the validity of these assessments.
  • Informant-report measures are linked to better social functioning, and importantly, the effectiveness of these empathy assessments does not change with age, suggesting stable outcomes across different life stages.
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Objectives: Normal adult aging is associated with changes in social cognition. Although 4 social cognitive domains have been identified (social perception, theory of mind [ToM], affective empathy, and social behavior), no study has tested all 4 domains concurrently in a life-span sample, limiting understanding of the relative magnitude of age-related changes across domains. This study addresses this gap by providing the first assessment of all 4 social cognitive domains in an adult life-span sample.

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  • Understanding the genetic basis of memory could help address neurodegenerative disorders, and a study examined this in a large group of adults without dementia or stroke (N=53,637).
  • Researchers identified new genetic locations associated with verbal short-term memory and learning, particularly in the genes CDH18 and APOE/APOC1/TOMM40, with results verified in a separate sample.
  • Analysis showed that a genetic score for verbal learning correlated with brain activity during memory tasks and linked memory traits to various cognitive and health outcomes.
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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.

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Cerebral white matter hyperintensities on MRI are markers of cerebral small vessel disease, a major risk factor for dementia and stroke. Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architecture remains incompletely understood. More specifically, the role of DNA methylation has received little attention.

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  • Polygenic risk scores (PRSs) enhance the prediction of late-onset Alzheimer's disease (LOAD) risk beyond what is provided by the apolipoprotein E (APOE) gene, but they haven't been used much to find genetic factors that offer resilience against the disease.
  • The study aimed to identify genetic variants that confer resilience in two groups: unaffected individuals with high PRSs for LOAD and unaffected carriers of the APOE-ε4 variant also with high PRSs.
  • The researchers employed genome-wide association studies (GWAS) to create polygenic resilience scores, successfully replicating two of them across eight studies, suggesting that certain common genetic variants can help mitigate the risk of developing LOAD despite high genetic predisposition.
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  • The human brain evolves over time, with changes in structure affecting mental health and diseases throughout life.
  • This study identifies genetic variants that influence brain growth and shrinkage, using data from 15,640 individuals and focusing on 15 brain structures.
  • Key genes linked to metabolism were found, highlighting connections to conditions like depression and schizophrenia, and suggesting that understanding these genetic factors could lead to insights about healthy and problematic brain development and aging.
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