709: When Complexity Fails: Chronic Pain Disrupts Cardiac Entropy�Cognition Coupling in Aging

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Pain Category (ICD-11), Chronic primary musculoskeletal pain, Psychology, Electrophysiology/Clinical neurophysiology (e.g. microneurography, EEG, MEG, OPMs, TMS)

Background and Aims: Cardiac rhythm measures derived from heart rate variability (HRV), including time, frequency, and nonlinear indices, provide information about autonomic control and are associated with executive functioning and adaptive behavioral regulation¹. Chronic pain in older adults is linked to autonomic dysregulation and greater vulnerability to cognitive decline², yet how these processes interact remains unclear. We aimed to examine the relationship between cognitive performance and autonomic control in aging and its modulation by chronic pain. We hypothesized that, unlike pain-free older adults, those with chronic pain would show inverse associations between cognition and HRV indices, particularly nonlinear entropy and vagally mediated indices.

Methods: Twenty-four older adults with chronic pain (67.9±4.0 years; 18 females) and 30 pain-free older adults (69.2±4.4 years; 17 females) underwent neuropsychological assessment, including Digit Span, Trail Making Test, WMS word list, Stroop, Wisconsin Card Sorting Test (WCST), and verbal fluency tasks (FAS, animals). Resting-state ECG was recorded for seven minutes to derive HRV time-domain, frequency-domain, and nonlinear indices. To examine whether chronic pain modifies the association between autonomic control and cognition, general linear models were performed, including main effects of HRV measures and group and HRV × GROUP interaction terms, adjusting for age and educational level.

Results: General linear models revealed significant GROUP × approximate entropy (ApEn) interactions for Digit Span (F(1,48)=8.53, p=.005, η²p=.151) and WCST % errors (F(1,47)=4.94, p=.031, η²p=.095). For Digit Span, estimated marginal means indicated that at higher ApEn (+1 SD), pain-free older adults showed better performance (M=0.641, 95%CI[0.126, 1.155]), whereas those with chronic pain showed poorer performance (M=-0.826, 95%CI[-1.302, -0.351]). Johnson–Neyman analysis showed group differences emerging above ApEn=-0.0198. For WCST, higher ApEn was associated with fewer errors in pain-free adults (M=-0.443) but more errors in chronic pain (M=0.746), with divergence beyond ApEn=-0.0085.

Conclusions: Our results suggest that chronic pain alters the functional meaning of cardiac entropy for cognition in aging. Whereas higher approximate entropy is associated with better cognitive performance in pain-free older adults—consistent with adaptive autonomic flexibility—in those with chronic pain it relates to poorer executive and working-memory outcomes. This reversal suggests that increased entropy in chronic pain may reflect dysregulated or inefficient autonomic control rather than adaptive complexity, potentially indicating altered signal-to-noise integration within brain–body regulatory systems. Together, these results refine and advance theoretical models of disrupted embodied cognition, clarifying bodily mechanisms underlying cognitive vulnerability in older adults with chronic pain.

References: 1: Arakaki, X., Arechavala, R. J., Choy, E. H., Bautista, J., Bliss, B., Molloy, C., Wu, D. A., Shimojo, S., Jiang, Y., Kleinman, M. T., & Kloner, R. A. (2023). The connection between heart rate variability (HRV), neurological health, and cognition: A literature review. Frontiers in Neuroscience, 17. https://doi.org/10.3389/fnins.2023.1055445
2: Zhao, L., Zhang, L., Tang, Y., & Tu, Y. (2025). Cognitive impairments in chronic pain: a brain aging framework. Trends in Cognitive Sciences, 29(6), 570–585. https://doi.org/10.1016/j.tics.2024.12.004

Presenting Author: Alejandro Dorado
Submitting Author: Alejandro Dorado

Senior Author: Ana María González-Roldán

IASP 2026 Global Year theme of Neuropathic Pain: No

• Ana María González-Roldán: PhD - Cognitive and Affective Neuroscience and Clinical Psychology, Research Institute of Health Sciences (IUNICS) and Balearic Islands Health Research Institute (IdISBa), University of the Balearic Islands (UIB), Palma, Spain.