Heart Rate Variability Associated With Increased Risk of Agitation Among Patients With Alzheimer Disease

Results from a prospective epidemiological cohort study indicated that individuals clinically diagnosed with dementia due to Alzheimer disease showed a positive association between heart rate variability (HRV) and risk of developing agitation.

Agitation in Alzheimer disease is generally common and may be related to impaired emotion regulation among this patient population. The beat-to-beat change in heart rate, known as heart rate variability, may be considered as an index of emotion regulation, and could potentially be associated with agitation tendency in Alzheimer disease.

To make this determination, researchers used data from the Atherosclerosis Risk in Communities (ARIC) Study cohort to investigate whether HRV was associated with agitation risk in individuals clinically diagnosed with dementia due to Alzheimer disease. The ARIC Study initially enrolled 15,792 participants aged 45 to 64 years between 1987 and 1989. Those individuals were followed over seven visits, spanning more than 2 decades, to 2020.

The primary outcome for this study was either the absence or presence of agitation at the fifth visit, which took place between 2011 and 2013. Agitation was based on the Neuropsychiatric Inventory (NPI) agitation/aggression subscale, or a composite score comprising the total number of NPI subscales, which were: agitation/aggression, disinhibition, irritability, and motor disturbance.

“To aid interpretability, heart rate variability data were scaled such that model outputs were expressed for each 0.05 log-unit change in heart rate variability (which approximated to the observed difference in heart rate variability with every 5 years of age),” the authors wrote.

The results showed that among 456 participants who had either mild cognitive impairment or dementia, 120 were clinically diagnosed with dementia due to Alzheimer disease. Among this group, when looking at regression models, a positive relationship between heart rate variability and agitation risk was found to be strongest for measures of HRV change during the preceding 2 decades.

“A 0.05 log-unit of heart rate variability change was associated with an up to 10-fold increase in the odds of agitation and around a half-unit increase in the composite agitation score,” the authors wrote.

The authors noted that the associations persisted even after controlling for participants’ cognitive status, heart rate, sociodemographic factors, comorbidities, and medications.

“Further confirmatory studies, incorporating measures of emotion regulation, are needed to support heart rate variability indices as potential agitation propensity markers in Alzheimer disease and to explore underlying mechanisms as targets for treatment development,” the authors concluded.

Reference:
Liu KY, Whitsel EA, Heiss G, et al. Heart rate variability and risk of agitation in Alzheimer's disease: the Atherosclerosis Risk in Communities Study. Brain Commun. 2023;5(6):fcad269. doi:10.1093/braincomms/fcad269