UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Association of Increase in White Matter Hyperintensity Volume With Rate of Hippocampal Atrophy in a Population-Based Study of Aging

Brown, Thomas M; James, Sarah-Naomi; Nicholas, Jennifer M; Keuss, Sarah; Keshavan, Ashvini; Malone, Ian B; Coath, William; ... Barnes, Josephine; + view all (2025) Association of Increase in White Matter Hyperintensity Volume With Rate of Hippocampal Atrophy in a Population-Based Study of Aging. Neurology , 105 (5) , Article e213975. 10.1212/WNL.0000000000213975. Green open access

[thumbnail of Association of Increase in White Matter Hyperintensity Volume With Rate of Hippocampal Atrophy in a Population-Based Study o.pdf]
Preview
PDF
Association of Increase in White Matter Hyperintensity Volume With Rate of Hippocampal Atrophy in a Population-Based Study o.pdf - Published Version

Download (1MB) | Preview

Abstract

BACKGROUND AND OBJECTIVES: Higher white matter hyperintensity volume (WMHV) is associated with hippocampal atrophy, cognitive decline, and dementia; however, it is unknown whether continually increasing WMHV is related to hippocampal atrophy. The aim of this study was to determine whether higher WMHV change rate (WMHVR) is related to higher hippocampal atrophy rate (HAR); this relationship is dependent on cardiovascular risk factors (CVRFs), Alzheimer disease (AD) pathology, and genetic risk; and this relationship is mediated by neuroaxonal degradation. METHODS: Participants from Insight46, a substudy of the 1946 British Birth Cohort, underwent combined [18F]florbetapir PET/MRI scans at University College London approximately 2.5 years apart. WMHVR was quantified from T2/fluid-attenuated inversion recovery and HAR from T1 sequences. Life-course blood pressure and CVRF data were measured at 6 and 3 time points, respectively. APOE genotype and neurofilament light chain (NfL) quantification were derived from blood samples. Participants with neurologic conditions were excluded from primary analyses. Linear regression was used to test the relationships between WMHVR and HAR, adjusting for sex, age, and total intracranial volume (TIV) and CVRF, APOE-ε4 status, and β-amyloid (Aβ) in separate models. Semipartial R2 was calculated from these models. In a post hoc analysis, structural equation modeling aimed to determine whether NfL mediated the relationship between WMHVR and HAR. RESULTS: A total of 317 individuals without neurologic conditions (48% female, 100% White British, mean baseline age [SD] = 70.5 [0.6] years) were included. The mean HAR was 0.04 [0.04] mL/y. Each 1 mL/y increase in WMHVR was associated with a 0.014 mL/y (95% CI 0.005–0.022) increase in HAR, adjusted for TIV, age, and sex (p = 0.002). Adjustment for additional variables did not meaningfully attenuate this association (≥0.012 mL/y, p ≤ 0.005, all models), and there was no indirect effect through NfL (0.0004 mL/y [95% CI −0.0006 to 0.0012], p < 0.1). DISCUSSION: Higher WMHVR was associated with HAR between approximately 70 and 73 years, independent of CVRF levels, APOE-ε4 status, and Aβ load, and not mediated by markers of neuroaxonal degradation. Although AD-specific pathology is typically considered the main cause of accelerated HAR, we demonstrated that HAR is also linked to deteriorating WM health. These results will need to be replicated in more diverse cohorts with longer follow-up periods to confirm the findings.

Type: Article
Title: Association of Increase in White Matter Hyperintensity Volume With Rate of Hippocampal Atrophy in a Population-Based Study of Aging
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1212/WNL.0000000000213975
Publisher version: https://doi.org/10.1212/wnl.0000000000213975
Language: English
Additional information: © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the Creative Commons Attribution License 4.0 (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine > MRC Unit for Lifelong Hlth and Ageing
URI: https://discovery.ucl.ac.uk/id/eprint/10214556
Downloads since deposit
1Download
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item