ArticleResearch square2026
Multimodal Free-Water Imaging Links Cardiometabolic Risk to Periarterial Dysfunction and Amyloid Accumulation in Early Alzheimer's.
Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
20 authors.
Funding
Abstract
The brain's waste-clearance (glymphatic) system removes metabolic byproducts via periarterial influx, interstitial exchange, and perivenous efflux. Although dysfunction is implicated in Alzheimer's disease (AD), current imaging markers emphasize perivenous changes and may overlook earlier periarterial impairment. We developed a diffusion MRI framework to quantify periarterial fluid mobility, white matter free water, and perivenous integrity, and applied it to 546 cognitively normal adults (HCP-Aging) and 173 participants across the AD spectrum (ADNI). Periarterial mobility was reduced with higher cardiometabolic risk and amyloid positivity, particularly in AD-vulnerable regions. Free water increased with aging and metabolic burden, whereas perivenous dysfunction was most pronounced in AD. Combined measures predicted amyloid positivity and cognitive impairment (AUC = 0.82). Mediation analyses showed that blood pressure influenced cognition through periarterial dysfunction and amyloid burden. These findings support a staged, compartment-specific trajectory of glymphatic dysfunction, with early periarterial impairment representing a potential biomarker and therapeutic target.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.