Heart rate variability changes during task shifting testing in pre‐symptomatic Alzheimer’s disease

Background. Early detection of Alzheimer’s disease (AD) is vital to begin and monitor treatments. However, as AD pathology begins long before the onset of symptoms, early detection is difficult. Previous studies have suggested differences in the cardiac and autonomic nervous systems (ANS) in AD patients, providing a possible non‐invasive marker of disease onset. The goal of this study is to compare heart rate variability (HRV) measures, representative of cardiac and ANS function, at rest as well as during cognitive testing to assess the use of HRV as a possible marker of pre‐symptomatic AD. Method. All participants are cognitively healthy (CH) separated into two subgroups based on ratios of amyloid/tau proteins in cerebrospinal fluid (CSF): normal (CH‐NAT, n=22) and pathological (CH‐PAT, n=36), which represents pre‐symptomatic AD. Heart rate variability (HRV) was assessed during 5‐minute intervals at rest and during Task Shifting testing. Participants were required to name the color or word of a colored word for each stimulus by pressing a button, with two sequential stimuli per trial. The trial could be switching (color‐word or word‐color) or repeat (color‐color or word‐word). ECG traces from subgroups of CH‐NATs (n=8) and CH‐PATs (n=13) were initially screened to remove ectopic beats, followed by identification of normal RR‐intervals (NN). HRV was analyzed as standard deviation of NN (SDNN), root mean squared of successive differences (RMSSD) in the time domain as well as high (HF) and low frequency (LF) in the frequency domain to assess changes to autonomic, and particularly parasympathetic, input to the heart. Result. Comparing HRV changes assessed during rest and the task shifting testing in each individual, differences became apparent between CH‐NAT and CH‐PAT groups. In the CH‐NAT group, little to no change in SDNN and RMSSD occurred during cognitive testing from rest. The CH‐PAT group however showed a 20 percent drop in both SDNN and RMSSD during testing, indicating an imbalance of the ANS. Conclusion. This study provides a new approach and technique using HRV to non‐invasively differentiate between normal and pre‐symptomatic AD in cognitively healthy people