Autonomic Imbalance and Risk of Dementia and Stroke: The Framingham Study

Background and Purpose: The autonomic nervous system has been implicated in stroke and dementia pathophysiology. High resting heart rate and low heart rate variability indicate the effect of autonomic imbalance on the heart. We examined the associations of resting heart rate and heart rate variability with incident stroke and dementia in a community-based cohort of middle- and old-aged adults. Methods: The study sample included 1581 participants aged >60 years and 3271 participants aged >45 years evaluated for incident dementia and stroke, respectively, who participated in the Framingham Offspring cohort third (1983-1987) examination and had follow-up for neurology events after the seventh (1998-2001) examination. Heart rate variability was assessed through the standard deviation (SD) of normal-to-normal RR intervals and the root mean square of successive differences between normal heartbeats from 2-hour Holter monitor. Participants were followed-up for stroke and dementia incidence from exam 7 to a maximum of 10 years. Cox regression models were used to assess the link of resting heart rate and heart rate variability with stroke and dementia risk while adjusting for potential confounders, and interactions with age and sex were assessed. Results: Of the dementia (mean age, 55±6 years, 46% men) and stroke (mean age, 48±9 years, 46% men) samples, 133 and 127 developed dementia and stroke, respectively, during the follow-up. Overall, autonomic imbalance was not associated with dementia risk. However, age modified the associations such that SD of normal-to-normal intervals and root mean square of successive differences were associated with dementia risk in older people (hazard ratio [HR] [95% CI] per 1SD, 0.61 [0.38-0.99] and HR [95% CI] per 1SD, 0.34 [0.15-0.74], respectively). High resting heart rate was associated with increased stroke risk (HR [95% CI] per 10 bpm, 1.18 [1.01-1.39]), and high SD of normal-to-normal intervals was associated with lower stroke risk in men (HR [95% CI] per 1SD, 0.46 [0.26-0.79]) but not women (HR [95% CI] per 1SD, 1.25 [0.88-1.79]; P for interaction=0.003). Conclusions: Some measures of cardiac autonomic imbalance may precede dementia and stroke occurrence, particularly in older ages and men, respectively.