Abstract
BACKGROUND: Cerebral small vessel disease (CSVD) is a major contributor to cognitive impairment and dementia. Growing evidence suggests that impaired perivascular clearance plays a pivotal role in CSVD pathogenesis, yet non-invasive biomarkers for early cognitive decline remain limited. This study aimed to explore the diagnostic value of the diffusion tensor imaging analysis along perivascular spaces (DTI-ALPS) index, enlarged perivascular spaces (EPVS) numbers/volume, and choroid plexus volume (CPV) across different cognitive stages of CSVD. METHODS: We retrospectively analyzed data from 102 CSVD patients [33 CSVD-cognitive normal (CSVD-CN); 39 CSVD-mild cognitive impairment (CSVD-MCI); 30 vascular dementia (VaD)] and 29 normal controls (NCs). Quantitative measurements of the DTI-ALPS index, EPVS numbers/volume, and CPV were obtained. Correlations with Montreal Cognitive Assessment (MoCA) scores and diagnostic performance were also evaluated. RESULTS: Progressive DTI-ALPS index reduction (NCs: 1.50±0.19, CSVD-CN: 1.41±0.17, CSVD-MCI: 1.34±0.16, VaD: 1.33±0.17; P<0.001, r=0.36) and increases in basal ganglia (BG)-EPVS numbers {NCs: 4 [3, 6], CSVD-CN: 14 [10, 17], CSVD-MCI: 16 [12, 25], VaD: 22 [13, 31]; P<0.001, r=-0.45} and CPV {NCs: 1.35 [1.02, 1.65] cm(3), CSVD-CN: 1.39 [1.11, 1.72] cm(3), CSVD-MCI: 1.88 [1.41, 2.94] cm(3), VaD: 2.89 [2.09, 3.39] cm(3); P<0.001, r=-0.43} correlated with cognitive decline. BG-EPVS numbers excellently distinguished CSVD from NCs [area under the receiver operating characteristic (ROC) curve (AUC) =0.926; 95% confidence interval (CI): 0.882-0.971; sensitivity =84.2%; specificity =89.7%]. CPV emerged as the optimal standalone biomarker for VaD (AUC =0.758; 95% CI: 0.647-0.869; sensitivity =82.8%; specificity =69.5%). The multiparametric model (DTI-ALPS + BG-EPVS numbers + CPV) achieved high diagnostic accuracy: NCs vs. CSVD: AUC =0.978, 95% CI: 0.958-0.998; VaD vs. NCs/CSVD-CN/CSVD-MCI: AUC =0.825, 95% CI: 0.747-0.903; CSVD-MCI/VaD vs. NCs/CSVD-CN: AUC =0.900, 95% CI: 0.847-0.952. CONCLUSIONS: Combining the DTI-ALPS index, BG-EPVS numbers, and CPV may enhance early diagnosis and subtype differentiation in CSVD-related cognitive impairment, supporting targeted interventions.