The fitness for the Ageing Brain Study II (FABS II): protocol for a randomized controlled clinical trial evaluating the effect of physical activity on cognitive function in patients with Alzheimer's disease

Background: Observational studies have documented a potential protective effect of physical exercise in older adults who are at risk for developing Alzheimer's disease. The Fitness for the Ageing Brain II (FABS II) study is a multicentre randomized controlled clinical trial (RCT) aiming to determine whether physical activity reduces the rate of cognitive decline among individuals with Alzheimer's disease. This paper describes the background, objectives of the study, and an overview of the protocol including design, organization and data collection methods

Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture

Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer's disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal P-threshold (P) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases and 35,675 family history proxy cases. We show that the discriminative ability of GRS in LOAD prediction is maximised when selecting a small number of SNPs. Both simulation results and direct estimation indicate that the number of causal common SNPs for LOAD may be less than 100, suggesting LOAD is more oligogenic than polygenic. The best GRS explains approximately 75% of SNP-heritability, and individuals in the top decile of GRS have ten-fold increased odds when compared to those in the bottom decile. In addition, 14 variants are identified that contribute to both LOAD risk and age at onset of LOAD

Effects of a multimodal exercise program on the functional capacity of Parkinson's disease patients considering disease severity and gender

The purpose of this study was to investigate the effects of a multimodal exercise program (MEP) on the functional capacity of patients with Parkinson's disease (PD) according to disease severity and gender. Fourteen patients with PD participated in the study and were distributed into groups according to 1) stage of disease and 2) gender. Functional capacity was evaluated before and after 6 months of intervention. The overall PD patient group improved their coordination and strength. Men and women improved in strength performance after exercise. Men also improved on coordination. For severity of disease, the unilateral group improved in strength, while the bilateral group improved in strength, balance, coordination and the UPDRS-functional score. In conclusion, a MEP is efficient in improving components of functional capacity in patients with PD, especially in strength. Gender may be considered in the exercise program. Individuals in the bilateral disease group appeared to benefit more from exercise

A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort

Alzheimer\u27s Disease (AD) is the most common form of dementia, characterised by extracellular amyloid deposition as plaques and intracellular neurofibrillary tangles of tau protein. As no current clinical test can diagnose individuals at risk of developing AD, the aim of this project is to evaluate a blood-based biomarker panel to identify individuals who carry this risk. We analysed the levels of 22 biomarkers in clinically classified healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer\u27s participants from the well characterised Australian Imaging, Biomarker and Lifestyle (AIBL) study of aging. High levels of IL-10 and IL-12/23p40 were significantly associated with amyloid deposition in HC, suggesting that these two biomarkers might be used to detect at risk individuals. Additionally, other biomarkers (Eotaxin-3, Leptin, PYY) exhibited altered levels in AD participants possessing the APOE ϵ4 allele. This suggests that the physiology of some potential biomarkers may be altered in AD due to the APOE ϵ4 allele, a major risk factor for AD. Taken together, these data highlight several potential biomarkers that can be used in a blood-based panel to allow earlier identification of individuals at risk of developing AD and/or early stage AD for which current therapies may be more beneficial

Updating the evidence relating to physical activity intervention studies in older people

For older adults, physical activity (PA) plays a central role in the prevention and management of chronic disease, and has the potential to reduce physical decline, maintain functional ability and prevent injuries. This review provides an update of the evidence relating to the effectiveness of PA intervention studies (both general PA and trials specific to progressive resistance training (PRT)) for older adults. The following electronic databases were searched for articles published since 1999: Medline, PubMed, EMBASE, CINAHL and Sport Discus. For the PRT section, a 2002 Cochrane review was also used. Eight general PA intervention studies were included in this review, ranging from one-on-one counselling in general practice to the community-wide promotion of walking. The aim of most of the trials was to increase moderate and/or vigorous activity levels. Most of the studies reviewed had some degree of success in getting older people to be more active. However, a major limitation was the use of self-report measures of PA. The review of PRT interventions included 21 trials. Participants in half the studies had either functional limitations or a chronic condition. Most trials were conducted in a supervised setting using specialised equipment. Increased strength and improvement in basic functional tasks were generally reported, but there was a paucity of strong evidence linking PRT with reduced physical disability and improved health-related quality of life. While considerable progress is being made in this area, further population-based studies that include home and whole-community interventions are required

A stepped-wedge randomised controlled trial assessing the implementation, effectiveness and cost-consequences of the EDDIE+ hospital avoidance program in 12 residential aged care homes: study protocol

Background: Older people living in residential aged care homes experience frequent emergency transfers to hospital. These events are associated with risks of hospital acquired complications and invasive treatments or interventions. Evidence suggests that some hospital transfers may be unnecessary or avoidable. The Early Detection of Deterioration in Elderly residents (EDDIE) program is a multi-component intervention aimed at reducing unnecessary hospital admissions from residential aged care homes by empowering nursing and care staff to detect and manage early signs of resident deterioration. This study aims to implement and evaluate the program in a multi-site randomised study in Queensland, Australia. Methods: A stepped-wedge randomised controlled trial will be conducted at 12 residential aged care homes over 58 weeks. The program has four components: education and training, decision support tools, diagnostic equipment, and implementation facilitation with clinical systems support. The integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework will be used to guide the program implementation and process evaluation. The primary outcome measure will be the number of hospital bed days used by residents, with secondary outcomes assessing emergency department transfer rates, admission rates, length of stay, family awareness and experience, staff self-efficacy and costs of both implementation and health service use. A process evaluation will assess the extent and fidelity of program implementation, mechanisms of impact and the contextual barriers and enablers. Discussion: The intervention is expected to improve outcomes by reducing unnecessary hospital transfers. Fewer hospital transfers and admissions will release resources for other patients with potentially greater needs. Residential aged care home staff might benefit from feelings of empowerment in their ability to proactively manage early signs of resident deterioration. The process evaluation will be useful for supporting wider implementation of this intervention and other similar initiatives. Trial registration: The trial is prospectively registered with the Australia New Zealand Clinical Trial Registry (ACTRN12620000507987, registered 23/04/2020).</p

Association between cognitive function and clustered cardiovascular risk of metabolic syndrome in older adults at risk of cognitive decline

Objectives: Metabolic syndrome (MetS) represents a cluster of obesity and insulin resistance-related comorbidities. Abdominal obesity, hypertension, elevated triglyceride and glucose levels are components of MetS and may have a negative effect on cognitive function, but few cognitive studies have examined the combined risk severity. We sought to determine which specific cognitive abilities were associated with MetS in older adults at risk of cognitive decline. Design: Cross-sectional study. Participants: 108 AIBL Active participants with memory complaints and at least one cardiovascular risk factor. Measurements: Cardiovascular parameters and blood tests were obtained to assess metabolic syndrome criteria. The factors of MetS were standardized to obtain continuous z-scores. A battery of neuropsychological tests was used to evaluate cognitive function. Results: Higher MetS z-scores were associated with poorer global cognition using ADAS-cog (adjusted standardized beta = 0.26, SE 0.11, p \u3c 0.05) and higher Trail Making B scores (adjusted beta = 0.23, SE 0.11, p \u3c 0.05). Higher MetS risk was related to lower cognitive performance. Conclusion: Combined risk due to multiple risk factors in MetS was related to lower global cognitive performance and executive function. A higher MetS risk burden may point to opportunities for cognitive testing in older adults as individuals may experience cognitive changes

A stepped-wedge randomised controlled trial assessing the implementation, effectiveness and cost-consequences of the EDDIE+ hospital avoidance program in 12 residential aged care homes: Study protocol

Background: Older people living in residential aged care homes experience frequent emergency transfers to hospital. These events are associated with risks of hospital acquired complications and invasive treatments or interventions. Evidence suggests that some hospital transfers may be unnecessary or avoidable. The Early Detection of Deterioration in Elderly residents (EDDIE) program is a multi-component intervention aimed at reducing unnecessary hospital admissions from residential aged care homes by empowering nursing and care staff to detect and manage early signs of resident deterioration. This study aims to implement and evaluate the program in a multi-site randomised study in Queensland, Australia. Methods: A stepped-wedge randomised controlled trial will be conducted at 12 residential aged care homes over 58 weeks. The program has four components: education and training, decision support tools, diagnostic equipment, and implementation facilitation with clinical systems support. The integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework will be used to guide the program implementation and process evaluation. The primary outcome measure will be the number of hospital bed days used by residents, with secondary outcomes assessing emergency department transfer rates, admission rates, length of stay, family awareness and experience, staff self-efficacy and costs of both implementation and health service use. A process evaluation will assess the extent and fidelity of program implementation, mechanisms of impact and the contextual barriers and enablers. Discussion: The intervention is expected to improve outcomes by reducing unnecessary hospital transfers. Fewer hospital transfers and admissions will release resources for other patients with potentially greater needs. Residential aged care home staff might benefit from feelings of empowerment in their ability to proactively manage early signs of resident deterioration. The process evaluation will be useful for supporting wider implementation of this intervention and other similar initiatives. Trial registration: The trial is prospectively registered with the Australia New Zealand Clinical Trial Registry (ACTRN12620000507987, registered 23/04/2020)