Cerebrovascular pathology can disrupt resting-state functional connectivity (rsFC), a measure of correlated activity in spatially disparate brain regions derived using MRI. White matter hyperintensities (WMHs), the most common MRI-detected feature of cerebral small vessel disease (SVD), are also prevalent in Alzheimer's disease (AD). We conducted a systematic review to better understand the association between cerebrovascular pathology and rsFC, in patients a) along the AD continuum with evidence of WMHs, or b) with genetically defined SVD (e.g. CADASIL). A PRISMA-guided systematic search was performed in PubMed/Embase/PsycInfo for articles published until February 2021. Articles were assessed by three authors using Rayyan (www.rayyan.ai). Included studies evaluated the association between rsFC and an index of cerebrovascular pathology in a) AD or its prodrome Mild Cognitive Impairment (MCI) or b) CADASIL/CARASIL. Duplicates, case reports, reviews, non-human and non-English articles were excluded. 12 of 508 papers met inclusion criteria (Figure1), indicating a knowledge gap. AD/MCI studies (N=8) suggested an association between WMH load and rsFC. The default mode network (DMN) was most investigated. In the majority of studies, increased global WMH load was associated with increased DMN rsFC in the MCI group, while no such association was found in the AD dementia group. CADASIL studies (N=4; none in CARASIL) reported decreased rsFC in the DMN, which was mostly associated with worse cognitive performance. Studies of rsFC in CADASIL suggest that cerebrovascular pathology has a detrimental impact on rsFC. Along the AD continuum, there may be a compensatory mechanism in response to WMH load in the MCI, but not dementia stage. Analysis of results from sporadic SVD are underway and will be presented. Emerging evidence suggests that differences in rsFC could act as a potential biomarker to aid in differential diagnosis or disease staging.
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