John D Crawford

UNSW Sydney | UNSW · Centre for Healthy Brain Ageing (CHEBA)

Background High‐income countries (HICs) are over‐represented in current global dementia incidence rates, skewing estimates. Variance in diagnostic methods between HICs and low‐ and middle‐income countries (LMICs) is speculated to contribute to the regional differences in rates. Cohort Studies of Memory in an International Consortium (COSMIC) offers...

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...

Background Cardiometabolic multimorbidity (CMM) and depression are often co-occurring in older adults and associated with neurodegenerative outcomes. The present study aimed to estimate the independent and joint associations of CMM and depression on cognitive function in multi-regional cohorts, and to validate the generalizability of the findings i...

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...

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...

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...

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...

Aim Recovery from stroke is adversely affected by neuropsychiatric complications, cognitive impairment, and functional disability. Better knowledge of their mutual relationships is required to inform effective interventions. Network theory enables the conceptualization of symptoms and impairments as dynamic and mutually interacting systems. We aime...

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...

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 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...

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...

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...

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...

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...

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...

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...

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...

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

Objective: Several movement disorders develop secondary to the use of psychotropic drugs, for which multiple symptom rating scales are in common use. We planned to develop the Unified Drug-Induced Movement Scale (UDIMS) to assess the severity and impact of drug-induced dyskinesia, tremor, drug-induced parkinsonism, akathisia, dystonia and myoclonus...

Introduction: Though consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear. Methods: We harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incid...

Objective The aim was to investigate the association of cognitive trajectories and overnight surgical hospitalization in older adults, while controlling for and comparing with the association with acute medical hospitalizations. Design This is a secondary analysis of data from a population-based, longitudinal cohort study of older Australians. Se...

Background: Cerebral small vessel disease (SVD) and Alzheimer's disease pathology, namely amyloid-β (Aβ) deposition, commonly co-occur. Exactly how they interact remains uncertain. Objective: Using participants from the Alzheimer's Disease Neuroimaging Initiative (n = 216; mean age 73.29±7.08 years, 91 (42.1%) females), we examined whether the p...

Objectives Computerised neuropsychological assessments (CNAs) are proposed as an alternative method of assessing cognition to traditional pencil-and-paper assessment (PnPA), which are considered the “gold standard” for diagnosing dementia. However, limited research has been conducted with culturally and linguistically diverse (CALD) individuals. Th...

Background Midlife hypertension is a known risk factor for cognitive decline and Alzheimer’s disease but in late life hypertension has been associated variously with better or no different cognition. New research suggests rather than average blood pressure, blood pressure variability best predicts cognitive decline because of excessive flow pulsati...

Background Previous studies have developed a latent continuous indicator of dementia phenotype, referred to as delta (δ), capturing the overlap of cognition and functional status in dementia (Royall & Palmer, 2012. J Neuropsy Clin Neurosci; Gravett et al., 2015. Neuropsy). To investigate this as a potential tool for harmonizing cognitive test and f...

Background Since the late 1980’s, Memory Clinics have been an integral part of Australia’s dementia assessment and care services. Despite their continuous growth over the past 30 years, little benchmarking data is available and no best practice standards have been established. The Australian Dementia Network‐Memory Clinics initiative (ADNeT‐MC) is...

Background and Purpose Poststroke cognitive impairment is common, but the trajectory and magnitude of cognitive decline after stroke is unclear. We examined the course and determinants of cognitive change after stroke using individual participant data from the Stroke and Cognition Consortium. Methods Nine longitudinal hospital-based cohorts from 7...

Background: Education and occupational complexity are main sources of mental engagement during early life and adulthood respectively, but research findings are not conclusive regarding protective effects of these factors against late-life dementia. Objective: This project aimed to examine the unique contributions of education and occupational co...

Objective: To synthesise international findings on the alcohol-dementia relationship and provide a cross-national comparison of the alcohol-dementia relationship with critical evidence for the relationship between alcohol use and dementia in under-studied populations. Design and setting: Individual participant data meta-analysis of 15 prospective e...

Background: Subjective cognitive complaints (SCCs) are a risk factor for dementia; however, little is known about their trajectories. Method: Participants were 873 older adults (Mage = 78.65 years; 55% females) from the Sydney Memory and Ageing Study that were followed-up biennially. SCCs were measured using the six-item Memory Complaint Questio...

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...

Lipidomics research could provide insights of pathobiological mechanisms in Alzheimer’s disease. This study explores a battery of plasma lipids that can differentiate Alzheimer’s disease (AD) patients from healthy controls and determines whether lipid profiles correlate with genetic risk for AD. AD plasma samples were collected from the Sydney Memo...

Background The interaction between cerebral vessel disease (CVD) pathology and Alzheimer’s disease (AD) pathology in the development of dementia is controversial. We examined the association of cerebral vascular neuropathology and cerebrovascular risk factors with the mild stage of Alzheimer's dementia and cognitive function. Methods This cross-se...

Objectives Conducting a national survey of clinicians and administrators from specialised dementia assessment services (memory clinics) in Australia to examine their current organisational aspects and assessment procedures and inform clinical tool harmonisation as part of the Australian Dementia Network—memory clinics project. Design A cross-secti...

Objective To determine if severe perivascular space (PVS) dilation is associated with longitudinal cognitive decline and incident dementia over four and eight years respectively, we analyzed data from a prospective cohort study. Methods 414 community dwelling older adults aged 72-92 were assessed at baseline and biennially for up to eight years, w...

Background Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer’s disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. Methods We combined individual participant data for 16 cohorts from 15 countries (member...

Background The latent continuous construct delta (δ) has been proposed as a novel approach to model dementia phenotype using structural equation modelling that reflects the “cognitive correlates of functional status” (Royall & Palmer, 2012. J Neuropsychiatry Clin Neurosci; Royall et al., 2012. J Alzheimers Dis). This δ factor has been demonstrated...

Background Social relationships create and emerge from social networks, which in turn promote social engagement and support (Berkman et al., 2000). Adults may focus on fewer and better relationships in older age (Carstensen and Scheibe, 2009). Yet meta‐analyses report that larger, supportive networks are protective for cognitive health (Penninkilam...

Background Subjective cognitive complaints (SCCs) are now an established risk factor for dementia, however, little is known about whether changing patterns in SCCs over time are associated with cognitive decline and dementia risk. We examine the trajectory of SCCs over a 6‐year period to determine whether intraindividual patterns of reporting SCCs...

Background Computer‐administered neuropsychological assessment batteries (CNAs) have the potential to allow large‐scale cognitive screening and monitoring, increasing older adults’ access to cognitive assessment, and earlier diagnosis of and intervention for cognitive impairment. There is, however, little research on whether experience with and att...

Background Computers and related technologies are increasingly used for cognitive assessment. However, few studies have considered older adults’ experience using computerized neuropsychological assessment (CNA), or individual characteristics that may influence acceptability and emotional responses to computerized tests. Method 205 community‐dwelli...

Background While midlife hypertension is deleterious, late-life hypertension has been associated with better cognitive outcomes in several studies. Many questions remain, including the relative benefit or harm of a blood pressure (BP) target and antihypertensive therapy of <120 in very old individuals. Methods The Sydney Memory and Aging Study (n...

Background Over the last decade resveratrol has been trialled for the prevention and treatment of cognitive decline; however, the results have shown a conflict between human studies compare with animal studies, especially on cognition, blood pressure, neuroimaging, and mood. Methods Human clinical trials and animal studies published prior to Janua...

Background Studying those who have achieved exceptional longevity can provide a model of successful ageing, however current research remains limited. Previous work on centenarians has primarily focused on depression and anxiety; life satisfaction remains understudied. Objectives To compare the psychological profile of near-centenarians (95-99) and...

Objectives: Many studies document cognitive decline following specific types of acute illness hospitalizations (AIH) such as surgery, critical care, or those complicated by delirium. However, cognitive decline may be a complication following all types of AIH. This systematic review will summarize longitudinal observational studies documenting cogn...

Objective: Type 2 diabetes (diabetes) is characterized by accelerated cognitive decline and higher dementia risk. Controversy exists regarding the impact of metformin, which is associated with both increased and decreased dementia rates. The objective of this study was to determine the association of metformin use with incident dementia and cognit...

Background: Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. Methods: We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries ove...

Background We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4). Methods Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies,...

Background: Subjective cognitive complaints (SCCs) are now an established risk factor for dementia, however, little is known about whether changing patterns in SCCs over time are associated with cognitive decline and dementia risk. We examine the trajectory of SCCs over a 6-year period to determine whether intraindividual patterns of reporting SCCs...

Vascular dementia (VaD) is a complex neurocognitive disorder secondary to a variety of cerebrovascular lesions. Numerous studies have shown that lipid metabolism is involved in the pathobiology of the disease. To examine the plasma lipid profiles in VaD, with the expectation of reliable lipid biomarkers for VaD emerging. 49 VaD patients and 48 heal...

Background The Reading the Mind in the Eyes Test (RMET) is a 36‐item assessment for theory of mind (ToM) performance. While this measure has been shown to be sensitive to age‐related ToM difficulties, there are no established cut‐offs or guidelines currently available that are specific to older adults. This paper seeks to validate a short‐form vers...

Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer`s disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. Therefore, we combined individual participant data for 16 cohorts from 15 countries (members of the...

Background and Purpose— Type 2 diabetes mellitus (T2D) is associated with cognitive impairment and an increased risk of dementia, but the association between prediabetes and cognitive impairment is less clear, particularly in a setting of major cerebrovascular events. This article examines the impact of impaired fasting glucose and T2D on cognitive...

Subjective Cognitive Complaints (SCCs) may represent one of the earliest stages of preclinical dementia. The objective of the present study was to extend previous work by our group to examine the relationship between participant-reported and informant-reported memory and non-memory SCCs, cognitive decline and incident dementia, over a six-year peri...

Background Metformin use in diabetes has been associated with both increased and decreased dementia rates in observational studies of people with diabetes. Objective: To examine changes in global cognition and specific cognitive domains over 6 years in older adults with diabetes treated with metformin, compared to other glucose lowering medications...

Background: Numerous studies have reported on cerebrospinal fluid (CSF) and blood biomarkers of Alzheimer's disease (AD); however, to date, none has compared biomarker patterns across the early-onset subtypes, i.e., early onset sporadic AD (EOsAD) and autosomal dominant AD (ADAD), qualitatively and quantitatively. Objective: To compare the fluid...

Centenarians without dementia can be considered as a model of successful ageing and resistance against age-related cognitive decline. Is there something special about their brain functional connectivity that helps them preserve cognitive function into the 11th decade of life? In a cohort of 57 dementia-free near-centenarians and centenarians (95-10...

Plasma fatty acids have been reported to be dysregulated in mild cognitive impairment (MCI) and Alzheimer’s disease (AD), though outcomes are not always consistent, and subject numbers often small. Our aim was to use a meta-analysis and systematic review approach to identify if plasma fatty acid dysregulation would be observed in case control studi...

Background Besides physical activity as a target for dementia prevention, sedentary behaviour is hypothesized to be a potential target in its own right. The rising number of persons with dementia and lack of any effective treatment highlight the urgency to better understand these modifiable risk factors. Therefore, we aimed to investigate whether h...

Background and purpose: To develop and validate a novel perivascular space rating scale, based on single axial slices in the basal ganglia and the centrum semiovale on T1-weighted and FLAIR images obtained on a 3T MRI scanner. Methods: 414 community dwelling older adults age 70-90 were assessed. The number of perivascular spaces in the slices 2...

Objective: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. Methods: We harmonized data from 13 stud...

Background: There is widespread consumer concern that statin use may be associated with impaired memory and cognitive decline. Objectives: This study sought to examine the association between statin use and changes in memory and global cognition in the elderly population over 6 years and brain volumes over 2 years. Interactions between statin us...

Background Depression is a common problem in older adults. The 15-item Geriatric Depression Scale (GDS-15) is a widely used psychometric tool for measuring depression in the elderly, but its psychometric properties have not been yet rigorously investigated. The aim was to evaluate psychometric properties of the GDS-15 and improve precision of the...

Early-life stress (ELS) has previously been identified as a risk factor for cognitive decline, but this work has predominantly focused on clinical groups and indexed traditional cognitive domains. It, therefore, remains unclear whether ELS is related to cognitive function in healthy community-dwelling older adults, as well as whether any effects of...

Apolipoprotein E (APOE) genotype is an established genetic risk factor for sporadic Alzheimer’s disease (AD) but the extent to which APOE genotype influences the plasma lipidome is unknown, even though lipids are potential diagnostic or prognostic biomarkers for AD. We quantified plasma lipids using untargeted liquid chromatography coupled mass spe...

Purpose of review: Cognitive decline is frequently reported after hospitalisation in the contexts of surgery, delirium and critical care. The question not adequately addressed is whether all types of acute hospitalisations increase the risk of cognitive decline. As acute hospitalisations are common in the elderly, who are also vulnerable to cognit...

Background: Hypertension is an established risk factor for stroke and vascular dementia but recent meta-analyses examining the association between Alzheimer's disease (AD) and hypertension have found no significant association. These meta-analyses included short term studies starting in late life which may have obscured the real effect of midlife...

Background With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. Methods and findings We harmoniz...

With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups.