Recent functional magnetic resonance imaging studies have demonstrated that moment-to-moment variability in the blood oxygen level–dependent (BOLD) signal is related to age differences, cognition, and symptomatic Alzheimer's disease (AD). However, no studies have examined BOLD variability in the context of preclinical AD. We tested relationships between resting-state BOLD variability and biomarkers of amyloidosis, tauopathy, and neurodegeneration in a large (N = 321), well-characterized sample of cognitively normal adults (age = 39–93), using multivariate machine learning techniques. Furthermore, we controlled for cardiovascular health factors, which may contaminate resting-state BOLD variability estimates. BOLD variability, particularly in the default mode network, was related to cerebrospinal fluid (CSF) amyloid-β42 but was not related to CSF phosphorylated tau-181. Furthermore, BOLD variability estimates were also related to markers of neurodegeneration, including CSF neurofilament light protein, hippocampal volume, and a cortical thickness composite. Notably, relationships with hippocampal volume and cortical thickness survived correction for cardiovascular health and also contributed to age-related differences in BOLD variability. Thus, BOLD variability may be sensitive to preclinical pathology, including amyloidosis and neurodegeneration in AD-sensitive areas.

Original languageEnglish
Pages (from-to)233-245
Number of pages13
JournalNeurobiology of Aging
StatePublished - Dec 2020


  • Alzheimer's disease
  • Amyloid
  • BOLD variability
  • Neurodegeneration
  • Resting-state fMRI


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