Perivascular Spaces in the Basal Ganglia Disrupt Fronto-Parietal Network Connectivity in Older Adults

Abstract

Introduction: Perivascular spaces (PVS) support clearance of metabolic waste and interstitial fluid from the brain. Enlarged PVS in the basal ganglia (BG-PVS) are a feature of small vessel disease and associated with increased risk of cognitive impairment, particularly executive dysfunction, which may be related to disruption of the fronto-parietal network. No prior study has examined whether PVS may be linked to functional connectivity in older adults. We hypothesized higher burden of enlarged BG-PVS may be associated with reduced fronto-parietal network connectivity, which is known to be vulnerable to cerebrovascular risk factors. Methods: Independently living older adults (N = 79, mean age = 70.1 years; SD = 7.3; age range 55-88 years; 29.1% male) free of dementia or clinical stroke were recruited from the community and underwent brain MRI. BG-PVS were qualitatively scored using an existing 5-point scale. Using resting state functional MRI, blood-oxygen level dependent (BOLD) time series from all voxels in each region of interest (ROI) was averaged to determine mean ROI activity. Lateral prefrontal cortex and posterior parietal cortex ROIs comprised the fronto-parietal network. Connectivity in the default mode network was also examined. Results: After accounting for age and sex, multiple linear regression analysis revealed a significant negative association between BG-PVS and resting state fronto-parietal network connectivity (B = -.09, 95% CI (-.15, -.02), p = .008). This association remained significant even after accounting for other features of cerebral small vessel disease. While BG-PVS was not associated with the default mode network independently, adjusting for fronto-parietal network connectivity revealed a positive association between BG-PVS and default mode network connectivity (B = .06, 95% CI (.001, .12), p = .047). Discussion: Dilation of PVS in the basal ganglia is associated with disruption of functional connectivity in the fronto-parietal network. Reduced connectivity in this network may actuate increased connectivity in the default mode network as a compensatory mechanism to maintain cognitive function. These findings suggest that damage to the microvasculature is associated with functional connectivity changes. Future longitudinal studies are warranted to examine the association between different networks and how changes in functional connectivity may influence risk for cognitive decline.