Brain-Heart Modulation of the Autonomic Nervous System in Older Adults ‘at-risk’ of Dementia: a Study of Heart Rate Variability During Sleep

Dementia is a devastating disease that currently cannot be effectively cured. A better understanding of the early physiologic processes in people ‘at-risk’ of developing dementia could improve our ability to differentiate various pathophysiological processes contributing to dementia pathology. Research examining the integrity of the autonomic nervous system is mixed for various types of dementia, as well as people who are ‘at-risk’ of dementia. Studying autonomic activities, especially parasympathetic activities during sleep - via heart rate variability can potentially shed light on the mixed findings of studies that have been conducted during the daytime. Furthermore, proper autonomic regulation is dependent on both the functional and structural integrity of the brain. It is therefore crucial to understand how the central nervous system interacts with the autonomic nervous system. The overarching aim of the current thesis is to examine autonomic function during sleep, specifically parasympathetic function via high-frequency heart rate variability in older adults ‘at-risk’ of dementia, and how such parasympathetic dysfunction during sleep is linked to cognition, and the morphological and functional integrity of the brain. In a series of three studies, the work of this thesis has revealed that reduced nocturnal high-frequency heart rate variability is: a) present in older adults with amnestic mild cognitive impairment, who are at high risk of developing dementia, especially dementia due to Alzheimer’s disease; b) associated with reduced verbal episodic memory performance and hippocampal atrophy; and c) associated with reduced brain functional connectivity in key regions modulating autonomic responses including the insula, cingulate cortex, thalamus and amygdala. The combined evidence has highlighted the potential of nocturnal heart rate variability as a marker of early neurogenerative disease in older adults ‘at-risk’ of cognitive decline