Female vulnerability to microvascular transport dysfunction emerges early across the Alzheimer's disease continuum.
| Publication Type | Academic Article |
| Authors | Xu M, Gao Y, Ou P, Yang H, Wang J, Liu W, Shu N, Sun Y, Fu L, Glodzik L, Butler T, Chaing G, Li Y, Wang Y, Zhou L, Ma G |
| Journal | Alzheimers Dement |
| Volume | 22 |
| Issue | 9 |
| Pagination | e71811 |
| Date Published | 09/01/2026 |
| ISSN | 1552-5279 |
| Keywords | Alzheimer Disease, Cerebrovascular Circulation, Cognitive Dysfunction, Brain, Microvessels |
| Abstract | INTRODUCTION: We tested whether quantitative transport mapping (QTM)-derived perfusion velocity would detect earlier and more sex-specific microvascular alterations than cerebral blood flow (CBF) across the Alzheimer's disease (AD) continuum. METHODS: In 182 participants (cognitively normal = 53, subjective cognitive decline [SCD] = 48, mild cognitive impairment [MCI] = 31, AD = 50), seven-delay arterial spin labeling was used to derive CBF and QTM velocity. Age/sex-adjusted models assessed diagnostic and sex effects, associations with plasma biomarkers and Mini-Mental State Examination (MMSE), and mediation of the hippocampal volume-cognition relationship. RESULTS: QTM velocity was reduced already in SCD, including the hippocampus, whereas CBF declined mainly in MCI/AD. Sex × Diagnosis interactions were significant for QTM in gray and white matter, but not for CBF. QTM, especially in females, was inversely associated with plasma NfL/GFAP, related to MMSE, and parietal QTM partially mediated the hippocampal volume-MMSE association. DISCUSSION: QTM is a non-invasive biomarker more sensitive than CBF to early, female-biased microvascular transport dysfunction in AD. |
| DOI | 10.1002/alz.71811 |
| PubMed ID | 42675347 |
| PubMed Central ID | PMC13529826 |