Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and impaired daily functioning. The glymphatic system removes neurotoxic waste, including amyloid-beta (Aβ), an important factor in AD pathogenesis. This study used the Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) index, which reflects glymphatic function, to explore its relationship with cognitive decline in patients with probable AD. We conducted a longitudinal study of 16 participants aged 60-79 years with probable AD who were evaluated using the Clinical Dementia Rating (CDR) and Mini-Mental State Examination (MMSE). Glymphatic function was assessed using the DTI-ALPS index; plasma Aβ 42/40 ratios were measured to account for amyloid pathology. The relationship between the DTI-ALPS index and baseline cognitive function was analyzed using multiple regression models adjusted for age, sex, and plasma Aβ 42/40 ratios. Associations between the DTI-ALPS index and cognitive decline over 1 year were assessed by a model using the percentage change in the MMSE z-score as the outcome variable. Higher DTI-ALPS index was significantly associated with better baseline cognitive function as assessed by MMSE (standardized beta = 1.17, p < 0.001) and lower clinical severity as assessed by CDR (standardized beta = - 1.00, p = 0.006). Over the 1-year follow-up, greater baseline DTI-ALPS index values were associated with less cognitive decline (standardized beta = - 0.85, p = 0.018). Our findings suggest that DTI-ALPS index is associated with cognitive performance and is a biomarker for predicting cognitive decline in AD. Future studies should consider larger sample sizes and longer follow-up periods to validate these findings.
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