White Matter and Perivascular Imaging Changes in Alzheimer's Disease and Cerebral Amyloid Angiopathy

Abstract

ABSTRACT Objective Peak‐width of skeletonized mean diffusivity (PSMD) and diffusion tensor imaging–analysis along the perivascular space (DTI‐ALPS), reflecting white matter integrity and glymphatic function, are altered in Alzheimer's disease (AD). We evaluated whether these biomarkers differ between AD participants with and without concomitant cerebral amyloid angiopathy (CAA). Methods The study included 50 AD participants with mild cognitive impairment/mild dementia, and intermediate to high AD neuropathologic change at autopsy. AD was categorized as AD with CAA and AD without CAA based on CAA neuropathology. We evaluated global and regional (frontal, parietal, temporal and occipital) PSMD; left, right and mean DTI‐ALPS indices and their association with clinical measures [Clinical dementia rating sum‐of‐boxes (CDR‐SB) from CDR Dementia Staging Instrument, mini mental state examination (MMSE), cognitive composites: memory, processing speed, executive function, and language]. Results AD participants with CAA (n = 17) had higher global [4.02 ± 1.44 (mean ± SD × 10−4 mm2/s) vs. 3.12 ± 0.91, β = −0.80, 95% CI (−1.42, −0.18), p = 0.012] and occipital PSMD [4.02 ± 1.10 vs. 3.00 ± 1.08, β = −0.88, 95% CI (−1.51, −0.26), p = 0.026] than those without CAA. No PSMD metric was associated with any clinical measure. However, imaging‐by‐group interactions showed global PSMD associated with language [β = −0.89, 95% CI (−1.53, −0.26), p = 0.027] and parietal PSMD with language [β = −1.05, 95% CI (−1.74, −0.36), p = 0.014] and memory [β = −0.83, 95% CI (−1.38, −0.28), p = 0.015]. DTI‐ALPS indices did not differ by group. Higher mean and right DTI‐ALPS indices were associated with preserved language function [mean: β = 9.33, 95% CI (2.05, 16.62), p = 0.036; right: β = 7.75, 95% CI (1.54, 13.95), p = 0.043] without imaging‐by‐group interactions. Interpretation Global and occipital PSMD may help identify AD participants with concomitant CAA.