Cerebral Cortical Microinfarcts on Magnetic Resonance Imaging and Their Association With Cognition in Cerebral Amyloid Angiopathy

Abstract

Background and Purpose: We aimed to explore the association between presence of cerebral cortical microinfarcts (CMIs) on MRI and other small vessel disease neuroimaging biomarkers in cerebral amyloid angiopathy (CAA) and to analyze the role of CMIs on individual cognitive domains and dementia conversion. Methods: Participants were recruited from an ongoing longitudinal research cohort of eligible CAA patients between March 2006 and October 2016. A total of 102 cases were included in the analysis that assessed the relationship of cortical CMIs to CAA neuroimaging markers. Ninety-five subjects had neuropsychological tests conducted within 1 month of MRI scanning. Seventy-five non-demented CAA patients had cognitive evaluation data available during follow-up. Results: Among 102 patients enrolled, 40 patients had CMIs (39%) on MRI. CMIs were uniformly distributed throughout the cortex without regional predilection (P=0.971). The presence of CMIs was associated with lower total brain volume (OR=0.85, 95% CI: 0.74, 0.98, P=0.025) and presence of cortical superficial siderosis (OR=2.66, 95% CI: 1.10, 6.39, P=0.029). In 95 subjects with neuropsychological tests, presence of CMIs was associated with impaired executive function (β= −0.23, 95% CI: −0.44, −0.02, P=0.036) and processing speed (β= −0.24, 95% CI: −0.45, −0.04, P=0.020). Patients with CMIs had a higher cumulative dementia incidence compared to patients without CMIs (P=0.043), while only baseline total brain volume (HR=0.76, 95% CI: 0.62, 0.92, P=0.006) independently predicted dementia conversion. Conclusions: MRI-detected CMIs in CAA correlated with greater overall disease burden. The presence of CMIs was associated with worse cognitive performance, while only total brain atrophy independently predicted dementia conversion.

Small Vessel Disease-Related Dementia: An Invalid Neurovascular Coupling?

“…Therefore, the modification of this system produces deleterious effects, whose results are an accumulation of catabolites and toxic substances, together with a great impoverishment of neural nutrition [357][358][359]. The enlargement and widening of PVS, lead a consequent leakage of fluid and plasma cells due to an obstructive process maintained by catabolites, proteins, and cell debris [35], together with the disruption of the BBB, which might eventually potentiate the perivascular inflammation, and all of the cascades of the inflammatory/obstructive/stagnation-induced process [360][361][362]. Therefore, many Authors have tried to propose a biochemical profile of SVD, in order to better evaluate and support the radiological progressions of the SVD and its clinical monitoring [320,[363][364][365][366] Low et al [367] systematically reviewed the existing literature on the associations between markers of inflammation and SVD in cohorts of older people with good health, cerebrovascular disease, or cognitive impairment.…”

Brain atrophy in cerebral small vessel diseases: Extent, consequences, technical limitations and perspectives: The HARNESS initiative

“…We found six studies in which links between brain volume or atrophy and various MRI markers were tested. 36,[47][48][49][50][51] These markers comprise MB in two studies, diffusion tensor imaging metrics in one, perivascular spaces in one and cortical microinfarcts in two.…”

“…57,58 In the study in CAA, the brain volume was calculated by multiplying by 2 that of the non-hemorrhagic hemisphere. 51 Three of the four studies in CADASIL reported significant associations between brain atrophy and cognitive worsening during follow-up. Surprisingly however, the fourth study reported a significant association between ventricular enlargement and cognitive worsening, which strongly questions the method to measure brain atrophy.…”

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

“…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].…”