Perivascular Spaces Volume in Sporadic and Hereditary (Dutch-Type) Cerebral Amyloid Angiopathy

Abstract

Background and Purpose- Magnetic resonance imaging visible perivascular spaces in the centrum semiovale (CSO-PVS) have been associated with cerebral amyloid angiopathy (CAA).We aimed to further confirm this link by evaluating CSO-PVS volume in pathologically-demonstrated sporadic and genetically-demonstrated hereditary forms of the disease. Methods- We studied a retrospective hospital-based cohort consisting of 63 individuals aged >55 having brain magnetic resonance imaging and pathological assessment of CAA (mean age, 73.6±8.5; 46% female), and a separate cohort consisting of 26 carriers, and 28 noncarriers of the hereditary cerebral hemorrhage with amyloidosis-Dutch type (mean age, 46.7±12.8; 61.1% female). CSO-PVS volume was quantified on a single magnetic resonance imaging slice using a computer-assisted segmentation method and expressed as the relative volume of the intracranial volume in that particular slice (CSO-PVS relative volume). We compared CSO-PVS relative volume (1) between subjects with and without the disease in both cohorts; (2) between non-CAA, CAA without hemorrhage, and CAA with hemorrhage cases in the sporadic CAA cohort. All variables reaching P<0.1 in bivariate analyses were entered in logistic regression models. Results- In both sporadic and Dutch cohorts, cases with CAA had significantly higher CSO-PVS relative volume than cases without (median [IQR]: 3.7% [2.5-5.3] versus 1.8% [1.2-2.4], P<0.0001; 3.8% [0.6-6.2] versus 0.7% [0.4-1.6], P=0.007; respectively). In linear regression models, sporadic CAA was associated with higher CSO-PVS relative volume ( P=0.008). In the sporadic CAA cohort, compared with non-CAA cases, CSO-PVS relative volume was higher in both CAA with hemorrhage and without hemorrhage (4.4% [2.6-6.1] and 3% [2.4-3.6] versus 1.8% [1.2-2.4], P<0.001 and P=0.005, respectively). Higher CSO-PVS relative volume was associated with CAA in regression models, both when hemorrhage was present (odds ratio, 2.63; [95% confidence interval, 1.33-5.18]; P=0.005) and absent (odds ratio, 4.55; [95% confidence interval, 0.98-21.04]; P=0.05). Conclusions- Increased CSO-PVS volume is a consistent magnetic resonance imaging marker of cerebrovascular amyloid deposition and a promising diagnostic tool for sporadic CAA without hemorrhagic manifestations.

Reduced Levels of Cerebrospinal Fluid/Plasma Aβ40 as an Early Biomarker for Cerebral Amyloid Angiopathy in RTg-DI Rats

“…For example, cortical superficial siderosis indicates perivascular iron accumulation in pial arteries and arterioles reflecting cerebral microbleeds [12,14,23]. Another noted perivascular change associated with CAA is the presence of dilated perivascular spaces, particularly around penetrating arterioles with amyloid deposition [8,24]. Although the cause of this perivascular alteration remains unclear this space contains CSF and interstitial fluid (ISF) that under normal conditions plays an important role in Aβ clearance from brain [25][26][27][28].…”

“…However, independent of AD, clinically CAA is a significant contributor to vascular-mediated cognitive impairment and dementia (VCID) [3,4,7]. As a prominent small vessel disease CAA contributes to the cognitive decline in VCID in several ways by promoting perivascular neuroinflammation, impaired cerebral blood flow and ischemic infarcts, cerebral microbleeds, and larger hemorrhages, all of which can result in neuronal dysfunction, neuronal loss and white matter damage [3,[8][9][10].…”

Imaging for central nervous system (CNS) interstitial fluidopathy: disorders with impaired interstitial fluid dynamics

“…Cerebral amyloid angiopathy shares Aβ pathology with AD, and an experimental study has demonstrated that CSF inflow and ISF clearance in the brain are suppressed in a mouse model of AD and in these the ISF/CSF dynamics is suppressed prior to the significant accumulation of Aβ [ 74 ]. One observational study on humans reported that the dilatation of perivascular space in the centrum semiovale, which may suggest impaired ISF drainage, significantly correlated with the existence of cerebral amyloid angiopathy even in the absence of any lobar hemorrhages [ 75 ].…”

Association Between Steno-Occlusive Middle Cerebral Artery and Basal Ganglia Perivascular Spaces

“…Slice thickness was 5 mm with 1.5 mm gap between slices. Parameters for 1.5T scanner, T1WI sequence: repetition time (TR), 1,990 ms; echo time (TE), 8 2 . MRI markers of CSVD, including BG-EPVS, WMH, and lacunes were assessed blinded to clinical information by a trained neuroradiologist (JW), according to previous literature (19,20).…”

“…Perivascular spaces (PVS) refer to tiny fluid-filled cavities surrounding the cerebral small perforating blood vessels that penetrate the brain parenchyma (1). PVS are normally invisible on conventional magnetic resonance image (MRI) and become visible on neuroimaging when PVS are presumably prominent or dilated (2). Basal ganglia (BG) is a common site for enlarged perivascular spaces (EPVS) formation where the largest cerebrospinal fluid (CSF) influxes occur along large ventral perforating arteries (3,4).…”