Periventricular diffusivity reflects APOE ε4-modulated amyloid accumulation and cognitive impairment in the Alzheimer's disease continuum

초록

INTRODUCTION: Altered glymphatic-related fluid dynamics are increasingly recognized as a feature of Alzheimer's disease (AD). We generalized an established diffusion imaging framework to quantify periventricular diffusivity (PVeD), hypothesizing that fast diffusion signals in the periventricular region can reflect amyloid beta (A beta) deposition across the AD continuum. METHODS: Participants from two multi-site cohorts (n = 440 and 414), comprising cognitively unimpaired individuals, those with mild cognitive impairment, and patients with AD, were included. We tested and validated the association of PVeD with A beta burden and core AD characteristics. RESULTS: Lower PVeD was extensively associated with greater A beta burden, neurodegeneration, cognitive impairment, and clinical severity in the clinical cohort. Importantly, the relationship between PVeD and A beta burden was significantly modulated by apolipoprotein E (APOE) epsilon 4 status; APOE epsilon 4 carriers exhibited a replicable stronger negative association. Baseline PVeD also predicted longitudinal cognitive decline. DISCUSSION: These findings suggest that periventricular diffusion signals reflect APOE epsilon 4-modulated A beta burden and cognitive decline in AD.

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