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March 13, 2026Journal of Alzheimer s Disease Reports0 citationsOpen Access

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

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SLSongbiao LiYZYan ZhangLKLi Kou

Key Result

Genetically determined peak-valley respiratory sinus arrhythmia was associated with increased risks of Lewy body dementia (OR 1.53) and frontotemporal dementia (OR 2.86).

Key Points

  • This study aims to determine whether heart rate variability (HRV) has a causal effect on dementia risk.
  • Conducted a two-sample Mendelian randomization analysis.
  • Examined the effects of HRV phenotypes on eight dementia types.
  • Utilized measures like peak-valley respiratory sinus arrhythmia, RMSSD, and SDNN.
  • Genetically determined pvRSA/HF was linked to a higher risk of Lewy body dementia with an odds ratio of 1.53.
  • Found a significant association with frontotemporal dementia, yielding an odds ratio of 2.86.
  • No significant relationships were observed for Alzheimer's disease, Parkinson's disease dementia, or vascular dementia.

Structured PICO

Does genetically determined heart rate variability affect the risk of dementia subtypes?

P
Population
Genetic datasets for 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])
I
Intervention
Genetically determined heart rate variability (HRV) phenotypes (peak-valley respiratory sinus arrhythmia or high frequency power [pvRSA/HF], root mean square of the successive differences of inter beat intervals [RMSSD], and normal-to-normal inter-beat intervals [SDNN])
O
Outcome
Risk of eight dementia phenotypes (any dementia, AD, early-onset AD, late-onset AD, DLB, FTD, PDD, and VaD)hard clinical

Genetically determined high frequency heart rate variability (pvRSA/HF) is associated with an increased risk of Lewy body dementia and frontotemporal dementia.

Abstract

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.

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Cite This Study

Li et al. (2026) studied this question. Genetically determined peak-valley respiratory sinus arrhythmia was associated with increased risks of Lewy body dementia (OR 1.53) and frontotemporal dementia (OR 2.86).

synapsesocial.com/papers/69b3ac8102a1e69014cce455https://doi.org/10.1177/25424823261431319
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