Dataset Information

Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: the COSMIC consortium.

ABSTRACT:

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 cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1,946) were examined for WMH and their associations with vascular risk factors and cognition.

Result

Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake and insufficient physical activity. Participants with moderate or higher physical activity had less WMH than those who never exercised, but the former two groups did not differ. Hypertension and stroke had stronger associations with WMH volumes in the White, compared to Asian subsample.

Discussion

The current study highlighted the ethnic differences in the contributions of vascular risk factors to WMH.

SUBMITTER: Lin K

PROVIDER: S-EPMC10491386 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: the COSMIC consortium.

Lin Keshuo K Wen Wei W Lipnicki Darren M DM Mewton Louise L Chen Rory R Du Jing J Wang Dadong D Skoog Ingmar I Sterner Therese Rydberg TR Najar Jenna J Kim Ki Woong KW Han Ji Won JW Kim Jun Sung JS Ng Tze Pin TP Ho Roger R Chua Denise Qian Ling DQL Anstey Kaarin J KJ Cherbuin Nicolas N Mortby Moyra E ME Brodaty Henry H Kochan Nicole N Sachdev Perminder S PS Jiang Jiyang J

medRxiv : the preprint server for health sciences 20230831

<h4>Introduction</h4>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.<h4>Method</h4>Magnetic resonance imaging data of five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1,946) were examined for WMH and their ass ...[more]

PMID: 37693599

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Project description:Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative disorders with both sporadic and genetic forms. Mutations in the progranulin gene (GRN) are a common cause of genetic FTD, causing either a behavioural presentation or, less commonly, language impairment. Presence on T2-weighted images of white matter hyperintensities (WMH) has been previously shown to be more commonly associated with GRN mutations rather than other forms of FTD. The aim of the current study was to investigate the longitudinal change in WMH and the associations of WMH burden with grey matter (GM) loss, markers of neurodegeneration and cognitive function in GRN mutation carriers. 336 participants in the Genetic FTD Initiative (GENFI) study were included in the analysis: 101 presymptomatic and 32 symptomatic GRN mutation carriers, as well as 203 mutation-negative controls. 39 presymptomatic and 12 symptomatic carriers, and 73 controls also had longitudinal data available. Participants underwent MR imaging acquisition including isotropic 1 mm T1-weighted and T2-weighted sequences. WMH were automatically segmented and locally subdivided to enable a more detailed representation of the pathology distribution. Log-transformed WMH volumes were investigated in terms of their global and regional associations with imaging measures (grey matter volumes), biomarker concentrations (plasma neurofilament light chain, NfL, and glial fibrillary acidic protein, GFAP), genetic status (TMEM106B risk genotype) and cognition (tests of executive function). Analyses revealed that WMH load was higher in both symptomatic and presymptomatic groups compared with controls and this load increased over time. In particular, lesions were seen periventricularly in frontal and occipital lobes, progressing to medial layers over time. However, there was variability in the WMH load across GRN mutation carriers - in the symptomatic group 25.0% had none/mild load, 37.5% had medium and 37.5% had a severe load - a difference not fully explained by disease duration. GM atrophy was strongly associated with WMH load both globally and in separate lobes, and increased WMH burden in the frontal, periventricular and medial regions was associated with worse executive function. Furthermore, plasma NfL and to a lesser extent GFAP concentrations were seen to be associated with increased lesion burden. Lastly, the presence of the homozygous TMEM106B rs1990622 TT risk genotypic status was associated with an increased accrual of WMH per year. In summary, WMH occur in GRN mutation carriers and accumulate over time, but are variable in their severity. They are associated with increased GM atrophy and executive dysfunction. Furthermore, their presence is associated with markers of WM damage (NfL) and astrocytosis (GFAP), whilst their accrual is modified by TMEM106B genetic status. WMH load may represent a target marker for trials of disease modifying therapies in individual patients but the variability across the GRN population would prevent use of such markers as a global outcome measure across all participants in a trial.

Dataset Information

Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: the COSMIC consortium.

Introduction

Method

Result

Discussion

Publications

Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: the COSMIC consortium.

Similar Datasets

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