Abstract
Objective: To investigate the integrated relationship between Cerebral Small Vessel Disease (CSVD) markers and quantitative facial soft-tissue measurements in Alzheimer's disease (AD) continuum, utilizing peripheral muscle health as a potential biomarker for systemic frailty and neurodegeneration. Methods: Retrospective analysis of 3T brain MRI data from 67 patients (AD, N = 45; Mild Cognitive Impairment [MCI], N = 22). CSVD markers were assessed using STRIVE and standardized scales (Fazekas, Potter). Facial soft-tissue metrics, including masseter and tongue volume, temporal muscle thickness (TMT), and fat infiltration (Mercuri Scale), were quantified via semi-automatic segmentation on T1-weighted sequences. Group comparisons (AD vs. MCI) used regression models adjusted for age and sex. The overall central-peripheral relationship was explored via Canonical Correlation Analysis (CCA). Results: The AD group showed a highly significant cognitive decline (MMSE: 23.2 ± 4.1 vs. 28.2 ± 1.4, p < 0.0001). Centrally, the presence of PVSs in the mesencephalic region was the most robust predictor for AD (p = 0.003). Peripherally, average masseter muscle volume was significantly lower in the AD group (p = 0.0273), and masseter fat infiltration was significantly higher (p = 0.025), supporting localized sarcopenia. The CCA demonstrated a statistically significant positive multivariate relationship (r = 0.51, Roy's Largest Root p = 0.015) between a higher combined CSVD burden and a worse soft tissue profile across the cohort. Conclusions: Quantitative indices of facial soft tissues, particularly masseter muscle volume and quality, reflect systemic frailty and cognitive deterioration along the AD continuum. The strong central-peripheral correlation suggests that sarcopenia and CSVD are interconnected manifestations of a shared pathobiological process. These easily measurable facial markers could serve as valuable, non-invasive peripheral biomarkers, complementing traditional neuroimaging risk stratification in AD.