The associations of osteoporosis and possible sarcopenia with disability, nutrition, and cognition in community-dwelling older adults.

BACKGROUND: Osteoporosis and sarcopenia, respectively, have detrimental impact on health, and combination of both conditions, termed osteosarcopenia, is becoming an increasingly important disorder in older adults as populations age. This study aimed to explore the relationship between osteoporosis and possible sarcopenia and their joint effect on physical performance, nutritional status, and cognition in community-dwelling older adults. METHODS: This study was conducted at a medical center in Taiwan, which included the adjacent community care station. The participants were recruited through regular activities at the community care station between January 01, 2015 and February 28, 2022. During the study period, dual-energy X-ray absorptiometry and comprehensive geriatric assessment consisting of comorbidity burden, functional status, cognition, mood, and nutritional status were performed during the study period. Possible sarcopenia was identified utilizing the criteria set by the Asian Working Group on Sarcopenia in 2019 using the criteria of low muscle strength alone, and osteoporosis was defined by the World Health Organization criteria. Accordingly, the study subjects were divided into four groups: normal, only osteoporosis, only possible sarcopenia, and possible osteosarcopenia. RESULTS: There were 337 participants (68.6% female) with a median age of 78.0 years (interquartile range: 71.0-85.0 y/o). According to the clinical definition of osteosarcopenia, 78 participants were normal, 69 participants showed possible sarcopenia, 61 participants had osteoporosis, and 129 had osteoporosis with possible sarcopenia. Among the four groups, the prevalence rates of chronic illness, functional capacity, physical performance, cognitive impairment, and malnutrition revealed statistically significant differences. Using logistic regression analysis after adjusting for the other covariates, osteoporosis with possible sarcopenia was associated with an increased odds ratio of cognitive impairment. CONCLUSIONS: The findings suggest that compared to osteoporosis or possible sarcopenia alone, osteoporosis with possible sarcopenia was more likely to be associated with cognitive impairment. Early identification and targeted interventions for cognitive impairment in older adults with osteosarcopenia may be valuable in maintaining cognitive well-being and overall quality of life.

Gender-specific linkages: frailty, polypharmacy, anti-cholinergic burden, and 5-year mortality risk-a real-world analysis.

Background: With higher age, frailty escalates the risk of falls, unexpected physical dysfunction, hospitalization, and mortality. Polypharmacy in the older population is a major challenge that not only increases medical costs, but also may worsen the risk of hospitalization and death. More importantly, the properties of anti-cholinergic drugs contribute various negative effects. This study aimed to investigate the sex difference in the association of polypharmacy, anticholinergic burden, and frailty with mortality. Methods: Participants older than 65 years who attended the geriatric outpatient clinic of the study center between January 2015 and July 2020 were invited to participate in this retrospective study. Comprehensive geriatric assessment data were collected and the phenotype of frailty was determined by Fried's criteria. Cox regression and the Kaplan-Meier curve were used to identify risk factors of 5-year survival along with intergroup differences in the risks. Results: Of the 2,077 participants, 47.5% were female. The prevalence of frailty and the rate of polypharmacy were 44.7% and 60.6%, respectively. Higher age, male sex, low body mass index, low Mini-Mental State Examination scores, low activities of daily living, frailty status, polypharmacy, and a high Charlson Comorbidity Index score, and greater anticholinergic burden were significant risk factors that were associated with the 5-year all-cause mortality. Male patients with frailty exhibited the highest risks of mortality compared with male patients without frailty and female patients with or without frailty. Polypharmacy was significantly associated with a higher 5-year mortality rate in the frail male group compared with the non-frail male. In frail female group, individuals with a higher anticholinergic burden (as indicated by the Anticholinergic Cognitive Burden Scale) from drug usage exhibited an elevated 5-year mortality rate. Conclusions: Polypharmacy and greater anticholinergic burden, synergistically interacted with frailty and intensified the 5-year mortality risk in a gender-specific manner. To mitigate mortality risks, clinicians should prudently identify polypharmacy and anticholinergic burden in the older population.

Prefrailty subtypes differentially predict 5-year mortality in the functionally independent geriatric population.

INTRODUCTION: Both frailty and prefrailty (PF) are related to mortality. However, there is no consensus about the PF subtypes for prediction of the mortality risk. We aimed to compare the 5-year mortality of functionally independent geriatric outpatients with nonfrailty, different PF subtypes and frailty. METHODS: This was a single-center, retrospective cohort study. Community-dwelling older adults who visited the geriatric outpatient clinic in a healthcare institution in Taiwan were enrolled. PF1 was defined based on exhaustion and/or body weight loss whereas PF2 was defined by one or two of the following criteria: weakness, slowness, and low physical activity. Frailty was defined by three or more above criteria. Demographics and results of comprehensive geriatric assessment were compared and Kaplan-Meier survival analysis was used to determine the 5-year survival among the nonfrail, PF1, PF2 and frail groups. RESULTS: Of the 982 participants, the proportion of PF and frailty was high (PF 45.7% and frailty 24.5%). The cumulative 5-year survival rate of the nonfrail group, PF1, PF2 subgroups and frail group was 98.6%, 95.8%, 89.1% and 81.3% respectively. Age, male sex, PF2 subtype and frailty were significantly associated with 5-year mortality [hazard ratio (95% confidence interval) 1.05 (1.01-1.08), 1.96 (1.08-3.57), 5.18 (1.57-17.09), and 6.87 (2.05-23.04), respectively]. DISCUSSION AND CONCLUSION: The proportion of PF and frailty was high in old outpatient population with functional independence. PF2 subtypes and frailty could influence the 5-year mortality risk in these participants. Identifying PF2 participants earlier and instituting prompt intervention may be beneficial in older patients.

Impact of Daycare Service Interruption during COVID-19 Pandemic on Physical and Mental Functions and Nutrition in Older People with Dementia.

This study evaluated changes of cognitive, physical, and nutritional status before and after the interruption and resumption of daycare services during the COVID-19 pandemic in older dementia people in a daycare center. Comprehensive geriatric assessment data were analyzed before and after the lockdown of daycare center services, including mini-mental state examination, activities of daily living (ADL) scores, mini-nutritional assessment-short forms (MNA-SF), and timed up-and-go (TUG) tests. Among 19 dementia people participating in daycare services, 17 participants were enrolled in the study with, finally, two excluded because of incomplete follow-ups. They had a median age of 81 years; their MNA-SF scores and TUG values deteriorated significantly after a 3-month closure of daycare services (p < 0.05), and after resumption of daycare services the MNA-SF scores and TUG values recovered to near the pre-lockdown levels (p < 0.05). Besides, baseline ADL scores predicted a decline and recovery of TUG and MNA-SF values. Our findings suggest that planning continuous support for older dementia adults is important for daycare facilities during COVID-19 pandemic confinement.

Effect of tissue inhibitor of metalloproteinases-3 genetics polymorphism on clinicopathological characteristics of uterine cervical cancer patients in Taiwan.

Single nucleotide polymorphisms (SNPs) of tissue inhibitor of metalloproteinases-3 (TIMP-3) have been revealed to be related to various cancers. To date, no study explores the relationships between TIMP-3 polymorphisms and uterine cervical cancer. The purposes of this research were to investigate the associations among genetic variants of TIMP-3 and development and clinicopathological factors of uterine cervical cancer, and patient 5 years survival in Taiwanese women. The study included 123 patients with invasive cancer and 97 with precancerous lesions of uterine cervix, and 300 control women. TIMP-3 polymorphisms rs9619311, rs9862 and rs11547635 were checked and their genotypic distributions were determined by real-time polymerase chain reaction. It showed that women with genotypes CT/TT in rs9862 were found to display a higher risk of developing cervical cancer with moderate and poor cell differentiation. Moreover, it revealed that cervical cancer patients carrying genotypes CC in rs9619311 exhibited a poorer 5 years survival, as compared to those with TT/TC in Taiwanese women, using univariate analysis. In addition, pelvic lymph node metastasis was determined to independently predict 5 years survival in cervical cancer patients using multivariate analysis. Conclusively, TIMP-3 SNPs polymorphisms rs9619311 are related to cervical patient survival in Taiwanese women.

Characteristics and Outcome Determinants of Hospitalized Older Patients with Cognitive Dysfunction.

Cognitive dysfunction commonly occurs among older patients during admission and is associated with adverse prognosis. This study evaluated clinical characteristics and outcome determinants in hospitalized older patients with cognitive disorders. The main outcomes were length of stay, readmission within 30 days, Barthel index (BI) score at discharge, BI score change (discharge BI score minus BI score), and proportion of positive BI score change to indicate change of activities of daily living (ADL) change during hospitalization. A total of 642 inpatients with a mean age of 79.47 years (76-103 years) were categorized into three groups according to the medical history of dementia, and Mini-Mental State Examination (MMSE) scores at admission. Among them, 74 had dementia diagnosis (DD), 310 had cognitive impairment (CI), and 258 had normal MMSE scores. Patients with DD and CI generally had a higher risk of many geriatric syndromes, such as multimorbidities, polypharmacy, delirium, incontinence, visual and auditory impairment, fall history, physical frailty. They had less BI score, BI score change, and proportion of positive BI score change ADL at discharge. (DD 70.0%, CI 79.0%), suggesting less ADL change during hospitalization compared with those with normal MMSE scores (92.9%; p < 0.001). Using multiple regression analysis, we found that among patients with DD and CI, age (p = 0.008) and walking speed (p = 0.023) were predictors of discharge BI score. In addition, age (p = 0.047) and education level were associated with dichotomized BI score change (positive vs. non-positive) during hospitalization. Furthermore, the number and severity of comorbidities predicted LOS (p < 0.001) and readmission (p = 0.001) in patients with cognitive disorders. It is suggested that appropriate strategies are required to improve clinical outcomes in these patients.

Prediction of 30-Day Readmission in Hospitalized Older Adults Using Comprehensive Geriatric Assessment and LACE Index and HOSPITAL Score.

(1) Background: Elders have higher rates of rehospitalization, especially those with functional decline. We aimed to investigate potential predictors of 30-day readmission risk by comprehensive geriatric assessment (CGA) in hospitalized patients aged 65 years or older and to examine the predictive ability of the LACE index and HOSPITAL score in older patients with a combination of malnutrition and physical dysfunction. (2) Methods: We included patients admitted to a geriatric ward in a tertiary hospital from July 2012 to August 2018. CGA components including cognitive, functional, nutritional, and social parameters were assessed at admission and recorded, as well as clinical information. The association factors with 30-day hospital readmission were analyzed by multivariate logistic regression analysis. The predictive ability of the LACE and HOSPITAL score was assessed using receiver operator characteristic curve analysis. (3) Results: During the study period, 1509 patients admitted to a ward were recorded. Of these patients, 233 (15.4%) were readmitted within 30 days. Those who were readmitted presented with higher comorbidity numbers and poorer performance of CGA, including gait ability, activities of daily living (ADL), and nutritional status. Multivariate regression analysis showed that male gender and moderately impaired gait ability were independently correlated with 30-day hospital readmissions, while other components such as functional impairment (as ADL) and nutritional status were not associated with 30-day rehospitalization. The receiver operating characteristics for the LACE index and HOSPITAL score showed that both predicting scores performed poorly at predicting 30-day hospital readmission (C-statistic = 0.59) and did not perform better in any of the subgroups. (4) Conclusions: Our study showed that only some components of CGA, mobile disability, and gender were independently associated with increased risk of readmission. However, the LACE index and HOSPITAL score had a poor discriminating ability for predicting 30-day hospitalization in all and subgroup patients. Further identifiers are required to better estimate the 30-day readmission rates in this patient population.

Using multiple-steps bioinformatic analysis to predict the potential microRNA targets by cardiogenic HoxA11.

BACKGROUND: In this study, our major aim is to using multiple-steps bioinformatic analysis to predict cardiogenic genes with targeting mRNA profiling for predicting cardiogenic HoxA11 gene. METHODS: We first analyzed the microarray data with bioinformatic measurement, including combining with panel module 1 (mouse embryonic stem cells), panel module 2 (mouse induced pluripotent stem cells), and panel module 3 (gene list form literature of heart development). A literature-based comparison of the two microarrays and a software-based (Targetscan program, www.targetscan.org) comparative analysis of the two datasets. Furthermore, we select the common central pathways and potential candidate genes involved in the cardiomyocyte-lineaged differentiation and development. RESULTS: Schematic presentation of a putative miR181a target site in Hox-A11 3'UTR. The bioinformatic result showed that potential interacted cardiogenic targets of Tbx5, Tbx20, Mal2c, Nkx2.5, cTNT, Cx43, MHC, and MCK in different treatment groups of pluripotent stem cells by using a literature-based comparison of the two microarrays and a software-based gene-lineage system. CONCLUSION: Our findings support that mir181a is an up-stream regulating microRNA to target the 3'UTR of HoxA11 mRNA during the process of cardiomyocyte differentiation.

Migraine as a Risk Factor for Peripheral Artery Occlusive Disease: A Population-Based Cohort Study.

We aim to evaluate the development of peripheral occlusive artery disease (PAOD) in patients with migraine by using the National Health Insurance Research Database in Taiwan. A retrospective cohort study was conducted and individuals with diagnostic codes of migraine were enrolled in the study group after excluding those diagnosed with PAOD before the index date. Each subject with migraine was propensity-score matched to another non-migraine patient and the latter served as the control group. A total of 37,288 patients were finally enrolled in the groups. The primary outcome was set as the development of PAOD between the two groups while multiple possible risk factors, including demographic data and comorbidities, were analyzed via the Cox proportional hazards regression. There were 885 and 530 PAOD events in the study and control groups, and the study group had a significantly higher adjusted hazard ratio (1.65, 95% confidential interval: 1.48-1.84, p < 0.001), and the cumulative incidence also revealed a correlation between migraine and PAOD. Other potential risk factors related to the existence of PAOD include age, hypertension, chronic kidney disease, diabetes mellitus, coronary artery disease, stroke, and asthma. For individuals without certain systemic diseases including hypertension, chronic liver disease, chronic kidney disease, coronary artery disease, stroke, asthma, or heart failure, the hazard ratio of subsequent PAOD was significantly higher in the migraine patients than that in the non-migraine individuals (all p < 0.001). In conclusion, the presence of migraine is a significant risk factor for the development of subsequent PAOD.

Impact of the Severities of Glaucoma on the Incidence of Subsequent Dementia: A Population-Based Cohort Study.

The aim of the present study was to survey the relationship between the severity of glaucoma and subsequent dementia using the National Health Insurance Research Database (NHIRD) in Taiwan. Subjects with glaucoma were selected into the study group after an exclusion process, and each subject in the study group was propensity score-matched to another non-glaucoma patient that constituted the control group. The Cox proportional hazard regression that considered multiple potential risk factors of dementia was used to yield the adjusted hazard ratios (aHR) of dementia in different severities of glaucoma. There were 1185 (5.63 percent) subjects in the study group and 1119 (5.32 percent) patients in the control group that developed dementia. After adjusting for multiple confounders, there were no differences in the rate of any dementia (aHR: 0.961, 95% CI: 0.886-1.043, p = 0.3443), vascular dementia (aHR: 0.928, 95% CI: 0.846-1.018, p = 0.1154), Alzheimer's disease (aHR: 1.018, 95% CI: 0.761-1.362, p = 0.9025) or Parkinson's disease (aHR: 1.021, 95% CI: 0.886-1.176, p = 0.7744) between the study and the control groups. Regarding the disease severity of glaucoma, no difference was found in any type of dementia whether the glaucoma patients received less than two medical treatments, received more than two medical treatments, received drainage surgeries or received destructive surgeries. In conclusion, the different severities of glaucoma do not alter the incidence of subsequent dementia.

Andrographolide suppresses the migratory ability of human glioblastoma multiforme cells by targeting ERK1/2-mediated matrix metalloproteinase-2 expression.

Glioblastoma multiforme (GBM) can be a fatal tumor because of difficulties in treating the related metastasis. Andrographolide is the bioactive component of the Andrographis paniculata. Andrographolide possesses the anti-inflammatory activity and inhibits the growth of various cancers; however, its effect on GBM cancer motility remains largely unknown. In this study, we examined the antimetastatic properties of andrographolide in human GBM cells. Our results revealed that andrographolide inhibited the invasion and migration abilities of GBM8401 and U251 cells. Furthermore, andrographolide inhibited matrix metalloproteinase (MMP)-2 activity and expression. Real-time PCR and promoter activity assays indicated that andrographolide inhibited MMP-2 expression at the transcriptional level. Such inhibitory effects were associated with the suppression of CREB DNA-binding activity and CREB expression. Mechanistically, andrographolide inhibited the cell motility of GBM8401 cells through the extracellular-regulated kinase (ERK) 1/2 pathway, and the blocking of the ERK 1/2 pathway could reverse MMP-2-mediated cell motility. In conclusion, CREB is a crucial target of andrographolide for suppressing MMP-2-mediated cell motility in GBM cells. Therefore, a combination of andrographolide and an ERK inhibitor might be a good strategy for preventing GBM metastasis.