Microstructural changes in the optic tract and optic radiation on diffusion tensor imaging as biomarkers of glymphatic dysfunction in Alzheimer’s disease

The role of ocular glymphatic function in Alzheimer’s disease (AD) remains incompletely understood. This study investigated whether diffusion tensor imaging (DTI) metrics of the optic tract (OT) and optic radiation (OR) are associated with putative glymphatic imaging markers across the AD continuum and evaluated their diagnostic value. Data from 226 participants in the Alzheimer’s Disease Neuroimaging Initiative, including 59 healthy controls, 120 patients with mild cognitive impairment, and 47 with AD, were analyzed. Group differences in DTI metrics and putative glymphatic imaging markers, including the DTI-ALPS index and choroid plexus volume fraction (CPVF), were assessed with adjustment for age, sex, education, and APOE ε4 status. Patients with AD showed significantly higher mean, axial, and radial diffusivity in both OT and OR than other groups ( p ≤ 0.02). The DTI-ALPS index was lower in AD than in healthy controls and mild cognitive impairment ( p ≤ 0.009), whereas CPVF was higher in AD ( p < 0.001). Diffusivity parameters correlated positively with CPVF ( r = 0.31–0.36) and negatively with Mini-Mental State Examination scores ( r = − 0.36 to − 0.47). Logistic regression achieved an AUC of 0.84 (95% CI, 0.78–0.88) for distinguishing AD from controls. OT and OR DTI parameters may be associated with putative glymphatic imaging markers in AD.