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The relationship between subjective cognitive decline and frailty, two components of the so-called reversible cognitive frailty, in the elderly remains unclear. This study aims to elucidate whether this association exists, independent of confounding factors such as nutritional status, kidney function, inflammation, and insulin resistance. 2386 participants (≥ 65 years of age) selected from the Healthy Aging Longitudinal Study in Taiwan (HALST) study. Fried frailty phenotype was adopted to quantify frailty status. We classified cognitive status into two categories-subjective cognitive decline (SCD), and normal cognition-and used polytomous logistic regressions to investigate the associations between SCD and frailty. There were 188 (7.88%), 1228 (51.47%), and 970 (40.65%) participants with frailty, pre-frailty, and robustness, respectively. Compared to those with normal cognition, elders with SCD were more likely to have pre-frailty (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.10-1.67, p = 0.004) or frailty (OR: 1.78, 95% CI: 1.23-2.58, p = 0.002) after adjusting for age, gender, education level, comorbidity, nutritional status, kidney function, and biochemical-related factors. A significant association between subjective cognitive decline and frailty was revealed in this study. Subjective cognitive decline was positively associated with pre-frailty or frailty even after adjusting for potential confounding factors. Our results can provide useful references in understanding mechanisms and developing suitable preventive strategies for the elderly with reversible cognitive frailty.

BackgroundThe objective of this study was to evaluate the efficacy and safety of induction chemotherapy (ICT), GOFL (gemcitabine, oxaliplatin plus fluorouracil (5-FU)/leucovorin) versus modified FOLFIRINOX (irinotecan, oxaliplatin plus 5-FU/leucovorin), followed by concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic adenocarcinoma (LAPC).MethodsChemo-naive patients with measurable LAPC were eligible and randomly assigned to receive biweekly ICT with either mFOLFIRINOX or GOFL for 3 months. Patients without systemic progression would have 5-FU- or gemcitabine-based CCRT (5040 cGy/28 fractions) and were then subjected to surgery or continuation of chemotherapy until treatment failure. The primary endpoint was 9-month progression-free survival (PFS) rate.ResultsBetween July 2013 and January 2019, 55 patients were enrolled. After ICT, 21 (77.8%) of 27 patients who received mFOLFIRINOX and 17 (60.7%) of 28 patients who received GOFL completed CCRT. Of them, one and five had per-protocol R0/R1 resection. On intent-to-treat analysis, the 9-month PFS rate, median PFS and overall survival in mFOLFIRINOX and GOFL arms were 30.5% versus 35.9%, 6.6 (95% confidence interval: 5.9–12.5) versus 7.6 months (3.9–12.3) and 19.6 (13.4–22.9) versus 17.9 months (13.4–23.9), respectively. Grade 3–4 neutropenia and diarrhoea during induction mFOLFIRINOX and GOFL were 37.0% versus 21.4% and 14.8% versus 3.6%, respectively.ConclusionInduction GOFL and mFOLFIRINOX followed by CCRT provided similar clinical outcomes in LAPC patients.Clinicaltrial.gov identifierNCT01867892.

ABSTRACTObjectivesTo estimate the risks of depressive symptoms for developing frailty, accounting for baseline robust or pre-frailty status. DesignAn incident cohort study design. SettingCommunity dwellers aged 55 years and above from urban and rural areas in seven regions in Taiwan. ParticipantsA total of 2,717 participants from the Healthy Aging Longitudinal Study in Taiwan (HALST) were included. Subjects with frailty at baseline were excluded. The average follow-up period was 5.9 years. MeasurementsDepressive symptoms were measured by the 20-item Center for Epidemiological Studies Depression (CES-D) Scale. Frailty was assessed using the Fried frailty measurement. Participants were stratified by baseline robust or pre-frailty status to reduce the confounding effects of the shared criteria between depressive symptoms and frailty. Overall and stratified survival analyses were conducted to assess risks of developing frailty as a result of baseline depressive symptoms. ResultsOne hundred individuals (3.7%) had depressive symptoms at baseline. Twenty-seven individuals (27.0%) with depressive symptoms developed frailty, whereas only 305 out of the 2,617 participants (11.7%) without depressive symptoms developed frailty during the follow-up period. After adjusting for covariates, depressive symptoms were associated with a 2.6-fold (95% CI 1.6, 4.2) increased hazard of incident frailty. The patterns of increased hazard were also observed when further stratified by baseline robust or pre-frailty status. ConclusionsDepressive symptoms increased the risk of developing frailty among the older Asian population. The impact of late-life depressive symptoms on physical health was notable. These findings also replicated results from Western populations. Future policies on geriatric public health need to focus more on treatment and intervention against geriatric depressive symptoms to prevent incident frailty among older population.

Background Declines in health, physical, cognitive, and mental function with age suggest a lower level of health-related quality of life (HRQoL) in late life; however, previous studies found that the associations were weak and varied, depending on the study designs and cohort characteristics. Methods The present study examined the paradox of aging in an East Asian context by regressing the age patterns of objective health indicators (physical, cognitive, and mental function), and subjective HRQoL (12-item Short Form, SF-12), on the independent and interactive effects of age and physical function in a cohort study of 5022 community-dwelling adults aged 55 and older in Taiwan. Results Age patterns differed across measures. The SF-12 mental health score (MCS) showed a slight positive association with age and this effect remained stable after controlling for various age-related covariates. The SF-12 physical health score (PCS), in turn, was negatively associated with age. Age differences in PCS were fully explained by age decrements in objective physical health. However, consistent with the so-called paradox of aging, the association between objective and subjective physical health weakened with age. Conclusion These findings add to prior evidence indicating that — in spite of objective health decrements — subjective HRQoL is maintained in later life among Asian Chinese. Also, these paradoxical patterns appear to vary for mental and physical components of HRQoL, and future research is needed to explore the underlying mechanism. Trial registration Healthy Aging Longitudinal Study in Taiwan (HALST) is retrospectively registered at ClinicalTrials.gov on January 24, 2016 with trial registration number NCT02677831 .

Aims/hypothesisAn elevated fasting glucose level in non-diabetic individuals is a key predictor of type 2 diabetes. Genome-wide association studies (GWAS) have identified hundreds of SNPs for fasting glucose but most of their functional roles in influencing the trait are unclear. This study aimed to identify the mediation effects of DNA methylation between SNPs identified as significant from GWAS and fasting glucose using Mendelian randomisation (MR) analyses.MethodsWe first performed GWAS analyses for three cohorts (Taiwan Biobank with 18,122 individuals, the Healthy Aging Longitudinal Study in Taiwan with 1989 individuals and the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance with 416 individuals) with individuals of Han Chinese ancestry in Taiwan, followed by a meta-analysis for combining the three GWAS analysis results to identify significant and independent SNPs for fasting glucose. We determined whether these SNPs were methylation quantitative trait loci (meQTLs) by testing their associations with DNA methylation levels at nearby CpG sites using a subsample of 1775 individuals from the Taiwan Biobank. The MR analysis was performed to identify DNA methylation with causal effects on fasting glucose using meQTLs as instrumental variables based on the 1775 individuals. We also used a two-sample MR strategy to perform replication analysis for CpG sites with significant MR effects based on literature data.ResultsOur meta-analysis identified 18 significant (p < 5 × 10−8) and independent SNPs for fasting glucose. Interestingly, all 18 SNPs were meQTLs. The MR analysis identified seven CpGs near the G6PC2 gene that mediated the effects of a significant SNP (rs2232326) in the gene on fasting glucose. The MR effects for two CpGs were replicated using summary data based on the European population, using an exonic SNP rs2232328 in G6PC2 as the instrument.Conclusions/interpretationOur analysis results suggest that rs2232326 and rs2232328 in G6PC2 may affect DNA methylation at CpGs near the gene and that the methylation may have downstream effects on fasting glucose. Therefore, SNPs in G6PC2 and CpGs near G6PC2 may reside along the pathway that influences fasting glucose levels. This is the first study to report CpGs near G6PC2, an important gene for regulating insulin secretion, mediating the effects of GWAS-significant SNPs on fasting glucose.

Frail older adults are vulnerable to stressors; thus, sleep related cognition impairment might more greatly affect frail than healthy older adults. In the present study, we investigated whether the association between sleep problems and cognition varies with physical frailty status (modified from Fried et al.). Participants 55 years and older who completed a baseline and follow-up questionnaire (median follow-up: 5.5 years), were included in the analysis. Sleep parameters were evaluated in an interview at the baseline. Cognitive decline was defined as a loss of 3 or more points on the Mini-Mental State Examination (MMSE) at follow-up. Associations between sleep problems and cognitive decline were examined using logistic regression and were stratified by baseline physical frailty status, adjusted for potential confounders. A short total sleep duration (< 5 vs. 7–9 h, odds ratio (OR) = 1.88, 95% confidence interval (CI) 1.18–3.00), excessive daytime sleepiness (OR = 1.49, 95% CI 1.04–2.13), low sleep efficiency (< 65% vs. ≥ 85%, OR = 1.62, 95% CI 1.07–2.46), and insomnia complaints (OR = 2.34, 95% CI 1.23–4.43) were associated with MMSE decline in physically robust. The association was stronger for the sleep summary score, which summarized abnormal sleep duration, excessive daytime sleepiness, and insomnia complaints ( ≥ 2 vs. 0, OR = 3.79, 95% CI 2.10–6.85, p < 0.0001). Due to the low prevalence of frailty in this community-dwelling population, the statistical power to detect an association was low. More evidence is needed to clarify the role of sleep in the progression of cognitive decline in frail individuals.

By means of a combination of genome-wide and follow-up studies, recent large-scale association studies of populations of European descent have now identified over 46 loci associated with coronary artery disease (CAD). As part of the TAICHI Consortium, we have collected and genotyped 8556 subjects from Taiwan, comprising 5423 controls and 3133 cases with coronary artery disease, for 9087 CAD SNPs using the CardioMetaboChip. We applied penalized logistic regression to ascertain the top SNPs that contribute together to CAD susceptibility in Taiwan. We observed that the 9p21 locus contributes to CAD at the level of genome-wide significance (rs1537372, with the presence of C, the major allele, the effect estimate is -0.216, standard error 0.033, p value 5.8x10-10). In contrast to a previous report, we propose that the 9p21 locus is a single genetic contribution to CAD in Taiwan because: 1) the penalized logistic regression and the follow-up conditional analysis suggested that rs1537372 accounts for all of the CAD association in 9p21, and 2) the high linkage disequilibrium observed for all associated SNPs in 9p21. We also observed evidence for the following loci at a false discovery rate >5%: SH2B3, ADAMTS7, PHACTR1, GGCX, HTRA1, COL4A1, and LARP6-LRRC49. We also took advantage of the fact that penalized methods are an efficient approach to search for gene-by-gene interactions, and observed that two-way interactions between the PHACTR1 and ADAMTS7 loci and between the SH2B3 and COL4A1 loci contribute to CAD risk. Both the similarities and differences between the significance of these loci when compared with significance of loci in studies of populations of European descent underscore the fact that further genetic association of studies in additional populations will provide clues to identify the genetic architecture of CAD across all populations worldwide.

Background: Obesity is a global health challenge associated with metabolic and cardiovascular diseases. Traditional Chinese Medicine (TCM) body constitution theory offers a unique perspective on individual susceptibility to obesity; however, its integration into public health strategies remains underexplored. Objective: To examine the associations between vegetarian dietary patterns, TCM body constitution types (Phlegm stasis, Yang deficiency, and Yin deficiency), and overweight/obesity in a large-scale national cohort. Methods: Data were obtained from 3597 participants enrolled in the Taiwan Biobank. Socio-demographic variables, lifestyle behaviors (diet, smoking, physical activity), and anthropometric indicators (BMI and waist circumference) were assessed. Participants were categorized by weight status and TCM body constitution. Polytomous logistic regression models were used to evaluate associations between vegetarian dietary patterns, constitution types, and overweight/obesity, adjusting for potential confounders. Results: Among participants (mean age, 50.1 ± 9.4 years), 55.6% had normal BMI, 27.3% were overweight, and 17.1% were obese. Vegetarian dietary patterns were significantly associated with lower odds of Phlegm stasis (OR: 0.96; p < 0.001), Yang deficiency (OR: 0.97; p < 0.001), and Yin deficiency (OR: 0.97; p < 0.001), as well as with lower odds of overweight (OR: 0.72; p < 0.05) and obesity (OR: 0.67; p < 0.05). Physical activity was also associated with lower odds of all three constitution types and obesity. Phlegm stasis constitution was associated with higher odds of obesity (range of ORs: 1.18–1.58; p < 0.001). Conclusions: Vegetarian dietary patterns and regular physical activity were associated with lower odds of obesity and TCM constitution imbalances, particularly Phlegm stasis. These findings suggest a potential role for constitution-informed strategies in obesity-related public health approaches. Longitudinal studies are warranted to clarify temporal relationships and mechanisms. Clinical Trials Registration: ClinicalTrials.gov NCT03938207 (Study Start: 1 October 2022).

Background Fasting glucose and fasting insulin are glycemic traits closely related to diabetes, and understanding the role of genetic factors in these traits can help reveal the etiology of type 2 diabetes. Although single nucleotide polymorphisms (SNPs) in several candidate genes have been found to be associated with fasting glucose and fasting insulin, copy number variations (CNVs), which have been reported to be associated with several complex traits, have not been reported for association with these two traits. We aimed to identify CNVs associated with fasting glucose and fasting insulin. Results We conducted a genome-wide CNV association analysis for fasting plasma glucose (FPG) and fasting plasma insulin (FPI) using a family-based genome-wide association study sample from a Han Chinese population in Taiwan. A family-based CNV association test was developed in this study to identify common CNVs (i.e., CNVs with frequencies ≥ 5%), and a generalized estimating equation approach was used to test the associations between the traits and counts of global rare CNVs (i.e., CNVs with frequencies <5%). We found a significant genome-wide association for common deletions with a frequency of 5.2% in the Scm-like with four mbt domains 1 ( SFMBT1 ) gene with FPG (association p -value = 2×10 −4 and an adjusted p -value = 0.0478 for multiple testing). No significant association was observed between global rare CNVs and FPG or FPI. The deletions in 20 individuals with DNA samples available were successfully validated using PCR-based amplification. The association of the deletions in SFMBT1 with FPG was further evaluated using an independent population-based replication sample obtained from the Taiwan Biobank. An association p -value of 0.065, which was close to the significance level of 0.05, for FPG was obtained by testing 9 individuals with CNVs in the SFMBT1 gene region and 11,692 individuals with normal copies in the replication cohort. Conclusions Previous studies have found that SNPs in SFMBT1 are associated with blood pressure and serum urate concentration, suggesting that SFMBT1 may have functional implications in some metabolic-related traits.

Vegetarian diets have been shown to improve glucose metabolism and reduce risk for diabetes in Westerners but whether Chinese vegetarian diets have the same benefits is unknown. We evaluated the association between diet and diabetes/impaired fasting glucose (IFG) among 4384 Taiwanese Buddhist volunteers and identified diabetes/IFG cases from a comprehensive review of medical history and fasting plasma glucose. Vegetarians had higher intakes of carbohydrates, fiber, calcium, magnesium, total and non-heme iron, folate, vitamin A, and lower intakes of saturated fat, cholesterol, and vitamin B12. Besides avoiding meat and fish, vegetarians had higher intakes of soy products, vegetables, whole grains, but similar intakes of dairy and fruits, compared with omnivores. The crude prevalence of diabetes in vegetarians versus omnivores is 0.6% versus 2.3% in pre-menopausal women, 2.8% versus 10% in menopausal women, and 4.3% versus 8.1% in men. Polytomous logistic regression adjusting for age, body mass index, family history of diabetes, education, leisure time physical activity, smoking and alcohol, showed that this vegetarian diet was negatively associated with diabetes and IFG in men (OR for diabetes: 0.49, 95% CI: 0.28-0.89; OR for IFG: 0.66, 95% CI: 0.46-0.95); in pre-menopausal women (OR for diabetes: 0.26, 95% CI: 0.06-1.21; OR for IFG: 0.60, 95% CI: 0.35-1.04); and in menopausal women (OR for diabetes: 0.25, 95% CI: 0.15-0.42; OR for IFG: 0.73, 95% CI: 0.56-0.95). We found a strong protective association between Taiwanese vegetarian diet and diabetes/IFG, after controlling for various potential confounders and risk factors.