Effects of Alzheimer’s disease of varying severity on cardiac and autonomic function

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in the elderly. The aim of this study was to explore the effects of AD on cardiac function and autonomic nervous function, and the feasibility of electrocardiogram (ECG) in monitoring the development of AD. APP/PS1 double transgenic mice were used in the Morris water maze (MWM) experiment to evaluate the changes of cognitive ability of AD mice, then the non-invasive ECG acquisition system was used and the changes of ECG intervals and heart rate variability (HRV) were analyzed. AD mice already had cognitive dysfunction at the age of 5 months, reaching the level of mild dementia, and the degree of dementia increased with the course of disease. There were no significant changes in ECG intervals in the AD group at each month. The mean square of successive RR interval differences, percentage of intervals 46 ms different from preceding interval, and normalized high frequency power component in the AD group were decreased and low-to-high frequency power ratio and normalized low frequency power component were increased. Combined with the results of the MWM, it was shown that the regulation mechanism of sympathetic and parasympathetic nerves in mice was already imbalanced in early stage AD, which was manifested as the increase of excessive activity of sympathetic nerves and the inhibition of parasympathetic activities. Therefore, ECG-based analysis of HRV may become a means of daily monitoring of AD and provide an auxiliary basis for clinical diagnosis.

Reduced slow-wave activity and autonomic dysfunction during sleep precede cognitive deficits in Alzheimer’s disease transgenic mice

“…Only one human study has explored HRV during sleep in patients with MCI and found that parasympathetic regulation during NREM sleep, but not during wakefulness or REM sleep, was impaired in patients with MCI compared with healthy controls 76 . In animal studies, only one study explored the changes of autonomic function during wakefulness with short-term HRV recordings during AD progression and found that APP/PS1 mice had no significant changes in autonomic function at 5 months of age but had significantly higher sympathetic function and lower parasympathetic function after 7 months of age when compared with their age-matched WT mice 77 . However, no relevant findings about autonomic function during sleep have been reported in animal studies.…”

Effect of Sleep Duration on Autonomic Nervous System Regulation in Patients with Plausible Alzheimer: A Cross-Sectional Pilot Study

“…PSNS input increases cerebral perfusion, whereas SNS input reduces cerebral perfusion during sleep [7]. The PSNS serves as a "brake" for the SNS [8][9][10]. The decline in PSNS activity accelerates with age, particularly in individuals with AD, which gradually results in ANS dysregulation [9,[11][12][13].…”

“…The PSNS serves as a "brake" for the SNS [8][9][10]. The decline in PSNS activity accelerates with age, particularly in individuals with AD, which gradually results in ANS dysregulation [9,[11][12][13]. Discoordination of SNS and PSNS activities in individuals with AD resulting in ANS dysregulation appears to be associated with unstable and irregular circadian rhythms.…”

“…Acetylcholine neurotransmitter levels are positively correlated with PSNS activity, suggesting that a reduction in nighttime PSNS activity is a key indicator of a decrease in dementia severity [10,[24][25][26]. Higher PSNS activation at night may indicate good sleep quality [9,27,28]. Reduced sleep duration and SWS activity impair the restoration of the frontal lobe; conversely, treatments for sleep quality that may facilitate amyloid-beta clearance and promote SWS have focused on memory encoding and consolidation [22].…”

“…The LF/HF ratio (low-frequency/high-frequency power ratio) reflects the modulation of sympathovagal balance [10,27,29,30]. HRV refers to the complex variation in heart rate that is produced by the interaction between the SNS and PSNS (vagal) neural activity at the sinus node [9,10,23,29,31]. Previous research has shown that sympathovagal balance is positively correlated with sleep apnea, insomnia, RLS, PLMD, and RBD [28].…”