ArticleThe journal of prevention of Alzheimer's disease2025
Microstructural white matter injury contributes to cognitive decline: Besides amyloid and tau.
Article in The journal of prevention of Alzheimer's disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- ENT1 inhibition links oligodendrocyte lipid metabolism to connectivity in tauopathy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Imaging study of white matter microstructural damage and glymphatic system dysfunction in patients with primary insomnia: a combined analysis based on PSMD, DTI-ALPS, and EPVS.Quantitative imaging in medicine and surgery · 2026Article
- White Matter and Perivascular Imaging Changes in Alzheimer's Disease and Cerebral Amyloid Angiopathy.Annals of clinical and translational neurology · 2026Article
- Genetic evidence links hypertension to accelerated brain aging.Biogerontology · 2026Article
- White matterAlzheimer's research & therapy · 2026Article
- Peak width of skeletonized mean diffusivity reveals early and multifactorial white matter injury across sporadic and Down syndrome-associated Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Retinal microvascular dysfunction in mild cognitive impairment: Associations with cerebral small vessel disease, plasma biomarkers, and cognitive decline.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Head-to-head comparison of diffusion imaging markers for cognitive decline and risk of dementia: The population-based Rotterdam Study.Imaging neuroscience (Cambridge, Mass.) · 2026Article
- Apolipoprotein E ε4 homozygosity exacerbates retinal and cerebral microvascular dysfunction in Alzheimer's disease: A mediation analysis of vascular contributions to cognitive decline.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Higher spatial resolution diffusion-weighted imaging improves characterization of white matter disconnection in Alzheimer's disease.Imaging neuroscience (Cambridge, Mass.)Article
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Authors and funding
11 authors.
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Abstract
backgroundCognitive decline and the progression to Alzheimer's disease (AD) are traditionally associated with amyloid-beta (Aβ) and tau pathologies. This study aims to evaluate the relationships between microstructural white matter injury, cognitive decline and AD core biomarkers.
methodsWe conducted a longitudinal study of 566 participants using peak width of skeletonized mean diffusivity (PSMD) to quantify microstructural white matter injury. The associations of PSMD with changes in cognitive functions, AD pathologies (Aβ, tau, and neurodegeneration), and volumes of AD-signature regions of interest (ROI) or hippocampus were estimated. The associations between PSMD and the incidences of clinical progression were also tested. Covariates included age, sex, education, apolipoprotein E4 status, smoking, and hypertension.
resultsHigher PSMD was associated with greater cognitive decline (β=-0.012, P < 0.001 for Mini-Mental State Examination score; β<0, P < 0.05 for four cognitive domains) and a higher risk of clinical progression from normal cognition to mild cognitive impairment (MCI) or AD (Hazard ratio=2.11 [1.38-3.23], P < 0.001). These associations persisted independently of amyloid status. PSMD did not predict changes in Aβ or tau levels, but predicted changes in volumes of AD-signature ROI (β=-0.003, P < 0.001) or hippocampus (β=-0.002, P = 0.010). Besides, the whole-brain PSMD could predict cognitive decline better than regional PSMDs.
conclusionsPSMD may be a valuable biomarker for predicting cognitive decline and clinical progression to MCI and AD, providing insights besides traditional Aβ and tau pathways. Further research could elucidate its role in clinical assessments and therapeutic strategies.
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