Associations of Vascular Risk Factors and APOE Genotype With Perivascular Spaces Among Community‐Dwelling Older Adults

Abstract

Background Evidence suggests that enlarged perivascular spaces (PVSs) may represent a marker for cerebral small‐vessel disease. We investigated whether vascular risk factors are correlated with visible PVS in older adults. Methods and Results This population‐based study included 530 participants (age ≥60 years) who were free from dementia and functional dependence, derived from the Swedish National study on Aging and Care in Kungsholmen (2001–2003). We collected data on demographics, vascular risk factors, and health conditions through interviews, clinical examinations, laboratory tests, and patient registers. Cerebral PVSs and white matter hyperintensities on magnetic resonance images were visually assessed with semiquantitative visual rating scales. Data were analyzed using the general linear regression models. After controlling for demographics and cardiovascular disease, very high blood pressure (≥160/100 mm Hg) was significantly associated with global PVS score (β‐coefficient, 1.30; 95% CI, 0.06–2.53) and orthostatic hypotension was associated with PVS score in the basal ganglia (β‐coefficient 0.37; 0.03–0.70), but the associations became non‐significant when adjusting for white matter hyperintensity load. Orthostatic hypotension was significantly associated with global and lobar PVS scores in carriers but not in noncarriers of the APOE ε4 allele. Global or regional PVS score was not significantly associated with other traditional vascular risk factors such as smoking, diabetes mellitus, physical inactivity, and overweight or obesity. Conclusions This study provides limited evidence supporting a correlation of magnetic resonance imaging–visible PVS with traditional vascular risk factors in older adults. The association of orthostatic hypotension with lobar PVS among APOE ε4 carriers suggests that lobar PVS may be a marker for amyloid‐associated small‐vessel disease.

Perivascular spaces are associated with tau pathophysiology and synaptic dysfunction in early Alzheimer’s continuum

“…Because APOE-ε4 enhances Aβ deposition [29], several studies focused on associations between APOE genotypes and ePVS, with controversial results. In studies carried out in older individuals and/or high cardiovascular risk, significant differences were found [30,31]. Contrary to them, some studies performed in healthy younger individuals were in line with our results and did not find significant associations between APOE and ePVS [27,32].…”

Blood–brain barrier link to human cognitive impairment and Alzheimer’s disease

“…PVS increases at older age, with cerebral SVD 82 , and BBB breakdown 80 , indicating that they are likely markers of BBB-related vascular dysfunction. Systematic reviews of population, vascular, and neurodegenerative diseases indicate that higher number of PVS is associated in cross-sectional studies with cognitive decline, AD-type dementia, and executive dysfunction [83][84][85][86] .…”

Aging-Related Alterations of Glymphatic Transport in Rat: In vivo Magnetic Resonance Imaging and Kinetic Study

“…The degree of reduction in infusion rate differs from clearance rate, likely reflecting the different aging effects on glymphatic influx and efflux. The suppression of this brain-wide perivascular transport may in part be attributed to the age-dependent alterations in the cerebral vascular system, including the decline in vascular pulsatility ( Kress et al, 2014 ; Jessen et al, 2015 ), increase in vessel stiffness ( Kyrtsos and Baras, 2015 ; Benveniste et al, 2019b ), loss of perivascular AQP4 polarization ( Kress et al, 2014 ; Zeppenfeld et al, 2017 ), abnormalities in perivascular space ( Laveskog et al, 2020 ; Zong et al, 2020 ), decrease in microvascular density ( Bullitt et al, 2010 ; Murugesan et al, 2012 ; Reed et al, 2018 ; Watanabe et al, 2020 ) and neurovascular uncoupling ( Venkat et al, 2016 ; Toth et al, 2017 ).…”