AbstractBackgroundDelirium is associated with increased risk for Alzheimer’s disease (AD) and mortality; it is characterized by acute confusion commonly after stressors of illness during hospitalization. Integration between the heart and brain via the autonomic nervous system, or cardio‐autonomic control (CAC) is thought to be potentially protective during such stressors. Related to CAC, heart rate (HR) fluctuations display fractal correlations (similar temporal autocorrelation across different time scales) that reflect a dynamic interplay between sympathetic and vagal outflows, where disruption is thought to contribute to neuronal damage. We hypothesized that fractal correlations in HR fluctuations can serve as a novel physiological biomarker for predicting incident delirium.MethodWe derived fractal correlations (α) using ECG data from 37,978 participants (mean age 57.4) free from delirium and AD within the UK Biobank who underwent a 7‐minute stationary bike stress test between 2009‐2010, and had ≥1 inpatient hospitalization episode through to August 2020. Cox proportional hazards models were used to examine the association between α and incident delirium. We adjusted for demographics, physical activity levels, BMI, smoking, alcohol, cholesterol, diabetes, hypertension, ischemic heart disease, stroke, as well as test‐specific peak exercise load and mean heart rate achieved.ResultIncident delirium was newly diagnosed in 247 cases (6.5/1,000) during a median follow‐up time of 8.1 years (SD: 2.0, range: 0.2‐10.2) following ECG assessment. α showed a normal distribution with mean of 1.27±0.3 (SD). Negative association between α and incident delirium was observed. The fully adjusted hazard ratio was 1.26 (95% confidence interval: 1.10‐1.45; p=0.001) for each 1‐SD decrease in α. Putting this into context, a subject with a lower α at the 10thpercentile (vs. 90th) showed a 59% increased risk of developing incident delirium, equivalent to the additional risk of being 5‐years older or a current smoker in this cohort.ConclusionFractal correlation of heartbeat fluctuations during an exercise ECG recording was independently associated with incident delirium, and may be a hidden measure of brain‐heart resilience. As this cohort ages, future work will be able to answer the crucial question of whether this is a shared marker of vulnerability between delirium and AD.
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