Cognitive change, A[beta] deposition, and glymphatic system dysfunction

We investigated the longitudinal association between cognitive decline, amyloid-beta (Aβ) deposition, and glymphatic function using Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) index. A two-year study was conducted with 224 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), categorized into four groups: sustained cognitively normal (sCN), incident mild cognitive impairment (iMCI), persistent MCI (pMCI), and incident AD (iAD). The DTI-ALPS index and Standardized Uptake Value Ratio (SUVR) from amyloid positron emission tomography were assessed at baseline and follow-up. The iAD group exhibited the largest decreases in the DTI-ALPS index and most pronounced increases in SUVR, while the sCN group showed the least changes. Cognitive decline was associated with both a decrease in the DTI-ALPS index and an increase in SUVR. These findings highlight the promising role of the DTI-ALPS index as a novel, non-invasive biomarker for the early diagnosis of AD, by demonstrating the association between glymphatic dysfunction with cognitive decline and Aβ accumulation, two hallmarks of AD pathogenesis.