Perminder S Sachdev

UNSW Sydney | UNSW · School of Psychiatry

Background We aimed to develop risk tools for dementia, stroke, myocardial infarction (MI), and diabetes, for adults aged ≥ 65 years using shared risk factors. Methods Data were obtained from 10 population-based cohorts (N = 41,755) with median follow-up time (years) for dementia, stroke, MI, and diabetes of 6.2, 7.0, 6.8, and 7.4, respectively. D...

Brain age has been widely investigated by using the whole brain image. However, the age of some specific brain regions, such as those related to the hippocampus, remains underexplored. This study developed age prediction models for left and right hippocampus-centred regions of interest (hippocampus ROI) using three-dimensional convolutional neural...

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon)...

Alzheimer’s disease (AD) is a devastating neurodegenerative condition that affects memory and cognition, characterized by neuronal loss and currently lacking a cure. Mutations in PSEN1 (Presenilin 1) are among the most common causes of early-onset familial AD (fAD). While changes in neuronal excitability are believed to be early indicators of AD pr...

Background: The SKT is a short cognitive performance test designed to assess impairments in memory and cognitive abilities such as attention and speed of information processing. In 2019, new regression-based norms for the English version of the SKT were calculated. This study has two aims: to establish valid cut-offs for distinguishing between no c...

Background We conducted a secondary analysis of a cohort study to examine the World Falls Guidelines algorithm’s ability to stratify older people into sizable fall risk groups or whether minor modifications were necessary to achieve this. Methods Six hundred and ninety-three community-living people aged 70–90 years (52.4% women) were stratified in...

Importance Poststroke cognitive impairment is common, but the cognitive trajectory following a first stroke, relative to prestroke cognitive function, remains unclear. Objective To map the trajectory of cognitive function before any stroke and after stroke in global cognition and in 4 cognitive domains, as well as to compare the cognitive trajecto...

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. We performed GWAS meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and, for the first time, the ventral diencephalon) in 74,898...

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 mo...

(1) Background The SKT is a short cognitive performance test designed to assess impairments in memory and cognitive abilities such as attention and speed of information processing. In 2019, new regression-based norms for the English version of the SKT were calculated applying data from older cognitively healthy adults living in the US, Ireland and...

Objective: To study general and subdomain performance in measures of social cognition in individuals with mild cognitive impairment (MCI), and dementia, and to explore associations between social cognitive and neuropsychological subdomains. Design: Cross-sectional study of participants from the Sydney Memory and Ageing Study (MAS). Setting: Curre...

Introduction: Social cognition is crucial to optimal social functioning outcomes in older adults, with implications for overall health and wellbeing. Moreover, poor social cognition is a diagnostic criterion for neurocognitive disorders (NCDs). Prior work has studied the social cognitive subdomains (theory of mind (ToM), affective empathy, emotion...

Introduction: The effects of the COVID-19 pandemic extend beyond the viral impact and include social and psychological effects of the ensuing lockdowns and restrictions. Australia’s lengthy lockdowns present an opportunity to study changes in the physical and mental wellbeing of older adults resulting from extended social isolation, a known risk fa...

Down syndrome regression disorder (DSRD) is a rare condition involving subacute cognitive decline, loss of previously acquired developmental skills, and prominent neuropsychiatric symptoms, particularly catatonia, in people with Down syndrome. It is thought to involve both autoimmune and neuropsychiatric mechanisms. Research, however, is largely re...

Background Few studies evaluated the contribution of long-term elevated blood pressure (BP) towards dementia and deaths. We examined the association between cumulative BP (cBP) load and dementia, cognitive decline, all-cause and cardiovascular deaths in older Australians. We also explored whether seated versus standing BP were associated with these...

Centenarians represent a phenomenon of successful aging. This systematic review aimed to understand lifestyles and health practices, focusing on diet and medication use for healthy longevity in community-based adults 95 years or over. Medline, CINAHL, Scopus, and gray literature were searched from 1 January 2000 to 10 December 2022. Study quality w...

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain‐age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain‐age has highlighted the need for robust and publicly available brain‐age model...

Background: The Australian population aged 70 and above is increasing and imposing new challenges for policy makers and providers to deliver accessible, appropriate and affordable health care. We examine pre-COVID patterns of health loss between 1990 and 2019 to inform policies and practices. Methods: Using the standardised methodology framework an...

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...

Increases in harmful drinking among older adults indicate the need for a more thorough understanding of the relationship between later‐life alcohol use and brain health. The current study investigated the relationships between alcohol use and progressive grey and white matter changes in older adults using longitudinal data. A total of 530 participa...

Aging is associated with progressive brain atrophy and declines in learning and memory, often attributed to hippocampal or cortical deterioration. The role of brain-derived neurotrophic factor (BDNF) in modulating the structural and functional changes in the brain and visual system, particularly in relation to BDNF Val66Met polymorphism, remains un...

Summary Background Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injur...

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 7,801 community-based adults (mean age 68.6 ± 8.0 years, 55.8% fema...

Background Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensiv...

Summary Background Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injur...

Depression is the largest global contributor to non-fatal disease burden(1). A growing body of evidence suggests that dietary behaviours, such as higher fruit and vegetable intake, may be protective against the risk of depression(2). However, this evidence is primarily from high-income countries, despite over 80% of the burden of depression being e...

Centenarians represent a phenomenon of successful aging, yet little is known about their lifestyle and health practices, including diet/nutrition, medication use, and health conditions. A protocol for this systematic review was registered previously(1). We systematically searched Medline, CINAHL, Scopus, and grey literature from 2000 to 2022, limit...

Structural neuroimaging studies have identified a combination of shared and disorder-specific patterns of gray matter (GM) deficits across psychiatric disorders. Pooling large data allows for examination of a possible common neuroanatomical basis that may identify a certain vulnerability for mental illness. Large-scale collaborative research is alr...

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread...

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...

Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes. However, environmental sensitivity genetic variants have proven challenging to detect. GWAS of monozygotic twin differences is a family-based variance analysis method, w...

Background Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-base...

Objectives: Subjective health (SH) is not just an indicator of physical health, but also reflects active cognitive processing of information about one's own health and has been associated with emotional health measures, such as neuroticism and depression. Behavior genetic approaches investigate the genetic architecture of SH, i.e., genetic and env...

The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of blood gene expression in older adults. The current study therefore aimed to investigate this question in a community sample of older adults. A total of 246 adults (71 MZ and 52 DZ t...

The morphologic properties of brain regions co-vary or correlate with each other. Here we investigated the structural covariances of cortical thickness and subcortical volumes in the ageing brain, along with their associations with age and cognition, using cross-sectional data from the UK Biobank (N = 42,075, aged 45–83 years, 53% female). As the s...

Background Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important follow...

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 sequencin...

Alzheimer’s disease (AD) is a devastating neurodegenerative condition that affects memory and cognition, characterized by neuronal loss and currently lacking a cure. Mutations in PSEN1 (Presenilin 1) are among the most common causes of early-onset familial AD (fAD). While changes in neuronal excitability are believed to be early indicators of AD pr...

Background The disruption of the neurovascular unit (NVU), which maintains the integrity of the blood brain barrier (BBB), has been identified as a critical mechanism in the development of cerebrovascular and neurodegenerative disorders. However, the understanding of the pathophysiological mechanisms linking NVU dysfunction to the disorders is inco...

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...

BACKGROUND Gray matter (GM) and white matter (WM) impairments are both associated with raised blood pressure (BP), although whether elevated BP is differentially associated with the GM and WM aging process remains inadequately examined. METHODS We included 37 327 participants with diffusion-weighted imaging (DWI) and 39 630 participants with T1-we...

As the brain ages, it almost invariably accumulates vascular pathology, which differentially affects the cerebral white matter. A rich body of research has investigated the link between vascular risk factors and the brain. One of the less studied questions is that among various modifiable vascular risk factors, which is the most debilitating one fo...

Background This study evaluates the dementia care system in a local area and aimed to include all specialised services designed to provide health and social services to people with dementia or age-related cognitive impairment, as well as general services with a high or very high proportion of clients with dementia. Methods The study used an intern...

Introduction: The data is limit for the association between osteoarthritis (OA) and cardiovascular disease (CVD) in community-based older populations and whether there is sex difference. This study aimed to examine the relationship between OA and prevalence and incidence of CVD over 10 years in community-dwelling older adults. Methods: Data on s...

The network nature of the brain is gradually becoming a consensus in the neuroscience field. A set of highly connected regions in the brain network called “rich‐club” are crucial high efficiency communication hubs in the brain. The abnormal rich‐club organization can reflect underlying abnormal brain function and metabolism, which receives increasi...

Objective:There is increasing focus on effective preventative interventions applicable at the population scale such as through technology and web-based approaches. We aimed to reduce cognitive decline with ageing using an online package of interventions delivered intensively for 12 months followed by monthly boosters for 24 months. Methods:Invitati...

Background:Good social connections are proposed to positively influence the course of cognitive decline by stimulating cognitive reserve and buffering harmful stress-related health effects. Prior meta-analytic research has uncovered links between social connections and the risk of poor health outcomes such as mild cognitive impairment, dementia, an...

Objective:The recognition of dementia as a multifactorial disorder encourages the exploration of new pathways to understand its origins. Social health might play a role in cognitive decline and dementia, but conceptual clarity is lacking and this hinders investigation of associations and mechanisms. Social health might provide a new perspective on...

Objectives To systematically review the literature pertaining to the definition and key clinical features of older adults with exceptional cognition with or without exceptional physical and social characteristics. Methods A systematic review according to PRISMA guidelines across PubMed (including MEDLINE), Embase, Web of Science, Scopus, PsycINFO...

Background: Superparamagnetic iron core iron oxide shell nanocubes have previously shown superior performance in magnetic resonance imaging T2 contrast enhancement compared with spherical nanoparticles. Methods: Iron core iron oxide shell nanocubes were synthesized, stabilized with dimercaptosuccinic acid (DMSA-NC) and physicochemically characteriz...

Background Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia. Methods We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delaye...

A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the “LIfestyle for BRAin health” (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for...

Background Depression is a known risk factor for dementia, and social support may lower the risk of depression in older adults. There is, however, a lack of longitudinal analyses examining the association between emotional versus instrumental support and depressive symptoms in older adults. We analyzed the association of emotional and instrumental...

Background Subjective cognitive complaints (SCCs) may be a precursor to mild cognitive impairment (MCI) and dementia. This study aimed to examine the heritability of SCCs, and the influence of personality and mood on the relationship between SCCs and memory performance. Method The heritability of SCCs were examined in 306 twin pairs using structur...

Background Cognitive super‐ageing, which refers to a subset of older individuals who maintain high level cognitive abilities into advanced age, has been variously defined as either superior cognitive performance for age, comparable cognitive performance to younger adults and/or maintenance of cognitive abilities over time. This study aimed to inves...

Background Computerised neuropsychological assessments (CNAs) are proposed as more accessible and culturally appropriate alternatives to traditional pencil‐and‐paper neuropsychological assessments (PnPAs) for diagnosing dementia in diverse populations. Whilst some PnPAs have demonstrated cultural and linguistic bias, research investigating the suit...