Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer’s Disease

Background Increased white matter hyperintensity (WMH) volume visible on MRI is a common finding in Alzheimer’s disease (AD). We hypothesized that WMH in preclinical AD is associated with the presence of advanced vessel amyloidosis manifested as microhemorrhages (MCH). Objectives 1) To assess the re...

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Published in:The journal of prevention of Alzheimer's disease 2024, Vol.11 (4), p.869-873
Main Authors: Shirzadi, Zahra, Schultz, A. P., Properzi, M., Yaari, R., Yau, W.-Y. W., Brickman, A. M., Rafii, M. S., Donohue, M. C., Ernstrom, K., Wang, S., Jack, C. R., Greenberg, S. M., Raman, R., Aisen, P., Sperling, R. A., Chhatwal, J. P.
Format: Article
Language:English
Subjects:
Geriatrics/Gerontology
Medicine
Medicine & Public Health
Neurology
Original Research
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Summary:Background Increased white matter hyperintensity (WMH) volume visible on MRI is a common finding in Alzheimer’s disease (AD). We hypothesized that WMH in preclinical AD is associated with the presence of advanced vessel amyloidosis manifested as microhemorrhages (MCH). Objectives 1) To assess the relationship between baseline WMH volume and baseline MCH. 2) To assess the relationship between longitudinal WMH accumulation and last MRI MCH during the double-blind phase of the A4 trial. Design A multicenter, randomized, double-blind, placebo-controlled, Phase 3 study comparing solanezumab with placebo given as infusions once every 4 weeks over 4.5 years in subjects with preclinical AD, defined as having evidence of elevated brain amyloid before the stage of clinically evident cognitive impairment, with an optional open-label extension period. Setting Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) study. Participants A sample of 1157 cognitively unimpaired older adults (mean age = 71.9 years [SD = 4.8 years], 59% women, 59% APOE ε4 carriers). Measurements A linear regression model was used to assess the impact of baseline MCH amount (0, 1, 2+) on WMH volume. A linear mixed-effects model was used to assess the impact of last MRI MCH on longitudinal WMH. All models were corrected for age, sex, grey matter volume, cortical amyloid PET, APOE ε4 status, and treatment group. Results Baseline WMH volume was greater in individuals with more than one MCH compared to those with no MCH (t=4.8, p
ISSN:2426-0266
2274-5807
2426-0266
DOI:10.14283/jpad.2024.139