Perminder S Sachdev

UNSW Sydney | UNSW · School of Psychiatry

Introduction: Providing integrated and evidence-based support to individuals and families following a diagnosis of dementia is essential in order to optimise their quality of life and assist them to live well. Memory clinics provide multidisciplinary services specialising in the assessment and post-diagnostic treatment of people with dementia. This...

In 2018, the Australian Dementia Network (ADNeT) was established to bring together Australia’s leading dementia researchers, people with living experience and clinicians to transform research and clinical care in the field. To address dementia diagnosis, treatment, and care, ADNeT has established three core initiatives: the Clinical Quality Registr...

We built a genetic risk score (GRS) from the most complete landscape of the Alzheimer disease (AD) genetics. We extended its analysis in 16 European countries and observed a consistent association of this GRS with AD risk, age at onset and cerebrospinal fluid (CSF) AD biomarker levels regardless of the Apolipoprotein E (APOE) genotype. This GRS was...

Psychiatric disorders such as schizophrenia, major depressive disorder, and bipolar disorder have areas of significant overlap across multiple domains including genetics, neurochemistry, symptom profiles, and regional gray matter alterations. Various structural neuroimaging studies have identified a combination of shared and disorder-specific patte...

Purpose: To investigate the relationship between the apolipoprotein E (APOE) ε4 allele and retinal structural and vascular characteristics in older adult participants from several research studies. We also studied the relationship between these structural and vascular characteristics with multifocal visual evoked potential (mfVEP) indices, neurops...

Nanoparticle-based magnetic contrast agents have opened the potential for magnetic resonance imaging (MRI) to be used for early non-invasive diagnosis of Alzheimer’s disease (AD). Accumulation of amyloid pathology in the brain has shown association with cognitive decline and tauopathy; hence, it is an effective biomarker for the early detection of...

Importance The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested. Objectives To assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age >60 years) with dementia and the moderating factors of age, sex, and rac...

Current practices and barriers to provide post-diagnostic support in Australian memory clinics: Health-professionals’ view Introduction Memory clinics are specialised services for the assessment of older people who experience cognitive or other changes. The recently published National Memory Clinics Service Guidelines includes recommendations on p...

Background: The 1q21.1 distal and 15q11.2 BP1-BP2 CNVs exhibit regional and global brain differences compared to non-carriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intra-individual variability measures can be used to test for regional differences beyond global diffe...

INTRODUCTION: White matter hyperintensities (WMH) 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. METHOD: Magnetic resonance imaging data of five population-based coh...

Background: This UK Biobank study uses a mendelian randomization approach to mitigate the variability and confounding that has affected previous analyses of the relationship between measured blood pressure (BP) and cognition and thus delineate the true association between the two. Methods: Systolic BP (SBP) and diastolic BP polygenic risk scores...

Background: Most strokes and cardiovascular diseases (CVDs) are potentially preventable if their risk factors are identified and well controlled. Digital platforms, such as the PreventS-MD webapp (PreventS-MD) may aid health care professionals (HCPs) in assessing and managing risk factors and promoting lifestyle changes for their patients. Method...

Objectives: To examine sex differences in the associations between vascular risk factors and 6-year changes in the volume of white matter hyperintensities (WMH), and between changes in WMH volumes and changes in cognitive performance, in a cohort of non-demented older adults. Methods: WMH volumes at 3 time-points (baseline, and 2- and 6-year follow...

The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of gene expression from peripheral blood in older adults. The current study therefore aimed to investigate this question in a community sample of older adults. A total of 246 adults (7...

Aims: This study assesses the association of antihypertensive medication use on the severities of neuropathological cerebrovascular disease (CVD excluding lobar infarction) in older individuals. Methods: Clinical and neuropathological data were retrieved for 149 autopsy cases >75 years old with or without CVD or Alzheimer's disease and no other...

Background Neuroinflammation and oxidative stress (OS) are implicated in the pathophysiology of Alzheimer’s disease (AD). However, the extent to which inflammation is attributable to disease progression in the central nervous system in the pre‐ and clinical stages of dementia or emerges in the periphery and is a long‐term risk factor for the develo...

Objective: Evidence is accumulating that components of the Cannabis sativa plant may have therapeutic potential in treating psychiatric disorders. Medicinal cannabis (MC) products are legally available for prescription in Australia, primarily through the Therapeutic Goods Administration (TGA) Special Access Scheme B (SAS-B). Here we investigated re...

Objectives: The 10-item Kessler Psychological Distress Scale (K-10) is a widely applied distress measure; however, its psychometric properties were not established with older populations using advanced methodology. The aim of this study was to examine psychometric properties of the K-10 through application of Rasch methodology and if possible, dev...

Objective Few studies have focused on the contribution of long-term exposure to elevated BP to dementia and deaths, particularly among older adults. We examined the prognostic value of cumulative BP (cBP) and cBP load in relation to incident dementia, cognitive decline, all-cause and cardiovascular deaths among adults aged 70 years and above, follo...

The Telephone Interview for Cognitive Status-modified (TICS-M) is a well-established and widely used screening instrument for dementia and assessment of global cognitive function in older people. This study aimed to evaluate the psychometric properties of the TICS-M and to enhance the accuracy of the instrument using Rasch methodology. Partial Cred...

Background: The modified Telephone Interview for Cognitive Status (TICS-M) is a widely used tool for assessing global cognitive functions and screening for cognitive impairments. The tool was conceptualised to capture various cognitive domains, but the validity of such domains has not been investigated against comprehensive neuropsychological asse...

Background: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. Methods: For this cross-sectional study, we...

Background: Evidence suggests that lifestyle activities impact cognitive and mental health in older populations. However, how lifestyle factors are associated with one another, and which factors are most important for cognitive function and mental health has received comparatively little attention. Design: Bayesian-Gaussian network analysis was...

Objective: Self-perceived cognitive functioning, considered highly relevant in the context of aging and dementia, is assessed in numerous ways-hindering the comparison of findings across studies and settings. Therefore, the present study aimed to link item-level self-report questionnaire data from international aging studies. Method: We harmoniz...

Introduction: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. Methods: We used individual participant data (N = 39271, Mage = 70.67 (40-102), 58.86% female, Med...

Objectives: We examined longitudinal changes in cognitive and physical function and associations between change in function and falls in people with and without mild cognitive impairment (MCI). Design: Prospective cohort study with assessments every 2 years (for up to 6 years). Setting: Community, Sydney, Australia. Participants: Four hundre...

Background and objectives: Past studies on post-stroke cognitive function have focused on the average performance or change over time, but few have investigated patterns of cognitive trajectories after stroke. This project used latent class growth analysis (LCGA) to identify clusters of patients with similar patterns of cognition scores over the f...

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 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk...

Background: Few studies have compared gait speed and its correlates among different ethnogeographic regions. The goals of this study were to describe usual and rapid gait speed, and identify their correlates, across Australia, Asia, and African countries. Methods: We used data from six population-based cohorts of adults 65+ from six countries an...

Cognitive, social, and physical activities, collectively linked to cognitive reserve, are associated with better late-life cognitive outcomes. To better understand the building of cognitive reserve, we investigated which of these activities, during which stages of life, had the strongest associations with late-life cognitive performance. From the S...

Neurocognitive disorders (NCDs) are characterized by the presence of cognitive impairment as the prominent and defining feature of the disorder. NCDs capture all conditions generally referred to as dementias and mild cognitive impairment (MCI), and in this chapter, we will be using the terms major and mild NCD for these conditions, respectively, in...

Background: Subjective cognitive complaints (SCCs) may be a precursor to mild cognitive impairment (MCI) and dementia. Objective: This study aimed to examine the heritability of SCCs, correlations between SCC and memory ability, and the influence of personality and mood on these relationships. Methods: Participants were 306 twin pairs. The her...

Objectives: This study aimed to test whether prospective memory (PM) was an early cognitive marker of future cognitive decline and incident dementia using longitudinal data spanning eight years from the Sydney Memory and Ageing Study. Methods: 121 participants aged 72-91 years were tested in PM at baseline using a validated PM task, Virtual Week...

Ischemic strokes (IS) and transient ischemic attacks (TIA) account for approximately 80% of all strokes and are leading causes of death worldwide. Assessing the risk of recurrence or functional impairment in IS and TIA patients is essential to both acute phase treatment and secondary prevention. Current risk prediction systems that rely on clinical...

Background: The Maintain Your Brain (MYB) trial aims to prevent cognitive decline and dementia through multidomain, web-based risk-reduction. To facilitate translation, it is important to understand drivers of participation. Objective: To describe characteristics associated with participation in MYB. Methods: This was an observational ancillar...

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 wome...

Objective: To investigate the contribution of alterations in brain structure and function to cognitive function and their interactions in individuals with diabetes and patients with type 2 diabetes mellitus (T2DM). Research design and methods: This population-based study included 2,483 participants who underwent structural MRI (n = 569 with norm...

Background Prior work suggests that higher fruit and vegetable consumption may protect against depression in older adults. Better understanding of the influence of genetic and environmental factors on fruit and vegetable intakes may lead to the design of more effective dietary strategies to increase intakes. In turn this may reduce the occurrence o...

Background: The 16-item Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE-16) is a well-validated and widely-used measure of cognitive changes (CCs) among older adults. This study aimed to use Rasch methodology to establish psychometric properties of the IQCODE-16 and validate the existing ordinal-to-interval transformation algor...

Background Individuals with subjective cognitive complaints (SCCs) are at an increased risk of dementia. Questions remain about participant-reported versus informant-reported SCCs as indicators of future dementia and about longitudinal changes in participant-and informant-reported SCCs and risk of incident dementia. Method Participants were 873 ol...

Normative modeling is a statistical approach to quantify the degree to which a particular individual-level measure deviates from the pattern observed in a normative reference population. When applied to human brain morphometric measures it has the potential to inform about the significance of normative deviations for health and disease. Normative m...

Objective To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD). Design Pooled analysis. Data sources A...

Background Feature selection is often used to identify the important features in a dataset but can produce unstable results when applied to high-dimensional data. The stability of feature selection can be improved with the use of feature selection ensembles, which aggregate the results of multiple base feature selectors. However, a threshold must b...

To examine the moderation effects of hormonal factors on the associations between vascular risk factors and white matter hyperintensities in men and women, separately. White matter hyperintensities were automatically segmented and quantified in the UK Biobank dataset (N = 18,294). Generalised linear models were applied to examine (1) the main effec...

The Social Health and Reserve in the Dementia patient journey (SHARED) project is an international collaboration investigating the association between social health and cognitive function. We conducted an individual participant‐level meta‐analysis of the associations between social health variables and cognitive function (global cognition, memory,...

Heritability estimates of dementia are ∼50‐60% of the total variance across older adulthood. Earlier age of onset, however, might be associated with greater genetic influence whereas older age of onset might be associated with greater environmental influences. The categorical nature of dementia diagnosis outcomes has made testing the relative impor...

Perivascular space (PVS) burden is an emerging MRI‐marker of cerebral small vessel disease (cSVD), a leading cause of stroke and dementia. Underlying mechanisms of PVS are unknown. PVS are thought to be related to the glymphatic system, involved in brain clearance of molecules such as amyloid beta. We aimed to decipher the genetic underpinnings of...

Using data from population-based cohorts of older adults 65+ from six countries across three continents (N=6472), we aimed to (1) describe and (2) identify predictors of usual and rapid gait speed from studies participating in the Cohort Studies of Memory in an International Consortium (COSMIC) collaboration. We investigated whether clinical (BMI,...

Introduction Epidemiological evidence suggests that both poor cardiovascular fitness and low muscle mass or strength markedly increase the rate of cognitive decline and incident dementia in older adults. Results from exercise trials for the improvement of cognition in older adults with mild cognitive impairment (MCI) have reported mixed results. Th...

Technology and web‐based approaches potentially provide scalable population‐based interventions to reduce modifiable risk factors for dementia such as physical inactivity, suboptimal nutrition and low cognitive activity. Our aim was to reduce cognitive decline with ageing using an online package of interventions delivered intensively for 12 months...

Subjective cognitive decline (SCD), in the absence of impaired clinical testing, may be a clinical indicator of early Alzheimer’s disease (AD) and other dementias. However, not all individuals with SCD have cognitive decline. Corroboration of decline by an informant (i.e., close friend or family member) is one feature of SCD thought to increase the...

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. The objective is to develop a conceptual framewor...

Introduction: There are limited data on prevalence of dementia in centenarians and near-centenarians (C/NC), its determinants, and whether the risk of dementia continues to rise beyond 100. Methods: Participant-level data were obtained from 18 community-based studies (N = 4427) in 11 countries that included individuals ≥95 years. A harmonization...

Access to a “gold‐standard” in‐person neuropsychological assessment to detect cognitive decline in older adults using paper‐and‐pencil (PnP) tests is limited. Computerized neuropsychological assessments (CNAs) potentially provide lower cost, scalable, accessible alternatives but critical psychometric data on the validity, reliability and user‐exper...

Background: Self-administered computerized neuropsychological assessments (CNAs) provide lower cost, more accessible alternatives to traditional in-person assessments but lack critical information on psychometrics and subjective experience of older adults in remote testing environments. Objective: We used an online brief battery of computerized...

Background Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. Previous studies on the prevalence of cSVD are mostly based on single geographically-defined cohorts in high-income countries. Studies investigating the prevalence of cSVD in low- and middle-income countries (LMICs) are expanding but have not been systematicall...

Empathy is a core component of social cognition that can be indexed via behavioral, informant-report, or self-report methods of assessment. However, concerns have been raised regarding the lack of convergence between these assessment approaches for cognitive empathy. Here, we provided the first comparison of all three measurement approaches for cog...

Background: Epidemiological research on dementia is hampered by differences across studies in how dementia is classified, especially where clinical diagnoses of dementia may not be available. Objective: We apply structural equation modeling to estimate dementia likelihood across heterogeneous samples within a multi-study consortium and use the t...

Understanding dementia and cognitive impairment is a global effort needing data from multiple sources across diverse ethno-regional groups. Methodological heterogeneity means that these data often require harmonization to make them comparable before analysis. We discuss the benefits and challenges of harmonization, both retrospective and prospectiv...

Background Poor social connections (eg, small networks, infrequent interactions, and loneliness) are modifiable risk factors for cognitive decline. Existing meta-analyses are limited by reporting aggregate responses, a focus on global cognition, and combining social measures into single constructs. We aimed to investigate the association between so...

The nondemented old-old over the age of 80 comprise a rapidly increasing population group; they can be regarded as exemplars of successful aging. However, our current understanding of successful aging in advanced age and its neural underpinnings is limited. In this study, we measured the microstructural and network-based topological properties of b...

Introduction: Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotox...

A novel framework is proposed for handling the complex task of modelling and analysis of longitudinal, multivariate, heterogeneous clinical data. This method uses temporal abstraction to convert the data into a more appropriate form for modelling, temporal pattern mining, to discover patterns in the complex, longitudinal data and machine learning m...

The world's population is aging, bringing about an ever‐greater burden of mental disorders in older adults. Given multimorbidities, the mental health care of these people and their family caregivers is labor‐intensive. At the same time, ageism is a big problem for older people, with and without mental disorders. Positive elements of aging, such as...

To examine the relationships of retinal structural (optical coherence tomography) and visual functional (multifocal visual evoked potentials, mfVEP) indices with neuropsychological and brain structural measurements in healthy older subjects. 95 participants (mean (SD) age 68.1 (9.0)) years were recruited in the Optic Nerve Decline and Cognitive Cha...

Aim: To synthesise international findings on the alcohol-dementia relationship, including representation from low- and middle-income countries. Methods: Individual participant data meta-analysis of 15 prospective epidemiological cohort studies from countries situated in six continents. Cox regression investigated the dementia risk associated wit...

Objectives Normal adult aging is associated with changes in social cognition. Although four social cognitive domains have been identified (social perception, theory of mind (ToM), affective empathy and social behavior), no study has tested all four domains concurrently in a lifespan sample, limiting understanding of the relative magnitude of age-re...

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1,...

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 ELP...