Dataset Information

Older adults with perivascular spaces exhibit cerebrovascular reactivity deficits.

ABSTRACT:

Background

Perivascular spaces on brain magnetic resonance imaging (MRI) may indicate poor fluid drainage in the brain and have been associated with numerous neurological conditions. Cerebrovascular reactivity (CVR) is a marker of cerebrovascular function and represents the ability of cerebral blood vessels to regulate cerebral blood flow in response to vasodilatory or vasoconstrictive stimuli. We aimed to examine whether pathological widening of the perivascular space in older adults may be associated with deficits in CVR.

Methods

Independently living older adults free of dementia or clinical stroke were recruited from the community and underwent brain MRI. Pseudo-continuous arterial spin labeling MRI quantified whole brain cerebral perfusion at rest and during CVR to hypercapnia and hypocapnia induced by visually guided breathing exercises. Perivascular spaces were visually scored using existing scales.

Results

Thirty-seven independently living older adults (mean age = 66.3 years; SD = 6.8; age range 55-84 years; 29.7% male) were included in the current analysis. Multiple linear regression analysis revealed a significant negative association between burden of perivascular spaces and global CVR to hypercapnia (B = -2.0, 95% CI (-3.6, -0.4), p = .015), adjusting for age and sex. Perivascular spaces were not related to CVR to hypocapnia.

Discussion

Perivascular spaces are associated with deficits in cerebrovascular vasodilatory response, but not vasoconstrictive response. Enlargement of perivascular spaces could contribute to, or be influenced by, deficits in CVR. Additional longitudinal studies are warranted to improve our understanding of the relationship between cerebrovascular function and perivascular space enlargement.

SUBMITTER: Kapoor A

PROVIDER: S-EPMC10033456 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Older adults with perivascular spaces exhibit cerebrovascular reactivity deficits.

Kapoor Arunima A Yew Belinda B Jang Jung Yun JY Dutt Shubir S Li Yanrong Y Alitin John Paul M JPM Gaubert Aimee A Ho Jean K JK Blanken Anna E AE Sible Isabel J IJ Marshall Anisa A Shao Xingfeng X Mather Mara M Wang Danny J J DJJ Nation Daniel A DA

NeuroImage 20221109

<h4>Background</h4>Perivascular spaces on brain magnetic resonance imaging (MRI) may indicate poor fluid drainage in the brain and have been associated with numerous neurological conditions. Cerebrovascular reactivity (CVR) is a marker of cerebrovascular function and represents the ability of cerebral blood vessels to regulate cerebral blood flow in response to vasodilatory or vasoconstrictive stimuli. We aimed to examine whether pathological widening of the perivascular space in older adults ma ...[more]

PMID: 36370956

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Project description:Background and purposeEnlarged perivascular spaces (EPVS) have been associated with aging, increased stroke risk, decreased cognitive function, and vascular dementia. However, the relationship of EPVS with age-related neuropathologies is not well understood. Therefore, the purpose of this study was to assess the neuropathologic correlates of EPVS in a large community-based cohort of older adults. The cognitive correlates of EPVS over and beyond those of other pathologies were also assessed.MethodsThis study included 654 older deceased and autopsied participants of 3 longitudinal community-based studies of aging that had available data on cognition, ex vivo brain magnetic resonance imaging, and detailed neuropathologic examination. EPVS seen on ex vivo magnetic resonance imaging were histologically validated. Experienced observers rated EPVS burden in ex vivo magnetic resonance imaging using a semiquantitative 4-level scale. Elastic-net regularized ordinal logistic regression was used to investigate associations of EPVS burden with age-related neuropathologies. Mixed-effects models of cognition controlling for neuropathologies, demographics, and clinical factors, were used to determine whether EPVS burden has additional contributions to cognitive decline.ResultsEPVS burden in the whole group was associated with gross infarcts (odds ratio=1.67, P=0.0017) and diabetes mellitus (odds ratio=1.73, P=0.004). When considering only nondemented participants (with mild or no cognitive impairment), EPVS burden was associated with gross infarcts (odds ratio=1.74, P=0.016) and microscopic infarcts (odds ratio=1.79, P=0.013). EPVS burden was associated with faster decline in visuospatial abilities (estimate=-0.009, P=0.028), in the whole group, as well as lower levels of semantic memory (estimate=-0.13, P=0.048) and visuospatial abilities (estimate=-0.11, P=0.016) at the time of death.ConclusionsEPVS and infarcts may share similar neurobiological pathways regardless of dementia status. EPVS burden is linked to diabetes mellitus independently of neuropathologies, extending recent findings in animal studies implicating diabetes mellitus in impairment of the glymphatic system. Finally, EPVS burden may reflect additional brain tissue injury that may contribute to cognitive decline, not captured with traditional neuropathologic measures.

Project description:BackgroundIt remains unknown whether perivascular spaces (PVS) are associated with delirium in older hospitalized patients. We aimed to determine the association between magnetic resonance imaging (MRI)-visible PVS and the risk of delirium in a cohort of older patients.MethodsWe consecutively recruited older patients (≥70 years) admitted to the Geriatric Department of West China Hospital between March 2016 and July 2017, and their imaging data within one year before admission were reviewed retrospectively. PVS was rated on axial T2-weighted images in the basal ganglia (BG) and centrum semiovale (CS) using the validated semiquantitative 4-point ordinal scale. Delirium was screened within 24 h of admission and three times daily thereafter, using the confusion assessment method. Binary logistic regression analyses were performed to investigate the associations between PVS and delirium.ResultsAmong 114 included patients (mean age 84.3 years, 72.8% male), delirium occurred in 20 (17.5%). In patients with MRI examined within 6 months before admission, CS-PVS was found to be associated with delirium (odds ratio [OR] 3.88, 95% confidence interval [CI] 1.07-14.06, unadjusted; and OR 4.24, 95% CI 1.11-16.28, adjusted for age). The associations were enhanced and remained significant even after full adjustment of covariates (OR 7.16, 95% CI 1.16-44.32, adjusted for age, cognitive impairment, smoking, and Charlson Comorbidity Index). Similarly, the relationships between high CS-PVS and delirium were also strengthened after sequentially adjusting all variables of interest, with OR 4.17 (95% CI 1.04-16.73) in unadjusted model and OR 7.95 (95% CI 1.14-55.28) in fully-adjusted model. Adding CS-PVS to the established risk factors improved the risk reclassification for delirium (continuous net reclassification index 62.1%, P = 0.04; and integrated discrimination improvement 12.5%, P = 0.01).ConclusionsCS-PVS on MRI acquired 6 months earlier predicts subsequent delirium in older patients and may have clinical utility in delirium risk stratification to enable proactive interventions.

Project description:BackgroundMechanisms underlying the association between age-related arterial stiffening and poor brain health remain elusive. Cerebral blood flow (CBF) homeostasis may be implicated. This study evaluates how aortic stiffening relates to resting CBF and cerebrovascular reactivity (CVR) in older adults.MethodsVanderbilt Memory & Aging Project participants free of clinical dementia, stroke, and heart failure were studied, including older adults with normal cognition (n=155; age, 72±7 years; 59% male) or mild cognitive impairment (n=115; age, 73±7 years; 57% male). Aortic pulse wave velocity (PWV; meters per second) was quantified from cardiac magnetic resonance. Resting CBF (milliliters per 100 g per minute) and CVR (CBF response to hypercapnic normoxia stimulus) were quantified from pseudocontinuous arterial spin labeling magnetic resonance imaging. Linear regression models related aortic PWV to regional CBF, adjusting for age, race/ethnicity, education, Framingham Stroke Risk Profile (diabetes mellitus, smoking, left ventricular hypertrophy, prevalent cardiovascular disease, atrial fibrillation), hypertension, body mass index, apolipoprotein E4 ( APOE ε4) status, and regional tissue volume. Models were repeated testing PWV× APOE ε4 interactions. Sensitivity analyses excluded participants with prevalent cardiovascular disease and atrial fibrillation.ResultsAmong participants with normal cognition, higher aortic PWV related to lower frontal lobe CBF (β=-0.43; P=0.04) and higher CVR in the whole brain (β=0.11; P=0.02), frontal lobes (β=0.12; P<0.05), temporal lobes (β=0.11; P=0.02), and occipital lobes (β=0.14; P=0.01). Among APOE ε4 carriers with normal cognition, findings were more pronounced with higher PWV relating to lower whole-brain CBF (β=-1.16; P=0.047), lower temporal lobe CBF (β=-1.81; P=0.004), and higher temporal lobe CVR (β=0.26; P=0.08), although the last result did not meet the a priori significance threshold. Results were similar in sensitivity models. Among participants with mild cognitive impairment, higher aortic PWV related to lower CBF in the occipital lobe (β=-0.70; P=0.02), but this finding was attenuated when participants with prevalent cardiovascular disease and atrial fibrillation were excluded. Among APOE ε4 carriers with mild cognitive impairment, findings were more pronounced with higher PWV relating to lower temporal lobe CBF (β=-1.20; P=0.02).ConclusionsGreater aortic stiffening relates to lower regional CBF and higher CVR in cognitively normal older adults, especially among individuals with increased genetic predisposition for Alzheimer's disease. Central arterial stiffening may contribute to reductions in regional CBF despite preserved cerebrovascular reserve capacity.

Dataset Information

Older adults with perivascular spaces exhibit cerebrovascular reactivity deficits.

Background

Methods

Results

Discussion

Publications

Older adults with perivascular spaces exhibit cerebrovascular reactivity deficits.

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