Diffusion tensor image analysis along the perivascular space index alterations in Alzheimer's disease: associated with cerebrospinal fluid Aβ40 and cognition.

The role of glymphatic system impairment in the pathogenesis of Alzheimer’s disease (AD) still requires further investigation. This study aimed to investigate the glymphatic system dysfunction in AD, and explore its association with AD Cerebrospinal Fluid (CSF) biomarkers and cognition. This study included 28 AD, 36 mild cognitive impairment [MCI Aβ+: 23, MCI Aβ-: 13], and 67 cognitively normal [CN Aβ+: 34, CN Aβ-: 33] from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohorts. Glymphatic system activity was assessed using the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index. This metric was combined with the basal ganglia perivascular space volume fraction (BG PVS-VF) to serve as MRI indicators investigated in this study. Group differences in MRI indicators were analyzed, and relationships between glymphatic system function, CSF Aβ/tau protein levels, and cognitive performance were explored. As a result, compared with CN, DTI-ALPS index was significantly lower in the AD. Both the DTI-ALPS index and BG PVS-VF showed significant correlations with age (R=-0.2 and R = 0.29; P < 0.05) and MMSE scores (R = 0.26 and R = 0.20; P < 0.05). The DTI-ALPS index was positively correlated with CSF Aβ40 levels (R = 0.44, P < 0.001). Mediation analysis revealed that the effects of both DTI-ALPS index on MMSE scores and CSF Aβ40/BG PVS-VF on MMSE scores occurred directly. In conclusion, the DTI-ALPS index was lowered in AD patients. The DTI-ALPS index demonstrated specific correlations with CSF Aβ40 levels and cognitive performance, suggesting a potential association with AD pathology.