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.
Highlights
Risk assessment of cognitive impairment is a major public health priority, especially given the increasing prevalence of dementia syndromes in the aging population
We previously reported that: (i) Heart rate fragmentation (HRF) monotonically increases with cross-sectional age both in healthy subjects and in those with coronary artery disease (Costa et al, 2017a,b); (ii) increased HRF is associated with both incident major adverse cardiovascular event (CVE) (Costa et al, 2018) and incident atrial fibrillation (AF) (Costa et al, 2021) in the Multi-Ethnic Study of Atherosclerosis (MESA), and (iii) HRF metrics add significant predictive value to cardiac risk indices such as Framingham (D’Agostino et al, 2008; Costa et al, 2018) and CHARGE-AF1 (Alonso et al, 2013; Costa et al, 2021), in MultiEthnic Study of Atherosclerosis (MESA)
Our key findings were: (1) in cross-sectional analyses, HRF was inversely associated with all cognitive scores other than the digit span (DS) forward scores; (2) in prospective analyses, HRF was inversely associated with all cognitive scores; (3) HRF was associated with the changes in all cognitive scores; (4) HRF metrics added predictive value to the CAIDE–APOE-ε4 risk index and to models with a combination of risk factors for cognitive impairment including NT-proBNP serum concentration; (5) slower heart rate (HR) was cross-sectionally associated with the Cognitive Abilities Screening Instrument (CASI) and digit symbol coding (DSC) scores, and prospectively associated with the DS backward scores; and (5) the heart rate variability (HRV) indices rMSSD, SDNN and HF power were not cross-sectionally or longitudinally associated with cognitive scores
Summary
Risk assessment of cognitive impairment is a major public health priority, especially given the increasing prevalence of dementia syndromes in the aging population. A PubMed search for “(heart rate variability) AND (cognitive function)” yields over 1,000 citations Despite this large body of work, traditional HRV measures have failed to gain traction in clinical practice as reliable predictors of mild cognitive impairment or of major adverse cardiovascular events (CVEs), which are strong correlates of cognitive decline and dementia syndromes (Zlokovic et al, 2020). 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 MultiEthnic 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
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