Metformin and the risk of dementia based on an analysis of 396,332 participants.

Background: AMPK has attracted widespread interest as a potential therapeutic target for age-related diseases, given its key role in controlling energy homeostasis. Metformin (Met) has historically been used to treat Type 2 diabetes and has been shown to counteract age-related diseases. However, studies regarding the relationship between Met and a variety of age-related classifications of cognitive decline have reported mixed findings. Objective: To assess the potential effect of Met on the onset of dementia and discuss the possible biological mechanisms involved. Methods: This study was registered in the PROSPERO database (CRD420201251468). PubMed, Embase, and Cochrane Library were searched from inception to 25 May 2021, for population-based cohort studies. Effect estimates with 95% confidence intervals (CIs) were pooled using the random-effects model. Meta-regression and subgroup analyses were performed to explore sources of heterogeneity and the stability of the results. Results: Fourteen population-based cohort studies (17 individual comparisons) involving 396,332 participants were identified. Meta-analysis showed that Met exposure was significantly associated with reduced risk of all subtypes of dementias [relative risk (RR) = 0.79, 95% CI = 0.68-0.91; p < 0.001]. Conversely, no significant reduction in risk was observed for those who received Met monotherapy at the onset of vascular dementia (VD), Parkinson's disease (PD), and Alzheimer's disease (AD). The effect was more prominent in patients who had long-term Met exposure (⩾4 years) (RR = 0.38, 95% CI = 0.32-0.46; p < 0.001), while no such significant effect was found with short-term Met exposure (1-2 years) (RR = 1.20, 95% CI = 0.87-1.66; p < 0.001). Moreover, no association was observed for Met exposure in participants of European descent (RR = 1.01, 95% CI = 0.66-1.54; p = 0.003) compared with those from other countries. Conclusion: Based on the evidence from population-based cohort studies, our findings suggest that the AMPK activator, Met, is a potential geroprotective agent for dementias, particularly among long-term Met users. Due to the significant heterogeneity among the included studies, we should interpret the results with caution.

Social support and mental health among health care workers during Coronavirus Disease 2019 outbreak: A moderated mediation model.

PURPOSES: During the outbreak of Coronavirus Disease 2019 (COVID-19) all over the world, the mental health conditions of health care workers are of great importance to ensure the efficiency of rescue operations. The current study examined the effect of social support on mental health of health care workers and its underlying mechanisms regarding the mediating role of resilience and moderating role of age during the epidemic. METHODS: Social Support Rating Scale (SSRS), Connor-Davidson Resilience scale (CD-RISC) and Symptom Checklist 90 (SCL-90) were administrated among 1472 health care workers from Jiangsu Province, China during the peak period of COVID-19 outbreak. Structural equation modeling (SEM) was used to examine the mediation effect of resilience on the relation between social support and mental health, whereas moderated mediation analysis was performed by Hayes PROCESS macro. RESULTS: The findings showed that resilience could partially mediate the effect of social support on mental health among health care workers. Age group moderated the indirect relationship between social support and mental health via resilience. Specifically, compared with younger health care workers, the association between resilience and mental health would be attenuated in the middle-aged workers. CONCLUSIONS: The results add knowledge to previous literature by uncovering the underlying mechanisms between social support and mental health. The present study has profound implications for mental health services for health care workers during the peak period of COVID-19.

Serum free Fatty acids and glucose metabolism, insulin resistance in schizophrenia with chronic antipsychotics.

BACKGROUND: Weight gain and type 2 diabetes mellitus (DM) are often linked to antipsychotics treatment. The aim of the study is to investigate serum free fatty acids (FFA) levels in schizophrenic patients who received long-term antipsychotics treatment, and to explore the associations between serum FFA and fasting blood glucose, and insulin resistance. METHODS: 308 inpatients with schizophrenia who met with the criteria of DSM-IV were recruited into this study, and were divided into four groups: control subjects, single obesity, impaired glucose tolerance (IGT) and type 2 DM according to different body mass index, fasting blood glucose level and 2-hour postprandial blood glucose. Serum FFA was measured with colorimetry. Serum insulin and leptin were measured with radioimmunoassay respectively. RESULTS: There was a significant elevation in serum FFA levels in schizophrenic patients who received long-term antipsychotics treatment, especially in single obesity, IGT, and DM groups. The elevated serum FFA was remarkably positive correlated with fasting blood glucose and insulin resistance. CONCLUSIONS: The study suggested the elevated serum FFA in schizophrenic patients with long-term antipsychotics treatment affected the blood glucose metabolism, may have played an important role in insulin resistance and type 2 DM, and was also an important trait of metabolic syndromes.