BACKGROUND: Altered autonomic modulation, measured by heart rate variability (HRV), has been found to be associated with dementia risk in the elderly. However, long-term follow-up study evaluating the association between autonomic modulation from middle-age and the incidence of dementia has been limited.
METHODS: This retrospective cohort analyzed data from Taiwan\'s National Health Insurance Database covering the period from 2001 to 2017, with a linkage to citywide health examinations conducted by Tainan Metropolitan City, Taiwan. We included subjects aged 45-64 years. The mean follow-up period was 15.75 ± 3.40 years. The measurements of HRV included resting heart rate, high frequency (HF), low frequency (LF), standard deviation of normal-to-normal R-R intervals (SDNN), ratio between the 30th and 15th R-R interval after standing up from the supine position (30/15 ratio), ratio between the R-R intervals during expiration and inspiration, and the ratio between the high- and low-frequency components (LF/HF). The main study outcome was the incidence of dementia. We performed multivariable Cox proportional hazard regression models to compare the risk of dementia among different HRV subgroups.
RESULTS: We included 565 participants with a mean age of 53 (SD: 6) years, of whom 44% were male. The risk of dementia was significantly increased in association with lower parasympathetic HRV modulation, including SDNN (HR: 3.23, 95% CI: 1.55-6.73) and 30/15 ratio (HR: 3.52, 95%CI: 1.67-7.42). Moreover, the risk of dementia was increased in subjects with higher LF/HF ratios (HR: 2.05, 95% CI: 1.12-3.72).
CONCLUSIONS: Lower parasympathetic activity and higher sympathetic-vagal imbalance in middle-age were associated with dementia risk.

Heart rate variability (HRV) has been used to explore the parasympathetic activity of individuals with problematic Internet use (PIU), but the results are controversial. We conducted a systematic review and meta-analysis of studies comparing HRV in PIU individuals and healthy participants from several databases. HRV was analyzed according to the parasympathetic activity in hierarchical order (primary analysis), and the total variability (secondary analysis). The baseline HRV and HRV reactivity were both considered. Of the 106 studies screened, 12 were included in the quantitative analysis. Significant differences were observed for baseline HRV in PIU individuals compared to the controls. Regarding HRV reactivity, PIU individuals did not have a significantly lower HRV value during pleasant or unpleasant stimuli. In summary, PIU individuals and healthy subjects had significantly different resting state parasympathetic activity. The finding of HRV reactivity in PIU individuals awaits further investigation.

Forest environment has many health benefits, and negative air ions (NAI) is one of the major forest environmental factors. Many studies have explored the effect of forest environment on cardiac autonomic nervous function, while forest NAI in the among function and the underlying mechanism still remain unclear. To explore the associations and molecular linkages between short-term exposure to forest NAI and heart rate variability (HRV), a repeated-measure panel study was conducted among 31 healthy adults. Participants were randomly selected to stay in a forest park for 3 days and 2 nights. Individual exposures including NAI were monitored simultaneously and HRV indices were measured repeatedly at the follow-up period. Urine samples were collected for non-targeted metabolomics analysis. Mixed-effect models were adopted to evaluate associations among NAI, HRV indices and metabolites. The median of NAI concentration was 68.11 (138.20) cm-3 during the study period. Short-term exposure to forest NAI was associated with the ameliorative HRV indices, especially the excitatory parasympathetic nerve. For instance, per interquartile range increase of 5-min moving average of NAI was associated with 9.99 % (95%CI: 8.95 %, 11.03 %) increase of power in high frequency. Eight metabolites were associated with NAI exposure. The down-regulated tyrosine metabolism was firstly observed, followed by other amino acid metabolic alterations. The NAI-related metabolic changes reflect the reduction of inflammation and oxidative stress. HRV indices were associated with 25 metabolites, mainly including arginine, proline and histidine metabolism. Short-term exposure to forest NAI is beneficial to HRV, especially to the parasympathetic nerve activity, by successively disturbing different metabolic pathways which mainly reflect the increased anti-inflammation and the reduced inflammation. The results will provide epidemiological evidences for developing forest therapy and improving cardiac autonomic nervous function.

OBJECTIVE: Patients with anxiety disorders (AD) have been found to have lower heart rate variability (HRV) than healthy individuals in some studies, but this was inconsistent. Furthermore, the influence of distinct diagnoses, study design, and demographic factors on the results was not comprehensively examined.
METHODS: We gathered studies comparing HRV in patients with AD and in healthy controls. The parasympathetic activity in the hierarchical order principle was adopted in the main analysis. We adopted the random effects model to calculate the standardized mean difference.
RESULTS: Of the 7805 screened studies, 99 were included in the quantitative analysis, with a total of 4897 AD patients and 5559 controls finally entered the meta-analysis. AD patients had a significantly lower resting-state HRV for parasympathetic activity compared to control (Hedges\' g = -0.3897). For the diagnostic subgroup analysis relative to the controls, resting-state HRV was significantly lower in post-traumatic stress disorder, panic disorder, generalized anxiety disorder, and social anxiety disorder patients. HRV reactivity (all reactivity data, data on physiological challenge, and psychological challenge) did not show significant inter-group differences between AD patients and healthy subjects.
CONCLUSIONS: The results supported that patients with AD had significantly lower resting-state HRV than the healthy population, but no alterations were found for HRV reactivity.

Heart rate variability, a quantitative measure of mainly parasympathetic activity, has been applied in evaluating many types of psychiatric and neurological disorders, including dementia (or neurocognitive disorders). However, although dementia patients often showed significantly lower heart rate variability (various indices) than healthy controls, and different types of dementia had distinct heart rate variability features, the results were not identical across studies. We designed a systematic review and meta-analysis for incorporating data from different studies.
We gathered studies comparing heart rate variability in patients with dementia and in healthy controls. Heart rate variability was analysed in several ways: parasympathetic function in hierarchical order (main analysis), total variability, comparison of heart rate variability between different subtypes of dementia, specific indices of heart rate variability and heart rate variability reactivity.
In the initial search, we found 3425 relevant articles, from which 24 studies with a total of 1107 dementia patients and 1017 control participants finally entered the main meta-analysis. The dementia patients had a significantly lower resting heart rate variability for parasympathetic function (Hedges\' g = -0.3596, p = 0.0002) and total variability (Hedges\' g = -0.3059, p = 0.0002) than the controls. For diagnostic subgroup analysis relative to the controls, heart rate variability was significantly lower in patients with mild cognitive impairment (Hedges\' g = -0.3060) and in patients with dementia with Lewy bodies (Hedges\' g = -1.4154, p < 0.0001). Relative to patients with Alzheimer\'s disease, heart rate variability in patients with dementia with Lewy bodies was significantly lower (Hedges\' g = -1.5465, p = 0.0381). Meta-regression revealed that gender proportion was significantly associated with effect size.
Our results show that dementia patients (especially those with dementia with Lewy bodies and mild cognitive impairment) have lower parasympathetic activity than healthy people. The influence of gender on the results should be carefully interpreted.

BACKGROUND: A growing body of literature has reported that a history of pre-eclampsia (PE) increases a woman\'s long-term risk of cardiovascular diseases (CVD). Autonomic nervous system dysfunction was found to be significant in this specific population, but most studies observed the role of sympathetic over-activation. The aim of this study was to assess whether parasympathetic impairment was involved in women 1 year after PE, and heart rate recovery (HRR) was used to represent parasympathetic tone.
METHODS: 47 women with previous PE (PE group) and 58 women with a healthy pregnancy (control group) were examined. Blood pressure levels, lipid profiles, homeostasis model assessment of insulin resistance (HOMA-IR), inflammatory biomarkers and HRR were compared between the two groups, and the association between the biochemical parameters and HRR in the PE group was evaluated.
RESULTS: Compared with the Control group, body mass index, 24-h mean diastolic blood pressure, low-density lipoprotein cholesterol and Ln(HOMA-IR) were higher, and HRR was slower in the PE group. Furthermore, body mass index, total cholesterol, and Ln(HOMA-IR) were independent determinants of HRR in the PE group according to multiple regression analysis.
CONCLUSIONS: Our findings suggest that parasympathetic impairment is involved in this specific female population, and its close association with body mass index, total cholesterol and insulin resistance might contribute to an increased risk of CVD development in women with PE history.

To study the dominant role of parasympathetic inputs at cellular level of baroreflex afferent pathway and underlying mechanism in neurocontrol of blood pressure regulation.
Whole-cell patch-clamp and animal study were conducted.
For the first time, we demonstrated the spontaneous activities from resting membrane potential in myelinated A- and Ah-type baroreceptor neurons (BRNs, the 1st-order), but not in unmyelinated C-types, using vagus-nodose slice of adult female rats. These data were further supported by the notion that the spontaneous synaptic currents could only be seen in the pharmacologically and electrophysiologically defined myelinated A- and Ah-type baroreceptive neurons (the 2nd-order) of NTS using brainstem slice of adult female rats. The greater frequency and the larger amplitude of the spontaneous excitatory postsynaptic currents (EPSCs) compared with the inhibitory postsynaptic currents (IPSCs) were only observed in Ah-types. The ratio of EPSCs:IPSCs was estimated at 3:1 and higher. These results confirmed that the afferent-specific spontaneous activities were generated from baroreflex afferent pathway in female-specific subpopulation of myelinated Ah-type BRNs in nodose and baroreceptive neurons in NTS, which provided a novel insight into the dominant role of sex-specific baroreflex-evoked parasympathetic drives in retaining a stable and lower blood pressure status in healthy subjects, particularly in females.
The data from current investigations establish a new concept for the role of Ah-type baroreceptor/baroreceptive neurons in controlling blood pressure stability and provide a new pathway for pharmacological intervention for hypertension and cardiovascular diseases.