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.

• Keywords
• Aetiological significance, Autonomic nervous system, Cognitive decline, Heart rate variability, Longitudinal cohort studies,
• Publication type
• Journal Article MeSH

PURPOSE: Memory plays an essential role in daily life and is one of the first functions to deteriorate in cognitive impairment and dementia. Transcutaneous vagus nerve stimulation (tVNS) is a promising therapeutic method; however, its ability to enhance memory is underexplored, especially considering long-term stimulation. We aimed to investigate the effect of a 2-week course of auricular tVNS (taVNS) on memory in a non-clinical population. METHODS: This single-blind randomized placebo-wait-list controlled trial recruited 76 participants (30 men; mean age 48.32 years) and randomized them into four groups: early active/sham taVNS and late active/sham taVNS. Participation in the study lasted 4 weeks; early groups underwent 2 weeks intervention immediately following the first study site visit (days 0-13) and late groups 2 weeks after the first study site visit (days 14-27). Active and sham taVNS included 2 weeks of daily 4-h neurostimulation at the tragus or earlobe, respectively. To assess memory, we used the Rey Auditory Verbal Learning Test. RESULTS: Two weeks of active taVNS, but not sham taVNS, improved immediate recall and short-term memory score both in early and late groups. Furthermore, the improvements persisted over subsequent follow-up in early active taVNS. Importantly, the effect of active taVNS was superior to sham for immediate recall in both early and late groups. There were no statistical differences in delayed recall. CONCLUSION: Our findings suggest that taVNS has potential to improve memory, particularly immediate recall, and may be an effective method in preventing memory loss and mitigating cognitive aging.

• Keywords
• Immediate recall, Memory, Memory modulation, Transcutaneous vagus nerve stimulation, Vagus nerve,
• MeSH
• Adult MeSH
• Single-Blind Method MeSH
• Middle Aged MeSH
• Humans MeSH
• Memory * physiology   MeSH
• Transcutaneous Electric Nerve Stimulation * methods   MeSH
• Vagus Nerve Stimulation * methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH