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Alzheimer's Association International Conference 2026
July 12-15, 2026 | London, United Kingdom, and Online
9484
Cerebrovascular Pathways Of Intergenerational Dementia Risk
Poster Presenter
Authors
Jeffrey D. Pyne, Mohamad Alshikho, Benjamin Huber, Rafael V. Lippert, Joncarlos Berroa, Natalie Morel, Natalie Edwards, A. Zarina Kraal, Edric Winford, Miguel Arce Rentería, Patrick J. Lao, Xingfeng Shao, Danny J. Wang, Jennifer J. Manly, Adam M. Brickman
Affiliations
Taub Institute for Research on Alzheimer’s disease and The Aging Brain, Department of Neurology, Columbia University, Keck School of Medicine, University of Southern California
Part of Topic
•Parental history of dementia confers an increased risk of dementia in offspring, yet the underlying pathways of this intergenerational risk transmission remain poorly understood
•One potential pathway is through cerebrovascular health including blood brain barrier (BBB) dysfunction
•Prior work points to sex-specific patterns in maternal versus paternal transmission of dementia risk to offspring
•We used a novel MR-based method, termed diffusion prepared pseudo continuous arterial spin labelling (DP-pCASL), to quantitate regional BBB intracellular water exchange rate (kw) and test its relationship with parental history of dementia in the midlife adult children (Offspring Study) of older, community-dwelling adults from the Washington Heights Inwood Columbia Aging Project (WHICAP)
•One hundred forty two midlife adults (55±10.6 mean±SD age, 68% women, 73% Latinx, 15% Black, and 11% White individuals) from the Offspring Study received DP-pCASL MR imaging
•Parental dementia status was determined prospectively by consensus diagnosis
•Mixed-effect models tested the association of parental history of dementia with medial temporal lobe blood brain barrier function in 1:1 propensity score matched and inverse probability weighting groups (based on age, sex, and years of education)
•Covariates include offspring intracranial volume, age, years of education, hypertension status, diabetes status, and random effect of family
•Both propensity score matching (n=50/142 matched) and inverse probability weighting (n=97/142 weighted) achieved adequate covariate balance (<0.1 SD tolerance)
•Parental history of dementia is associated with a midlife cerebrovascular profile that reflects BBB dysfunction (lower kw) in the entorhinal cortex and fusiform gyrus
•Effect estimates showed some sensitivity to matching parameters and methods
•These findings support the hypothesis that one pathway though which parental history of dementia may increase offspring dementia risk is through endogenous cerebrovascular factors that may affect neurodegeneration in midlife
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