Subtypes of functional brain connectivity as early markers of neurodegeneration in Alzheimer’s disease

Abstract

HighlightsO_LIReliable functional brain network subtypes accompany cognitive impairment in AD\nC_LIO_LISymptom-related subtypes exist in the default-mode, limbic and salience networks\nC_LIO_LIA limbic subtype is associated with a familial risk of AD in healthy older adults\nC_LIO_LILimbic subtypes also associate with beta amyloid deposition and ApoE4\nC_LI\n\nIn BriefWe found reliable subtypes of functional brain connectivity networks in older adults, associated with AD-related clinical symptoms in patients as well as several AD risk factors/biomarkers in asymptomatic individuals.\n\nSummaryThe heterogeneity of brain degeneration has not been investigated yet for functional brain network connectivity, a promising biomarker of Alzheimers disease. We coupled cluster analysis with resting-state functional magnetic resonance imaging to discover connectivity subtypes in healthy older adults and patients with cognitive disorders related to Alzheimers disease, noting associations between subtypes and cognitive symptoms in the default-mode, limbic and salience networks. In an independent asymptomatic cohort with a family history of Alzheimers dementia, the connectivity subtypes had good test-retest reliability across all tested networks. We found that a limbic subtype was overrepresented in these individuals, which was previously associated with symptoms. Other limbic subtypes showed associations with cerebrospinal fluid A{beta}1-42 levels and ApoE4 genotype. Our results demonstrate the existence of reliable subtypes of functional brain networks in older adults and support future investigations in limbic connectivity subtypes as early biomarkers of Alzheimers degeneration.