# Cardiac Autonomic Function, Cognitive Performance, and Neurocognitive Outcomes

> **NIH NIH K01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $97,092

## Abstract

Project Summary
Prevalence of Alzheimer’s disease and related dementias (ADRD), currently affecting an estimated 47 million
people worldwide, is expected to triple by 2050. A poor understanding of its etiology has hindered progress
toward treatments and preventive strategies. Several lines of evidence suggest that cardiovascular diseases
(CVD) and various CVD risk factors are strongly associated with incidence of dementia. Vascular risk factors
are easily identifiable and often modifiable. Therefore, discovery of vascular risk factors that precede CVD and
cognitive impairment or decline would significantly enhance our understanding of the vascular etiology of
ADRD. Heart rate variability (HRV) and QT interval variability (QTV), derived from electrocardiogram (ECG)
analysis, are well-known indices of autonomic control over the heart. Lower HRV and higher QTV, indicating
worse cardiac autonomic function, are strongly predictive of future cardiovascular morbidity and mortality.
Notably, lower HRV and QT abnormalities have been noted in ADRD and mild cognitive impairment (MCI).
Thus, the study of HRV and QTV may provide valuable insight into the role of cardiac autonomic function in the
development of dementia. However, in most studies HRV and QTV are derived from standard short-term ECG
(ranging from 10 seconds to several minutes duration), which does not reflect real-world conditions due to the
requirement of stationarity. Although wearable devices such as Zio XT Patch allow ECG recording of up to 14
days duration, methods used to analyze HRV and QTV are based on the stationarity assumption, resulting in
measures that may be uninterpretable or misleading when applied to such extra long-term recordings. Thus,
innovative signal analysis tools are required to utilize the full potential of these ECGs. Recently, a new signal
processing method was developed specifically to derive novel measures of HRV and QTV from extra long-term
ECG that better represent cardiac autonomic function in real-world settings. The primary goal of this K01
mentored career development award is to implement this innovative analysis tool in a large, ongoing cohort
study of older adults to derive novel measures of HRV and QTV from recently collected 14-day Zio Patch
recordings. In Aim 1, we will evaluate the association of these novel measures with cognitive performance and
risk of prevalent or incident MCI or dementia. In Aim 2, we will determine if their diurnal variation is related to
worse cognitive performance or risk of MCI or dementia. Finally, we will leverage recent neuroimaging data in
a subset of participants to determine if extra long-term HRV or QTV is associated with neuroimaging
biomarkers of ADRD or cerebrovascular disease. If successful, the proposed study may provide insight into the
mechanisms linking vascular risk factors and CVD to ADRD, and potentially identify cardiac autonomic function
as a modifiable intervention target. In addition, this K01 award will pr...

## Key facts

- **NIH application ID:** 10867268
- **Project number:** 5K01AG073581-04
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Christopher Schaich
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $97,092
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10867268

## Citation

> US National Institutes of Health, RePORTER application 10867268, Cardiac Autonomic Function, Cognitive Performance, and Neurocognitive Outcomes (5K01AG073581-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10867268. Licensed CC0.

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