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.

• Klíčová slova
• Aetiological significance, Autonomic nervous system, Cognitive decline, Heart rate variability, Longitudinal cohort studies,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: No study to date has investigated longitudinal trajectories of cardiac autonomic modulation changes with aging; therefore, we lack evidence showing whether these changes occur naturally or are secondary to disease or medication use. This study tested whether heart rate variability (HRV) trajectories from middle to older age are largely normative or caused by pathological changes with aging in a large prospective cohort. We further assessed whether HRV changes were modified by socioeconomic status, ethnicity, or habitual physical activity. METHODS AND RESULTS: This study involved 3176 men and 1238 women initially aged 44 to 69 years (1997-1999) from the UK Whitehall II population-based cohort. We evaluated time- and frequency-domain HRV measures of short-term recordings at 3 time points over a 10-year period. Random mixed models with time-varying covariates were applied. Cross-sectionally, HRV measures were lower for men than for women, for participants with cardiometabolic conditions, and for participants reporting use of medications other than beta blockers. Longitudinally, HRV measures decreased significantly with aging in both sexes, with faster decline in younger age groups. HRV trajectories were not explained by increased prevalence of cardiometabolic problems and/or medication use. In women, cardiometabolic problems were associated with faster decline in the standard deviation of all intervals between R waves with normal-to-normal conduction, in low-frequency HRV, and in low-frequency HRV in normalized units. Socioeconomic status, ethnicity, and habitual physical activity did not have significant effects on HRV trajectories. CONCLUSIONS: Our investigation showed a general pattern and timing of changes in indices of cardiac autonomic modulation from middle to older age. These changes seem likely to reflect the normal aging process rather than being secondary to cardiometabolic problems and medication use.

• Klíčová slova
• cardiac autonomic modulation, epidemiology, ethnicity, longitudinal trajectory, normative aging, socioeconomic status,
• MeSH
• autonomní nervový systém fyziologie   MeSH
• cvičení MeSH
• dospělí MeSH
• etnicita MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• socioekonomické faktory MeSH
• srdce inervace   MeSH
• srdeční frekvence * MeSH
• stárnutí * MeSH
• věkové faktory MeSH
• zdravotní stav MeSH
• zvyky MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Londýn MeSH