Abstract
BACKGROUND: Autonomic dysfunction is common in dementia, yet its contribution to neurocognitive changes remains unknown. We investigated whether midlife cardiac vagal modulation, indexed by heart rate variability, associates with subsequent cognitive decline in adults without prior coronary heart disease or stroke. METHODS: The sample comprised 2702 (1924 men) individuals initially aged 44-69 years from the UK Whitehall II cohort. Data from the fifth (1997-1999), seventh (2002-2004) and ninth (2007-2009) phases were analysed. Global cognitive function was ascertained from tests assessing memory, reasoning, vocabulary, and fluency. We used 12-lead-ECG-based heart rate variability measures, that primarily reflect vagal modulation (i.e. RMSSD and HF-HRV). Linear mixed-effects models and logistic regression were employed. RESULTS: Results showed consistent associations between both vagally-mediated HRV measures and faster decline in global cognitive function. Specifically, low RMSSD and HF-HRV (lowest versus upper four quintiles) were associated with 0.07 SD (95% CI: -0.13, -0.01) and 0.06 SD (95% CI: -0.12, -0.004) accelerated 10-year cognitive decline after sociodemographic adjustments and faster decline in older ages. Further adjustments for lifestyle factors, medication use and other cardiometabolic conditions did not change the findings. Cognitive decline in individuals with low RMSSD and HF-HRV was estimated to progress 3 and 3.5 years faster per decade, respectively, compared to their counterparts. Additionally, participants with low RMSSD had 37% higher odds of low cognitive function (lowest quintile) at follow-up (OR 1.37: 95% CI,1.03, 1.80). CONCLUSION: Our findings support the aetiological significance of the autonomic nervous system, specifically vagal modulation, in the processes of cognitive decline and neurodegeneration. Low heart rate variability emerges as a potential biomarker indicative of acclerated cognitive decline that may extend over decades.