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 Increased vagal modulation is a mechanism that may partially explain the protective effect of healthy lifestyles. However, it is unclear how healthy lifestyles relate to vagal regulation longitudinally. We prospectively examined associations between a comprehensive measure of 4 important lifestyle factors and vagal modulation, indexed by heart rate variability (HRV) over 10 years. Methods and Results The fifth (1997-1999), seventh (2002-2004), and ninth (2007-2009) phases of the UK Whitehall II cohort were analyzed. Analytical samples ranged from 2059 to 3333 (mean age: 55.7 years). A healthy lifestyle score was derived by giving participants 1 point for each healthy factor: physically active, not smoking, moderate alcohol consumption, and healthy body mass index. Two vagally mediated HRV measures were used: high-frequency HRV and root mean square of successive differences of normal-to-normal R-R intervals. Cross-sectionally, a positively graded association was observed between the healthy lifestyle score and HRV at baseline (Poverall≤0.001). Differences in HRV according to the healthy lifestyle score remained relatively stable over time. Compared with participants who hardly ever adhered to healthy lifestyles, those with consistent healthy lifestyles displayed higher high-frequency HRV (β=0.23; 95% CI, 0.10-0.35; P=0.001) and higher root mean square of successive differences of normal-to-normal R-R intervals (β=0.15; 95% CI, 0.07-0.22; P≤0.001) at follow-up after covariate adjustment. These differences in high-frequency HRV and root mean square of successive differences of normal-to-normal R-R intervals are equivalent to ≈6 to 20 years differences in chronological age. Compared with participants who reduced their healthy lifestyle scores, those with stable scores displayed higher subsequent high-frequency HRV (β=0.24; 95% CI, 0.01-0.48; P=0.046) and higher root mean square of successive differences of normal-to-normal R-R intervals (β=0.15; 95% CI, 0.01-0.29; P=0.042). Conclusions Maintaining healthy lifestyles is positively associated with cardiac vagal functioning, and these beneficial adaptations may be lost if not sustained.

• Klíčová slova
• autonomic nervous system, heart rate variability, lifestyle,
• MeSH
• časové faktory MeSH
• chování snižující riziko * MeSH
• cvičení MeSH
• dospělí MeSH
• hodnocení rizik MeSH
• index tělesné hmotnosti MeSH
• kardiovaskulární nemoci epidemiologie   patofyziologie   prevence a kontrola   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nekuřáci MeSH
• nervus vagus patofyziologie   MeSH
• ochranné faktory MeSH
• pití alkoholu epidemiologie   MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• srdce inervace   MeSH
• srdeční frekvence * MeSH
• zdravotní stav MeSH
• zdravý životní styl * 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 epidemiologie   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