Enlarged Perivascular Spaces and Dementia: A Systematic Review

Abstract

Perivascular compartments surrounding the penetrating arteries in the brain are part of a physiologic system, which facilitates fluids exchange and clearance of solutes from the brain. The perivascular compartments become visible on MRI when enlarged and are commonly referred to as perivascular spaces (ePVS). Previous studies on the association between ePVS and dementia have been inconsistent due to varying methods of measuring ePVS. As a frame of reference for future MRI studies on ePVS, we systematically review the literature on ePVS as a marker of vascular brain injury related to dementia from population-based as well as hospital-based settings. We identified three longitudinal and ten cross-sectional studies involving 7,581 persons. Potential outcomes were all-cause dementia, Alzheimer's disease, and vascular dementia. There was considerable heterogeneity in ePVS assessment: with studies using either visual inspection or segmentation, examining different brain locations and implementing different grading scales. Moreover, out of the total of 13 studies, all five studies on vascular dementia reported an association with presence of basal ganglia ePVS after adjustment for age, gender, and white matter hyperintensities. For seven studies on Alzheimer's disease and all-cause dementia, the results were ambiguous. This review did not identify an independent association of ePVS with prevalent or incident dementia. Harmonized methods for ePVS assessment, tested across different populations, may benefit future MRI studies on ePVS and dementia.

MRI-Visible Perivascular Spaces in the Centrum Semiovale Are Associated with Brain Amyloid Deposition in Patients with Alzheimer Disease–Related Cognitive Impairment

“…35 Consequently, the visibility of MR imaging-visible PVS is increased on MR imaging and appears as spaces with a signal intensity similar to that of CSF, resulting in a high burden of MR imaging-visible PVS. 8 Consistent with this hypothesis, a postmortem study of AD demonstrated that the degree of white matter PVS on histopathologic examination was positively correlated with cortical b -amyloid deposition, 16 which is in line with our observation. Therefore, visible PVS on brain MR imaging may result from abnormal amyloid accumulation in the cortex and cortical/leptomeningeal vessels.…”

“…5 MR imaging-visible PVS are also associated with various diseases, such as traumatic brain injury, Parkinson disease, and dementia. [6][7][8][9] The location of MR imaging-visible PVS is an important factor to consider when predicting disease status because MR imaging-visible PVS in the basal ganglia may be associated with markers of arteriolosclerosis, whereas MR imaging-visible PVS in the centrum semiovale (PVS-CS) are linked to diseases involving amyloid pathology, such as Alzheimer disease (AD) and cerebral amyloid angiopathy. 10,11 Many different studies on cerebral amyloid angiopathy have demonstrated a strong relationship between MR imaging-visible PVS-CS and cerebral amyloid angiopathy.…”

Altered perivascular fibroblast activity precedes ALS disease onset

“…This could help to re-evaluate ALS etiology and to inform appropriate future therapeutic approaches although validity of SPP1 as a therapeutic target remains to be addressed with interventions. Since enlarged perivascular spaces are repeatedly observed in aging brains 38 , in dementia 39 and in other neurological disorders 40 , perivascular fibroblast cell activity within those spaces could represent a common therapeutic target in cerebral injury.…”

Identification of the clinical and neuroimaging characteristics in children with neuromyelitis optica spectrum disorders: a case series

“…The PVS has been suggested as a pathway for lymphatic drainage of the brain, containing macrophages, dendritic cells, lymphocytes, and T cells, which may interact with immune cells (18). Although enlarged PVS has been found in a proportion of healthy adults, numerous studies have reported an association between enlarged PVS and adult neurological diseases, such as multiple sclerosis, dementia, inflammation and small vessel disease, cognitive function, and epileptic seizures (19)(20)(21)(22). However, there is little evidence of enlarged PVS in healthy children and adolescents (23).…”