Heart rate variability: a novel biomarker for agitation propensity in Alzheimer’s disease?

Abstract

AbstractBackgroundAgitation, a common symptom in Alzheimer’s disease (AD), may be related to impaired emotion regulation capacity with involvement of autonomic networks. Heart rate variability (HRV), an index of integrity of neural networks involved in autonomic function and emotion regulation, could be a potential marker of agitation propensity. We investigated the cross‐sectional and longitudinal association between HRV and agitation prevalence in AD using the Atherosclerosis Risk in Communities (ARIC) Study cohort that followed up participants from 1987–2013.MethodParticipants at ARIC visit 5 who were clinically diagnosed with dementia (or MCI that subsequently progressed to dementia) primarily or wholly attributed to AD were included. Agitation at visit 5 was defined based on the Neuropsychiatric Inventory agitation/aggression subscale alone, or a composite score comprising agitation/aggression, irritability, disinhibition, and aberrant motor behavior subscales. HRV measures at visits 1–5 were the root mean square of successive differences in R‐R intervals (RMSSD) and standard deviation of normal‐to‐normal R‐R intervals (SDNN) obtained from resting, supine, standard twelve‐lead electrocardiograms. The associations between agitation and visit 5 HRV or visit 1–5 change in HRV (defined as individual slope coefficients from mixed effects models) were assessed using simple regression models.ResultsAmong 456 participants who had dementia during the study, N = 302 received a primary diagnosis of AD, of whom N = 120 were classified with pure AD (see Flowchart). In the pure AD subgroup, a 0.1 log‐unit higher RMSSD (odds ratio = 1.14 [1.03‐1.29]) and positive RMSSD change over the preceding two decades (odds ratio = 2.23 [1.24‐4.38]) were associated with agitation point prevalence after accounting for heart rate (change), age, sex, cognitive status, study site and race. A 0.1 log‐unit change in HRV approximated the observed difference in HRV with each decade of age. The associations persisted after accounting for use of medications with autonomic effects.ConclusionThe finding that higher HRV was associated with agitation point prevalence in N = 120 participants clinically diagnosed with dementia solely due to AD supports the potential use of HRV as a biomarker of agitation propensity, and autonomic dysfunction as a target of treatment. Future studies are needed to explore this relationship alongside measures of emotion regulation and locus coeruleus‐noradrenergic system integrity.