Prediction of Cognitive Decline Using Heart Rate Fragmentation Analysis: The Multi-Ethnic Study of Atherosclerosis
Madalena D Costa1, Susan Redline2,3, Timothy M Hughes4,5
1Margret and H. A. Rey Institute for Non-linear Dynamics in Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Insights
Increased heart rate fragmentation (HRF), a measure of cardiac neuroautonomic function, is linked to poorer cognitive performance and accelerated cognitive decline. This finding highlights the connection between heart health and brain function, suggesting HRF
Area of Science:
- Cardiology
- Neurology
- Gerontology
Background:
- Heart rate fragmentation (HRF) quantifies cardiac neuroautonomic function and is associated with aging and cardiovascular disease.
- These factors are known risks for cognitive decline and dementia.
Purpose of the Study:
- To investigate the association between disrupted cardiac neuroautonomic function (increased HRF) and cognitive function.
- To assess if HRF predicts cognitive decline over time.
Main Methods:
- HRF was derived from ECG in polysomnographic recordings from 1,897 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) exam 5.
- Cognitive function (global, processing speed, working memory) was assessed at MESA exams 5 and 6 (6.4 years later).
- Multivariable regression models analyzed associations between HRF and cognitive scores.
Main Results:
- Higher baseline HRF was independently associated with lower cognitive scores at both exams 5 and 6.
- A one-SD increase in HRF correlated with reduced scores in global cognition (CASI) and processing speed (DSC).
- HRF demonstrated predictive value beyond established risk scores for cognitive decline.
Conclusions:
- Elevated HRF during sleep is independently linked to diminished cognitive performance and greater cognitive decline.
- Findings support a connection between cardiac neuroautonomic regulation and cognitive function.
- HRF may serve as a valuable, non-invasive tool for monitoring cognitive status and dementia risk.
Abstract:
Background: Heart rate fragmentation (HRF), a new non-invasive metric quantifying cardiac neuroautonomic function, is associated with increasing age and cardiovascular disease. Since these are risk factors for cognitive decline and dementia, in the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated whether disrupted cardiac neuroautonomic function, evidenced by increased HRF, would be associated with worse cognitive function assessed concurrently and at a later examination, and with greater cognitive decline. Methods: HRF was derived from the ECG channel of the polysomnographic recordings obtained in an ancillary study (n = 1,897) conducted in conjunction with MESA exam 5 (2010-2012). Cognitive function was assessed at exam 5 and 6.4 ± 0.5 years later at exam 6 (2016-2018) with tests of global cognitive performance (the Cognitive Abilities Screening Instrument, CASI), processing speed (Digit Symbol Coding, DSC) and working memory (Digit Span). Multivariable regression models were used to quantify the associations between HRF indices and cognitive scores. Results: The participants' mean age was 68 ± 9 years (54% female). Higher HRF at baseline was independently associated with lower cognitive scores at both exams 5 and 6. Specifically, in cross-sectional analyses, a one-standard deviation (SD) (13.7%) increase in HRF was associated with a 0.51 (95% CI: 0.17-0.86) points reduction in CASI and a 1.12 (0.34-1.90) points reduction in DSC. Quantitatively similar effects were obtained in longitudinal analyses. A one-SD increase in HRF was associated with a 0.44 (0.03-0.86) and a 1.04 (0.28-1.81) points reduction in CASI and DSC from exams 5 to 6, respectively. HRF added predictive value to the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE-APOE-ε4) risk score and to models adjusted for serum concentration of NT-proBNP, an analyte associated with cognitive impairment and dementia. Conclusion: Increased HRF assessed during sleep was independently associated with diminished cognitive performance (concurrent and future) and with greater cognitive decline. These findings lend support to the links between cardiac neuroautonomic regulation and cognitive function. As a non-invasive, repeatable and inexpensive probe, HRF technology may be useful in monitoring cognitive status, predicting risk of dementia and assessing therapeutic interventions.
