Locus of control (LOC) describes whether an individual thinks that they themselves (internal LOC) or external factors (external LOC) have more influence on their lives. LOC varies by domain, and a person’s LOC for their intellectual capacities (LOC-Cognition) may be a marker of resilience in older adults at risk for dementia, with internal LOC-Cognition relating to better outcomes and improved treatment adherence. Vagal control, a key component of parasympathetic autonomic nervous system (ANS) regulation, may reflect a neurophysiological biomarker of internal LOC-Cognition. We used canonical correlation analysis (CCA) to identify a shared neurophysiological marker of ANS regulation from electrocardiogram (during auditory working memory) and functional connectivity (FC) data. A canonical variable from root mean square of successive differences (RMSSD) time series and between-network FC was significantly related to internal LOC-Cognition (β = 0.266, SE = 0.971, CI = [0.190, 4.073], p = 0.031) in 65 participants (mean age = 74.7, 32 female) with amnestic mild cognitive impairment (aMCI). Follow-up data from 55 of these individuals (mean age = 73.6, 22 females) was used to show reliability of this relationship (β = 0.271, SE = 0.971, CI = [0.033, 2.630], p = 0.047), and a second sample (40 participants with aMCI/healthy cognition, mean age = 72.7, 24 females) showed that the canonical vector biomarker generalized to visual working memory (β = 0.36, SE = 0.136, CI = [0.023, 0.574], p = 0.037), but not inhibition task RMSSD data (β = 0.08, SE = 1.486, CI = [− 0.354, 0.657], p = 0.685). This canonical vector may represent a biomarker of autonomic regulation that explains how some older adults maintain internal LOC-Cognition as dementia progresses. Future work should further test the causality of this relationship and the modifiability of this biomarker.
