Autonomic Nervous System Dysfunction in Mild Cognitive Impairment and Early Dementia: A Systematic Review of Heart Rate Variability and Autonomic Markers

Abstract Mild cognitive impairment (MCI) and early-stage dementia represent critical prodromal phases of neurodegenerative disease, during which subtle physiological alterations may precede overt cognitive decline. The autonomic nervous system plays a central role in cardiovascular, metabolic, and neuroimmune homeostasis, and emerging evidence suggests that autonomic dysfunction may be an early physiological correlate of cognitive vulnerability. Heart rate variability (HRV) provides a noninvasive quantitative index of autonomic modulation and may offer translational value as a biomarker of early neurodegenerative risk. A systematic literature search was conducted across PubMed, Scopus, and Google Scholar to identify human studies assessing autonomic function using HRV or standardized autonomic testing in individuals with MCI or early or mild dementia. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided screening and methodological quality appraisal, 11 studies met the predefined inclusion criteria and were included in the final synthesis. Across heterogeneous study designs, populations, and HRV acquisition protocols, a consistent pattern of autonomic dysregulation was observed. Reduced parasympathetic (vagal) modulation, reflected by lower high-frequency power, reduced root mean square of successive differences, and diminished Standard Deviation of Normal-to-Normal intervals (SDNN), was the most reproducible abnormality in cognitively impaired populations. Autonomic dysfunction was evident not only in established dementia but also in prodromal cognitive states, including amnestic and nonamnestic MCI. Several studies demonstrated impaired autonomic adaptability during physiological challenges, including blunted sympathetic responsiveness during head-up tilt and reduced baroreflex sensitivity. Ambulatory and longer-duration HRV recordings further revealed lower global autonomic tone in cognitively impaired individuals. Importantly, longitudinal evidence indicated that reduced baseline HRV predicted subsequent cognitive decline, supporting a temporal relationship between autonomic impairment and neurodegenerative progression.