Gait Analysis with Wearable Sensors in Isolated REM Sleep Behavior Disorder Associated with Phenoconversion: An Explorative Study.

Background: Gait disturbance is a vital characteristic of motor manifestation in α- synucleinopathies, especially Parkinson's disease. Subtle gait alterations are present in isolated rapid eye movement sleep behavior disorder (iRBD) patients before phenoconversion; it is yet unclear, if gait analysis may predict phenoconversion. Objective: To investigate subtle gait alterations and explore whether gait analysis using wearable sensors is associated with phenoconversion of iRBD to α-synucleinopathies. Methods: Thirty-one polysomnography-confirmed iRBD patients and 33 healthy controls (HCs) were enrolled at baseline. All participants walked for a minute while wearing 6 inertial sensors on bilateral wrists, ankles, and the trunk (sternal and lumbar region). Three conditions were tested: (i) normal walking, (ii) fast walking, and (iii) dual-task walking. Results: Decreased arm range of motion and increased gait variation (stride length, stride time and stride velocity) discriminate converters from HCs at baseline. After an average of 5.40 years of follow-up, 10 patients converted to neurodegenerative diseases (converters). Cox regression analysis showed higher value of stride length asymmetry under normal walking condition to be associated with an early conversion of iRBD to α- synucleinopathies (adjusted HR 4.468, 95% CI 1.088- 18.349, p = 0.038). Conclusions: Stride length asymmetry is associated with progression to α- synucleinopathies in patients with iRBD. Gait analysis with wearable sensors may be useful for screening, monitoring, and risk stratification for disease-modifying therapy trials in patients with iRBD.

Dysregulation of acyl carnitines, pentose phosphate pathway and arginine and ornithine metabolism are associated with decline in intrinsic capacity in Chinese older adults.

BACKGROUND: Intrinsic capacity is the combination of individual physical and mental abilities, reflecting the aging degree of the older adults. However, the mechanisms and metabolic characteristics of the decline in intrinsic capacity are still unclear. AIMS: To identify metabolic signatures and associated pathways of decline in intrinsic capacity based on the metabolite features. METHODS: We recruited 70 participants aged 77.19 ± 8.31 years. The five domains of intrinsic capacity were assessed by Short Physical Performance Battery (for mobility), Montreal cognition assessment (for cognition), 30-Item Geriatric Depression Scale (for psychology), self-reported hearing/visual impairment (for sensory) and Nutritional risk screening (for vitality), respectively. The serum samples of participants were analyzed by liquid chromatography-mass spectrometry-based metabolomics, followed by metabolite set enrichment analysis and metabolic pathway analysis. RESULTS: There were 50 participants with a decline in intrinsic capacity in at least one of the domains. A total of 349 metabolites were identified from their serum samples. Overall, 24 differential metabolites, 5 metabolite sets and 13 pathways were associated with the decline in intrinsic capacity. DISCUSSION: Our results indicated that decline in intrinsic capacity had unique metabolomic profiles. CONCLUSION: The specific change of acyl carnitines was observed to be a feature of decline in intrinsic capacity. Dysregulation of the pentose phosphate pathway and of arginine and ornithine metabolism was strongly associated with the decline in intrinsic capacity.

Potential role of APOE ɛ4 allele as a modifier for the association of BDNF Val66Met polymorphisms and cognitive impairment in community-dwelling older adults.

Objective: To determine whether the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with cognitive impairment (CI) in community-dwelling Chinese older adults, and to investigate whether this relationship is modified by the Apolipoprotein E (APOE) ɛ4 allele. Methods: The study is a secondary analysis of 703 participants aged ≥60 years randomly enrolled from the Beijing Longitudinal Study of Aging II prospective cohort. The education-adjusted Mini-Mental State Examination and the Clinical Dementia Rating Scale were used to measure the cognitive performance of the subjects. The main effects and interactions (additive and multiplicative) of the BDNF Met and the APOE ε4 alleles on CI were estimated by logistic regression models. Results: In total, 84 out of 703 older adults aged ≥60 years old had CI. No significant difference was observed in the risk of CI between participants with the BDNF Met allele and that of subjects without the BDNF Met allele (p = 0.213; p = 0.164). Individuals carrying both the BDNF Met and APOE ε4 alleles had an almost 1.5-fold increased odds of CI compared with carriers of the BDNF Met allele but without the APOE ε4 allele. The additive association indicated a positive interaction of both BDNF Met and APOE ε4 alleles with wide CIs (p = 0.021; p = 0.018). Conclusion: The results suggest that the APOE ε4 allele may be a potential modifier for the association of the BDNF Val66Met polymorphism with CI in community-dwelling older adults.

Implementation and impact of the World Health Organization integrated care for older people (ICOPE) program in China: a randomised controlled trial.

BACKGROUND: Fragmentation of services increases health and social care burden as people live longer with higher prevalence of diseases, frailty and dependency. Local evidence for implementing person-centred integrated care is urgently needed to advance practice and policies to achieve healthy ageing. OBJECTIVE: To test the feasibility and impact of World Health Organization's (WHO) Integrated Care for Older People (ICOPE) approach in China. DESIGN: A randomised controlled trial examining the feasibility of implementing ICOPE approach, evaluating its impact on health outcomes and health resource utilisation. SETTING: Primary care setting in urban and suburban communities of Chaoyang District, Beijing, China. SUBJECTS: Community-dwelling older adults screened as at-risk of functional declines and randomised into intervention (537) and control (1611) groups between September 2020 and February 2021. METHODS: A 6-month intervention program following WHO's ICOPE care pathways implemented by integrated care managers compared to standard available care. RESULTS: After 1 to 1 propensity score matching, participants in intervention and control groups (totally 938) had comparable baseline characteristics, demonstrated feasibility of implementing ICOPE with satisfaction by participants (97-99%) and providers (92-93%). All outcomes showed improvements after a 6-month intervention, while statistically significant least-squares mean differences (control-intervention) in vitality (Mini-Nutritional Assessment Short Form to measure vitality, -0.21, 95% CI, -0.40-0.02), mobility (Short Physical Performance Battery to measure mobility, -0.29, 95% CI, -0.44-0.14) and psychological health (Geriatric Depression Scale five items to measure psychological health, 0.09, 95% CI, 0.03-0.14) were observed (P < 0.05). CONCLUSIONS: It is feasible to localise and implement WHO's ICOPE approach in regions with fragmented resources such as China. Preliminary evidence supports its acceptance among key stakeholders and impact on health outcomes.

New horizons in Parkinson's disease in older populations.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Ageing is considered to be the greatest risk factor for PD, with a complex interplay between genetics and the environment. With population ageing, the prevalence of PD is expected to escalate worldwide; thus, it is of utmost importance to reduce the burden of PD. To date, there are no therapies to cure the disease, and current treatment strategies focus on the management of symptoms. Older adults often have multiple chronic diseases and geriatric syndromes, which further complicates the management of PD. Healthcare systems and care models necessary to address the broad needs of older PD patients are largely unavailable. In this New Horizon article, we discuss various aspects of PD from an ageing perspective, including disease management. We highlight recent advancements in PD therapies and discuss new care models with the potential to improve patient's quality of life.

Biomarkers of aging.

Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need. Here, we summarize our current knowledge of biomarkers developed for cellular, organ, and organismal levels of aging, comprising six pillars: physiological characteristics, medical imaging, histological features, cellular alterations, molecular changes, and secretory factors. To fulfill all these requisites, we propose that aging biomarkers should qualify for being specific, systemic, and clinically relevant.

Age as a risk factor for orthostatic hypotension induced by the levodopa challenge test in patients with Parkinson's disease: Results from a single-center trial.

BACKGROUND: Hypotension can occur in patients receiving levodopa (L-dopa) treatment for parkinsonism. However, only few studies have focused on the characteristics of orthostatic hypotension (OH) induced by the L-dopa challenge test (LCT). This study aimed to investigate the characteristics and influencing factors of LCT-induced OH in a relatively large sample of patients with Parkinson's disease (PD). METHODS: Seventy-eight patients with PD without a previous diagnosis of OH underwent the LCT. Blood pressure (BP) in the supine and standing positions was measured before and 2 hours after the LCT. If diagnosed with OH, the patients' BP was monitored again 3 hours after the LCT. The clinical features and demographics of the patients were analyzed. RESULTS: Eight patients were diagnosed with OH 2 hours after the LCT (median dose of 375 mg L-dopa/benserazide; incidence = 10.3%). One patient without symptoms had OH 3 hours after the LCT. Compared with patients without OH, patients with OH had lower 1- and 3-minutes standing systolic BP and 1-minute standing diastolic BP at baseline and 2 hours after the LCT. Patients in the OH group were of older age (65.31 ± 4.17 years vs 59.74 ± 5.55years) and had lower Montreal Cognitive Assessment scores (17.5 vs 24) and higher L-dopa/benserazide levels (375 [250, 500] mg vs 250 [125, 500] mg). Older age markedly increased the odds of having LCT-induced OH (odds ratio, 1.451; 95% confidence interval, 1.055-1.995; P = .022). CONCLUSIONS: LCT increased the odds of OH in non-OH PD, causing symptomatic OH in 10.3% of patients in our study, thereby raising safety concerns. Increase in age was observed to be a risk factor for LCT-induced OH in PD patients. A study with a larger sample size is warranted to confirm our results. TRIAL REGISTRATION NUMBER: Clinical Trials Registry under ChiCTR2200055707. DATE OF REGISTRATION: January 16, 2022.

Fatigue in Patients with Idiopathic/Isolated REM Sleep Behavior Disorder.

Introduction: Fatigue is one of the most common and disabling symptoms of Parkinson's Disease (PD). The occurrence and clinical features of fatigue in patients with prodromal PD remain largely elusive. This study aimed to investigate the prevalence and clinical characteristics of fatigue in patients with idiopathic/isolated REM sleep behavior disorders (iRBD). Methods: A total of 97 polysomnography-confirmed iRBD patients were enrolled in this study. A comprehensive neurological assessment (including motor and non-motor assessment) was performed. Fatigue was assessed using the Fatigue Severity Scale (FSS). Motor and non-motor characteristics were compared between iRBD patients with and without fatigue. Logistic regression was used to identify the factors associated with fatigue. Results: The prevalence of fatigue was 35.05%. Compared to the non-fatigue patients, patients with fatigue had higher non-motor symptom scale (NMSS) score (p = 0.009), higher Hamilton Depression Rating Scale (HAMD) score (p = 0.002), and a higher prevalence of orthostatic hypotension (p = 0.021). Multivariate regression analysis showed that depression (OR 4.17, 95% CI 1.13−15.49, p = 0.033) and orthostatic hypotension (OR 2.80, 95% CI 1.09−7.18, p = 0.032) were significantly associated with fatigue in iRBD patients. Additionally, both NMSS (rs = 0.310, p = 0.002) and HAMD (rs = 0.385, p < 0.001) scores were mildly correlated with fatigue severity. Conclusion: Our study showed that fatigue is common in patients with iRBD. In addition, depression and orthostatic hypotension were independently associated with fatigue in iRBD patients.

Physical resilience in older adults: Potential use in promoting healthy aging.

Physical resilience is a dynamic concept referring to the physiological response when the body is exposed to stressors. The level of physical resilience is the sum of underlying physiological reserves. Moreover, it may not only be determined by age, genetics, or exposure to a variety of diseases, but is also closely related to the psychological, social, and environmental factors of an individual. This paper summarizes our present understanding of the relationship between physical resilience and other concepts closely related to it. Furthermore, we illustrate the current research progress on physical resilience models and clinical resilience assessment. Besides, this paper intends to present a better understanding of physical resilience and its use in treatment decision-making, personalized diagnosis and disease management, and prevention and rehabilitation strategies.

Physical Resilience: A novel approach for healthy aging.

Population aging is evident globally. The traditional model of care based on disease management is not sufficient to develop a generation of functional older adult population. The construct of Physical Resilience (PR) holds great potential to make the agenda of healthy aging a reality if we were to properly understand it and develop intervention strategies to maintain PR through life. There are several difficulties and challenges with this novel construct that need to be resolved through research, so as to foster its vast possibilities to maintain functional ability in old age.

Gait variability is sensitive to detect Parkinson's disease patients at high fall risk.

BACKGROUND: Gait disturbance is an important risk factor for falls in Parkinson's disease (PD). Using wearable sensors, we can obtain the spatiotemporal parameters of gait and calculate the gait variability. This prospective study aims to objectively evaluate the gait characteristics of PD fallers, and further explore the relationship between spatiotemporal parameters of gait, gait variability and falls in PD patients followed for six months. METHODS: Fifty-one PD patients were enrolled in this study. A seven-meter timed up and go test was performed. Gait characteristics were determined by a gait analysis system. Patients were followed monthly by telephone until the occurrence of falls or till the end of six months. The patients were categorized into fallers and non-fallers based on whether fell during the follow-up period. Gait parameters were compared between two groups, and binary logistic regression was used to establish the falls prediction model. In the receiver-operating characteristic curve, area under the curve (AUC) was utilized to evaluate the prediction accuracy of each indicator. RESULTS: All subjects completed the follow-up, and 14 (27.5%) patients reported falls. PD fallers had greater gait variability. The range of motion of the trunk in sagittal plane variability was an independent risk factor for falls and achieved moderate prediction accuracy (AUC = 0.751), and the logistic regression model achieved a good accuracy of falls prediction (AUC = 0.838). CONCLUSIONS: Increased gait variability is a significant feature of PD fallers and is more sensitive to detect PD patients at high risk of falls than spatiotemporal parameters.

Intrinsic Capacity vs. Multimorbidity: A Function-Centered Construct Predicts Disability Better Than a Disease-Based Approach in a Community-Dwelling Older Population Cohort.

Objective: This study aimed to assess the status of intrinsic capacity (IC)-a novel function-centered construct proposed by the WHO and examine whether impairment in IC predicts subsequent 1-year activities of daily living (ADL) disability better than a disease-based approach, i. e., multimorbidity status. Methods: This study included data of community-dwelling older adults from the Beijing Longitudinal Study on Aging II aged 65 years or older who were followed up at 1 year. Multivariate logistic regressions were performed to estimate the odds of ADL disability at baseline and 1-year follow-up. Results: A total of 7,298 older participants aged 65 years or older were included in the current study. About 4,742 older adults were followed up at 1 year. At baseline, subjects with a higher impairment in IC domains showed higher odds of ADL disability [adj. odds ratio (OR) = 9.51 for impairment in ≥3 domains, area under the curve (AUC) = 0.751] compared to much lower odds of ADL disability in subjects with a higher number (≥3) of chronic diseases (adj. OR 3.92, AUC = 0.712). At 1-year follow-up, the overall incidence of ADL disability increased with the impairment in IC domains higher than the increase in multimorbidity status. A higher impairment in IC domains showed higher odds of incidence ADL disability for impairment in 2 or ≥3 IC domains (adj. OR 2.32 for impairment in ≥3 domains, adj. OR 1.43 for impairment in two domains, AUC = 0.685). Only subjects who had ≥3 chronic diseases had higher odds of 1-year incident ADL disability (adj. OR 1.73, AUC = 0.681) that was statistically significant. Conclusion: Our results imply that a function-centered construct could have higher predictability of disability compared to the multimorbidity status in community older people. Our results need to be confirmed by studies with longer follow-up.

Severity of frailty as a significant predictor of mortality for hemodialysis patients: a prospective study in China.

Background: Frailty is known to be highly prevalent in older hemodialysis (HD) patients. We studied the prevalence of frailty and its associated factors in Chinese HD patients. We further studied if frailty could predict survival in HD patients. Methods: This is a prospective study involving patients receiving maintenance HD in the dialysis center of Xuanwu Hospital, Beijing. Study subjects were enrolled from October to December, 2017 and followed up for two years. Demographic data, comorbidities and biological parameters were collected. Frailty was assessed using the Fried frailty phenotype at baseline. Cox regression analysis was performed to identify the relationship between frailty and mortality in HD patients. Kaplan-Meier was plotted using the cutoff value obtained by ROC curve to evaluate survival rates in different frailty status. Results: Total of 208 HD patients were enrolled with a mean age of 60.5±12.7 years. According to the frailty criteria, at baseline the prevalence of robust, pre-frail and frail in HD patients was 28.7%, 45.9%, and 25.4%, respectively. The two-year all-cause mortality was 18.8% (39/207) and underlying causes of death included coronary artery disease (CAD), cerebrovascular disease (CVD), hyperkalemia, severe infection, malignant tumor and others. Survival curve showed the patients with frailty score ≥4 to have significantly shorter survival time as compared to patients with frailty score ≤ 3. Frailty predicted two-year mortality when frailty score ≥4 with a sensitivity of 70% and a specificity of 83.67% with an AUC of 0.819. Frailty score was positively associated with age and ratio of ultrafiltration volume to dry weight, while negatively associated with levels of serum albumin, uric acid and diastolic blood pressure after HD. Conclusions: Our results confirm frailty to be very common among HD patients and severity of frailty was a significant predictor of mortality for HD patients. Factors such as age, malnutrition and low blood pressure are the factors to be associated with frailty. Interdialytic weight gain inducing excessive ultrafiltration volume is an important risk factor.

Cross-sectional study examining the status of intrinsic capacity decline in community-dwelling older adults in China: prevalence, associated factors and implications for clinical care.

OBJECTIVES: Intrinsic capacity (IC) was proposed by the WHO as a new concept for capturing an individual's functional capacities across their lifetime. We aimed to investigate the prevalence and factors associated with IC decline and examine associations between IC and adverse outcomes among community-dwelling older adults in China. DESIGN: A cross-sectional study. SETTING: Community, China. PARTICIPANTS: Data were derived from the China Comprehensive Geriatric Assessment Study, a population-based nationally representative sample. IC comprises of five domains: locomotion, cognition, vitality, sensory and psychology. Participants were deemed to have IC decline if they showed a decline in any of the five domains. Sociodemographic characteristics, chronic diseases, geriatric syndromes and adverse outcomes were also examined. RESULTS: Of the 5823 community-dwelling participants aged 60-98 years, 2506 had IC decline (weighted 39.9%): 57.7% in western, 38.3% in northern, 33.7% in northwest, 36.1% in middle, 16.9% in eastern and 19.8% in northeast China. The number of participants with decline in the locomotion, cognition, vitality, sensory and psychological domains were 1039 (17.8%), 646 (11.1%), 735 (12.6%), 824 (14.2%) and 713 (12.2%), respectively. Age, northern residence, low education, being unmarried, low income, less exercise, less meat intake, insomnia, memory loss, urinary incontinence, constipation, slowness, chronic obstructive pulmonary disease and osteoarthritis were related to IC decline. After adjusting for age, sex, area, district, marriage, education, waist-hip ratio, smoking, alcohol consumption, exercise, income and chronic diseases, IC decline was independently associated with risk of frailty, disability, falls, fractures and immobility. CONCLUSION: The prevalence of IC decline in China is high. IC decline was significantly associated with adverse outcomes, after adjustment for related variables. Efforts promoting IC to delay functional dependence should focus on modifiable factors, including negative social factors, poor lifestyle, chronic diseases and geriatric syndromes.

Assessing the life cycle of pests, Diaphania pulverulentalis (Hampson) and Maconellicoccus hirsutus Green, reared on transgenic mulberry.

The study aims at investigating the growth and development of two common pests in mulberry namely the leaf roller (Diaphania pulverulentalis) and mealy bug (Macconellicoccus hirsutus), reared on transgenic mulberry plants in comparison with the wild type plants V1, a ruling variety. Both the pests completed normal life cycle on all the four different transgenic plants (Ip::HVA1, Cp::HVA1, Cp::BCH1, Cp::osmotin and Ip::osmotin) expressing three different transgenes (HVA1, BCH1 and osmotin) in the presence of the marker gene NPTII. There was no significant difference in the incubation period of the eggs, growth of first to fifth instar larvae and total larval period of the leaf roller reared on transgenic and non-transgenic mulberry. The pre-pupal, pupal, adult stages and adult fecundity also did not differ. The variations in the duration of the different nymphal instars, and their total duration was not significant in the case of mealy bug, when reared on the transgenics. The adult longevity and total life span of female mealy bugs, and the pupal period and total life span of the male bugs were on par with those reared on the wild type plants. The study indicates that the life cycle of both the pests, which are common in a mulberry ecosystem, were not affected by feeding on any of the transgenic mulberry plants at any stage of their growth and development.