Association of Enlarged Perivascular Spaces and Measures of Small Vessel and Alzheimer Disease

Abstract

ObjectiveTo investigate the relationship between enlarged perivascular spaces (EPVS) and measures of Alzheimer disease (AD), small vessel disease (SVD), cognition, vascular risk factors, and neuroinflammation, we tested associations between EPVS and different relevant neuroimaging, biochemical, and cognitive variables in 778 study participants.MethodsFour hundred ninety-nine cognitively unimpaired (CU) individuals, 240 patients with mild cognitive impairment, and 39 patients with AD from the Swedish Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study were included. EPVS with diameter >1 mm in centrum semiovale (CSO), basal ganglia (BG), and hippocampus (HP); hippocampal volume; white matter lesions (WML); and other SVD markers were determined from MRI. CSF levels of β-amyloid42 (Aβ42), phosphorylated tau, total tau, and neuroinflammatory markers; amyloid accumulation determined with [18F]-flutemetamol PET; and vascular risk factors and results from cognitive tests were determined and collected.ResultsEPVS in CSO, BG, and HP were associated with WML volume and Fazekas score in individuals without dementia. No associations were found between EPVS and CSF Aβ42, total tau and phosphorylated tau, neuroinflammatory markers, vascular risk factors, and cognitive tests. EPVS in HP were associated with hippocampal atrophy. In a matched group of individuals with AD and CU, EPVS in HP were associated with AD diagnosis.ConclusionsEPVS are related to SVD, also in early disease stages, but the lack of correlation with cognition suggests that their importance is limited. Our data do not support a role for EPVS in early AD pathogenesis.

Association Between Large Numbers of Enlarged Perivascular Spaces in Basal Ganglia and Motor Performance in Elderly Individuals: A Cross-Sectional Study

“… 38 The incidence of cognitive impairment in patients with large numbers of BG-EPVSs is not clear, research on the relationship between large numbers of BG-EPVSs and cognitive impairment insufficient, and results have not been consistent. 14 , 16 …”

“…Recent studies have shown a relationship between EPVSs and cognitive disturbances; 14 , 15 but others have found EPVSs not to be related to cognitive impairment. 16 Therefore, the association between EPVSs and cognitive impairment is attributed to a direct effect of EPVSs or accompanying CSVD markers, eg, white-matter hyperintensity (WMH), cerebral microbleeds (CMBs), and lacunae, and remains incompletely understood.…”

Evaluation of the Glymphatic System With Diffusion Tensor Imaging-Along the Perivascular Space in Cancer Pain

“…Because glymphatic system function can be influenced by age, sex, white matter lesions, and emotional state ( Nedergaard and Goldman, 2020 ; Gertje et al, 2021 ), we firstly compared the age and sex compositions and brain white matter T2-hyperintensity among the CP, PLC and NC group. After analysis, no significant differences were found among groups in age (54.33 ± 7.28 years vs. 56.30 ± 6.31 years vs. 52.77 ± 10.34 years, p = 0.387), age composition ( p = 0.069), or sex composition ( p = 0.444).…”

Advances in brain barriers and brain fluids research in 2021: great progress in a time of adversity

“…There is debate about the role of an enlarged perivascular space, a component of the glymphatic system, in cerebral small vessel disease and Alzheimer’s disease. Gertje et al [ 73 ] found that enlargement of these spaces was associated with small vessel disease, but their data did not support a role in the early stages of Alzheimer’s disease pathology. In contrast, Paradise et al [ 74 ] found that severe perivascular space dilation was associated with increased chance of cognitive decline and dementia and Ciampa et al [ 75 ] reported that genetic risk factors for Alzheimer’s disease are associated with enlarged perivascular spaces in the centrum semiovalae region of the brain.…”