Altered cerebellar and caudate gray-matter volumes and structural covariance networks preceding dual cognitive and mobility impairments in older people.

INTRODUCTION: The neuroanatomical changes driving both cognitive and mobility impairments, an emerging preclinical dementia syndrome, are not fully understood. We examined gray-matter volumes (GMVs) and structural covariance networks (SCNs) abnormalities in community-based older people preceding the conversion to physio-cognitive decline syndrome (PCDS). METHODS: Voxel-wise brain GMV and established SCNs were compared between PCDS and non-PCDS converters. RESULTS: The study included 343 individuals (60.2 ± 6.9 years, 49.6% men) with intact cognitive and mobility functions. Over an average 5.6-year follow-up, 116 transitioned to PCDS. Identified regions with abnormal GMVs in PCDS converters were over cerebellum and caudate, which served as seeds for SCNs establishment. Significant differences in cerebellum-based (to right frontal pole and left middle frontal gyrus) and caudate-based SCNs (to right caudate putamen, right planum temporale, left precentral gyrus, right postcentral gyrus, and left parietal operculum) between converters and nonconverters were observed. DISCUSSION: This study reveals early neuroanatomic changes, emphasizing the cerebellum's role, in dual cognitive and mobility impairments. HIGHLIGHTS: Neuroanatomic precursors of dual cognitive and mobility impairments are identified. Cerebellar GMV reductions and increased right caudate GMV precede the onset of PCDS. Altered cerebellum- and caudate-based SCNs drive PCDS transformation. This research establishes a foundation for understanding PCDS as a specific dementia syndrome.

Butyrate reduction and HDAC4 increase underlie maternal high fructose-induced metabolic dysfunction in hippocampal astrocytes in female rats.

Maternal nutrient intake influences the health of the offspring via microenvironmental systems in digestion and absorption. Maternal high fructose diet (HFD) impairs hippocampus-dependent memory in adult female rat offspring. However, the underlying mechanisms remain largely unclear. Maternal HFD causes microbiota dysbiosis. In this study, we find that the plasma level of butyrate, a major metabolite of microbiota, is significantly decreased in the adult female maternal HFD offspring. In these rats, GPR43, a butyrate receptor was downregulated in the hippocampus. Moreover, the expressions of mitochondrial transcription factor A (TFAM), and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) were downregulated in the hippocampus. The decreases of these functional proteins were reversed by fructooligosaccharides (FOS, a probiotic) treatment in adulthood. Astrocytes are critical for energy metabolism in the brain. Primary astrocyte culture from female maternal HFD offspring indicated that GPR43 and the mitochondrial biogenesis were significantly suppressed, which was reversed by supplemental butyrate incubation. The oxygen consumption rate (OCR) was reduced in the HFD group and rescued by butyrate. Intriguingly, the nuclear histone deacetylase 4 (HDAC4) was enhanced in the HFD group, suggesting an inhibitory role of butyrate on histone deacetylase activity. Inhibition of HDAC4 effectively restored the OCR, bioenergetics, and biogenesis of mitochondria. Together, these results suggested that the impaired butyrate signaling by maternal HFD could underlie the reduced mitochondrial functions in the hippocampus via HDAC4-mediated epigenetic changes.

Multi-Trajectories of Intrinsic Capacity Decline and Their Impact on Age-Related Outcomes: A 20-Year National Longitudinal Cohort Study.

The existence of intrinsic capacity (IC) subtypes and their distinct impacts on age-related outcomes remain unexplored. This study sought to investigate IC impairment trajectories across domains and their associations with the risk of age-related outcomes, including falls, functional limitations, reduced quality of life (QoL) and mortality at 4- and 8-year follow-ups. The study sample comprised 1,782 older adults residing in the community from the Taiwan Longitudinal Study on Ageing (TLSA). Utilizing group-based multitrajectory modeling, distinct subtypes of IC decline trajectories across various domains were identified. Cox proportional hazard models and multivariable logistic regression analyses were employed to assess the associations between the identified subtypes and age-related outcomes. We identified four subtypes of IC decline: robust with mild decline (n=902), hearing loss with cognitive decline (n=197), physio-cognitive decline (PCD) with depression (n=373), and severe IC decline (n=310). Over the 4-year study period, compared to the robust with mild decline group, hearing loss with cognitive decline group exhibited a significantly higher risk of diminished QoL (OR=2.53 [1.66-3.86], p>0.01), whereas those in the PCD with depression group experienced an elevated risk of falls (OR=1.62 [1.18-2.23], p>0.01), as well as functional limitation (OR=2.61 [1.81-3.75], p>.01). Individuals in the severe IC decline group faced a substantially increased risk of all outcomes of interest. Distinct subtypes of IC decline across different domains have varying impacts on age-related outcomes, highlighting the need for a personalized approach to promote healthy ageing at the population level, while further investigation into specific pathophysiological mechanisms is warranted as well.

Diagnosis and outcomes of cachexia in Asia: Working Consensus Report from the Asian Working Group for Cachexia.

Chronic diseases often lead to metabolic disorders, causing anabolic resistance and increased energy consumption, which result in cachexia. Cachexia, in turn, can lead to major clinical consequences such as impaired quality of life, shortened life expectancy, and increased healthcare expenditure. Existing international diagnostic criteria for cachexia employ thresholds derived from Western populations, which may not apply to Asians due to differing body compositions. To address this issue, the Asian Working Group for Cachexia (AWGC) was initiated. The AWGC comprises experts in cachexia research and clinical practice from various Asian countries and aims to develop a consensus on diagnostic criteria and significant clinical outcomes for cachexia in Asia. The AWGC, composed of experts in cachexia research and clinical practice from several Asian countries, undertook three-round Delphi surveys and five meetings to reach a consensus. Discussions were held on etiological diseases, essential diagnostic items for cachexia, including subjective and objective symptoms and biomarkers, and significant clinical outcomes. The consensus highlighted the importance of multiple diagnostic factors for cachexia, including chronic diseases, either or both weight loss or low body mass index, and at least one of the following: anorexia, decreased grip strength (<28 kg in men and <18 kg in women), or elevated C-reactive protein levels (>5 mg/L [0.5 mg/dL]). The AWGC proposed a significant weight change of 2% or more over a 3-6 month period and suggested a tentative cut-off value of 21 kg/m2 for low body mass index in diagnosing cachexia. Critical clinical outcomes were determined to be mortality, quality of life as assessed by tools such as EQ-5D or the Functional Assessment of Anorexia/Cachexia Therapy, and functional status as measured by the Clinical Frailty Scale or Barthel Index, with significant emphasis on patient-reported outcomes. The AWGC consensus offers a comprehensive definition and user-friendly diagnostic criteria for cachexia, tailored specifically for Asian populations. This consensus is set to stimulate future research and enhance the multidisciplinary approach to managing cachexia. With plans to develop further guidelines for the optimal treatment, prevention, and care of cachexia in Asians, the AWGC criteria are expected to drive research across chronic co-morbidities and cancer in Asia, leading to future refinement of diagnostic criteria.

Physical activity plays a crucial role in multidomain intervention for frailty prevention.

BACKGROUND AND AIMS: Taiwan is one of the most rapidly aging countries worldwide. Both physical activity and frailty affect older adults, and multidomain interventions prevent frailty. This study investigated the associations between physical activity, frailty, and the effects of multidomain intervention. METHODS: This study enrolled individuals aged 65 years or older. The physical activity level was assessed using the Physical Activity Scale for the Elderly (PASE). Enrollees participated in a multidomain intervention program that consisted of twelve 120-min sessions administered over a 12-week period that included health education, cognitive training, and exercise programs. The effects of the intervention were evaluated using the instrumental activities of daily living scale (IADL), Mini Nutritional Assessment short form (MNA-SF), five-item Geriatric Depression Scale (GDS-5), Mini-Mental State Examination (MMSE), timed up and go test (TUGT), and Fried's frailty phenotype. RESULTS: In total, 106 older adults (aged 65-96 years) were enrolled in this study. The mean age was 77.47 ± 7.19 years, and 70.8% of participants were women. PASE scores were significantly lower among participants who were of older age, frail, and had a history of falls in the last 12 months. Frailty could be improved by multidomain interventions and was significantly positively correlated with depression, and negatively correlated with physical activity, mobility, cognition and daily living skills. Moreover, daily living skills were significantly positively correlated with cognition, mobility and physical activity, and negatively correlated with age, sex, and frailty. However, multidomain interventions did not affect daily living skills suggesting daily living skills may need to be maintained from a young age. Finally, results from multiple regressions suggest that physical activity, mobility and depression may be predictors of frailty. CONCLUSIONS: Physical activity has an important role in frailty, may be a predictor of frailty, and strongly contributes to reducing frailty through multidomain intervention. Policies that encourage healthy aging should focus on increasing physical activity, maintaining basic daily living skills and reducing frailty.

Automated Video Analysis of Audio-Visual Approaches to Predict and Detect Mild Cognitive Impairment and Dementia in Older Adults.

BACKGROUND: Early identification of different stages of cognitive impairment is important to provide available intervention and timely care for the elderly. OBJECTIVE: This study aimed to examine the ability of the artificial intelligence (AI) technology to distinguish participants with mild cognitive impairment (MCI) from those with mild to moderate dementia based on automated video analysis. METHODS: A total of 95 participants were recruited (MCI, 41; mild to moderate dementia, 54). The videos were captured during the Short Portable Mental Status Questionnaire process; the visual and aural features were extracted using these videos. Deep learning models were subsequently constructed for the binary differentiation of MCI and mild to moderate dementia. Correlation analysis of the predicted Mini-Mental State Examination, Cognitive Abilities Screening Instrument scores, and ground truth was also performed. RESULTS: Deep learning models combining both the visual and aural features discriminated MCI from mild to moderate dementia with an area under the curve (AUC) of 77.0% and accuracy of 76.0%. The AUC and accuracy increased to 93.0% and 88.0%, respectively, when depression and anxiety were excluded. Significant moderate correlations were observed between the predicted cognitive function and ground truth, and the correlation was strong excluding depression and anxiety. Interestingly, female, but not male, exhibited a correlation. CONCLUSION: The study showed that video-based deep learning models can differentiate participants with MCI from those with mild to moderate dementia and can predict cognitive function. This approach may offer a cost-effective and easily applicable method for early detection of cognitive impairment.

The association of potentially inappropriate medications, polypharmacy and anticholinergic burden with readmission and emergency room revisit after discharge: A hospital-based retrospective cohort study.

AIMS: While certain drug-use indicators are known to be associated with clinical outcomes, the relationship is unclear for some highly prevalent conditions in in patients aged ≥65 years. We examine correlations between 3 drug-use indicators and postdischarge healthcare services use by older patients according to the presence of dementia, advanced age and frailty. METHODS: This retrospective cohort study analysed data collected from hospital electronic health records between April and December 2017. Potentially inappropriate medications (PIMs) and anticholinergic burden were assessed using the 2015 Beers Criteria and anticholinergic cognitive burden scale (ACBS) score. Minor and major polypharmacy were defined as the use of 5-9 and ≥10 drugs, respectively. Outcomes were set as emergency room revisits and readmissions at 1, 3 and 6 months postdischarge. The correlation between drug-use indicators and outcomes was analysed by multivariable logistic regression. RESULTS: The final cohort included 3061 patients for the analysis, and 2930, 2671 and 2560 patients were followed up to 1, 3 and 6 months after discharge. After controlling for confounders, all 3 drug-use indicators were significantly associated with readmission and emergency room revisits except for the relationship between PIMs and readmission within 6 months. These associations were significantly observed among patients without dementia, aged >80 years and with frailty. CONCLUSION: PIMs, polypharmacy and anticholinergic burden are common at discharge and correlate with future use of healthcare services. In older patients, the absence of dementia, advanced age and frailty should be given extra consideration with regard to medication safety.

Lipopolysaccharide-induced Autophagy Increases SOX2-positive Astrocytes While Decreasing Neuronal Differentiation in the Adult Hippocampus.

Inflammation alters the neural stem cell (NSC) lineage from neuronal to astrogliogenesis. However, the underlying mechanism is elusive. Autophagy contributes to the decline in adult hippocampal neurogenesis under E. coli lipopolysaccharide (LPS) stimulation. SRY-box transcription Factor 2 (SOX2) is critical for NSC self-renewal and proliferation. In this study, we investigated the role of SOX2 in induced autophagy and hippocampal adult neurogenesis under LPS stimulation. LPS (5 ng•100 g-1•hour-1 for 7 days) was intraperitoneally infused into male Sprague-Dawley rats (8 weeks old) to induce mild systemic inflammation. Beclin 1 and autophagy protein 12 (Atg12) were significantly upregulated concurrent with decreased numbers of Ki67- and doublecortin (DCX)-positive cells in the dentate gyrus. Synchronically, the levels of phospho(p)-mTOR, the p-mTOR/mTOR ratio, p-P85s6k, and the p-P85s6k/P85s6k ratio were suppressed. In contrast, SOX2 expression was increased. The fluorescence micrographs indicated that the colocalization of Beclin 1 and SOX2 was increased in the subgranular zone (SGZ) of the dentate gyrus. Moreover, increased S100ß-positive astrocytes were colocalized with SOX2 in the SGZ. Intracerebroventricular infusion of 3-methyladenine (an autophagy inhibitor) effectively prevented the increases in Beclin 1, Atg12, and SOX2. The SOX2+-Beclin 1+ and SOX2+-S100ß+ cells were reduced. The levels of p-mTOR and p-P85s6k were enhanced. Most importantly, the number of DCX-positive cells was preserved. Altogether, these data suggest that LPS induced autophagy to inactivate the mTOR/P85s6k pathway, resulting in a decline in neural differentiation. SOX2 was upregulated to facilitate the NSC lineage, while the autophagy milieu could switch the SOX2-induced NSC lineage from neurogenesis to astrogliogenesis.

Accurately Identifying Cerebroarterial Stenosis from Angiography Reports Using Natural Language Processing Approaches.

Patients with intracranial artery stenosis show high incidence of stroke. Angiography reports contain rich but underutilized information that can enable the detection of cerebrovascular diseases. This study evaluated various natural language processing (NLP) techniques to accurately identify eleven intracranial artery stenosis from angiography reports. Three NLP models, including a rule-based model, a recurrent neural network (RNN), and a contextualized language model, XLNet, were developed and evaluated by internal-external cross-validation. In this study, angiography reports from two independent medical centers (9614 for training and internal validation testing and 315 as external validation) were assessed. The internal testing results showed that XLNet had the best performance, with a receiver operating characteristic curve (AUROC) ranging from 0.97 to 0.99 using eleven targeted arteries. The rule-based model attained an AUROC from 0.92 to 0.96, and the RNN long short-term memory model attained an AUROC from 0.95 to 0.97. The study showed the potential application of NLP techniques such as the XLNet model for the routine and automatic screening of patients with high risk of intracranial artery stenosis using angiography reports. However, the NLP models were investigated based on relatively small sample sizes with very different report writing styles and a prevalence of stenosis case distributions, revealing challenges for model generalization.

COVID-19 Vaccines in Older Adults: Challenges in Vaccine Development and Policy Making.

The coronavirus disease 2019 (COVID-19) pandemic has had strong adverse impacts on vulnerable populations, such as frail older adults. The success of COVID-19 vaccine development, together with extensive global public health efforts, has brought hope to the control of the COVID-19 pandemic. Nevertheless, challenges in COVID-19 vaccine development and vaccination strategies among older people remain. This article reviews vaccinations in older adults, compares COVID-19 vaccine platforms, the efficacy and safety of COVID-19 vaccines in frail older people in long-term care settings, and the challenges of COVID-19 vaccine development and policy making for vaccination strategies in older adults.

Insomnia in older adult females is highly associated with metabolic syndrome.

PURPOSE: The aim of this study is to investigate the relationships between insomnia and metabolic syndrome among Taiwanese older adults. METHODS: This cross-sectional study enrolled participants aged over 60 years from outpatient clinics between July and September 2018. Demographic characteristics of all participants and questionnaire data for sleep duration, use of hypnotic agents, baseline activities of daily living, 5 items of the geriatric depression scale, comorbidities, medications, and risk of obstructive sleep apnea were obtained. Insomnia was defined by scores of questionnaires of the Chinese version of the Athens Insomnia Scale higher or equal to 6 points. Metabolic syndrome was diagnosed according to criteria of the National Cholesterol Education Program Adult Treatment Panel III. Multivariable forward stepwise logistic regression analysis was applied to investigate independent associations between insomnia and metabolic syndrome before and after stratifying by gender. RESULTS: Among the 336 participants (mean age 74.9 ± 8.5 years, female 49.1%), 63.1% participants had metabolic syndrome, with significantly higher prevalence among females than males (males 56.7%; females 69.7%). Participants with metabolic syndrome had higher rates of insomnia (34.0% vs. 21.8%, P = 0.018). The significant associations between insomnia and metabolic syndrome disappeared after adjusting for all covariates. However, insomnia was independently associated with metabolic syndrome in older females (adjusted OR 2.614, 95% CI 1.011-6.763, P = 0.048) after adjusting for all covariates. CONCLUSIONS: Insomnia is significantly associated with metabolic syndrome among older female adults. These findings suggest that gender may play a role in the pathogenesis of insomnia and metabolic syndrome in older adults.

Muscle-to-fat ratio identifies functional impairments and cardiometabolic risk and predicts outcomes: biomarkers of sarcopenic obesity.

BACKGROUND: Sarcopenic obesity aims to capture the risk of functional decline and cardiometabolic diseases, but its operational definition and associated clinical outcomes remain unclear. Using data from the Longitudinal Aging Study of Taipei, this study explored the roles of the muscle-to-fat ratio (MFR) with different definitions and its associations with clinical characteristics, functional performance, cardiometabolic risk and outcomes. METHODS: (1) Appendicular muscle mass divided by total body fat mass (aMFR), (2) total body muscle mass divided by total body fat mass (tMFR) and (3) relative appendicular skeletal muscle mass (RASM) were measured. Each measurement was categorized by the sex-specific lowest quintiles for all study participants. Clinical outcomes included all-cause mortality and fracture. RESULTS: Data from 1060 community-dwelling older adults (mean age: 71.0 ± 4.8 years) were retrieved for the study. Overall, 196 (34.2% male participants) participants had low RASM, but none was sarcopenic. Compared with those with high aMFR, participants with low aMFR were older (72 ± 5.6 vs. 70.7 ± 4.6 years, P = 0.005); used more medications (2.9 ± 3.3 vs. 2.1 ± 2.5, P = 0.002); had a higher body fat percentage (38 ± 4.8% vs. 28 ± 6.4%, P < 0.001), RASM (6.7 ± 1.0 vs. 6.5 ± 1.1 kg/m2 , P = 0.001), and cardiometabolic risk [fasting glucose: 105 ± 27.5 vs. 96.8 ± 18.7 mg/dL, P < 0.001; glycated haemoglobin (HbA1c): 6.0 ± 0.8 vs. 5.8 ± 0.6%, P < 0.001; triglyceride: 122.5 ± 56.9 vs. 108.6 ± 67.5 mg/dL, P < 0.001; high-density lipoprotein cholesterol (HDL-C): 56.2 ± 14.6 vs. 59.8 ± 16 mg/dL, P = 0.010]; and had worse functional performance [Montreal Cognitive Assessment (MoCA): 25.7 ± 4.2 vs. 26.4 ± 3.0, P = 0.143, handgrip strength: 24.7 ± 6.7 vs. 26.1 ± 7.9 kg, P = 0.047; gait speed: 1.8 ± 0.6 vs. 1.9 ± 0.6 m/s, P < 0.001]. Multivariate linear regression showed that age (ß = 0.093, P = 0.001), body mass index (ß = 0.151, P = 0.046), total percentage of body fat (ß = 0.579, P < 0001) and RASM (ß = 0.181, P = 0.016) were associated with low aMFR. Compared with those with high tMFR, participants with low tMFR were older (71.7 ± 5.5 vs. 70.8 ± 4.7 years, P = 0.075); used more medications (2.8 ± 3.3 vs. 2.1 ± 2.5, P = 0.006); had a higher body fat percentage (38.1 ± 4.7 vs. 28 ± 6.3%, P < 0.001), RASM (6.8 ± 1.0 vs. 6.5 ± 1.1 kg/m2 , P < 0.001), and cardiometabolic risk (fasting glucose: 104.8 ± 27.6 vs. 96.9 ± 18.7 mg/dL, P < 0.001; HbA1c: 6.1 ± 0.9 vs. 5.8 ± 0.6%, P < 0.001; triglyceride: 121.4 ± 55.5 vs. 108.8 ± 67.8 mg/dL, P < 0.001; HDL-C: 56.4 ± 14.9 vs. 59.7 ± 15.9 mg/dL, P = 0.021); and had worse functional performance (MoCA: 25.6 ± 4.2 vs. 26.5 ± 3.0, P = 0.056; handgrip strength: 24.6 ± 6.7 vs. 26.2 ± 7.9 kg, P = 0.017; gait speed: 1.8 ± 0.6 vs. 1.9 ± 0.6 m/s, P < 0.001). Low tMFR was associated with body fat percentage (ß = 0.766, P < 0.001), RASM (ß = 0.476, P < 0.001) and Mini-Nutritional Assessment (ß = -0.119, P < 0.001). Gait speed, MoCA score, fasting glucose, HbA1c and tMFR were significantly associated with adverse outcomes, and the effects of aMFR were marginal (P = 0.074). CONCLUSIONS: Older adults identified with low MFR had unfavourable body composition, poor functional performance, high cardiometabolic risk and a high risk for the clinical outcome.

Factors associated with insomnia in older adult outpatients vary by gender: a cross-sectional study.

BACKGROUND: Insomnia is a common sleep disturbance in older adults and is associated with many poor health outcomes. This study aimed to explore factors associated with insomnia in older adult outpatient clinics, and to further analyze the influence of gender on factors associated with insomnia. METHODS: This cross-sectional study was conducted in the outpatient clinics of a tertiary hospital in Southern Taiwan from July to September 2018. A total of 400 consecutive subjects aged 60 years or older were recruited. Insomnia was defined as a score of ≥6 points on the Athens Insomnia Scale (AIS). Socio-demographics, health behaviors and clinical data were collected by face-to-face interview. Multivariable logistic regression was adopted for statistical analysis of the entire sample and stratified by gender. RESULTS: Participants' mean age was 74.74 ± 8.54 years, and the majority (93%) had more than one chronic disease. The prevalence of insomnia accounted for 30% (120/400) of all subjects, with males 22.9% (46/201) and females 37.2% (74/199). Gender, appetite, exercise, depressive symptoms, and sleep-related conditions such as short sleep duration, sleeping pills usage, medium-high risk of obstructive sleep apnea (OSA) and restless leg syndrome (RLS) were factors associated with insomnia in older adults. Exercise, sleeping pills usage, and RLS were independently associated with insomnia only in men, while appetite and medium-high risk of OSA were associated with insomnia in women only. In addition, after further adjusting for covariates, prevalence of the insomnia-related symptoms such as sleep induction, total sleep duration, sleep quality and sleepiness during the day was significantly higher in females than in males. CONCLUSIONS: Insomnia symptoms are highly prevalent among older adults, predominantly females. Significant differences are found between genders in factors associated with insomnia and insomnia-related symptoms. Understanding gender differences may help clinicians to modify associated factors when managing older adults with insomnia.

Cost and Effectiveness of Long-Term Care Following Integrated Discharge Planning: A Prospective Cohort Study.

Little is known about the effects of seamless hospital discharge planning on long-term care (LTC) costs and effectiveness. This study evaluates the cost and effectiveness of the recently implemented policy from hospital to LTC between patients discharged under seamless transition and standard transition. A total of 49 elderly patients in the standard transition cohort and 119 in the seamless transition cohort were recruited from November 2016 to February 2018. Data collected from medical records included the Multimorbidity Frailty Index, Activities of Daily Living Scale, and Malnutrition Universal Screening Tool during hospitalization. Multiple linear regression and Cox regression models were used to explore risk factors for medical resource utilization and medical outcomes. After adjustment for effective predictors, the seamless cohort had lower direct medical costs, a shorter length of stay, a higher survival rate, and a lower unplanned readmission rate compared to the standard cohort. However, only mean total direct medical costs during hospitalization and 6 months after discharge were significantly (p < 0.001) lower in the seamless cohort (USD 6192) compared to the standard cohort (USD 8361). Additionally, the annual per-patient economic burden in the seamless cohort approximated USD 2.9-3.3 billion. Analysis of the economic burden of disability in the elderly population in Taiwan indicates that seamless transition planning can save approximately USD 3 billion in annual healthcare costs. Implementing this policy would achieve continuous improvement in LTC quality and reduce the financial burden of healthcare on the Taiwanese government.

All-cause mortality, cardiovascular mortality, major cardiovascular events and hypoglycaemia of patients with diabetes onset at an older age: results from the 10-year nationwide cohort study.

BACKGROUND: Longitudinal adverse outcomes are unclear among adults with diabetes according to the age of onset. OBJECTIVE: To investigate the longitudinal diabetes-related outcomes in adults with new-onset diabetes stratified by age. DESIGN: Retrospective cohort study. SETTING: Taiwan National Health Insurance Research Database claims data from 2000 to 2015. SUBJECTS: In total, 115,751 participants aged ≥40 years with new-onset diabetes in 2003 were recruited and stratified by the ages 40-64 (64.3%), 65-74 (21.2%), 75-84 (11.8%) and ≥85 years (2.7%) at the time of diagnosis. METHODS: Time-varying multivariate Cox proportional hazards model adjusted for covariates was used to examine the associations between the ages of the patients at diabetes onset and the outcomes of interest [all-cause mortality, cardiovascular (CV) mortality, major cardiovascular events (MACE) and hypoglycaemia] during a 10-year follow-up period. RESULTS: The results showed that compared with those patients aged 40-64 at diagnosis, patients with older-onset diabetes had significantly higher comorbidities (P < 0.01) and a higher diabetes severity (P < 0.01). Patients with older-onset diabetes had a higher risk of all-cause mortality [adjusted hazard ratio (aHR) 2.28, 4.48 and 10.07 in 65-74, 75-84 and ≥85 years old, respectively], CV mortality (aHR = 2.82, 6.06 and 15.91), MACE (aHR = 2.19, 3.01 and 4.15) and hypoglycaemia (aHR = 2.41, 3.59 and 4.62) than patients aged 40-64 during a 10-year follow-up period. CONCLUSIONS: Patients with diabetes onset at an older age was associated with increased risks of all-cause mortality, CV mortality, MACE and hypoglycaemia after adjusting for the severity of diabetes and anti-diabetic treatment.

Differential moderation effects of ApoE and 5-HTTLPR genotypes on social vulnerability in predicting mortality among community-dwelling middle-aged and older adults: a nationwide population-based study.

Aging is a dynamic complex process involving social vulnerability over time. The social vulnerability index (SVI) was developed that predicted adverse health outcomes. This study examined effects between SVI status and two genotypes, apolipoprotein E (ApoE) and Serotonin transporter genotyping (5-HTTLPR), on all-cause mortality. Data from the Social Environment and Biomarkers of Aging Study (SEBAS) were obtained, and SVI was constructed using 32 self-reported items of social determinants. Data from 985 participants (age: 65.73 ± 9.47 years, 54.62% males) were obtained for analysis, and the median SVI was 0.35 (IQR 0.29-0.42) with a near normal distribution. Participants with a higher SVI were more likely to be women and have poor cognitive function, more depressive symptoms and poor physical function. Adjusted for age and sex, each incremental deficit in SVI was associated with a 12% increase in mortality risk (HR: 1.12, 95% CI: 1.04-1.20, p = 0.002). An interaction was found between ApoE and SVI but not 5-HTTLPR. The strata-specific hazard ratio confirmed that associations between SVI and mortality was only in non-ε4 carriers (HR: 1.15, 95% CI: 1.07-1.24, p < 0.001), and SVI did not significantly predict mortality among ε4 carriers (HR: 0.84, 95% CI: 0.65-1.10). Differential SVI effects on mortality among middle-age and older adults were identified. In conclusion, a higher SVI was associated with all-cause mortality among middle-aged and older adults, and the association was moderated by ApoE genotypes but not 5-HTTLPR. Further study is needed to evaluate the clinical efficacy of healthy aging intervention programs considering gene-environment interactions and social vulnerability.

A disease-specific language representation model for cerebrovascular disease research.

BACKGROUND: Effectively utilizing disease-relevant text information from unstructured clinical notes for medical research presents many challenges. BERT (Bidirectional Encoder Representation from Transformers) related models such as BioBERT and ClinicalBERT, pre-trained on biomedical corpora and general clinical information, have shown promising performance in various biomedical language processing tasks. OBJECTIVES: This study aims to explore whether a BERT-based model pre-trained on disease-related clinical information can be more effective for cerebrovascular disease-relevant research. METHODS: This study proposed the StrokeBERT which was initialized from BioBERT and pre-trained on large-scale cerebrovascular disease related clinical text information. The pre-trained corpora contained 113,590 discharge notes, 105,743 radiology reports, and 38,199 neurological reports. Two real-world empirical clinical tasks were conducted to validate StrokeBERT's performance. The first task identified extracranial and intracranial artery stenosis from two independent sets of radiology angiography reports. The second task predicted the risk of recurrent ischemic stroke based on patients' first discharge information. RESULTS: In stenosis detection, StrokeBERT showed improved performance on targeted carotid arteries, with an average AUC compared to that of ClinicalBERT of 0.968 ± 0.021 and 0.956 ± 0.018, respectively. In recurrent ischemic stroke prediction, after 10-fold cross-validation on 1,700 discharge information, StrokeBERT presented better prediction ability (AUC±SD = 0.838 ± 0.017) than ClinicalBERT (AUC±SD = 0.808 ± 0.045). The attention scores of StrokeBERT showed better ability to detect and associate cerebrovascular disease related terms than current BERT based models. CONCLUSIONS: This study shows that a disease-specific BERT model improved the performance and accuracy of various disease-specific language processing tasks and can readily be fine-tuned to advance cerebrovascular disease research and further developed for clinical applications.

Sarcopenia is independently associated with parietal atrophy in older adults.

INTRODUCTION: As populations age, sarcopenia becomes a major health problem among adults aged 65 years and older. However, little information is available about the relationship between sarcopenia and brain structure abnormalities. The objective of this study was to investigate associations between sarcopenia and brain atrophy in older adults and relationships with regional brain areas. METHODS: This prospective cohort study recruited 102 retirement community residents aged 65 years and older. All participants underwent gait speed measurement, handgrip strength measurement and muscle mass measurement by dual X-ray absorptiometry. Diagnosis of sarcopenia was made according to criteria of the Asian Working Group for Sarcopenia (AWGSOP). All patients underwent magnetic resonance imaging (MRI), and images were analysed for global cortical atrophy (GCA) (range 0-3), parietal atrophy (PA) (range 0-3) and medial temporal atrophy (MTA) (range 0-4). RESULTS: Among 102 older adult participants (81.4 ± 8.2 years), 47 (46.1%) were diagnosed with sarcopenia according to AWGSOP criteria. The sarcopenia group had more moderate to severe PA (Grade 2: 19.1% vs. 5.5%; grade 3:6.4% vs. 0%, P = 0.016) and GCA (Grade 2: 40.4% vs. 18.2%, P = 0.003) and a trend of more moderate to severe MTA (Grade 2: 46.8% vs. 30.9%; grade 3: 8.5% vs. 1.8%, P = 0.098) than the non-sarcopenia group. In univariate logistic regression, sarcopenia was significantly associated with PA (OR 5.94, 95% CI 1.56-22.60, P = 0.009), GCA (OR 3.05, 95% CI 1.24-7.51, P = 0.015), and MTA (OR 2.55, 95% CI 1.14-5.69, P = 0.023). In multivariable logistic regression analysis, sarcopenia was an independent risk factor for PA (adjusted OR 6.90, 95% CI 1.30-36.47, P = 0.023). After adjusting for all covariates, only age had a significant relationship with GCA (Adjusted OR 1.09, 95% CI 1.00-1.19, P = 0.044) and MTA (Adjusted OR 1.09, 95% CI 1.01-1.17, P = 0.022). CONCLUSIONS: This is the first study to explore associations between sarcopenia and global as well as regional brain atrophy in older adults. The sarcopenia group had higher rates of moderate to severe PA, GCA and MTA than the non-sarcopenia group. PA was significantly associated with sarcopenia in older adults. Further longitudinal studies are needed to address the mechanism and pathogenesis of brain atrophy and sarcopenia.

Developing a predictive model for hospital-associated disability among older patients hospitalized for an acute illness: the HAD-FREE Score.

PURPOSE: To develop a predictive model to identify hospitalized older patients at risk of functional decline. METHODS: This retrospective cohort study recruited participants aged 65 years and over admitted to internal medicine wards of a tertiary medical center in Taiwan during May to October 2017 for developing predictive model (n = 1698) and those admitted during November to December 2017 for validation study (n = 530) of the model. Demographic data, geriatric assessments and hospital conditions (admission route and length of hospital stay) were collected for analysis. RESULTS: Overall, of the 1698 participants (mean age 75.8 ± 7.9 years, 60.9% male) enrolled in the development study, 20.1% had functional decline. Results of multivariate logistic regression showed that older age, hearing impairment, history of falls within one year, risk of malnutrition, physical restraint, admission via emergency department and hospital stay ≥ 5 days were independent predictive factors for decline. A scoring system, HAD-FREE Score, constructed from the above predictive factors ranged from 0 to 18 points and ≥ 6 points was chosen as the cut-off point. The area under the receiver operating characteristic analysis was 0.748 (95% confidence interval: 0.720-0.776), the sensitivity was 65.3% and the specificity was 71.3%. Validation of the HAD-FREE Score showed moderate discriminative ability in the validation study. CONCLUSION: A HAD-FREE Score developed from seven independent factors could predict functional decline with moderate discriminative ability and good validation. This scoring system can be the basis of an automatic dynamic tracking within the electronic medical record to identify those older patients at risk of functional decline during hospitalization.