A multimodal MRI study of DTI-ALPS and cerebral blood flow changes across the Alzheimer's disease continuum

Alzheimer's disease (AD) is characterized by cerebral blood flow (CBF) abnormalities and alterations in the neurofluid-related brain tissue environment, but their evolution along the AD continuum and links to cognitive decline and plasma biomarkers remain unclear. Using multimodal MRI, we quantified the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index and CBF alterations and examined their associations with cognitive performance and plasma biomarkers across the AD continuum.

This study enrolled 78 healthy controls (HC), 53 subjective cognitive decline (SCD), 40 mild cognitive impairment (MCI), 110 AD. All subjects received MRI and neurocognitive assessments. The DTI-ALPS index was used as a diffusion-based marker of directional water diffusivity within periventricular white matter and the neurofluid-related tissue environment. CBF changes were calculated, and plasma biomarkers associated with neurodegeneration were measured. Partial correlation analysis explored relationships among ALPS index, CBF in cognition-related brain regions, cognitive scores, and plasma biomarkers. Statistical mediation analyses were performed to assess indirect effects involving the ALPS index and plasma biomarkers in the association between regional CBF and cognitive performance.

ALPS index decreased stage-dependently along the AD continuum, significantly lower in MCI and AD versus HC and SCD. HC and SCD showed higher CBF than AD in right middle cingulate and left inferior parietal lobule. CBF in bilateral angular gyri and right superior frontal gyrus positively correlated with MoCA and RAVLT scores. Cognition-related CBF positively correlated with bilateral mean ALPS index, and negatively with NfL and p-tau217. Statistical mediation analyses identified significant indirect effects involving the bilateral mean ALPS index and plasma NfL in the association between regional CBF and cognitive performance.

Cerebral hypoperfusion, altered DTI-ALPS measures, and axonal injury were closely associated across the AD continuum, suggesting interrelated neurovascular, neurofluid-related tissue, and neurodegenerative alterations associated with cognitive impairment.