Unraveling the brain-heart axis: Mendelian randomization study on the causal relationship between heart rate variability and dementia

Background A growing number of observational studies have suggested a potential association between heart rate variability (HRV) and dementia. However, the causal nature of this relationship remains unclear. Objective This study aims to investigate the causal relationship between HRV and dementia using two-sample Mendelian randomization (MR) analysis. Methods Two-sample MR analysis was conducted to examine the causal effects of HRV phenotypes, including the peak-valley respiratory sinus arrhythmia or high frequency power (pvRSA/HF), the root mean square of the successive differences of inter beat intervals (RMSSD), and normal-to-normal inter-beat intervals (SDNN), on eight dementia phenotypes (any dementia, Alzheimer's disease [AD], early-onset AD, late-onset AD, Lewy body dementia [DLB], frontotemporal dementia [FTD], Parkinson's disease dementia [PDD], and vascular dementia [VaD]). Results Genetically determined pvRSA/HF was associated with an elevated risk of DLB (odds ratio [OR] 1.53; 95% CI 1.04–2.25; p = 0.032) and FTD (OR 2.86; 1.06–7.66; p = 0.037). There was no significant association between HRV and the increased risks of AD, PDD, VaD, or any dementia. Conclusions Our study provides suggestive evidence that pvRSA/HF has a potential causal relationship with elevated risks of DLB and FTD. These findings contribute to a better understanding of the potential role of HRV in specific dementia subtypes.