Heart Rate Variability during Slow Wave Sleep is Linked to Resting‐state Functional Connectivity in the Central Autonomic Network among Older Adults ‘at‐risk’ of Dementia

Abstract

AbstractBackgroundReduced heart rate variability (HRV) can be an early sign of autonomic dysfunction in neurodegenerative diseases, and may be related to brain dysfunction in the central autonomic network (CAN). As yet, such autonomic dysfunction has not been examined during sleep – which is an ideal physiological state to study brain‐heart interaction as both the central and peripheral nervous systems behave differently compared to during wakefulness. Therefore, we aimed to examine whether nocturnal HRV, especially slow wave sleep (SWS), is associated with CAN functional connectivity in older adults ‘at‐risk’ of dementia.MethodOlder adults (n = 78; age range = 50‐88 years; 64% female) attending a memory clinic for cognitive concerns underwent resting‐state functional magnetic resonance imaging and an overnight polysomnography. From these, CAN functional connectivity strength and HRV data during sleep were derived, respectively. High‐frequency heart rate variability (HF‐HRV) was extracted to index parasympathetic activity during distinct periods of sleep, including SWS as well as secondary outcomes of non‐rapid eye movement sleep, wake after sleep onset, and rapid eye movement sleep. General linear models were used to examine associations between CAN functional connectivity and HF‐HRV.ResultAnalyses revealed that increased HF‐HRV during SWS was associated with stronger functional connectivity (F = 3.98, p = 0.022) in two core brain regions within the CAN, the right anterior insular and posterior midcingulate cortex, as well as stronger functional connectivity (F = 6.21, p = 0.005) between broader CAN brain regions – the right amygdala with three sub‐nuclei of the thalamus. There were no significant associations between HF‐HRV and CAN functional connectivity during wake after sleep onset or rapid eye movement sleep.ConclusionThese findings show that in older adults ‘at‐risk’ of dementia, parasympathetic regulation during SWS is uniquely linked to differential functional connectivity within both core and broader CAN brain regions. It is possible that dysfunctional brain‐heart interactions manifest primarily during this specific period of sleep known for its role in memory and metabolic clearance. Further studies elucidating the pathophysiology and directionality of this relationship should be conducted to determine if HRV drives neurodegeneration, or if brain degeneration within the CAN promotes aberrant HRV.