Cerebral amyloid angiopathy is associated with decreased functional brain connectivity

Nadieh Drenth,Jeroen Van Der Grond,Serge A.R.B Rombouts,Mark A Van Buchem,Gisela M Terwindt,Marieke J.H Wermer,Jasmeer P Chhatwal,M Edip Gurol,Steven M Greenberg,Sanneke Van Rooden

doi:10.1016/j.nicl.2020.102546

Abstract

Cerebral amyloid angiopathy (CAA) is a major cause of intracerebral hemorrhage and neurological decline in the elderly. CAA results in focal brain lesions, but the influence on global brain functioning needs further investigation. Here we study functional brain connectivity in patients with Dutch type hereditary CAA using resting state functional MRI. Twenty-four DNA-proven Dutch CAA mutation carriers (11 presymptomatic, 13 symptomatic) and 29 age-matched control subjects were included. Using a set of standardized networks covering the entire cortex, we assessed both within- and between-network functional connectivity. We investigated group differences using general linear models corrected for age, sex and gray matter volume. First, all mutation carriers were contrasted against control subjects and subsequently presymptomatic- and symptomatic mutation carriers against control subjects separately, to assess in which stage of the disease differences could be found. All mutation carriers grouped together showed decreased connectivity in the medial and lateral visual networks, default mode network, executive control and bilateral frontoparietal networks. Symptomatic carriers showed diminished connectivity in all but one network, and between the left and right frontoparietal networks. Presymptomatic carriers also showed diminished connectivity, but only in the frontoparietal left network. In conclusion, global brain functioning is diminished in patients with CAA, predominantly in symptomatic CAA and can therefore be considered to be a late consequence of the disease.

Highlights

Sporadic cerebral amyloid angiopathy (CAA) is an increasingly recognized cause of intracerebral hemorrhages (ICHs), loss of neuro logical function and cognitive decline
A standardized set of criteria have been developed based on these radiological findings with which a diagnosis of CAA can be made in vivo with a sensitivity of 94.7% and specificity of 81.2%
Our data show that functional connectivity is decreased in D-CAA mutation carriers across the brain compared to agematched control subjects

Summary

Introduction

Sporadic cerebral amyloid angiopathy (CAA) is an increasingly recognized cause of intracerebral hemorrhages (ICHs), loss of neuro logical function and cognitive decline. The disease is caused by an excessive deposition of amyloid β peptides in the small leptomeningeal and cortical vessels (Charidimou et al, 2017). CAA is a common finding among the elderly and often accompanies other brain pathologies, such as Alzheimer’s disease (AD) (Keage et al, 2009; Brenowitz et al, 2015). Other key neuroimaging markers of the disease include strictly lobar cerebral microbleeds (CMBs), posterior dominant white matter hyperintensities (WMHs), centrum semiovale enlarged perivascular spaces (CSO-EPVS), and cortical superficial siderosis (cSS) (Charidimou et al, 2017)

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