Abstract
BACKGROUND: Early detection of Alzheimer's disease (AD) remains challenging due to limited biomarkers. This retrospective longitudinal study evaluated whether alterations in the deep medullary veins (DMVs) predict cognitive decline. METHODS: We analyzed 170 participants from the Open Access Series of Imaging Studies-3 (OASIS-3) database [95 cognitive normal (CN), 36 mild cognitive impairment (MCI), and 39 AD]. DMVs were scored on susceptibility-weighted imaging (SWI). Cox proportional hazard models assessed the association between DMVs and longitudinal cognitive decline. Mediation analysis tested whether amyloid-β (Aβ) partially mediates the effect of DMVs on cognition. RESULTS: DMVs scores increased across groups {7 [6, 8] in CN, 13 [8.25, 15] in MCI, and 14 [13, 15] in AD; P<0.001}. DMVs score correlated with age (r=0.371, P<0.001), Mini-Mental State Examination (MMSE) (r=-0.494, P<0.001), cortical volume (r=-0.371, P<0.001), and Aβ burden (r=0.498, P<0.001). A higher DMVs score was associated with an increased risk of cognitive progression in AD [hazard ratio (HR) =1.13, 95% confidence interval (CI): 1.02-1.24, P=0.014], demonstrating good classification performance [area under the curve (AUC) =0.800, P<0.001]. Mediation analysis showed Aβ burden partially mediated the DMVs effect on MMSE (indirect effect β=-0.154, 95% CI: -0.337 to -0.017). CONCLUSIONS: DMVs alterations increase with AD severity, correlate with Aβ deposition, and predict cognitive decline, suggesting DMVs score as a promising imaging biomarker for early identification of individuals at risk of AD progression.