Functional connectivity changes in cerebral small vessel disease - a systematic review of the resting-state MRI literature

Maximilian Schulz,Götz Thomalla,Eckhard Schlemm,Bastian Cheng,Caroline Malherbe

doi:10.1186/s12916-021-01962-1

Maximilian Schulz, Götz Thomalla + Show 3 more

Open Access

https://doi.org/10.1186/s12916-021-01962-1

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Abstract

BackgroundCerebral small vessel disease (CSVD) is a common neurological disease present in the ageing population that is associated with an increased risk of dementia and stroke. Damage to white matter tracts compromises the substrate for interneuronal connectivity. Analysing resting-state functional magnetic resonance imaging (fMRI) can reveal dysfunctional patterns of brain connectivity and contribute to explaining the pathophysiology of clinical phenotypes in CSVD.Materials and methodsThis systematic review provides an overview of methods and results of recent resting-state functional MRI studies in patients with CSVD. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol, a systematic search of the literature was performed.ResultsOf 493 studies that were screened, 44 reports were identified that investigated resting-state fMRI connectivity in the context of cerebral small vessel disease. The risk of bias and heterogeneity of results were moderate to high. Patterns associated with CSVD included disturbed connectivity within and between intrinsic brain networks, in particular the default mode, dorsal attention, frontoparietal control, and salience networks; decoupling of neuronal activity along an anterior–posterior axis; and increases in functional connectivity in the early stage of the disease.ConclusionThe recent literature provides further evidence for a functional disconnection model of cognitive impairment in CSVD. We suggest that the salience network might play a hitherto underappreciated role in this model. Low quality of evidence and the lack of preregistered multi-centre studies remain challenges to be overcome in the future.

Highlights

Cerebral small vessel disease (CSVD) is a common neurological disease present in the ageing population that is associated with an increased risk of dementia and stroke
We identified a total of 493 potentially relevant papers, 471 of which were obtained by searching PubMed and 22 through personal communication or as references cited in other works
Based on patient characteristics and research objective, studies could be divided into three groups: (1) group comparisons of patients with clinically and/or radiologically manifest CSVD, often involving a control group of healthy participants or patients with CSVD at different levels of cognitive impairment; (2) cohort studies of clinically healthy individuals in which white matter hyperintensities are reported as one of several parameters, often with the aim of characterising structure–function relationships or patterns of brain ageing; (3) investigations of resting-state connectivity in clinical conditions not primarily related to vascular pathology, in which measures of white matter disease were reported as covariates

Summary

Introduction

Cerebral small vessel disease (CSVD) is a common neurological disease present in the ageing population that is associated with an increased risk of dementia and stroke. Even in its pre-symptomatic stage, CSVD is associated with structural brain changes on neuroimaging, in particular white matter hyperintensities (WMH) of presumed vascular origin, lacunes, cerebral microbleeds, enlarged perivascular spaces, and brain atrophy [6]. Cardiovascular risk factors, such as hypertension, diabetes, smoking, or dyslipidaemia, are associated with both WMH and the clinical sequelae associated with CSVD [7, 8]. There remains considerable variability in clinical phenotypes, such as cognitive impairment or affective functions, that is not explained by structural markers alone [17,18,19]

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