Predictive value of synaptic plasticity for functional decline in patients with multiple sclerosis.

Background: Previous research suggested that quadripulse (QPS)-induced synaptic plasticity is associated with both cognitive and motor function in patients with multiple sclerosis (MS) and does not appear to be reduced compared to healthy controls (HCs). Objective: This study aimed to explore the relationship between the degree of QPS-induced plasticity and clinically significant decline in motor and cognitive functions over time. We hypothesized that MS patients experiencing functional decline would exhibit lower levels of baseline plasticity compared to those without decline. Methods: QPS-induced plasticity was evaluated in 80 MS patients (56 with relapsing-remitting MS and 24 with progressive MS), and 69 age-, sex-, and education-matched HCs. Cognitive and motor functions, as well as overall disability status were evaluated annually over a median follow-up period of 2 years. Clinically meaningful change thresholds were predefined for each outcome measure. Linear mixed-effects models, Cox proportional hazard models, logistic regression, and receiver-operating characteristic analysis were applied to analyse the relationship between baseline plasticity and clinical progression in the symbol digit modalities test, brief visuospatial memory test revised (BVMT-R), nine-hole peg test (NHPT), timed 25-foot walk test, and expanded disability status scale. Results: Overall, the patient cohort showed no clinically relevant change in any functional outcome over time. Variability in performance was observed across time points in both patients and HCs. MS patients who experienced clinically relevant decline in manual dexterity and/or visuospatial learning and memory had significantly lower levels of synaptic plasticity at baseline compared to those without such decline (NHPT: ß = -0.25, p = 0.02; BVMT-R: ß = -0.50, p = 0.005). Receiver-operating characteristic analysis underscored the predictive utility of baseline synaptic plasticity in discerning between patients experiencing functional decline and those maintaining stability only for visuospatial learning and memory (area under the curve = 0.85). Conclusion: Our study suggests that QPS-induced plasticity could be linked to clinically relevant functional decline in patients with MS. However, to solidify these findings, longer follow-up periods are warranted, especially in cohorts with higher prevalences of functional decline. Additionally, the variability in cognitive performance in both patients with MS and HCs underscores the importance of conducting further research on reliable change based on neuropsychological tests.

Mobility Assessment Instruments.

OBJECTIVES: Review commonly used mobility assessment instruments and discuss their use in multidisciplinary research and clinical practice. METHODS: Data sources include peer-reviewed articles sourced in electronic databases (PubMed, CINAHL), government websites, national, and international best practice guidelines to describe frequently used mobility assessment instruments. RESULTS: Numerous clinician-, observer-, patient-reported, and performance outcome instruments and evidence-based implementation program resources exist, though these vary in their intended purpose and setting. Wearable and ambient sensors provide new opportunities to collect passive, objective physical activity data and observe changes in mobility across settings. CONCLUSIONS: Selection among multiple assessment tools requires consideration of the available evidence for use in the desired population, the outcomes of interest, whether use is feasible for the setting, and the strength of validity and reliability data for the tool. IMPLICATIONS FOR NURSING PRACTICE: Nurses, especially in the inpatient setting, are typically in most frequent contact with patients and are well-positioned to assess mobility and ensure that safe, progressive mobility care plans are in place. Development of an organization-wide mobility culture requires a systematic, multidisciplinary approach and long-term commitment.

Revisiting the "Timed Up and Go" test: a 12-s cut-off can predict Hospitalization Associated Functional Decline in older adults.

Early detection of functional decline, a major risk among hospitalized older adults, can facilitate interventions that could significantly reduce it. We aimed to examine the contribution of the Timed Up and Go (TUG) test in predicting Hospitalization Associated Functional Decline (HAFD) among older adults, able to independently ambulate before admission. We used a cross-sectional study design; a total of 310 older adults (age ≥ 65) hospitalized in internal medicine wards between December 2018 and August 2020 were included; exclusion criteria were inability to ambulate, a diagnosis restricting mobility, hospitalization for end-of-life care, or impaired cognition. The Modified Barthel Index was used to assess HAFD; it was administered at admission to evaluate patients' independence in activities of daily living 2 weeks prior hospitalization, and at discharge. The TUG test was performed on admission and to predict significant functional decline (defined by a reduction of three points or more in the Modified Barthel Index), while accounting for demographics, length of hospitalization, comorbidity burden (Charlson's comorbidity index), and cognitive function (ALFI-MMSE). Participants were divided into three groups according to their TUG score-under or over a cut-off score of 12 s, or inability to complete the test. Adjusting for age, comorbidity, cognitive ability, and duration of hospitalization, the group that performed the test in less than 12 s showed no statistically significant change in the Modified Barthel Index, therefore no significant HAFD. The other groups showed a statistically significant decline in function. Risk for significant HAFD is currently underestimated in clinical settings, limited to subjective assessment, and underused in the context of implementing early interventions to prevent HAFD. The TUG may support screening for those at risk of hospitalizing-associated functional decline and could help identify patients suitable for preventative interventions.

[Comparaison du déclin fonctionnel entre des patients atteints de démence à corps de Lewy et de la maladie d'Alzheimer]. / Functional decline in Lewy body dementia compared to Alzheimer disease.

Lewy body dementia (LBD) is the second most frequent neurodegenerative disorder after Alzheimer disease (AD). In this study, we compared functional decline between LBD and AD patients, considering motor dysfunction, over an 18-month follow-up period. We included all patients >70 years of age, with initial MMSE ≥ 20 and a diagnosis of possible or probable LBD or AD, who consulted at the memory centre of the Pitié-Salpêtrière hospital. Statistical analyses were performed using univariate tests and multivariate linear regression. Thirty-seven AD and 36 LBD patients were included, with a median age of 81 and a median MMSE score of 24/30. Global ADL Katz score decreased significantly for LBD people, compared to AD patients: -0.40 ± 0.75 versus 0 ± 0.24; p=0.003. Global IADL score decreased in the two populations but without a significant difference between the two groups: -1.71 ± 2.19 in LBD versus -1.32 (± 1.55); p=0.38. This study shows a significant decrease in autonomy in LBD patients over time that was faster than that in AD patients, related, in particular, to bathing, dressing and personal care.

The FITNESS study: longitudinal geriatric assessment, treatment toxicity, and biospecimen collection to assess functional disability among older adults with lung cancer.

Introduction: Older adults with chronic disease prioritize functional independence. We aimed to describe the feasibility of capturing functional disability and treatment toxicity among older adults with lung cancer using a longitudinal comprehensive geriatric assessment (CGA) and molecular biomarkers of aging. Methods: This prospective study included adults ≥60 years with any newly diagnosed non-small-cell lung cancer. Participants were recruited from central Ohio (2018-2020). Study assessments included the Cancer and Aging Research Group CGA (CARG-CGA), short physical performance battery (SPPB), and the blessed orientation-memory concentration (BOMC) test at baseline, 3, 6, and 12 months. Activities of daily living (ADLs) and instrumental ADLs (IADLs), quality of life (QoL, PROMIS 10), and treatment toxicity were captured monthly. Stool and blood were collected to characterize the gut microbiome and age-related blood biomarkers. Results: This study enrolled 50 participants with an average age of 71.7 years. Ninety-two percent of participants were Caucasian, 58% were male, and all were non-Hispanic. Most had advanced stage (stage III/IV: 90%; stage I/II: 10%), with adenocarcinoma the predominant histologic subtype (68% vs. 24% squamous). First-line treatments included chemotherapy (44%), immune checkpoint inhibitors (ICIs, 22%), chemotherapy and ICIs (30%), or tyrosine kinase inhibitors (4%). The median baseline CARG toxicity score was 8 (range 2-12). Among patients with treatment-related toxicity (n = 49), 39 (79.6%) cases were mild (grade 1-2), and 10 (20.4%) were moderate to severe (≥ grade 3). Treatment toxicity was greater among those with a CARG score ≥8 (28.0% vs. 13.6%). Higher IADL independence, QoL, and SPPB scores at baseline were positively associated with Candidatus Gastranaerophilales bacterium, Lactobacillus rogosae, and Enterobacteria phage P4. Romboutsia ilealis, Streptococcus, and Lachnoclostridium sp An138 and T cell lag3 and cd8a were associated with worse IADLs, QoL, and SPPB scores at baseline. Discussion: A longitudinal CGA and biomarker collection is feasible among older adults undergoing lung cancer treatment. Gut microbe and T cell gene expression changes correlated with subjective and objective functional status assessments. Future research will test causality in these associations to improve outcomes through novel supportive care interventions to prevent functional disability.

Amyloid-PET imaging predicts functional decline in clinically normal individuals.

BACKGROUND: There is good evidence that elevated amyloid-ß (Aß) positron emission tomography (PET) signal is associated with cognitive decline in clinically normal (CN) individuals. However, it is less well established whether there is an association between the Aß burden and decline in daily living activities in this population. Moreover, Aß-PET Centiloids (CL) thresholds that can optimally predict functional decline have not yet been established. METHODS: Cross-sectional and longitudinal analyses over a mean three-year timeframe were performed on the European amyloid-PET imaging AMYPAD-PNHS dataset that phenotypes 1260 individuals, including 1032 CN individuals and 228 participants with questionable functional impairment. Amyloid-PET was assessed continuously on the Centiloid (CL) scale and using Aß groups (CL < 12 = Aß-, 12 ≤ CL ≤ 50 = Aß-intermediate/Aß± , CL > 50 = Aß+). Functional abilities were longitudinally assessed using the Clinical Dementia Rating (Global-CDR, CDR-SOB) and the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q). The Global-CDR was available for the 1260 participants at baseline, while baseline CDR-SOB and A-IADL-Q scores and longitudinal functional data were available for different subsamples that had similar characteristics to those of the entire sample. RESULTS: Participants included 765 Aß- (61%, Mdnage = 66.0, IQRage = 61.0-71.0; 59% women), 301 Aß± (24%; Mdnage = 69.0, IQRage = 64.0-75.0; 53% women) and 194 Aß+ individuals (15%, Mdnage = 73.0, IQRage = 68.0-78.0; 53% women). Cross-sectionally, CL values were associated with CDR outcomes. Longitudinally, baseline CL values predicted prospective changes in the CDR-SOB (bCL*Time = 0.001/CL/year, 95% CI [0.0005,0.0024], p = .003) and A-IADL-Q (bCL*Time = -0.010/CL/year, 95% CI [-0.016,-0.004], p = .002) scores in initially CN participants. Increased clinical progression (Global-CDR > 0) was mainly observed in Aß+ CN individuals (HRAß+ vs Aß- = 2.55, 95% CI [1.16,5.60], p = .020). Optimal thresholds for predicting decline were found at 41 CL using the CDR-SOB (bAß+ vs Aß- = 0.137/year, 95% CI [0.069,0.206], p < .001) and 28 CL using the A-IADL-Q (bAß+ vs Aß- = -0.693/year, 95% CI [-1.179,-0.208], p = .005). CONCLUSIONS: Amyloid-PET quantification supports the identification of CN individuals at risk of functional decline. TRIAL REGISTRATION: The AMYPAD PNHS is registered at www.clinicaltrialsregister.eu with the EudraCT Number: 2018-002277-22.

Interventions to Promote Physical Activity and Reduce Functional Decline in Medical Inpatients: An Umbrella Review.

OBJECTIVES: Physical inactivity in hospitals is common and is associated with poor patient and clinical outcomes. This review was undertaken to identify and describe the effectiveness of interventions implemented at the ward or system level for improving physical activity and reducing functional decline in general medical inpatients. The secondary aim was to describe the effects on length of stay, discharge destination, falls, and hospital costs. DESIGN: Umbrella review. SETTING AND PARTICIPANTS: Systematic reviews that evaluated ward- or system-level interventions aiming to improve physical activity or reduce functional decline in medical inpatients. METHODS: PubMed, EMBASE, Cochrane Database, CINAHL, JBI, and Web of Science databases were searched for English-language reviews published between 2000 and 2023. AMSTAR 2 was used to assess methodologic quality. Two reviewers independently assessed eligibility and methodologic quality and completed data abstraction, with results presented as a narrative synthesis. RESULTS: The search yielded 568 systematic reviews of which 12 met criteria, half of which were published since 2020. Reviews included 76 unique primary studies with 72,645 participants. Most reviews were of low quality. Interventions that focused on progressive mobilization likely increased physical activity participation, reduced functional decline, and improved discharge home. Multicomponent interventions that employed multiple strategies targeting a broader range of barriers likely improved functional decline and discharge home and may have been associated with shorter length of stay. No interventions were associated with increased frequency of falls. Few studies reported costs. CONCLUSIONS AND IMPLICATIONS: Progressive mobilization interventions and multicomponent interventions appear to be effective for improving physical activity participation and reducing functional decline in medical inpatients. Further high-quality studies may help to determine the most important aspects of multicomponent interventions. Standardized terminology related to inpatient physical activity may help promote a shared understanding and purpose across professions.

Definitions and adverse outcomes of sarcopenia in older patients in orthopedic and trauma care: A scoping review on current evidence.

PURPOSE: Sarcopenia, defined as the loss of muscle mass and strength, can hinder postoperative recovery and raise mortality rates. However, the current evidence on the harmful effects of sarcopenia in older patients in orthopedic and trauma care is unclear. This scoping review investigates different definitions that were used for the diagnosis of sarcopenia in older patients in orthopedic and trauma care and what adverse consequences have been examined. METHODS: We performed a comprehensive literature search in PubMed and Embase, following the PRISMA guidelines. We included original studies that examined clinical outcomes (such as length of hospital stay, rate of non-home discharge, rate of subsequent falls, rate of refractures, mortality, and functional outcome/quality of life) in older patients in orthopedic and trauma care (aged 65 years and above) with diagnosed sarcopenia (S) compared to a group without sarcopenia (NS). RESULTS: Our search identified 2,748 publications. Out of these, 23 articles met the inclusion criteria. Most publications were from Asia (n = 13). A total of 6174 patients were examined, with a prevalence of sarcopenia in 14-92%. 11 articles focused on patients with hip joint pathologies. Most studies diagnosed sarcopenia according to the Asian Working Group on Sarcopenia (AWGSOP1 or AWGSOP2) definitions (n = 10). Length of hospital stay was investigated in 13 studies. Seven studies assessed rates of non-home discharge rates. Subsequent falls were not investigated in any of the studies. 1 study reported the overall refracture rate (S: 10.4%; NS: 5.8%). Mortality was assessed in 11 studies (S: 1-60.5%; NS: 0-39.5%). The functional outcome/quality of life was investigated by 17 studies (Barthel Index decline S: -4.5 to -15.3 points; NS: -11.7 to -54.7 points). CONCLUSION: Sarcopenia has been increasingly studied in older patients in orthopedic and trauma care but there is a lack of consistent definition criteria. This scoping review suggests that sarcopenia may be associated with prolonged length of stay, higher rates of non-home discharge, and increased mortality among older patients in orthopedic and trauma care. However, prospective studies are necessary to establish the relationship between sarcopenia and refractures, falls, and functional outcome/quality of life among older patients in orthopedic and trauma care.

Phase 1 randomized trial of inpatient high-intensity interval training after major surgery.

BACKGROUND: High-intensity interval training (HIT) can provide physiologic benefits and may improve postoperative recovery but has not been evaluated in inpatients. This study aimed to evaluate the safety and tolerability of HIT after major surgery. METHODS: We performed a phase I randomized study comparing HIT with low-intensity continuous ambulation (40 m) during the initial inpatient stay after major surgery at a large academic center. Clinicopathologic and pre- and post-exercise physiologic data were captured. Perceived exertion was measured throughout the intervention. RESULTS: Twenty-two subjects were enrolled and randomized with 90% (20 subjects, 10 per arm) completing all aspects of the study. One patient declined participation in the exercise intervention. The HIT and continuous ambulation groups were relatively similar in terms of median age (65.5 vs 63.5), female sex (20% vs 40%), White race (90% vs 90%), having a cancer diagnosis (100% vs 80%), undergoing gastrointestinal surgery (60% vs 80%), median Karnofsky score (60 vs 60), and ability to independently ambulate preoperatively (100% vs 90%). All subjects completed the exercise without protocol deviation, cohort crossover, or safety events. Compared with the continuous ambulation group, the HIT group had higher end median perceived exertion (5.0 [IQR, 5.5] vs 3.0 [IQR, 1.8]), shorter overall time to complete assigned exercise (56.6 seconds vs 91.8 seconds), and a trend toward higher median gait speed over 40 m (0.71 m/s vs 0.44 m/s, P = .126). CONCLUSION: HIT in the hospitalized postoperative patient is safe and may be implemented to help promote positive physiologic outcomes and recovery.

Household Environments and Functional Decline Among Middle-Aged and Older Adults in China: Variations by Gender, Age, and Residence.

This study examined the associations between household social, economic, and physical environments and the trajectory of functional limitations over time among middle-aged and older adults in China, and how this relationship differs by gender, age, and residence. Linear growth curve models were applied to a sample of 13,564 respondents aged 45 years and older from four waves of the China Health and Retirement Longitudinal Study (CHARLS 2011-2018). Living alone, particularly for rural, female, and older respondents, was associated with a faster functional decline when compared to living with a spouse and without children. Improved housing quality was associated with a slower functional decline. Living with young descendants and without adult children for urban residents and a lower expenditure per capita for younger respondents were associated with a faster functional decline. These findings suggest that policies aimed at enhancing living conditions have the potential to improve physical functioning of older adults.

Association of cancer with functional decline at old age: a longitudinal study in Danish twins.

INTRODUCTION: There is evidence that older adults with cancer have a higher risk of functional decline than cancer-free older adults. However, few studies are longitudinal, and none are twin studies. Thus, we aimed to investigate the relationship between cancer and functional decline in older adult (aged 70+ years) twins. MATERIALS AND METHODS: Cancer cases in the Longitudinal Study of Aging Danish Twins were identified through the Danish Cancer Registry. Functional status was assessed using hand grip strength (6 years follow-up), and self-reported questions on mobility (10 years follow-up), and cut-offs were defined to assess functional decline. Cox regression models were performed for all the individual twins. In addition, we extended the analysis to discordant twin pairs (twin pairs with one having cancer and the other being cancer-free), to control to a certain extent for (unmeasured) shared confounders (genetic and environmental factors). RESULTS: The analysis based on individual twins showed that individual twins with cancer are at increased hazard of worsening hand grip strength (hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.04, 1.80) than cancer-free twins. Among the discordant twin pairs, twins with cancer had a higher hazard of worsening hand grip strength (HR 3.50, 95% CI 1.15, 10.63) than cancer-free cotwins. In contrast, there was no evidence of a difference between the hazard of experiencing mobility decline for twins with cancer compared with cancer-free twins, in both individual twins and discordant twin pairs analyses. DISCUSSION: Cancer was associated with hand grip strength functional decline in old individual twins and discordant pairs. Our results strengthen the importance of comprehensive geriatric assessment in older adults with cancer, as well as the importance of routine assessment of functional status. Promoting physical activity through exercise training programmes could enable the prevention of functional decline in older adults with cancer.

Frailty in Older Adults with Dengue Fever.

Background and objectives: Dengue is one of the most common epidemic infections around the world. Dengue infections in older adults are related to an atypical presentation and a high mortality. Frailty is associated with poor recovery from hospitalization due to infection. However, few studies describe frailty and functional decline after dengue infection. The current case series study aims to investigate the baseline frailty status, functional decline, and time to recovery in older adults after dengue infection. Method: We studied seven patients with post-dengue frailty who had been admitted to the geriatric ward in one tertiary medical center in Taiwan during the 2023 dengue fever outbreak. Result: The mean age was 82 years old. The clinical frailty scale worsened from a mean of 4.7 at baseline to 6.3 at dengue diagnosis. The mean Katz Index of independence in activities of daily living decreased from 10.6 at baseline to 4.7 with dengue, and it recovered to 6.7 one month after discharge. Conclusions: Our preliminary data suggest that there is indeed an increase in frailty in older adults due to dengue. Post-dengue frailty and functional decline might be profound and persistent. Acute geriatric care intervention rehabilitation for frailty after dengue may benefit this population.

A Prospective Intervention Study With 6 Months Follow-up of the Effect of Reablement in Home Dwelling Elderly: Patient-reported and Observed Outcomes.

Objectives: To investigate the effect of a reablement intervention (a person-centered, interdisciplinary rehabilitation approach) compared with usual care services in home-dwelling elderly experiencing functional declines in activities of daily living. Design: A non-randomized controlled trial comparing a reablement intervention with usual care; outcomes were measured at baseline, after intervention, and at a 6-month from baseline in both groups. Setting: Municipal public health service. Participants: Sixty-five home-dwelling elderly with functional decline were assigned by the participants home care service zone to a reablement group (n=35), or a usual care group (n=30). The mean participant age was 80±11 years in the reablement group and 78±12 in the usual care group. Intervention: The reablement group received a person-centered and tailored reablement program provided by an interdisciplinary team, consisting of a physiotherapist, an occupational therapist, and a nurse. The usual care group received standard home care services. Main Outcome Measures: The dimension "Your health today" from the European Quality of Life-Visual Analog Scale (HRQOL), the patient-specific functional scale for goals in ADL (PSFS), the short physical performance battery (SPPB), and home care services in hours per week. Results: There were significant differences over time in favor of the reablement group with between-group effect sizes of Cohen h2=0.36 (P=.001) for HRQOL, h2=0.60 (P=.001) for PSFS, h2=0.30 (P=.001) for SPPB, and h2=0.10 (P=.013) for hours of home care services per week. The within-group effect size for PSFS was h2=0.15 (P=.010) in favor of the reablement group. The mean number of hours of home care services per week was mean 0.38±1.07 (P=.001) in the reablement group and mean 30.38±64.13 (P=.023) in the usual care group. Conclusions: The participants in the reablement group achieved and maintained better physical function, a higher HRQOL and needed considerably less home care services than the usual care group participants. Thus, reablement appears to be a more beneficial and sustainable approach than the usual care services for the home-dwelling elderly with functional decline.

Preoperative Age and Its Impact on Long-Term Renal Functional Decline after Robotic-Assisted Partial Nephrectomy: Insights from a Tertiary Referral Center.

Background and Objectives: to investigate the impact of age on renal function deterioration after robotic-assisted partial nephrectomy (RAPN) focusing on a decline to moderate and severe forms of chronic kidney disease (CKD). Materials and Methods: This is a single center prospective analysis of patients who underwent RAPN. The outcomes include the development of de novo CKD-S 3a [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2)] and de novo CKD-S 3b (eGFR < 45 mL/min/1.73/m2). Multivariable analysis (MVA) via Cox regression identified predictors for CKD-S 3a/b. Kaplan -Meier Analyses (KMA) were fitted for survival assessment. Multivariable linear regression was utilized to identify the predictors of last-eGFR. Results: Overall, 258 patients were analyzed [low age (<50) n = 40 (15.5%); intermediate age (50-70) n = 164 (63.5%); high age (>70) n = 54 (20.9%)] with a median follow-up of 31 (IQR 20-42) months. MVA revealed an increasing RENAL score [Hazard Ratio (HR) 1.32, p = 0.009], age 50-70 (HR 6.21, p = 0.01), age ≥ 70 (HR 10.81, p = 0.001), increasing BMI (HR 1.11, p < 0.001) and preoperative CKD 2 (HR 2.43, p = 0.014) are independent risk factors associated with an increased risk of CKD-S 3a; conversely, post-surgical acute kidney injury was not (p = 0.83). MVA for CKD-S 3b revealed an increasing RENAL score (HR 1.51, p = 0.013) and age ≥ 70 (HR 2.73, p = 0.046) are associated with an increased risk of CKD-S 3b. Linear regression analysis revealed increasing age (Coeff. -0.76, p < 0.001), increasing tumor size (Coeff. -0.31, p = 0.03), and increasing BMI (Coeff. -0.64, p = 0.004) are associated with decreasing eGFR at last follow-up. We compare the survival distribution of our cohort stratified by age elderly patients experienced worsened CKD-S 3a/b disease-free survival (p < 0.001; p < 0.001, respectively). Conclusions: Age is independently associated with a greater risk of significant and ongoing decline in kidney function following RAPN. Recognizing the impact of aging on renal function post-surgery can guide better management practices. Further investigations are required.

Effectiveness of exercise intervention on physical and health outcomes in patients admitted to an acute medical ward: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of inpatient medical ward exercise on physical and health outcomes in adults compared with usual care. DATA SOURCES: Medline, CINAHL and EMBASE were searched from inception to 20 April 2023. REVIEW METHODS: Randomised-controlled trials in English that reported physical and health outcomes of adults who received an exercise intervention on an acute medical ward were included. Two reviewers independently extracted data. Methodological quality was assessed using the PEDro and TESTEX scales. The GRADE rating assessed the quality of evidence to evaluate the certainty of effect. Meta-analyses were performed where possible. RESULTS: Thirteen studies were included, with 1273 unique participants (mean [SD] age, 75.5 [11] years), which compared exercise intervention with usual care. Low quality evidence demonstrated a significant improvement in aerobic capacity ([MD], 1.39 m [95% CI, 0.23, 2.55], p = 0.02) and maximum isometric strength ([MD], 2.3 kg [95% CI, 2.2, 2.4], p < 0.001) for the exercise intervention compared with usual care. Low quality evidence demonstrated no difference for in-hospital falls count ([OR], 1.93 [95% CI, 0.61, 6.12] p = 0.27) or mortality ([OR], 0.77 [95% CI, 0.48, 1.23], p = 0.27). Moderate quality evidence demonstrated no difference for length of stay ([MD], -0.10 days [95% CI, -0.31, 0.11] p = 0.36). CONCLUSION: Exercise prescribed during an acute medical ward stay improves aerobic capacity and maximum isometric strength but may not reduce length of stay, in-hospital falls or mortality.

Weight loss and functional decline in older Japanese people: A cohort study using large-scale claims data.

BACKGROUND: The association between weight loss and subsequent functional decline is uncertain. The study aims to elucidate the association between weight loss over a year and subsequent functional decline requiring assistance in performing their activities of daily living in older individuals. METHODS: The study used data from the publicly funded Long-Term Care Insurance service in Japan, which provides coverage for long-term care services for individuals unable to perform activities of daily living due to physical or cognitive impairment. The study enrolled people born in or before 1949, who underwent health checkups in both 2014 and 2015. The participants were followed from 2015 to the worsening of functional decline requiring long-term care services, death, or February 28, 2019, whichever occurred first. The risk of subsequent functional decline in each weight loss category was estimated using a Cox regression model adjusted for age, sex, baseline body mass index, smoking, and Charlson comorbidity index. RESULTS: We identified 67,452 eligible individuals from the database. The median follow-up period was 1,284 days. The hazard ratios (95 % confidence interval) of functional decline for -1 %, -2 %, -3 %, -4 %, and ≤-5% weight change compared to 0 % weight change were 1.17 (1.03-1.32), 1.26 (1.11-1.43), 1.29 (1.12-1.49), 1.61 (1.39-1.87), and 1.79 (1.58-1.99), respectively. CONCLUSIONS AND IMPLICATIONS: Older people with weight loss of 1 % or more were at risk of functional decline. Close weight monitoring may serve as an easy and inexpensive means of identifying older individuals at risk of functional decline.

How donanemab data address the coverage with evidence development questions.

The Centers for Medicare & Medicaid Services (CMS) established a class-based National Coverage Determination (NCD) for monoclonal antibodies directed against amyloid for Alzheimer's disease (AD) with patient access through Coverage with Evidence Development (CED) based on three questions. This review, focused on donanemab, answers each of these CED questions with quality evidence. TRAILBLAZER-ALZ registration trials are presented with supporting literature and real-world data to answer CED questions for donanemab. TRAILBLAZER-ALZ registration trials demonstrated that donanemab significantly slowed cognitive and functional decline in amyloid-positive early symptomatic AD participants, and lowered their risk of disease progression while key safety risks occurred primarily within the first 6 months and then declined. Donanemab meaningfully improved health outcomes with a manageable safety profile in an early symptomatic AD population, representative of Medicare populations across diverse practice settings. The donanemab data provide the necessary level of evidence for CMS to open a reconsideration of their NCD. HIGHLIGHTS: Donanemab meaningfully improved outcomes in trial participants with early symptomatic Alzheimer's disease. Comorbidities in trial participants were consistent with the Medicare population. Co-medications in trial participants were consistent with the Medicare population. Risks associated with treatment tended to occur in the first 6 months. Risks of amyloid-related imaging abnormalities were managed with careful observation and magnetic resonance imaging monitoring.

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.

Comparison of anticholinergic burden with chronic polypharmacy on functional decline and mortality in Korean older people: a retrospective nationwide cohort study.

BACKGROUND: We aimed to evaluate the association of anticholinergic burden and chronic polypharmacy with the incidence of functional decline and all-cause mortality, and to determine the difference between anticholinergic burden and chronic polypharmacy among Korean older people. METHODS: This nationwide cohort study included 42,132 older people aged ≥ 65 years who underwent Korean National Health Insurance Service health examinations from 2007 to 2008. Odds ratios (ORs) and 95% confidence intervals (CIs) for abnormal Timed Up and Go (TUG) test results were assessed using multivariate logistic regression analyses. Hazard ratios (HRs) and 95% CIs for all-cause mortality until the end of 2015 were estimated using multivariable Cox proportional hazards regression analysis. RESULTS: Of the participants, 37.19% had abnormal TUG test results, and 7.66% of those died during the 5.7-year mean follow-up. The abnormal TUG test results OR increased by 27% among individuals with Korean Anticholinergic Burden Scale (KABS) scores ≥ 3 (OR 1.27, 95% CI 1.02-1.58) compared to those with KABS scores of 0. The HRs for all-cause mortality increased for individuals with higher KABS scores (P for trend < 0.001) or chronic polypharmacy (P for trend < 0.001) compared to those for individuals without these conditions. The combination of a higher KABS or chronic polypharmacy and abnormal TUG test results increased the risk of all-cause mortality (All P for trend < 0.001). CONCLUSION: Anticholinergic drug burden shows a better association with functional decline than chronic polypharmacy, and the use of medications and functional decline may be important risk factors for all-cause mortality among older people.