Perivascular spaces contribute to cognition beyond other small vessel disease markers

Abstract

ObjectiveTo cross-sectionally relate multiple small vessel disease (SVD) neuroimaging markers to cognition among older adults.MethodsVanderbilt Memory & Aging Project participants free of clinical dementia and stroke (n = 327, age 73 ± 7 years, 59% male, 40% with mild cognitive impairment) completed neuropsychological assessment and 3T MRI to measure white matter hyperintensities (WMH), perivascular spaces (PVS), cerebral microbleeds (CMBs), and lacunes. Linear regressions related each SVD marker to neuropsychological performances and adjusted for age, sex, race/ethnicity, education, cognitive diagnosis, APOE ε4 presence, Framingham Stroke Risk Profile, and intracranial volume.ResultsWMH related to the most neuropsychological measures, including the Boston Naming Test, Animal Naming, Coding, Number Sequencing, Executive Function Composite, and Hooper Visual Organization Test performances (p ≤ 0.01). PVS related to multiple information processing and executive function performances (p ≤ 0.02). Lacunes and CMBs related to fewer measures than expected. Combined models simultaneously testing multiple statistically significant SVD predictors suggested that WMH, PVS, and CMBs each independently related to information processing and executive function performances; however, compared to other SVD markers, PVS remained statistically significant in models related to information processing and executive functioning performances.ConclusionsAs expected, increased WMH corresponded to poorer performances across multiple cognitive domains. PVS, previously considered a benign neuroimaging feature in older adults, may have important clinical implications because PVS was related to information processing and executive function performances even in combined models. On the basis of models with multiple SVD predictors, WMH, PVS, and CMBs may each reflect a separate pathway of small vessel injury.

The Relationship Between Enlarged Perivascular Spaces and Cognitive Function: A Meta-Analysis of Observational Studies

“…Three case-control studies using Spearman's rank correlation coefficients all reported that increased ePVS counts may contribute to cognitive decline (Chen et al, 2011;Yun, 2013;Favaretto et al, 2017). With further review of the cohort studies, most of them have suggested that ePVS were related to cognitive decline (Van Westen et al, 2017;Jimenez-Balado et al, 2018;van Westen et al, 2018;Passiak et al, 2019). However, one smallsample cohort study reported that it was lacunes but not ePVS that were a predictor of cognitive decline (Trippier et al, 2018).…”

The role of brain perivascular space burden in early-stage Parkinson’s disease

“…But the emotional status of most HCs was at a normal level, the correlation might be in different extent while focusing on patients with depression. As PVS dysfunction might relate to neuro-neurophysiology and clinical motor features of PD, it also related to cognitive decline in PD 3 , 4 , 15 . The PVS burden, particularly correlated with executive functioning 4 and visuospatial ability 43 , which were frequently involved cognitive domains in PD.…”

“…It’s a normal anatomical structure in the central nervous system, commonly observed in basal ganglia (BG), white matter centrum semiovale, midbrain and hippocampus 2 . Although the results of PVS studies remained controversial, the PVS burden had been shown to correlate with aging, cognitive capacity 3 , 4 , sleep quality 5 , and depressive states 6 . It was described as a characteristic of neurological diseases including, small vessel disease 7 , Alzheimer’s disease (AD) 8 , multiple sclerosis 9 , as well as Parkinson’s disease (PD) 10 , 11 .…”

Innovative MRI Techniques in Neuroimaging Approaches for Cerebrovascular Diseases and Vascular Cognitive Impairment

“…The multifaceted role of the PVS in maintaining the Blood Brain Barrier (BBB) equilibrium and brain homeostasis makes the study of its alterations of utmost importance to identify markers of damage associated with cerebrovascular pathologies [18]. Similarly to WMH, it is possible to evaluate the PVS alterations both with a semi-quantitative grading system [19] or with quantitative automatic methods [20,21]. The latter category produces quantitative measures, which can contribute to an estimate of the global cerebrovascular risk, together with other brain measurements.…”