Multidomain Intervention for the Reversal of Cognitive Frailty Using a Personalized Approach (AGELESS Trial): Recruitment and Baseline Characteristics of Participants.

BACKGROUND: Reversal of cognitive frailty through a multidomain intervention is desirable to prevent dementia. AGELESS Trial was conducted to determine the effectiveness of a comprehensive, multidomain intervention on older adults with cognitive frailty in Malaysia. However, conducting a clinical trial, particularly during and after Covid-19, posed unique challenges. OBJECTIVE: We aimed to investigate the recruitment process and baseline characteristics of the AGELESS Trial participants to better understand an at-risk population and those who agree to participate in an intervention. DESIGN/SETTING: 24-month, randomized controlled trial. PARTICIPANTS: Community-dwelling older adults with independent mobility, aged ≥ 60 years, with a mini mental state examination score of 19-25, a clinical dementia rating of 0.5 ≥ 1 Fried's physical frailty criteria, and < 22 Beck depression inventory. INTERVENTION: Participants were randomized 1:1 to a structured multidomain intervention consisting of vascular management, diet, exercise, cognitive and psychosocial stimulation, or to the arm, including routine care and general health consultation. MEASUREMENT: We analyzed the group differences between (1) cognitive frailty and non- cognitive frailty screened subjects, (2) recruited and non-recruited participants, (3) baseline characteristics of participants by arm, (4) adherence to AGELESS intervention at 12 months, and (5) preliminary findings on the effectiveness of the intervention at 12 months. RESULTS: A total of 957 older adults from two locations, i.e., urban (n = 764) and rural (n = 193) areas, were screened, of whom 38.9% had cognitive frailty and were eligible to participate. Those with cognitive frailty had fewer years of education (B = -0.08; 95%CI = 0.88-0.97; p = 0.002), and lower functioning cognition (B = -0.24; 95%CI = 0.74-0.84; p < 0.001). Among those from urban areas, only 33.1% (n = 106) agreed to participate, particularly those with multimorbidity (B = 0.86; 95%CI = 1.31-4.30; p = 0.01), higher physical activity (B = -1.02; 95%CI = 0.19-0.69; p = 0.002), slower walking speed (B = 1.26; 95%CI = 1.62-7.61; p = 0.001), and higher systolic blood pressure (B = 0.02; 95%CI = 1.00-1.03; p = 0.03). At baseline, participants' mean age was 68.1±5.6, years of education was 8.3±3.9, body mass index was 27.5±5.3 kg/m2, and mini mental state examination score was 22.7±4.0. Generally, there were no significant differences between the intervention and control groups for the main outcomes, except those in the intervention group had higher body mass index, mid-upper-arm circumference, and waist circumference (p < 0.05 for all parameters). Overall intervention adherence at 12 months was 52.8%, ranging from 52.8%-90.6% for each of the modules. Preliminary analysis of the effectiveness of the intervention at 12 months was positive on most of the cognitive domains, some of the nutrient intake and food groups, physical function, and vascular outcomes (p < 0.05 for all parameters). CONCLUSION: Despite the challenges posed by the pandemic, screening, recruitment, and 12-month intervention delivery were achieved in a Malaysian multidomain preventive randomized controlled trial in older adults at risk of dementia, with a satisfactory adherence rate and cognitive benefits at 12 months.

Effect of non-pharmacological interventions in people with cognitive frailty: a systematic review and network meta-analysis.

ABSRTACT: OBJECTIVE: To evaluate the effects of various non-pharmacological interventions on patients with cognitive impairment by systematic search and network meta-analysis, and to rank the effects of the included non-pharmacological interventions. METHODS: The databases of PubMed, Cochrane Library, EMbase, Web of Science, CNKI, VIP, WANFANG, and SinoMed were searched by computer. All randomized controlled trials (RCTs) of non-pharmacological interventions for people with cognitive frailty were collected. The search was conducted from 2000 to February 2024. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias of the included studies, and then used Stata15 and R4.3.1 software to conduct network meta-analysis, with physical function and cognitive function as the main outcome indicators. RESULTS: A total of 19 randomized controlled trials involving 1738 patients were included. The results of network meta-analysis showed that among the non-pharmacological interventions, nutritional support had the best effect on improving frailty scores and cognitive function scores in patients with cognitive frailty. Aerobic training combined with resistance training is best for improving grip strength. For improving the patient's motor status, cognitive training had the best effect on improving TUG test scores. High-speed resistance training is best for improving walking speed. CONCLUSION: This review analyses the current study of non-pharmacological interventions to improve physical performance in patients with cognitive frailty. Current evidence suggests that nutritional support is most effective at improving physical frailty and cognitive decline in patients with cognitive frailty, and that exercise and cognitive training interventions significantly improve grip strength and motor ability. TRIAL REGISTRATION: This meta-analysis was prospectively registered with PROSPERO (registration number: CRD42023486881).

Transition of Physical, Psychological, and Cognitive Frailty and Its' Associated Determinants in Malaysian Older Adults: A 5-Year Follow-up Study.

Frailty, a multifaceted syndrome, affects approximately 26% of older adults globally, yet there are limited data on the prevalence and longitudinal impact of frailty subtypes. Therefore, in this study, we aim to determine the prevalence of physical, psychological, and cognitive frailty, transitions between subtypes, and associated health determinants among Malaysian community-dwelling older adults. This study is part of the longitudinal aging study in Malaysia (LRGS Ageless and TUA). We assessed 815 older adults in 2014, with successful follow-up of 402 participants (mean age: 67.08 ± 5.38 years) after 5 years. Frailty subtypes were assessed at baseline, and transitions were evaluated at the 5-year mark. At baseline, the prevalence of older adults categorized as robust, physical frailty, cognitive frailty, and psychological frailty was 26.7%, 36.3%, 12.1%, and 16.7%, respectively, with 8.1% exhibiting concurrent psychological and cognitive frailty. Follow-up results showed that 22.9% remained robust, 46.8% experienced no change, 24.9% deteriorated (adversed), and 5.5% improved (reversed). Logistic regression analysis identified living alone (p < 0.001), increased body fat percentage (p < 0.05), increased waist circumference (p < 0.05), reduced fat-free mass (p < 0.05), decreased lower limb flexibility (p < 0.05), and declined cardiorespiratory fitness (p < 0.05) as significant predictors of frailty deterioration. Higher Mini Mental State Examination (MMSE) scores and improved Timed Up and Go and Chair Stand test results (p < 0.05) were significantly associated with the reversal of frailty subtypes (p < 0.05). Younger older adults (p < 0.001), males (p < 0.05), those with lower WHO Disability Scale scores (p < 0.05), and higher MMSE scores (p < 0.05) were significantly less likely to develop frailty subtypes. Intervention strategies that focus on combined physical, cognitive, and psychosocial functions are crucial for both reversing and preventing the progression of frailty subtypes in older adults.

Multidimensional frailty and sleep quality in late adulthood: A UK biobank examination.

Frailty and sleep disturbances are two major concerns in late adulthood, that not only profoundly threaten health and wellbeing at the individual level but place enormous demands on our healthcare systems. Given that both constructs represent dynamic states that are preventable and reversible, understanding the potential pathways to and effects of these variables on one another is critical in providing effective and tailored support. However, despite growing interest in the relationship between sleep and frailty, only one study to date has directly explored their potential bidirectionality. Accordingly, this study was designed to extend the current understanding by investigating the reciprocal relationship of frailty and sleep quality at the multidimensional level. Specifically, the bidirectionality of these relationships was considered separately for physical, psychological, cognitive, and social frailty. Four random-intercept cross-lagged panel models with three time points were conducted, using 3192 older adults (Mage = 60.21; 46.37% female at baseline) from the UK Biobank. The results revealed that while physical, psychological, and cognitive frailty were neither predictive of, nor predicted by, sleep quality, social frailty and sleep share a reciprocal relationship. These data therefore offer important preliminary evidence for the efficacy of early intervention and prevention strategies aimed at enhancing sleep quality to reduce social frailty, and vice versa.

Construction and verification of a risk prediction model for cognitive frailty in older patients with chronic obstructive pulmonary disease and diabetes mellitus.

OBJECTIVE: We explored risk factors for cognitive frailty in older patients with chronic obstructive pulmonary disease (COPD) and diabetes mellitus to develop and verify a risk prediction model for cognitive frailty. METHODS: This was a cross-sectional study. Convenience sampling was used to randomly select 378 patients hospitalized between February 2022 and December 2023. We allocated 265 patients who visited between February 2022 and February 2023 to a modeling group to analyze risk factors for cognitive frailty and create a logistic regression model for risk prediction. Another 113 patients who visited between March 2023 and December 2023 were included in a validation group for model verification. RESULTS: The cognitive frailty incidence in the 265 patients was 35.09% (93/265). Regression analysis showed that age >80 years (odds ratio [OR] = 4.576), regular exercise (OR = 0.390, polypharmacy (OR = 3.074), depression (OR = 2.395) duration of COPD combined with diabetes (OR = 1.902), Family APGAR index score (OR = 0.428), and chronic pain (OR = 2.156) were factors influencing the occurrence of cognitive frailty in older patients with COPD accompanied by diabetes. CONCLUSIONS: The constructed risk prediction model for cognitive frailty in older patients with COPD and diabetes showed good predictive value, aiding in the clinical identification of high-risk patients and facilitating timely intervention and guidance.

Cognitive frailty in relation to vitamin B12 and 25-hydroxyvitamin D in an elderly population: a cross-sectional study from NHANES.

Background: Nutritional support has been identified as a potential intervention for cognitive frailty; however, the association between 25-hydroxyvitamin D [25-(OH)D], vitamin B12, and cognitive frailty remains ambiguous. Methods: This study utilized data from two cycles (2011-2012, 2013-2014) of the National Health and Nutrition Examination Survey (NHANES) to investigate this relationship. The researchers constructed a 41-item frailty index encompassing diverse aspects of physical functioning, psychological evaluation, and medical conditions, and evaluated each participant individually. The study utilized Spearman's rank correlation coefficient and univariate ordered logistic regression to assess the relationships between variables and cognitive frailty. Recursive feature elimination and cross-validation methods were employed to identify the most influential variables for building and optimizing multivariate ordered logistic regression models. Subgroup analyses and interaction tests were further conducted to validate the identified correlations. Results: The findings of this study confirm a negative linear correlation between 25-(OH)D levels and cognitive frailty in older adults. Specifically, a one-unit increase in 25-(OH)D levels was associated with a 12% reduction in the risk of cognitive frailty. The result was further supported by subgroup analyses and interaction tests. Conclusion: The existence of a negatively correlated linear association between 25-(OH)D levels and cognitive frailty in older adults is plausible, but further rigorously designed longitudinal studies are necessary to validate this relationship.

Association of Cognitive Frailty With Subsequent All-Cause Mortality Among Middle-Aged and Older Adults in 17 Countries.

OBJECTIVES: Cognitive frailty refers to the co-occurrence of cognitive impairment and frailty without concurrent Alzheimer's disease or dementia. Studies of cognitive frailty and mortality have been limited to single country or older people. However, frailty and cognitive decline may occur much earlier. We aimed to examine the association between different cognitive frailty status and subsequent all-cause mortality among middle-aged and older people in 17 countries. METHODS: Participants aged 50 and over were drawn from six prospective cohorts of aging. We classified participants according to their cognitive impairment and frailty status into the following groups: none, only cognitive impairment, only frailty and cognitive frailty. Competing-risks regression models were used to evaluate the association of different cognitive frailty status at baseline with subsequent all-cause mortality. RESULTS: The cognitive frailty group had a higher mortality risk compared to those without cognitive impairment and frailty groups. Meta-analysis results showed participants with cognitive frailty (pooled subhazard ratio [SHR] = 2.34, 95% confidence interval [CI]: 2.01-2.72, I2 = 68.0%) had a higher mortality risk compared with those with only cognitive impairment status (pooled SHR = 1.36, 95% CI: 1.25-1.48, I2 = 3.0%) or only frailty status (pooled SHR = 1.83, 95% CI: 1.72-1.95, I2 = 31.0%). The association between cognitive frailty and mortality were stronger among those who were aged 70 years and older, males, single and nonconsumers of alcohol. CONCLUSIONS: Cognitive frailty, frailty or cognitive impairment alone, is associated with an increased risk of all-cause mortality in Asian, European and American countries. Physical and cognitive function screening should be conducted as early as possible in middle-aged and older people, and targeted intervention approaches should be developed to reduce the incidence of adverse health outcomes.

Understanding exogenous factors and biological mechanisms for cognitive frailty: A multidisciplinary scoping review.

Cognitive frailty (CF) is the conjunction of cognitive impairment without dementia and physical frailty. While predictors of each element are well-researched, mechanisms of their co-occurrence have not been integrated, particularly in terms of relationships between social, psychological, and biological factors. This interdisciplinary scoping review set out to categorise a heterogenous multidisciplinary literature to identify potential pathways and mechanisms of CF, and research gaps. Studies were included if they used the definition of CF OR focused on conjunction of cognitive impairment and frailty (by any measure), AND excluded studies on specific disease populations, interventions, epidemiology or prediction of mortality. Searches used Web of Science, PubMed and Science Direct. Search terms included "cognitive frailty" OR (("cognitive decline" OR "cognitive impairment") AND (frail*)), with terms to elicit mechanisms, predictors, causes, pathways and risk factors. To ensure inclusion of animal and cell models, keywords such as "behavioural" or "cognitive decline" or "senescence", were added. 206 papers were included. Descriptive analysis provided high-level categorisation of determinants from social and environmental through psychological to biological. Patterns distinguishing CF from Alzheimer's disease were identified and social and psychological moderators and mediators of underlying biological and physiological changes and of trajectories of CF development were suggested as foci for further research.

Effects of Virtual Reality Motor-Cognitive Training for Older People With Cognitive Frailty: Multicentered Randomized Controlled Trial.

BACKGROUND: Cognitive frailty refers to a clinical syndrome in which physical frailty and mild cognitive impairment coexist. Motor-cognitive training and virtual reality (VR) have been used to launch various therapeutic modalities to promote health in older people. The literature advocates that motor-cognitive training and VR are effective in promoting the cognitive and physical function of older people. However, the effects on older people with cognitive frailty are unclear. OBJECTIVE: This study examined the effects of VR motor-cognitive training (VRMCT) on global cognitive function, physical frailty, walking speed, visual short-term memory, inhibition of cognitive interference, and executive function in older people with cognitive frailty. METHODS: This study used a multicentered, assessor-blinded, 2-parallel-group randomized controlled trial design. Participants were recruited face-to-face in 8 older adult community centers. Eligible participants were aged ≥60 years, were community dwelling, lived with cognitive frailty, had no dementia, and were not mobility restricted. In the intervention group, participants received VRMCT led by interventionists with 16 one-hour training sessions delivered twice per week for 8 weeks. In the control group, participants received the usual care provided by the older adult community centers that the investigators did not interfere with. The primary outcome was global cognitive function. The secondary outcomes included physical frailty, walking speed, verbal short-term memory, inhibition of cognitive interference, and executive function. Data were collected at baseline (T0) and the week after the intervention (T1). Generalized estimating equations were used to examine the group, time, and interaction (time × group) effects on the outcomes. RESULTS: In total, 293 eligible participants enrolled in the study. The mean age of the participants was 74.5 (SD 6.8) years. Most participants were female (229/293, 78.2%), had completed primary education (152/293, 52.1%), were married (167/293, 57.2%), lived with friends (127/293, 43.3%), and had no VR experience (232/293, 79.5%). In the intervention group, 81.6% (119/146) of participants attended >80% (13/16, 81%) of the total number of sessions. A negligible number of participants experienced VR sickness symptoms (1/146, 0.7% to 5/146, 3%). VRMCT was effective in promoting global cognitive function (interaction effect: P=.03), marginally promoting executive function (interaction effect: P=.07), and reducing frailty (interaction effect: P=.03). The effects were not statistically significant on other outcomes. CONCLUSIONS: VRMCT is effective in promoting cognitive functions and reducing physical frailty and is well tolerated and accepted by older people with cognitive frailty, as evidenced by its high attendance rate and negligible VR sickness symptoms. Further studies should examine the efficacy of the intervention components (eg, VR vs non-VR or dual task vs single task) on health outcomes, the effect of using technology on intervention adherence, and the long-term effects of the intervention on older people with cognitive frailty at the level of daily living. TRIAL REGISTRATION: ClinicalTrials.gov NCT04730817; https://clinicaltrials.gov/study/NCT04730817.

Development of cognitive frailty screening tool among community-dwelling older adults.

Purpose: To develop a brief screening tool consisting of twelve items that can be self-administered for rapid identification of older adults at risk of cognitive frailty (CF), named as Cognitive Frailty Screening Tool (CFST). Patients and methods: A total of 1318 community-dwelling individuals aged 60 years and above were selected and assessed for cognitive frailty using a set of neuropsychology batteries and physical function tests. A binary logistic regression (BLR) was used to identify predictors of CF to be used as items in the screening tool. A suitable cut-off point was developed using receiver operating characteristic analysis. Results: Twelve items were included in the screening tool, comprising of gender, education years, medical history, depressive symptoms and functional status as well as lifestyle activities. The area under the curve (AUC) was 0.817 (95 % CI:0.774-0.861), indicating an excellent discriminating power. The sensitivity and specificity for cut-off 7 were 80.8 % and 79.0 %, with an acceptable range of positive predictive value (PPV) (73.3 %) and negative predictive value (NPV) (85.2 %) for screening tools. Concurrent validity of CFST score with standard cognitive and frailty assessment tools shows a significant association with the total score of CFST with low to moderate correlation (p < 0.05 for all parameters). Conclusion: CFST had good sensitivity and specificity and was valid for community-dwelling older adults. There is a need to evaluate further the cost-effectiveness of implementing CFST as a screening for the risk of CF in the community. Its usage in clinical settings needs further validation.