Instrumental Activities Research Articles

Association of frailty assessed by a ten-item frailty index (FI-CGA-10) with health-related quality of life in older adults with cancer.

11047 Background: A 10-item frailty index based on a comprehensive geriatric assessment (FI-CGA-10) is a recently developed measure of frailty in the geriatric oncology setting [Oncologist, 26, e1751 (2021)]. Our objective was to investigate the association between frailty defined by the FI-CGA-10 and health-related quality of life (HRQOL) in older adults with cancer. Methods: This study included 1015 consecutive older adults with cancer who underwent a CGA before cancer treatment decision at a geriatric oncology service in Japan from February 2020 through September 2023. Fitness and frailty level was evaluated using the FI-CGA-10 that assesses 10 domains: cognition, mood, communication, mobility, balance, nutrition, base and instrumental activities of daily living, social support, and comorbidity. Deficits in each domain were scored as 0 (no problem), 0.5 (minor problem), and 1.0 (major problem). FI-CGA-10 scores (range 0-1) were calculated by dividing the sum of the scores for each domain by 10 and then categorized as fit (<0.2), pre-frail (0.2–0.35), and frail (>0.35). HRQOL was measured by the EQ-5D-5L index score and visual analogue scale (VAS) at the CGA consultation. The minimally important difference (MID) values for the EQ-5D-5L Japan-based index and VAS scores are 0.048 and 7, respectively. Associations between EQ-5D-5L and FI-CGA-10 scores were analyzed by Pearson’s correlation and linear regression models adjusting for covariates (age, sex, cancer type, and stage). Results: Median age was 80 years, 60% were male, and 68% had gastrointestinal cancer. The mean +- SD of the FI-CGA-10 score was 0.35 +- 0.19. The FI-CGA-10 negatively correlated with the EQ-5D-5L index (Pearson’s r = -0.69; 95% CI -0.72 to -0.66; P<.001) and VAS (r = -0.47; 95% CI -0.52 to -0.42; P<.001) scores. After adjusting for the covariates, each 0.1 unit increase in FI-CGA-10 score was associated with 0.070 decrease in EQ-5D-5L index (95% CI -0.075 to -0.066; P<.001) and 4.9 decrease in VAS scores (95% CI -5.5 to -4.4; P<.001). Using the three-level classification, 22% of patients (n = 221) were categorized as fit, 38% (n = 384) as pre-frail, and 40% (n =410) as frail. Overall, the fit group had the highest EQ-5D-5L index and VAS scores followed by the pre-frail and frail groups (table). The score differences between the frailty categories were statistically significant and clinically meaningful according to the MID values. Conclusions: This study demonstrated that frailty assessed by the FI-CGA-10 cross-sectionally correlated with HRQOL measured by the EQ-5D-5L in older Japanese adults with cancer. The observed association further supports construct validity of the FI-CGA-10 as a CGA-based frailty measure. [Table: see text]

Animal models to study cognitive impairment of chronic kidney disease.

Mild cognitive impairment (MCI) is common in people with chronic kidney disease (CKD), and its prevalence increases with progressive loss of kidney function. MCI is characterized by a decline in cognitive performance greater than expected for an individual age and education level but with minimal impairment of instrumental activities of daily living. Deterioration can affect one or several cognitive domains (attention, memory, executive functions, language, and perceptual motor or social cognition). Given the increasing prevalence of kidney disease, more and more people with CKD will also develop MCI causing an enormous disease burden for these individuals, their relatives, and society. However, the underlying pathomechanisms are poorly understood, and current therapies mostly aim at supporting patients in their daily lives. This illustrates the urgent need to elucidate the pathogenesis and potential therapeutic targets and test novel therapies in appropriate preclinical models. Here, we will outline the necessary criteria for experimental modeling of cognitive disorders in CKD. We discuss the use of mice, rats, and zebrafish as model systems and present valuable techniques through which kidney function and cognitive impairment can be assessed in this setting. Our objective is to enable researchers to overcome hurdles and accelerate preclinical research aimed at improving the therapy of people with CKD and MCI.

Adherence to Mediterranean, Dietary Approaches to Stop Hypertension and Healthy Eating Indices are associated with lower risk of disability among Puerto Rican adults from the longitudinal Boston Puerto Rican Health Study

BackgroundEmerging evidence suggests that poor dietary quality is an important risk factor for disability. However, few studies have compared adherence to dietary patterns with disability and none among Puerto Rican adults. ObjectivesThis study was designed to examine relationships between 3 dietary patterns—including Dietary Approaches to Stop Hypertension (DASH), Mediterranean dietary score (MeDS), and Healthy Eating Index (HEI)-2010—and ∼6-y incidence of activities of daily living (ADL) and instrumental activities of daily living (IADL) disability and to assess potential mediation by handgrip strength. MethodsData are from the Boston Puerto Rican Health Study, a longitudinal cohort of Puerto Rican adults aged 45–75 y (N = 1502). Adherence to dietary pattern variables were derived from food frequency questionnaire (FFQ) data averaged at baseline and ∼2 y. Handgrip strength was assessed at baseline. Cox proportional hazards models were used to assess longitudinal associations between DASH, MeDS, and HEI-2010 and incident ∼6-y ADL (and subscales) and IADL disability. Mediation by handgrip strength was also tested. ResultsParticipants with higher adherence DASH had lower risk of ADL, ADL mobility, and ADL manual dexterity disabilities (hazards ratio [HR]: 0.96; 95% confidence interval [CI]: 0.91, 0.98; HR: 0.96; 95% CI: 0.92, 0.99; and HR: 0.95; 95% CI: 0.92, 0.98, respectively). Higher adherence to MeDS was associated with lower risk of ADL and ADL mobility disabilities (HR: 0.89; 95% CI: 0.81, 0.98; HR: 0.90; 95% CI: 0.82, 1.00), and higher adherence to HEI with lower risk of ADL manual dexterity (HR: 0.98; 95% CI: 0.97, 0.99) in fully adjusted models. Only DASH tended to be associated with IADL (HR: 0.97; 95% CI: 0.94, 1.00). Baseline handgrip strength was a mediator between HEI and ADL manual dexterity (23.7% of the indirect effect was explained through handgrip strength). ConclusionsHigher adherence to a healthy diet pattern may decrease risk of disability and may be an important prevention strategy for ADL and IADL disability associated with aging.

Gait analysis and geriatric syndromes: An association among elderly patients attending a teaching hospital of Delhi

ABSTRACT Background: Gait abnormalities are prevalent, affecting a substantial portion of the elderly population, and leading to mobility limitations, reduced quality of life, falls, hospitalizations, and premature death. Objectives: The study aims to assess gait patterns among individuals aged 75 years and above attending the geriatric OPD of a tertiary care hospital in New Delhi and evaluate their association with various geriatric syndromes. Materials and Methods: This cross-sectional study, conducted at a tertiary care hospital in Delhi, from May 2019 to November 2021, involved 100 participants aged 75 and above. It encompassed a thorough assessment protocol covering demographics, health history, clinical and functional evaluations, depression, cognition, balance, frailty, urinary incontinence, polypharmacy, nutrition, comorbidities, and gait analysis. Results: In this study of elderly individuals, the mean age was 78.56 years, and the mean BMI was 23.11. The participants had an average of 1.74 comorbidities, with hypertension being the most prevalent (62%), followed by diabetes (25%), chronic obstructive airway disease (COAD) (11%), and coronary artery disease (15%). Geriatric assessments revealed varying proportions of frailty (34%), polypharmacy (40%), and urinary incontinence (9%). The mean scores for activities of daily living, instrumental activities of daily living, nutritional status, cognitive function, Timed Up and Go Test, and depression scale were also reported. Various gait parameters demonstrated significant correlations with these geriatric factors, including frailty, comorbidities, BMI, and mobility scores. Conclusion: The study identified significant associations between gait patterns and various geriatric syndromes, emphasizing the importance of gait analysis in assessing the health and mobility of elderly individuals.

Ophthalmological traits in older adult and risk of Alzheimer's disease: results from a French geriatric cohort

Ophthalmological changes have been reported in Alzheimer's patients. Our objectives were to determine whether: i) GCC (ganglion cell complex) and RNFL (retinal nerve fibre layer) thickness were associated with different stages of AD (i.e., no AD, prodromal AD, dementia-stage AD), and ii) GCC and RNFL thickness predicted disease progression in older non-demented patients with subjective memory complaints followed for four years. Ninety-one French older community-dwellers with memory complaint and without open-angle glaucoma or age-related macular degeneration (mean, 71.60 ±4,73 years; 44% women) from the GAIT study underwent examination with HD-OCT, measuring the thickness of the macula, the macular GCC and the RNFL. They also had a complete cognitive diagnosis (i.e., cognitively healthy, prodromal AD, or dementia AD), and a cognitive follow-up 4 years later looking for a possible conversion. Age, sex, body mass index (BMI), number of comorbidities, and Instrumental activities of daily living (IADL) score were considered as potential confounders. At baseline, 37 (40.7%) patients were diagnosed as cognitively healthy, 47 (51.6%) as MCI, and 7 (7.7%) as AD. Mean GCC thickness was higher in cognitively healthy patients than in MCI patients (79.23 vs. 76.27μm, p =0.023), particularly in the inferior and nasal fields (p =0.023 and p =0.005, respectively). This difference was also found between cognitively healthy patients and others (MCI and AD) in the superior, inferior and nasal fields (p =0.030, p =0.014 and p =0.002, respectively). There was no difference in RNFL thickness between the different cognitive statuses. After 4 years of follow-up, 12patients (70.6%) of the 17 followed had not changed their cognitive status, while 5 (29.4%) had converted to a more advanced stage of AD. There were no significant differences between the two groups in either GCC thickness (p =0.429) or RNFL thickness (p =0.286). We found decreased CGG thicknesses in Alzheimer's patients at prodromal and dementia stages, compared with cognitively healthy participants. There was no association between RNFL thickness and cognitive status, nor between CCG or RNFL thicknesses and the risk of progressing to AD stages after 4 years of follow-up.

The subgroup analysis by age and geriatric assessment in a phase III study comparison of trastuzumab emtansine with trastuzumab, pertuzumab, and docetaxel in older patients with advanced stage HER2-positive breast cancer (JCOG1607 HERB TEA study).

1031 Background: The JCOG1607, HERB TEA Study, is a phase III trial that compared trastuzumab emtansine (T-DM1) with the HPD regimen (trastuzumab, pertuzumab, docetaxel) in older patients with advanced HER2-positive breast cancer. The primary objective was to confirm the non-inferiority of T-DM1 to HPD in overall survival (OS), with a margin of 1.35 for hazard ratio (HR). The trial was terminated early due to futility at the planned first interim analysis. T-DM1 didn't show non-inferiority to HPD in OS (HR 1.263; 95% confidence interval [CI], 0.677-2.357). Median progression-free survival (PFS) was 11.3 months for T-DM1 and 15.6 months for HPD (HR 1.373; 95% CI, 0.917-2.056). However, the condition of older patients varies widely, and we conducted a subgroup analysis to investigate the subgroup that could benefit from T-DM1 with fewer side effects as a first-line treatment. Methods: Subgroup analysis for OS and PFS involved 148 patients enrolled in JCOG1607, considering age and PS (<75 years old and PS 0,1 or <75 years old and PS 2 or ≥75 years old), Geriatric 8 (G8) score (≥15 or <15), Instrumental Activity of Daily Living (IADL) score (8 or <8), visceral/brain metastasis presence (with or without), and other factors. Results: Subgroup of <75 and PS 2 was not evaluable. For OS, HR of T-DM1 arm to HPD arm was 0.749 (95% CI: 0.310-1.808) in the group aged <75 years, while 2.867 (95%CI: 1.018-8.069) in the group aged ≥75 years (Table). G8 score and the IADL score did not show significant differences in HR for OS, although low G8 score group and low IADL score group tended to have higher OS in HPD arm than T-DM1 arm: HR of T-DM1 arm to HPD arm of 1.541 (95% CI: 0.755-3.142) in low G8 score group and 2.147 (95% CI: 0.656-7.025) in low IADL score group. For PFS, patients with visceral/brain metastasis had HR of T-DM1 arm to HPD arm of 1.794 (95% CI: 1.092-2.948). No other subgroup showed a significant difference in HR for PFS. Conclusions: No subgroups benefiting from T-DM1 as first-line treatment were identified. HPD remains the standard for advanced HER2-positive breast cancer, regardless of age (even in ≥75 years) G8 score, or IADL. Clinical trial information: UMIN000030783. [Table: see text]

Quality of life for older patients with metastatic cancer in Brazil: A telehealth-based geriatric assessment and supportive care intervention (GAIN-S).

1514 Background: Older adults with cancer often present unique geriatric and supportive care needs. We sought to evaluate the impact of a telehealth-based multimodal geriatric assessment (GA)-guided supportive care interventions (GAIN-S) program among older patients with metastatic cancer in a Brazilian cancer center. Methods: This is a randomized trial. Patients aged 65+ years with metastatic cancer, undergoing treatment, regardless of ECOG status, were enrolled. Following the baseline assessment, patients were randomized 1:1 to receive usual care or GAIN-S. The GAIN-S intervention provided remote, telehealth-based consultations with a nutritionist, psychologist, psychiatrist, and certified fitness trainer. At baseline and 3-months, patients were assessed for emotional symptoms (Geriatric Depression Scale), functional status (Instrumental Activities of Daily Living), coping (BriefCope), and quality of life (Functional Assessment of Cancer Therapy-General). Independent t-tests and linear mixed model were used. Results: Out of 86 approached patients, 80 were enrolled (40 per arm), with 3 deceased during treatment (usual care: 2, GAIN-S: 1). Most patients were female (56%), with a median age of 73 years (range, 65-68). Most common cancers were genitourinary (28%) and breast (23%). At baseline, there were no differences in the outcome measures between arms. However, from baseline to 3-months, patients assigned to GAIN-S had improvements in emotional symptoms, functional status, and quality of life compared to usual care (Table). Additionally, those assigned to GAIN-S reported increased utilization of active coping, acceptance, and positive reframing at 3-months. Conclusions: GAIN-S demonstrated significant improvements in emotional well-being, functional status, and quality of life among older patients with metastatic cancer. These findings underscore the potential of such telehealth-driven approaches to enhance the supportive care experience in diverse healthcare settings. [Table: see text]

Effects of computerized cognitive training on biomarker responses in older adults with mild cognitive impairment: A scoping review.

Mild cognitive impairment (MCI) is a widespread condition in older individuals, posing significant risk of dementia. However, limited research has been conducted to explore effective interventions and clarify their impact at the neural level. Therefore, this study aimed to investigate the effects of computerized cognitive training (CCT) and explore the associated neural mechanisms in preventing dementia in older individuals with MCI, with a view to inform future intervention efforts. We reviewed the effects of CCT on biomarker outcomes in older adults with MCI. The search was conducted for studies published between 2010 and May 10, 2023, using three search engines: PubMed, Scopus, and Cumulative Index to Nursing and Allied Health Literature. The inclusion criteria were as follows: studies that involved participants diagnosed with MCI, included CCT, included quantitative assessment of biomarker results, and conducted randomized controlled trials. Sixteen studies that used biomarkers, including magnetic resonance imaging, electroencephalography (EEG), functional near-infrared spectroscopy (fNIRS), and blood or salivary biomarkers, were extracted. The results showed that CCT caused changes in structure and function within the main brain network, including the default mode network, and decreased both theta rhythm activity on EEG and prefrontal activity on fNIRS, with improvement in cognitive function. Furthermore, CCT combined with physical exercise showed more significant structural and functional changes in extensive brain regions compared with CCT alone. Virtual reality-based cognitive training improved not only executive function but also instrumental activities of daily living. CCT causes functional and structural changes in extensive brain regions and improves cognitive function in older adults with MCI. Our findings highlight the potential of individualized intervention methods and biomarker assessment according to the specific causes of MCI. Future research should aim to optimize these personalized therapeutic strategies to maximize the benefits of CCT in older adults with MCI.

Predictors and consequences of visual trajectories in Chinese older population: A growth mixture model.

Given the relatively high prevalence of vision impairment and the heterogeneity of visual changes among the elderly population, we aimed to identify the visual trajectories and to examine the predictors and consequences associated with each trajectory class. We analysed data from 2235 participants involved in the 5th, 6th, 7th, and 8th waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), where vision impairment was evaluated using an adapted Landolt-C chart during each wave. We employed a growth mixture model (GMM) to identify distinct visual trajectories and logistic regression analysis to examine the predictors associated with each trajectory class. Furthermore, we investigated the effect of visual trajectories on distal consequences, including cognitive function, activities of daily living (ADL), instrumental activities of daily living (IADL), depression, anxiety, and fall risk. Within the CLHLS study, cognitive function was assessed using the Chinese version of the Mini-Mental State Examination (CMMSE), ADL via the Katz index, and IADL through a modified version of Lawton's scale. Lastly, depression was assessed using the 10-item version of the Centre for Epidemiologic Studies (CES-D-10), while anxiety was measured using the Generalized Anxiety Disorder scale (GAD-7). Fall risk was determined by asking the question: 'Have you experienced any falls within the past year?' We identified two distinct visual trajectories in our analysis. Most older adults (n = 1830, 81.9%) initially had a good vision level that diminished ('high-baseline decline' group). Conversely, the remaining participants (n = 405, 18.1%) initially had a lower vision level that improved over time ('low-baseline improvement' group). The 'high-baseline decline' group was more likely to include older adults with relatively higher body mass index (BMI) (odds ratio (OR) = 1.086; 95% confidence interval (CI) = 1.046, 1.127), individuals with higher formal educational qualifications (OR = 1.411; 95% CI = 1.068, 1.864), those current engaging in exercise (OR = 1.376; 95% CI = 1.046, 1.811), and individuals reporting more frequent consumption of fruit (OR = 1.357; 95% CI = 1.053, 1.749). Conversely, the 'low-baseline improvement' group had a higher likelihood of including older individuals (OR = 0.947; 95% CI = 0.934, 0.961), residents of nursing homes (OR = 0.340; 95% CI = 0.116, 0.993) and those self-reporting cataracts (OR = 0.268; 95% CI = 0.183, 0.391) and glaucoma (OR = 0.157; 95% CI = 0.079, 0.315). Furthermore, the 'high-baseline decline' group showed a positive impact on distal consequences, adjusting for sex, birthplace, residence, main occupation, education, economic status, and marital status. This impact included cognitive function (correlation coefficient (β) = 2.092; 95% CI = 1.272, 2.912), ADL (β = -0.362; 95% CI = -0.615, -0.108), IADL (β = -1.712; 95% CI = -2.304, -1.121), and reported lower levels of depression (β = 0.649; 95% CI = 0.013, 1.285). We observed no significant influence on fall risk and anxiety within the identified visual trajectories in the adjusted model. Vision in older adults with ocular disease could potentially be improved. Having formal education, maintaining an appropriate BMI, engaging in exercise, and consuming fruit more frequently appear to be beneficial for the visual health of the elderly. Considering the negative impact of visual impairment experience on distal cognition, self-care ability, and depression symptoms, stakeholder should prioritise long-term monitoring and management of vision impairment among older adults.

Change in Risk Factors for Depression among The Elderly Due to the COVID-19 Outbreak

Objectives: This study aimed to investigate changes in risk factors for depression among the elderly due to the Coronavirus disease-2019 (COVID-19) outbreak. Methods: We analyzed data from individuals aged ≥ 65 years who participated in both the 7th (2018) and 8th (2020) waves of the Korean Longitudinal Study of Aging (KLoSA). Depression is defined as a Center for Epidemiologic Studies Depression Scale (CES-D10) score ≥ 4. We conducted multivariable logistic regression analyses to assess risk factors for depression across periods before and after the outbreak of COVID-19. For the multivariable analysis, we included variables that showed a p-value < 0.2 in the univariable analysis and applied a stepwise selection method. Results: A total of 3,857 elderly individuals were included in the analysis. Regardless of the COVID-19 outbreak, factors such as economically inactive status, a lower frequency of social interactions, worsening subjective health status, and difficulties in performing instrumental activities of daily living were identified as risk factors for depression. Before the COVID-19 outbreak, residing in urban areas was not a significant risk factor for depression, but it emerged as a significant risk factor after the outbreak (p = 0.009). In contrast, living alone was a significant risk factor for depression before the COVID-19 outbreak (p < 0.001), but this association was not significant after the outbreak. Conclusions: After the COVID-19 outbreak, residing in urban areas emerged as a new risk factor for depression, while living alone, previously a significant risk factor, was no longer associated with depression in the elderly.

Assessing intrinsic capacity in Taiwan: Initial psychometric properties of the Integrated Care for Older People Screening Tool for Taiwanese (ICOPES-TW)

BackgroundThe World Health Organization (WHO) proposed the concept of intrinsic capacity (comprising composite physical and mental capacity) which aligns with their concepts of healthy aging and functional ability. Consequently, the WHO promotes the Integrated Care for Older People (ICOPE) framework as guidance for geriatric care. Consequently, each government should have a screening tool corresponding to ICOPE framework to promote geriatric care. The present study examined the initial psychometric properties of the Taiwan version of ICOPE (i.e., ICOPES-TW).MethodsOlder people (n = 1235; mean age = 72.63 years; 634 females [51.3%]) were approached by well-trained interviewers for participation. A number of measures were administered including the ICOPES-TW, WHOQOL-AGE (assessing quality of life [QoL]), Clinical Frailty Scale (assessing frailty), Barthel Index (assessing basic activity of daily living [BADL]), and Lawton Instrumental Activities of Daily Living Scale (assessing instrumental activity of daily living [IADL]).ResultsThe ICOPES-TW had a two-factor structure (body functionality [eigenvalue = 1.932] and life adaptation [eigenvalue = 1.170]) as indicated by the results of exploratory factor analysis. Internal consistency of the ICOPES-TW was low (Cronbach’s α = 0.55 [entire ICOPES-TW], 0.45 (body functionality factor), and 0.52 (life adaptation factor). ICOPES-TW scores were significantly (i) positively correlated with age (r = 0.321), IADL (r = 0.313), and frailty (r = 0.601), and (ii) negatively correlated with QoL (r=–0.447), and BADL (r=–0.447), with all p-values < 0.001.ConclusionThe ICOPES-TW could be a useful screening tool for healthcare providers to quickly evaluate intrinsic capacity for Taiwanese older people given that it has moderate to strong associations with age, BADL, IADL, QoL, and frailty.

Does Social Support Moderate the Relationship Between Frailty and Functional Ability Trajectory Among Community-Dwelling Older Adults?

Functional ability is the important prerequisite to live independently and achieve aging in place, which depends on the complex interaction of intrinsic and extrinsic factors. Identifying the trends and influencing factors of functional ability would contribute to the accurate assessment and intervention of geriatric health. This study aimed to disentangle the moderating effect of 3 types of social support, namely objective support, subjective support, and support utilization, on the relationship between frailty and functional ability trajectories. This was a secondary analysis using data from a prospective 3-wave study with a sample of 777 Chinese community-dwelling older adults. Social support was assessed using the Social Support Rating scale. Frailty was assessed using the FRAIL scale. Functional ability was measured by the Lawton Instrumental Activities of Daily Living scale. Latent growth curve models were implemented to test their relationships. Objective support but not subjective support or support utilization moderated on the relationship between frailty and functional ability slope. Functional ability decline over time was buffered by objective support among robust individuals but exacerbated among (pre)frail individuals. The moderating effect of social support on the relationship between frailty and functional ability trajectory varies by support types, which reminded that social support may be a promising intervention target to maintain functional independence for frail individuals, opening up a new perspective on social support in the field of disability prevention. Effective interventions should particularly address objective support in conjunction with empowering the frail older population to optimize the trajectory of functional ability.

Exploring the Relationship between Behavioral and Neurological Impairments Due to Mild Cognitive Impairment: Correlation Study between Virtual Kiosk Test and EEG-SSVEP.

Amnestic mild cognitive impairment (aMCI) is a transitional stage between normal aging and Alzheimer's disease, making early screening imperative for potential intervention and prevention of progression to Alzheimer's disease (AD). Therefore, there is a demand for research to identify effective and easy-to-use tools for aMCI screening. While behavioral tests in virtual reality environments have successfully captured behavioral features related to instrumental activities of daily living for aMCI screening, further investigations are necessary to establish connections between cognitive decline and neurological changes. Utilizing electroencephalography with steady-state visual evoked potentials, this study delved into the correlation between behavioral features recorded during virtual reality tests and neurological features obtained by measuring neural activity in the dorsal stream. As a result, this multimodal approach achieved an impressive screening accuracy of 98.38%.

Alemtuzumab, Cladribine, Fingolimod, Natalizumab, and Rituximab as First-Line Treatments in Adults With Highly Active Relapsing-Remitting Multiple Sclerosis

What Is the Problem? Relapsing-remitting multiple sclerosis (RRMS), the most common disease course of multiple sclerosis (MS), is a chronic immune-mediated disease with clearly defined episodes of new or increasing neurologic symptoms followed by periods of relative stability. In contrast, the highly active, aggressive disease course leads to rapid disability, and these patients face an unmet need. The principal goal of MS treatment is to delay and prevent the accumulation of disability by reducing the frequency of relapses. Currently reimbursed first-line drugs fail to prevent the consequences of irreversible damage to the nervous system. There has been a paradigm shift in clinical practice toward the use of a high-efficacy treatment strategy as early as possible during the inflammatory process to provide optimal clinical benefits in preserving neurologic function in patients with highly active RRMS. What Did We Do? A systematic review of the clinical effectiveness and safety of alemtuzumab, natalizumab, cladribine, fingolimod, and rituximab relative to current first-line drugs in adults with highly active RRMS was conducted; it identified post hoc subgroup analyses from 5 randomized controlled trials (RCTs) and 1 prospective comparative cohort study. What Did We Find? Evidence was uncertain and conclusions were limited by risk of bias and small sample sizes; conclusions for some outcome comparisons were also limited by imprecision and incomplete reporting. Compared to placebo, cladribine and natalizumab may result in a clinically important reduction in relapses, disability, and key MRI lesions. Alemtuzumab may result in a clinically important reduction in relapses compared to interferon, while fingolimod may result in a clinically important reduction in relapses compared to placebo. The clinical evidence was insufficient to determine the effect of fingolimod on relapses when compared with interferon. Harms outcomes, when reported, appeared consistent with the known harms profile of the drugs. Assessment of the effectiveness and safety of rituximab could not be performed due to the lack of evidence. Evidence was also lacking for many important outcomes such as health-related quality of life (HRQoL), instrumental activities of daily living, symptoms, and cognitive outcomes. No evidence could be identified to inform on treatment sequencing. Two pragmatic RCTs (the TREAT-MS and DELIVER-MS trials) are currently ongoing, aiming to compare an early, high-efficacy treatment strategy versus a traditional escalation treatment strategy, which may inform treatment sequencing. Further research is needed to compensate for clinical data gaps to inform an appropriate and relevant economic evaluation. What Does This Mean? Jurisdictions may reconsider the current reimbursement criteria for drugs used in the first-line setting specifically for adults demonstrating highly active RRMS; however, caution should be taken given the gaps and uncertainty in evidence. Upon request from public drug plans, this review may inform a future implementation advice panel or expert committee recommendation.

An immersive virtual reality shopping task detects declines in instrumental activities of daily living in individuals with Parkinson's disease

IntroductionDeclines in instrumental activities of daily living (IADLs) have been proposed as a prodromal marker of Parkinson's disease (PD). The Cleveland Clinic Virtual Reality Shopping (CC-VRS) platform combines an omnidirectional treadmill with a virtual reality headset to create a virtual grocery store that a user physically walks through and completes a shopping task. The primary aim of this project was to determine the known-group validity of the CC-VRS platform in discriminating IADL performance and to characterize specific motor and cognitive declines responsible for PD-related IADL impairments. MethodsSixteen individuals with PD and 15 healthy adults completed traditional motor, cognitive, and IADL assessments and the CC-VRS task. Group differences were evaluated using Welch's t-test. ResultsThere were no between-group differences in traditional performance measures of motor, cognitive, or IADL function. Regarding CC-VRS performance, participants in the PD group completed the task significantly slower than controls (690 vs. 523 sec, respectively). Participants with PD spent 25 % more time walking and turning and were stopped 46 % longer than controls. Average gait speed when viewing the shopping list, a measure of dual-task performance, was significantly slower in the PD group compared to controls (0.26 vs. 0.17 m/s, respectively). ConclusionUnlike traditional performance measures of motor, cognitive, and IADL function, the CC-VRS discriminated participants with PD from healthy older adults. For the PD group, motor and dual-task declines contributed to diminished CC-VRS performance. Identifying underlying contributors to IADL declines supports using ecological assessments, such as the CC-VRS, for the routine clinical evaluation of IADLs.

Analysis of the life course effects of the disability dilemma among rural older adults in China.

To analyse whether the accumulation of early adverse experiences among individuals of different generations has an impact on disabilities and evaluate the cumulative effects of disadvantages in rural older adults in China. A Binary Logit Model was used to analyse the life course effects of the disability dilemma among rural older adults. Regarding Activities of Daily Life (ADLs), there was no significant difference between older adults that experienced 1 adverse events and the control group. The probability of older adults experiencing difficulties in 2, 3, 4, or more types of ADLs was 1.486 times, 2.173 times, and 3.048 times higher than that of the control group, respectively. Regarding Instrumental Activities of Daily Life (IADLs), there was no significant difference between the population that experienced 1 or 2 adverse events and the control group. The probability of experiencing difficulties in 3, 4, or more types of IADLs was 1.527 times and 1.937 times higher than that of the control group, respectively. Early adverse events had a cumulative disadvantageous effect on disability in older adults. The longer the duration of adverse experiences, the higher the risk of disability in old age. Education had a significant mitigating effect on health risks. Pay attention to early factors in the life course, strengthen the promotion of health prevention concepts, and pay attention to the moderating and relieving effects of education on health. We should also gradually improve the rural disability care system and family health security capabilities in China's rural areas.

Long-term inequalities in health among older Mexican adults: An outcome-wide analysis

The relationship between socioeconomic level and health outcomes in older people has been widely studied, but less information about health inequalities associated with gender and place of residence exists. Also, there is scarce evidence of longitudinal inequalities, particularly in countries from the global south. This study aimed to describe the longitudinal patterns of health inequalities associated with wealth, gender, and residence area among older Mexican adults. We used data from two longitudinal studies in Mexico: The Study on Global AGEing and Adult Health (SAGE) and the Mexican Health and Aging Study (MHAS). Three domains to characterize health inequities were used: wealth, gender, and rurality. We conducted an outcome-wide analysis with nine health indicators assessing older adults' physical and cognitive function. The Slope Index of Inequality and the Relative Index of Inequality were used as inequality measurements. Our results indicate that the greatest inequalities are observed in relation to wealth and gender. Older adults with lower socioeconomic status demonstrated higher rates of depression, sarcopenia, falls, and limitations in both basic and instrumental activities of daily living compared to their wealthier counterparts, with increasing trends in physical functionality over time. Furthermore, women experienced higher rates of depression, sarcopenia, frailty, and physical limitations compared to men. The only significant difference related to rurality was a lower rate of frailty among rural older adults. Longitudinal trajectories revealed an increase in the gap of inequality for various health indicators, especially in terms of wealth and gender. Health inequalities in old age are one of the greatest challenges facing health systems globally. Actions like universal coverage of health services for older people and the empowerment of individuals and their communities to have control over their lives and circumstances must be guaranteed.

#2856 Sleep disturbances in non-dialysis dependent chronic kidney disease—The CKD-REIN cohort study

Abstract Background and Aims Sleep disturbances are common in patients on dialysis, but little is known about their prevalence and determinants in earlier chronic kidney disease (CKD) stages. We assessed the prevalence of insomnia, excessive daytime sleepiness (EDS), and sleep apnea, and studied their relation with kidney function, before and after accounting for various other potential determinants in patients with moderate or severe CKD. Method This study included 2657 nephrology outpatients with non-dialysis dependent CKD (mean age, 67 ± 12 years; 66% men; mean eGFR, 33 ± 12 mL/min/1.73 m2) from the French CKD-REIN (CKD-Renal Epidemiology and Information Network) cohort study who completed the Basic Nordic Sleep Questionnaire at baseline. Insomnia was defined as having badly or rather badly been sleeping, or having had difficulties falling asleep or awakened too early without being able to fall asleep again at least 3 times per week, over the past 3 months. And EDS, as feeling excessively sleepy during daytime at least 3 times per week over the past 3 months. Sleep apnea with or without continuous positive airway pressure use were identified from medical records. For each sleep disturbance, we assessed the crude prevalence by sex and by estimated glomerular filtration rate (eGFR) categories. We estimated adjusted odds ratios (OR) with 95% confidence interval (95% CI) associated with eGFR decrease (per 10 mL/min/1.73 m2) and urinary albumin-to-creatinine ratio (ACR) categories (A1-A3), as well as with age, sex, education (years), smoking, alcohol consumption, physical activity (estimated by the Global Physical Activity Questionnaire), performance score in Instrumental Activities of Daily Living [IADL], obesity, diabetes, cardiovascular disease, depression, patient-reported cramps, itching and stress or worry about CKD, and relevant drug use. Results Overall prevalence of insomnia, EDS, and sleep apnea were 23%, 15%, and 14%, respectively, with differences between women and men for insomnia, 30% vs 19%, EDS, 17% vs 13%, and sleep apnea, 10% vs 17%, respectively (all P-values &amp;lt;.001). Crude prevalence of EDS significantly increased with decreasing eGFR category (without interaction with sex), but not those for insomnia and sleep apnea (Figure). ACR categories were not associated with either sleep disturbances. In multivariable analyses, factors significantly associated with higher prevalence of insomnia included female sex, smoking, low physical activity, depression, and thyroid hormone use. There were also strong dose-response relations between insomnia prevalence and to what extend patients reported being bothered by cramps or itching, or stressed/worried about CKD. The crude relation of eGFR with EDS tended to weaken (ORs [95% CI], 1.10 [0.99-1.22] per 10 mL/min decrease, p-value 0.09) in multivariable analysis, which showed higher ORs associated with past smoking, depression, lower IADL score, insomnia, and betablocker use, as well as dose-response relations with itching, and stress/worry about CKD. Factors significantly associated with increased prevalence of sleep apnea included male sex, alcohol consumption, lower IADL score, obesity, depression, and cardiovascular disease. Conclusion This analysis of baseline data from the CKD-REIN cohort shows that, in patients with non-dialysis dependent CKD, EDS alone appeared to be related to kidney function level. The study, however, suggests the potential role of modifiable CKD-related symptoms, cramps and itching, and of being stressed or worried about CKD, in addition to that well-documented for behavioral and clinical risk factors, and drugs in the risk of insomnia and EDS.

Brain health index as a predictor of possible vascular dementia in the Mexican health and aging study 2012-2015.

To determine the burden of disease among subjects at risk of developing stroke or dementia, brain health indexes (BHI) tend to rely on anatomical features. Recent definitions emphasize the need of a broader perspective that encompasses cardiovascular risk factors (CVRFS) and lifestyle components which can be considered partial contributors to optimal brain health. In this study, we aimed to establish the association and risk detected by a Brain Health Index and the risk of possible vascular dementia (PVD) using data from the Mexican Health and Aging Study (MHAS) 2012-2015. The MHAS is a longitudinal study of adults aged ≥ 50 years. We analyzed the data obtained between 2012 and 2015. CVRFS included in the index were diabetes mellitus, hypertension, myocardial infarction, depression, obesity, physical inactivity, and smoking history. A PVD diagnosis was established when scores in the Cross-Cultural Cognitive Examination were below reference norms and limitations in ≥1 instrumental activities of daily living and a history of stroke were present. A multinomial regression model was developed to determine the association between BHI scores and PVD. In 2015, 75 PVD cases were identified. Mean age was 67.1 ±13.2 years, 35.8% were female, and the mean educational level was 5.8 ±5.5 years. In cases with a higher score in the BHI, the model revealed a hazards ratio of 1.63 (95% CI: 1.63-1.64, p< 0.001) for PVD. In this longitudinal study, with the use of a feasible multifactorial BHI in the Mexican population, a greater score was associated with a 1.63-fold risk of developing PVD during the 3-year follow-up, while the risk for stroke was 1.75. This index could potentially be used to predict the risk of PVD in adults with modifiable CVRFS.

Association between multisite musculoskeletal pain and disability trajectories among community-dwelling older adults

BackgroundPain is linked to disability, but how multisite musculoskeletal pain leads to disability over time is not well elaborated.ObjectiveTo examine the associations of multisite musculoskeletal pain with disability among a nationally representative cohort.DesignWe used data from the National Health and Aging Trends Study (NHATS) 2015-22. Disability was assessed by basic activities of daily living (ADL) and instrumental activities of daily living (IADL).ParticipantsA total of 5557 individuals with multisite musculoskeletal pain dwelling in the community were included in this study.MethodsGroup-based trajectory models were applied to identify distinct profiles of disability in ADL and IADL. Design-based logistic regressions were used to examine associations among multisite musculoskeletal pain, disability, and dual trajectory group memberships, adjusted for sociodemographic, health status, behavioral, and mental characteristics.ResultsPersons who experienced multisite musculoskeletal pain were at higher risk of disability in ADL and IADL. We identified five heterogeneous disability trajectories and named them based on baseline levels and rates of increase over time. Approximately, 52.42% of older adults with multisite musculoskeletal pain were in trajectories with ADL and IADL declines, and 33.60% experienced a rapid decline. Multisite musculoskeletal pain was associated with elevated relative risk for the adverse disability trajectories, which generally increases with multisite musculoskeletal pain frequency and number of sites.ConclusionsPersons with multisite musculoskeletal pain had a higher risk of disability. It is essential to adopt effective pain management strategies to maintain the independent living ability of older adults and to realize active aging.