The influence of cognitive status on perivascular space enlargement trajectories in a longitudinal aging cohort

Abstract

AbstractBackgroundPerivascular space (PVS) enlargement is associated with dysfunctional waste clearance and can hinder the removal of toxic metabolic substrates, such as amyloid beta (Aβ). Increased PVS visibility in white matter has been observed in cross‐sectional studies of patients with Alzheimer’s disease (AD) and mild cognitive impairment (AD). However, the utility of PVS morphology as a diagnostic biomarker for AD pathology is hindered by the lack of knowledge regarding the time course of PVS alterations across diagnostic groups. In the present study, we characterize the relationship between cognitive status and PVS morphological trajectories with age in a longitudinal cohort. Findings from this study will provide insight into the role of waste clearance processes in AD disease pathogenesis.MethodLongitudinal neuroimaging data from 500 cognitively normal (CN) subjects, patients with stable MCI (sMCI), and patients with MCI that later convert to AD (cMCI) were obtained from ADNI3. White matter PVS morphological features were automatically defined according to the methods described in (4) using optimally thresholded vesselness maps on high resolution T1w scans. The influence of class membership on the rate of PVS alterations over time were assessed with a linear mixed effects models with REML after controlling for baseline age, gender, years of education and total white matter volume.ResultWe found a significant interaction between cognitive status and time on mean PVS cross‐sectional diameter in the white matter, where the rate of change of PVS enlargement in patients with cMCI was greater compared to CN controls (B=‐.22, t(491)=‐2.06, p=.039) and patients with sMCI (B=‐.21, t(491)=‐2.03, p=.043). No significant differences in the age‐related change to PVS count or volume were observed between groups.ConclusionOur findings show patients with MCI that later progress to AD show accelerated PVS enlargement compared to patients that remain in the preclinical stages of cognitive decline. Our results support the growing body of research that demonstrates a relationship between pathological PVS enlargement and neurodegenerative disorders characterized by dysfunctional waste clearance. Parenchymal PVS caliber may therefore provide an informative biomarker to aid in the early diagnosis of AD and other amyloidopathies prior to the formal onset of deleterious symptoms.