Alteration of perivascular spaces in early cognitive decline

Sepehrband, Farshid; Barisano, Giuseppe; Sheikh‐Bahaei, Nasim; Choupan, Jeiran; Cabeen, Ryan P.; Crawford, Malcolm S; Mack, Wendy J.; Chui, Helena C.; Ringman, John M.; Toga, Arthur W.

doi:10.1101/2020.01.30.927350

Cited by 5 publications

(5 citation statements)

References 91 publications

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“…Contrary to previous theories that MRI-visible EPVS indicates poor waste clearance and predicts worse clinical outcomes (Abbott et al, 2018), we found iRBD patients had significantly higher EPVS burdens (CSO, BG, SN, and BS) than PD patients. Recently, a study found a significantly lower MRI-visible EPVS volume in the anterosuperior medial temporal lobe in some patients with early cognitive decline (Sepehrband et al, 2020). This suggested impaired signaling due to MRI-visible EPVS might be a manifestation of severe brain waste drainage dysfunction, which is consistent with our result.…”

Section: Discussionsupporting

confidence: 92%

Different Perivascular Space Burdens in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease

Song

et al. 2020

Front. Aging Neurosci.

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Background: Excessive aggregation of α-synuclein is the key pathophysiological feature of Parkinson's disease (PD). Rapid eye movement sleep behavior disorder (RBD) is also associated with synucleinopathies and considered as a powerful predictor of PD. Growing evidence suggests the diminished clearance of α-synuclein may be partly attributable to poor interstitial fluid drainage, which can be reflected by magnetic resonance imaging (MRI)-visible enlarged perivascular space (EPVS). However, the effect of MRI-visible EPVS on iRBD and PD, and their correlation with clinical characteristics remain unclear. Objective: To evaluate the clinical and neuroimaging significance of MRI-visible EPVS in iRBD and PD patients. Methods: We enrolled 33 iRBD patients, 82 PD (with and without RBD) patients, and 35 healthy controls (HCs), who underwent clinical evaluation and 3.0 Tesla MRI. Two neurologists assessed MRI-visible EPVS in centrum semiovale (CSO), basal ganglia (BG), substantia nigra (SN), and brainstem (BS). Independent risk factors for iRBD and PD were investigated using multivariable logistic regression analysis. Spearman analysis was used to test the correlation of MRI-visible EPVS with clinical characteristics of patients. Results: iRBD patients had significantly higher EPVS burdens (CSO, BG, SN, and BS) than PD patients. Higher CSO-EPVS and BS-EPVS burdens were independent risk factors for iRBD. Furthermore, higher CSO-EPVS and SN-EPVS burdens were positively correlated with the severity of clinical symptom in iRBD patients, and higher BG-EPVS burden was positively correlated with the severity of cognitive impairment in PD patients. Conclusion: iRBD and PD patients have different MRI-visible EPVS burdens, which may be related with a compensatory mechanism in glymphatic system. Lower MRI-visible EPVS burden in PD patients may be a manifestation of severe brain waste drainage dysfunction. These findings shed light on the pathophysiologic relationship between iRBD and PD with respect to neuroimaging marker of PD.

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Section: Discussionsupporting

confidence: 92%

Different Perivascular Space Burdens in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease

Song

et al. 2020

Front. Aging Neurosci.

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“…7,8 Hypertension and EPVS are independently associated with cognitive impairment. [9][10][11] A certain relationship may exist between these 2 factors in the pathological process by which cognitive impairment is induced, but pertinent previous research has merely focused on the separate correlations among hypertension, EPVS, and cognitive impairment. To achieve a better understanding of the relationships among the above 3 factors, we measured cumulative blood pressure (cBP), which is a better representation of exposure compared with single BP readings, for the analysis of the association of cBP exposure with cognitive impairment and EPVS.…”

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confidence: 99%

Enlarged Perivascular Spaces in Relation to Cumulative Blood Pressure Exposure and Cognitive Impairment

et al. 2023

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BACKGROUND: Hypertension and enlarged perivascular spaces (EPVS) are thought to be associated with cognitive impairment. However, the correlations among hypertension, EPVS, and cognitive impairment have not been studied yet. We aimed to investigate the relationships between cumulative blood pressure (cBP) exposure with EPVS and cognitive impairment and whether EPVS may mediate the relationship between cBP and cognitive impairment. METHODS: A total of 1507 subjects from the Kailuan prospective cohort study were enrolled. cBP was calculated from 2006 to 2022. The effects of cBP, EPVS scores, and cognitive impairment were evaluated using a logistic regression model. The relationships among cBP, EPVS score, and cognitive impairment were analyzed using a mediation model. RESULTS: An increase in cBP was positively correlated with an increase in EPVS score. For every SD increase in cBP, the odds ratios (95% CI) of increased EPVS score of the centrum semiovale were 1.67 (1.43–1.95), 1.63 (1.4–1.9), and 1.35 (1.17–1.56), respectively; the odds ratios (95% CI) of increased EPVS score of the basal ganglia were 1.83 (1.56–2.15), 2.01 (1.7–2.36), and 1.31 (1.13–1.52), respectively; and the odds ratios (95% CI) of developing cognitive impairment were 1.28 (1.06–1.53), 1.13 (0.95–1.34), and 1.28 (1.07–1.5), respectively. Basal ganglia-EPVS score accounted for 10.46% to 18.32% of the mediating effects on the relationships of cBP/SD with cognitive impairment. CONCLUSIONS: High cBP exposure was an independent risk factor for EPVS, and basal ganglia-EPVS score mediated the effects of cBP on cognitive impairment. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: ChiCTR-TNRC-11001489.

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“…Consistently, Sepehrband et al automatically measured EPVS in a biomarker-proven AD cohort found an inverse correlation between EPVS and tau PET in the superior mesial temporal lobe. 48 In a post-mortem MRI study, EPVS burden was associated with pre-mortem faster decline in visuospatial abilities, lower levels of semantic memory and visuospatial abilities at the time of death in patients with dementia and without dementia. 49 It is possible that the existing literature reflects the different stages in a dynamic role that EPVS play in brain health and disease.…”

Section: Discussionmentioning

confidence: 95%

Divergent enlarged perivascular spaces volumes in early versus late age-of-onset Alzheimer’s disease

Younes,

Cobbigo,

Tsuie

et al. 2023

Preprint

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STRUCTURED ABSTRACTINTRODUCTIONEnlarged perivascular spaces (EPVS) are considered a conduit for the brain’s waste clearance system. With aging, the brain’s ability to clear molecules is thought to decline, contributing to the retention of Alzheimer’s disease (AD) neuropathology. However, the role of EPVS in late-onset AD (LOAD) is complicated by co-morbidities. Early-onset AD (EOAD) offers a unique opportunity to understand the role of EPVS in AD.METHODSAutomatically-segmented EPVS volumes in biomarker-confirmed EOAD (n=58), LOAD (n=43), and age-matched controls (n=60) were correlated with amyloid and tau PET and cognition. Linear regression models were used.RESULTSIn LOAD, higher EPVS volumes were associated with better memory and functional performance. However, this association was not observed in EOAD. Additionally, higher tau was linked to increased EPVS in LOAD, but not in EOAD.DISCUSSIONEOAD and LOAD demonstrate distinct associations between EPVS, AD hallmarks, and cognition, suggesting differences in EPVS’s role in these AD subtypes, necessitating further investigation.

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Alteration of perivascular spaces in early cognitive decline

Cited by 5 publications

References 91 publications

Different Perivascular Space Burdens in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease

Different Perivascular Space Burdens in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease

Enlarged Perivascular Spaces in Relation to Cumulative Blood Pressure Exposure and Cognitive Impairment

Divergent enlarged perivascular spaces volumes in early versus late age-of-onset Alzheimer’s disease

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