Skip to main content

ORIGINAL RESEARCH article

Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1520069
This article is part of the Research Topic Advancing Early Alzheimer's Detection Through Multimodal Neuroimaging Techniques View all 3 articles

Connecting the Dots: Microstructural Properties of White Matter Hyperintensity Predict Longitudinal Cognitive Changes in Aging

Provisionally accepted
Michael Courtney Michael Courtney 1,2*Daniel Carey Daniel Carey 3Stephen Murphy Stephen Murphy 2Silvin P. Knight Silvin P. Knight 3James F Meaney James F Meaney 1,2Rose Anne Kenny Rose Anne Kenny 3Céline De Looze Céline De Looze 3
  • 1 St. James's Hospital, Dublin, Ireland
  • 2 The Thomas Mitchell Centre for Advanced Medical Imaging, St James’s Hospital, Dublin, Ireland, Dublin, Ireland
  • 3 Irish Longitudinal Study on Ageing, Trinity College Dublin, Dublin, County Dublin, Ireland

The final, formatted version of the article will be published soon.

    This study investigates the relationship between white matter hyperintensities (WMHs) and longitudinal cognitive decline in older adults. Using data from The Irish Longitudinal Study on Ageing (TILDA), we examined WMH characteristics, including volume, location, and microstructural integrity, in a community-dwelling population of 497 individuals over a sixyear period. WMHs were categorised into phenotypes based on their size, fractional anisotropy (FA), and mean diffusivity (MD), with subtypes for periventricular and deep white matter lesions. We hypothesised that larger, microstructurally compromised lesions would be associated with accelerated cognitive decline. We isolated 11,933 WMHs, with an average of 24 WMHs per individual. Of these lesions, 6,056 (51%) were classified as Low Volume -High FA, 3193 (27%) were classified as Low Volume -Low FA and 2684 (22%) were classified as High Volume, Low FA. Our findings demonstrate that high-volume, low FA deep (p=0.05) and periventricular (p=.004) lesions were significantly linked to cognitive decline (X=12.9, p=0.004), whereas small periventricular lesions with near normal microstructural properties do not predict cognitive decline. These results suggest that distinct WMH phenotypes may serve as markers for differential risks of cognitive impairment, providing potential targets for early intervention in at-risk populations.

    Keywords: white matter hyperintensities, cognitive decline, Aging, Vascular Dementia, cardiovascular risk factors, Neuroimaging

    Received: 30 Oct 2024; Accepted: 10 Feb 2025.

    Copyright: © 2025 Courtney, Carey, Murphy, Knight, Meaney, Kenny and De Looze. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Michael Courtney, St. James's Hospital, Dublin, Ireland

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.