Diffusion tensor imaging analysis along the perivascular space suggests impaired glymphatic clearance in Lewy body dementia subtypes

Abstract

Background: Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) are subtypes of Lewy body dementia (LBD) and overlap in symptoms and pathology. Glymphatic function is implicated in LBD pathophysiology due to reduced clearance of abnormal proteins. We aimed to investigate differences in diffusion tensor imaging along the perivascular space (DTI-ALPS), a candidate in vivo measure of glymphatic function, between LBD sub-types. We compared DTI-ALPS between DLB, PDD, Parkinson’s with normal cognition (PD-NC), and control participants. Methods: We recruited participants with DLB, PDD, PD-NC, and controls from neurology clinics and patient support groups. Participants were aged 50–80, clinically diagnosed. Exclusions were confounding neurological or psychiatric conditions or metal precluding MRI scanning. Participants underwent MRI brain, plasma sampling and clinical and cognitive assessments. DTI-ALPS was calculated for each participant. As DTI-ALPS can be influenced by white matter distribution, we also calculated a metric called “complexity”. We tested group differences in DTI-ALPS, and associations with clinical variables across all patient groups including cognition, motor scores, sleep and fluctuations. Results: Fifty-one DLB (43 M, 72.7 ± 5.5 years), 35 PDD (25 M, 69.5 ± 7.8 years), 60 PD-NC (27 M, 63.1 ± 7.33 years), and 26 controls (13 M, 66.7 ± 9.28 years), were included for analysis. DTI-ALPS significantly differed between groups (F(3, 165) = 22.68, p <0.05). DTI-ALPS was further reduced in DLB relative to PDD. These findings held when corrected for complexity, which accounts for differences in white matter distribution (F(3, 161) = 28.11, p