CCA identifies a neurophysiological marker of adaptation capacity that is reliably linked to internal locus of control of cognition in amnestic MCI.

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.