Annals Of Clinical And Translational Neurology | June 26, 2020

Romero JR, Demissie S, Beiser A, Himali JJ, DeCarli C, Levy D and Seshadri S.

Ann Clin Transl Neurol. 2020 Jun 26

DOI: https://doi.org/10.1002/acn3.51066

Abstract

Objective

Cerebral microbleeds (CMBs) are associated with higher risk of stroke and dementia, predating clinical diagnosis by several years. CMB are considered markers of cerebral small vessel disease (CSVD): hypertensive (deep CMB) and cerebral amyloid angiopathy (lobar CMB). We related plasma β ‐Amyloid (40, 42 and their ratio), clusterin, and tau levels to CMB to elucidate their role as biomarkers for the angiopathies represented by CMB.

Methods

Dementia, stroke, and other neurological disease‐free Framingham Heart Study participants with available CMB and biomarker measurements were included. We related biomarker levels (standardized for analyses) to CMB presence overall and stratified by brain topography (any, lobar, deep), using multivariable logistic regression analyses.

Results

CMB were observed in 208 (5.7%) participants (mean age 57 years, 54% women). After multivariable adjustment, Aβ 1‐40 was associated with any CMB (OR (95%CI) 1.20 (0.99, 1.45) P  = 0.062)) and lobar CMB (OR (95%CI) 1.33 (1.05, 1.68) P  = 0.019), but not with deep CMB. Log‐Aβ 1‐42 levels were not associated with CMB overall. Clusterin was related to mixed CMB (1.70 [1.05, 2.74], P  = 0.031). Tau levels were associated with any CMB (OR (95%CI) 1.26 (1.07, 1.49) P  = 0.006), lobar CMB (OR (95%CI) 1.26 (1.05, 1.52) P  = 0.013), and with deep CMB (OR (95% CI) 1.46 (1.13, 1.89) P  = 0.004).

Interpretation

We found that plasma Aβ 1‐40 and Tau are associated with CMB but further studies are needed to confirm their role in hemorrhage prone CSVD represented by CMB and as indicators of ongoing subclinical neuronal injury.