Yueh-Hsiang Huang

Background: Cognitive decline is a common aspect of aging, and identifying modifiable lifestyle factors, such as physical activity and sleep, is crucial for promoting healthy brain aging. While both are individually linked to cognition, few studies have simultaneously assessed their independent and combined effects using objective wearable-based data, particularly in older Asian populations. Objective: This study aimed to examine the independent and interactive effects of wearable-assessed sleep and physical activity parameters on memory performance in healthy older adults. We also explored whether age and hippocampal volume moderated these associations. Methods: This prospective cross-sectional analysis included 88 cognitively healthy community-dwelling adults (≥60 years of age) from the Integrating Systematic Data of Geriatric Medicine to Explore the Solution for Healthy Aging cohort in Taiwan. Participants underwent 12-day wrist-worn actigraphy, brain magnetic resonance imaging, and neuropsychological assessments. Light-intensity physical activity (LPA) and wake after sleep onset (WASO) were selected based on age-adjusted partial correlations with Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery memory scores. Multivariate regressions, age-stratified models (cutoff=72 years), and PROCESS moderation and mediation analyses were conducted, adjusting for age, education, daytime sleepiness, and hippocampal volume. Results: Partial correlation analyses adjusting for age showed that higher LPA (r=0.260; P=.02) and lower WASO (r=–0.251; P=.02) were significantly associated with better memory scores. Age significantly moderated both effects: LPA was beneficial beyond 73.8 years of age, and WASO was detrimental beyond 71.1 years of age. Multivariate regression models confirmed that both WASO (β=–.044; P=.04) and LPA (β=.042; P=.01) were significant predictors of memory. In subgroup analyses (age ≥72 years), both LPA (β=.054; P=.04) and WASO (β=–.111; P=.01) remained significant predictors. Moderated mediation analyses showed that WASO was associated with reduced LPA (β=–.325; P=.03), but the indirect effect on memory via LPA was not significant. Instead, WASO exerted a direct and age-moderated effect on memory performance. Hippocampal volume moderated both associations, supporting the brain reserve hypothesis. Conclusions: Our findings highlight WASO and LPA, as measured by wearable devices, as modifiable behavioral factors linked to memory function in older adults. The impact of these factors intensifies with advancing age and may be influenced by hippocampal reserve. Promoting daily light physical activity and maintaining sleep continuity may serve as accessible, age-tailored strategies for preserving cognitive health in aging populations. Trial Registration: ClinicalTrials.gov NCT04207502; https://classic.clinicaltrials.gov/ct2/show/NCT04207502

BACKGROUND Cognitive decline is a common aspect of aging, and identifying modifiable lifestyle factors, such as physical activity and sleep, is crucial for promoting healthy brain aging. While both are individually linked to cognition, few studies have simultaneously assessed their independent and combined effects using objective wearable-based data, particularly in older Asian populations. OBJECTIVE This study aimed to examine the independent and interactive effects of wearable-assessed sleep and physical activity parameters on memory performance in healthy older adults. We also explored whether age and hippocampal volume moderated these associations. METHODS This prospective cross-sectional analysis included 88 cognitively healthy community-dwelling adults (≥60 years of age) from the Integrating Systematic Data of Geriatric Medicine to Explore the Solution for Healthy Aging cohort in Taiwan. Participants underwent 12-day wrist-worn actigraphy, brain magnetic resonance imaging, and neuropsychological assessments. Light-intensity physical activity (LPA) and wake after sleep onset (WASO) were selected based on age-adjusted partial correlations with Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery memory scores. Multivariate regressions, age-stratified models (cutoff=72 years), and PROCESS moderation and mediation analyses were conducted, adjusting for age, education, daytime sleepiness, and hippocampal volume. RESULTS Partial correlation analyses adjusting for age showed that higher LPA (r=0.260; P=.02) and lower WASO (r=–0.251; P=.02) were significantly associated with better memory scores. Age significantly moderated both effects: LPA was beneficial beyond 73.8 years of age, and WASO was detrimental beyond 71.1 years of age. Multivariate regression models confirmed that both WASO (β=–.044; P=.04) and LPA (β=.042; P=.01) were significant predictors of memory. In subgroup analyses (age ≥72 years), both LPA (β=.054; P=.04) and WASO (β=–.111; P=.01) remained significant predictors. Moderated mediation analyses showed that WASO was associated with reduced LPA (β=–.325; P=.03), but the indirect effect on memory via LPA was not significant. Instead, WASO exerted a direct and age-moderated effect on memory performance. Hippocampal volume moderated both associations, supporting the brain reserve hypothesis. CONCLUSIONS Our findings highlight WASO and LPA, as measured by wearable devices, as modifiable behavioral factors linked to memory function in older adults. The impact of these factors intensifies with advancing age and may be influenced by hippocampal reserve. Promoting daily light physical activity and maintaining sleep continuity may serve as accessible, age-tailored strategies for preserving cognitive health in aging populations. CLINICALTRIAL ClinicalTrials.gov NCT04207502; https://classic.clinicaltrials.gov/ct2/show/NCT04207502

The relationship between inflammatory bowel disease and sleep disturbances is complicated and of increasing interest. We investigated the inflammatory and immunological consequences of EA in sleep-deprived colitis and found that dextran sulfate sodium (DSS)-induced colitis in sleep-fragmented (SF) mice was more severe than that in mice with normal sleep. This increase in the severity of colitis was accompanied by reduced body weight, shortened colon length, and deteriorated disease activity index. DSS with SF mice presented obvious diminished intestinal tight junction proteins (claudin-1 and occludin), elevated proinflammatory cytokines (CRP, IFN-γ, IL-6), lowered melatonin and adiponectin levels, downregulated vasoactive intestinal peptide (VIP) type 1 and 2 receptor (VPAC1, VPAC2) expression, and decreased diversity of gut bacteria. EA ameliorated colitis severity and preserved the performance of the epithelial tight junction proteins and VIP receptors, especially VPAC2. Meanwhile, the innate lymphoid cells-derived cytokines in both group 2 (IL-4, IL5, IL-9, IL-13) and group 3 (IL-22, GM-CSF) were elevated in mice colon tissue. Furthermore, dysbiosis was confirmed in the DSS group with and without SF, and EA could maintain the species diversity. Firmicutes could be restored, such as Lachnospiraceae, and Proteobacteria become rebalanced, mainly Enterobacteriaceae, after EA intervention. On the other hand, SF plays different roles in physiological and pathological conditions. In normal mice, interrupted sleep did not affect the expression of claudin-1 and occludin. But VPAC1, VPAC2, and gut microbiota diversity, including Burkholderiaceae and Rhodococcus, were opposite to mice in an inflamed state.

Rhizoma Coptidis is a popular phytomedicine for the treatment of type 2 diabetes in Asia, but its effective dose for diabetes treatment remains confused because of diverse origins. This study aimed to investigate the dose-response effects of Rhizoma Coptidis extract granules (RCEG), produced with standardized quality control, on hypoglycemic effects in patients with type 2 diabetes. We conducted a retrospective analysis of Chang Gung Research Database from January 01, 2008 to November 30, 2017. Outpatients visiting traditional Chinese medicine clinics and receiving RCEG for type 2 diabetes treatment were included. Plasma glucose, lipid, and other parameters were analyzed from 93 patients with a total of 737 visits within 60 weeks. Scatter plots with the LOESS analysis were used to explore the association between RCEG dose and hypoglycemic effect. The minimal effective dose was chosen to divide the study population into the high-dose and low-dose RCEG groups. Non-parametric tests were used for between-group and within-group comparisons. The multivariate nonlinear mixed-effects model was applied to access the effect of treatment length and groups simultaneously on the change of HbA1c and fasting plasma glucose. The “arule” package in R was used to present the network diagram of RCEG and other co-prescriptions. We first discovered a significant relationship between RCEG dose and HbA1c reduction when the dose reached 0.08 g/kg/day or higher. We thus defined 0.08 g/kg/day of RCEG as the minimum effective dose, and a threshold to separate patients into the high-dose (≥0.08 g/kg/d) and low-dose (<0.08 g/kg/d) RCEG groups. In the high-dose RCEG group, a significant decrease in total cholesterol and a trend toward triglyceride reduction were also noted. Patients more effectively responded to RCEG treatment if they had a higher initial HbA1c level, higher heart rates, better liver function tests, and better tolerance to the higher dose and treatment duration of RCEG. In addition, digestive/tonic/dampness draining formulas and blood regulation recipes were two of the most frequent co-prescriptions with RCEG. This study concluded that RCEG at a dose exceeding 0.08 g/kg/d had beneficial effects on glycemic and lipid control, without showing nephro- or hepatotoxicity, in patients with type 2 diabetes.

Background In Asian countries, many patients with type 2 diabetes fail to achieve controlled glycated hemoglobin (HbA(1c)) levels while taking several classes of oral hypoglycemic agents (OHAs). Traditional Chinese medicine could be an alternative therapeutic option for poorly controlled type 2 diabetes. YH1 is a concentrated Chinese herbal extract formula that combines Rhizoma Coptidis and Shen-Ling-Bai-Zhu-San. This randomized, double-blind, placebo-controlled pilot study evaluated YH1 as an add-on medication for poorly controlled type 2 diabetes. Methods Forty-six patients with poorly controlled type 2 diabetes were randomly assigned 1:1 to the YH1 or placebo group. Before the trial, all subjects had received three or more classes of OHAs with HbA(1c) > 7.0% (53 mmol/mol) and a body mass index >= 23 kg/m(2). During the 12-week trial, participants continued to take OHAs without any dose or medication changes. The primary endpoint was the percentage change in HbA(1c) level. Per-protocol analysis was applied to the final evaluation. Results At week 12, there was an 11.1% reduction in HbA(1c) from baseline and a 68.9% increase in homeostatic model assessment (HOMA) of beta cell function in the YH1 group, which also exhibited significant reductions in two-hour postprandial glucose (-26.2%), triglycerides (-29.5%), total cholesterol (-21.6%), low-density lipoprotein cholesterol (-17.4%), body weight (-0.5%), and waist circumference (-1.1%). The changes in fasting plasma glucose, HOMA insulin resistance and symptom scores were not significantly different between the YH1 and placebo groups. No serious adverse events occurred during this clinical trial. Conclusions This pilot study indicates that YH1 together with OHAs can improve hypoglycemic action and beta-cell function in overweight/obese patients with poorly controlled type 2 diabetes. YH1 is a safe add-on medication for OHAs and has beneficial effects on weight control and lipid metabolism. A larger study population with longer treatment and follow-up periods is required for further verification.

Introduction. The purpose of this study was to determine the influence of Chinese medicine in a Chinese medicine ward (CMW) on weight loss and quality of life in patients with head and neck (HN) cancers during radiotherapy (RT). Methods. From 2006 to 2010, patients with HN cancers hospitalized in the CMW for ≥10 days during RT were included. Outpatients with HN cancers from the Department of Radio-oncology were also enrolled. Body weight was evaluated near the beginning and the end of RT. Quality of life was assessed near the end of RT. Results. Sixty-nine inpatients and 74 outpatients with radiation doses ≥60 Gy were included. Inpatients had significantly lesser weight loss than outpatients (P = .016) during RT or chemoradiation. Patients hospitalized for ≥40 days had lesser weight reduction than those hospitalized for a shorter period (P = .025). In the quality-of-life assessment, inpatients had significantly lower score for the item “lack of appetite” on the M.D. Anderson Symptom Inventory than outpatients (P = .002). Conclusions. Patients with HN cancers receiving hospitalization and Chinese medicine in the CMW had lesser weight loss than outpatients. By monitoring the patient’s condition to adjust the prescription of Chinese medicine, this treatment minimized the weight loss resulting from RT or chemoradiation potentially because of a better functioning of appetite. Patients receiving integrated medicine early showed better results than those starting this treatment later.