International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines.

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.

Intrinsic Capacitiy Monitoring by Digital Biomarkers in Integrated Care for Older People (ICOPE).

The WHO action plan on aging expects to change current clinical practices by promoting a more personalized model of medicine. To widely promote this initiative and achieve this goal, healthcare professionals need innovative monitoring tools. Use of conventional biomarkers (clinical, biological or imaging) provides a health status assessment at a given time once a capacity has declined. As a complement, continuous monitoring thanks to digital biomarkers makes it possible to remotely collect and analyze real life, ecologically valid, and continuous health related data. A seamless assessment of the patient's health status potentially enables early diagnosis of IC decline (e.g. sub-clinical or transient events not detectable by episodic evaluations) and investigation of its probable causes. This narrative review aims to develop the concept of digital biomarkers and its implementation in IC monitoring.

A Community Program of Integrated Care for Frail Older Adults: +AGIL Barcelona.

OBJECTIVES: To assess the 3-month impact on physical function of a program for community-dwelling frail older adults, based on the integration of primary care, geriatric medicine, and community resources, implemented in "real life". DESIGN: Interventional cohort study. SETTING: Primary care in Barcelona, Spain. PARTICIPANTS: Individuals aged ≥80 years (n=134), presenting at least one sign of frailty (i.e., slow gait speed, weakness, memory complaints, involuntary weight loss, poor social support). INTERVENTION: After frailty screening by the primary care team, candidates were referred to a geriatric team (geriatrician + physical therapist), who performed a comprehensive geriatric assessment and designed a tailored multidisciplinary intervention in the community, including a) multi-modal physical activity (PA) sessions, b) promotion of adherence to a Mediterranean diet c) health education and d) medication review. MEASUREMENTS: Participants were assessed based on a comprehensive geriatric assessment including physical performance (Short Physical Performance Battery -SPPB- and gait speed), at baseline and at a three month follow-up. RESULTS: A total of 112 (83.6%) participants (mean age=80.8 years, 67.9% women) were included in this research. Despite being independent in daily life, participants' physical performance was impaired (SPPB=7.5, SD=2.1, gait speed=0.71, SD=0.20 m/sec). After three months, 90.2% of participants completed ≥7.5 physical activity sessions. The mean improvements were +1.47 (SD 1.64) points (p<0.001) for SPPB, +0.08 (SD 0.13) m/sec (p<0.001) for gait speed, -5.5 (SD 12.10) sec (p<0.001) for chair stand test, and 53% (p<0.001) improved their balance. Results remained substantially unchanged after stratifying the analyses according to the severity of frailty. CONCLUSIONS: Our results suggested that a "real-world" multidisciplinary intervention, integrating primary care, geriatric care, and community services may improve physical function, a marker of frailty, within 3 months. Further studies are needed to address the long-term impact and scalability of this implementation program.

Prevention of Disability in the Frail Chinese Older Population.

As aging is becoming a global phenomenon, the burden of population aging is increasing rapidly, and is soon expected to be the highest in low-and middle-income countries. China represents the world's largest population, and will face the largest number of older individuals, while the economy still remains developing. There is an urgent need to address the negative consequences of aging such as disability, that creates a myriad of challenges, including financial burden to the economy. In order to achieve successful aging-i.e., aging without being frail or disabled, the traditional healthcare model based on a disease-centered approach is not enough, but require a more holistic course. Here, we briefly outline the current scenario of aging and disability in the Chinese older population, its impact and challenges. We strongly believe that public health initiatives centered on frailty, a clinically distinguishable state of extreme vulnerability in older adults, could be the most relevant approach to meet the current needs of the aging population. Such initiatives are immediately needed to reshape the existing model of geriatric healthcare, to promote healthy aging and to reduce the burden of disability in the Chinese population.

International Clinical Practice Guidelines for Sarcopenia (ICFSR): Screening, Diagnosis and Management.

OBJECTIVES: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR). METHODS: To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefit-harm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process. RECOMMENDATIONS: We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.

Interventions Against Disability in Frail Older Adults: Lessons Learned from Clinical Trials.

As the population ages, the number of older people with frailty is expected to increase worldwide with consequent rising of expenditures for healthcare and long-term care. Effective methods for preventing or delaying the onset of disability are urgently required. Frailty is a common and important geriatric condition characterized by age-associated declines in multiple physiological mechanisms, leading to increased vulnerability to stressors and higher risk for adverse health outcomes. Significant advancements have been made in the understanding of the frailty pathophysiological background. Given its multidimensional nature, reversing frailty requires a comprehensive approach. In this context, several studies testing the effects of pharmacological approach, physical activity, nutritional intervention, or cognitive training showed evidence of efficacy in frail older adults. Important innovations in ongoing trials include the development of multidomain interventions. Challenges include the use of trial designs, the development of standardized, sensitive outcome measures, and the need for interventions that can be implemented in resource-poor settings. In this viewpoint paper, based on recent literature, our aim was to identify relevant studies performed to reverse or delay disability in frail older adults.

Trajectory of the MAPT-PACC-Preclinical Alzheimer Cognitive Composite in the Placebo Group of a Randomized Control Trial: Results from the MAPT Study: Lessons for Further Trials.

Defining the primary cognitive endpoint is a major decision for Alzheimer's disease preventive trials. As an example for further trials we present in detail the three-year cognitive decline in the placebo group of MAPT trial, a randomized controlled trial (RCT) using a cognitive composite score (MAPT-PACC). Participants were dementia-free adults 70 years or older, with subjective memory complaints. Our findings as expected showed subjects with older age (>75), higher beta amyloid brain deposition, APOE-ε4 allele carriers, with low RBC DHA+EPA levels and higher CDR level are at higher risk of cognitive decline. The data presented in this paper can be useful for future preventive trials to choose the primary cognitive end point, assess the clinical relevance of cognitive changes and perform sample size calculation for several targeted population eg. ApoE4, amyloid +, oldest old, lower n3-PUFA. We believe that the trial group with CDR 0.5, without being selected by a memory test endpoint is a good target population for AD preventive trials.

Does nutrition play a role in the prevention and management of sarcopenia?

There is a growing body of evidence that links nutrition to muscle mass, strength and function in older adults, suggesting that it has an important role to play both in the prevention and management of sarcopenia. This review summarises the discussions of a working group [ESCEO working group meeting 8th September 2016] that met to review current evidence and to consider its implications for preventive and treatment strategies. The review points to the importance of 'healthier' dietary patterns that are adequate in quality in older age, to ensure sufficient intakes of protein, vitamin D, antioxidant nutrients and long-chain polyunsaturated fatty acids. In particular, there is substantial evidence to support the roles of dietary protein and physical activity as key anabolic stimuli for muscle protein synthesis. However, much of the evidence is observational and from high-income countries. Further high-quality trials, particularly from more diverse populations, are needed to enable an understanding of dose and duration effects of individual nutrients on function, to elucidate mechanistic links, and to define optimal profiles and patterns of nutrient intake for older adults.

Cross-Sectional Associations of Total Plasma Homocysteine with Cortical ß-Amyloid Independently and as a Function of Omega 3 Polyunsaturated Fatty Acid Status in Older Adults at Risk of Dementia.

OBJECTIVES: Elevated total plasma homocysteine is a risk factor for Alzheimer's disease (AD) and there is some evidence that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can modulate the effects of homocysteine-lowering B vitamins on AD related pathologies. Hence we investigated the relationship between total plasma homocysteine and cortical ß-amyloid (Aß) in older adults at risk of dementia. The role of erythrocyte membrane n-3 PUFAs (omega 3 index) on this relationship was also explored. DESIGN: This is a cross-sectional study using data from the Multidomain Alzheimer Preventive Trial (MAPT); a randomised controlled trial. SETTING: French community dwellers aged 70 or over reporting subjective memory complaints, but free from a diagnosis of clinical dementia. PARTICIPANTS: Individuals were from the MAPT trial (n = 177) with data on total plasma homocysteine at baseline and cortical Aß load. MEASUREMENTS: Cortical-to-cerebellar standard uptake value ratios were assessed using [18F] florbetapir positron emission tomography (PET). Total baseline plasma homocysteine was measured using an enzymatic cycling assay. Baseline omega 3 index was measured using gas chromatography. Cross-sectional associations were explored using adjusted multiple linear regression models. RESULTS: We found that total baseline plasma homocysteine was not significantly associated with cortical Aß as demonstrated using multiple linear regression models adjusted for age, sex, education, cognitive status, time interval between baseline and PET-scan, omega-3 index, MAPT group allocation and Apolipoprotein E ε4 status (B-coefficient -0.001, 95 % CI: -0.008,0.006, p = 0.838). Exploratory analysis showed that homocysteine was however significantly associated with cortical Aß in subjects with low baseline omega-3 index (< 4.72 %) after adjustment for Apolipoprotein E ε4 status (B-coefficient 0.041, 95 % CI: 0.017,0.066, p = 0.005, n = 10), but not in subjects with a high baseline omega-3 index (B-coefficient -0.010, 95 % CI: -0.023,0.003, p = 0.132, n = 66). CONCLUSIONS: The role of n-3 PUFAs on the relationship between homocysteine and cerebral Aß warrants further investigation.

Cognitive Changes with Omega-3 Polyunsaturated Fatty Acids in Non-Demented Older Adults with Low Omega-3 Index.

OBJECTIVES: To investigate the changes in specific domains of cognitive function in older adults reporting subjective memory complaints with a low omega-3 index receiving omega 3 polyunsaturated fatty acid (n-3 PUFA) supplementation or placebo. DESIGN: This is a secondary exploratory analysis of the Multidomain Alzheimer Preventive Trial (MAPT) using subjects randomized to the n-3 PUFA supplementation or placebo group. SETTING: French community dwellers aged 70 or over reporting subjective memory complaints, but free from clinical dementia. PARTICIPANTS: A subgroup of MAPT subjects in the lowest quartile of omega-3 index distribution with baseline values ≤ 4.83 % (n = 183). INTERVENTION: The n-3 PUFA supplementation group consumed a daily dose of DHA (800 mg) and EPA (a maximum amount of 225 mg) for 3 years. The placebo group received identical capsules comprising liquid paraffin oil. MEASUREMENTS: Linear mixed-model repeated-measures analyses were used including baseline, 6, 12, 24 and 36-month follow-up data to assess between-group differences in the change in eight cognitive tests over 36 months. RESULTS: There was less decline on the Controlled Oral Word Association Test (COWAT) in the n-3 PUFA supplementation group compared to placebo (p = 0.009; between group mean difference over 36 months, 2.3; 95% CI, 0.6,4.0). No significant differences for any of the other cognitive tests were found, including other tests of executive functioning, although, numerically all results were in favour of the n-3 PUFA supplementation. CONCLUSIONS: We found some evidence that n-3 PUFAs might be beneficial for the maintenance of executive functioning in older adults at risk of dementia with low omega-3 index, but this exploratory finding requires further confirmation. A larger specifically designed randomised controlled trial could be merited.

How Older Persons Perceive the Loss of Independence: The Need of a Holistic Approach to Frailty.

BACKGROUND: Since 2004, the definition of the frailty syndrome has shifted from purely physical criteria to a more comprehensive consideration of the individual, including their psychosocial criteria. In this study, qualitative research methods were used as a complementary approach in order to enrich the existing quantitative results in this area. OBJECTIVE: To understand the views of older persons on the risk of loss of independence. METHODS: The study population comprised people over 75 years of age who were living at home in the south-west of France and were considered to be at risk of losing their independence. Data were collected using individual semi-structured in-depth interviews, accompanied by observations. Inductive analysis was carried out according to grounded theory methods. RESULTS: Fifteen individual interviews were conducted to achieve theoretical data saturation. Analysis of the content of the interviews revealed seven risk factors for the loss of independence: poor mental health, poor physical health, social isolation, no longer leaving the home, an unsuitable environment, unsuitable living conditions, and few resources. CONCLUSIONS: These results complement the purely physical approach to screening for the frailty syndrome and lead us to reconsider our screening approach to include a more holistic view of the older person and their circumstances.

MAPT STUDY: A MULTIDOMAIN APPROACH FOR PREVENTING ALZHEIMER'S DISEASE: DESIGN AND BASELINE DATA.

OBJECTIVE: The Multidomain Alzheimer Preventive Trial (MAPT study) was designed to assess the efficacy of isolated supplementation with omega-3 fatty acid, an isolated multidomain intervention (consisting of nutritional counseling, physical exercise, cognitive stimulation) or a combination of the two interventions on the change of cognitive functions in frail subjects aged 70 years and older for a period of 3 years. Ancillary neuroimaging studies were additionally implemented to evaluate the impact of interventions on cerebral metabolism (FDG PET scans) and atrophy rate (MRIs), as well as brain amyloïd deposit (AV45 PET scans). DESIGN PATIENTS: 1680 subjects (mean age: 75.3 years; female: 64.8 %), enrolled by 13 memory clinics, were randomized into one of the following four groups: omega-3 supplementation alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo. Participants underwent cognitive, functional and biological assessments at M6, M12, M24 and M36 visits. The primary endpoint is a change of memory function at 3 years, as assessed by the Free and Cued Selective Reminding test. All participants will be followed for 2 additional years after the 3-years intervention (MAPT PLUS extension study). INTERVENTIONS: 1/Omega-3 supplementation: two soft capsules daily as a single dose, containing a total of 400 mg docosahexaenoic acid (DHA), i.e., 800 mg docosahexaenoic acid per day, for 3 years. 2/ Multidomain intervention: collective training sessions conducted in small groups (6-8 participants) in twelve 120-minute sessions over the first 2 months (two sessions a week for the first month, and one session a week the second month) then a 60-minute session per month in the following three areas: nutrition, physical activity, and cognition until the end of the 3 years. In addition to the collective sessions, individualized preventive outpatient visits exploring possible risk factors for cognitive decline are performed at baseline, M12 and M24. BASELINE POPULATION: For cognition, the mean MMSE at baseline was 28.1 (± 1.6). About 58% and 42% of participants had a CDR score equal to 0 and 0.5, respectively. Regarding mobility status, 200 (11.9%) had a 4-m gait speed lower or equal to 0.8 m/s. According to the Fried criteria, 673 (42.1%) participants were considered pre frail, and 51 (3.2%) frail. The red blood cell DHA content was 26.1 ± 8.1 µg/g. Five hundred and three participants underwent baseline MRI. AV45 PET scans were performed in 271 individuals and preliminary results showed that 38.0% had a cortical SUVR > 1.17, which gave an indication of significant brain amyloïd deposit. DISCUSSION: The MAPT trial is presently the first largest and longest multidomain preventive trial relevant to cognitive decline in older adults with subjective memory complaints. The multidomain intervention designed for the MAPT trial is likely to be easily implemented within the general population.

Vitamin D supplementation in older adults: searching for specific guidelines in nursing homes.

BACKGROUND: The prevalence of vitamin D insufficiency is very high in the nursing home (NH) population. Paradoxically, vitamin D insufficiency is rarely treated despite of strong clinical evidence and recommendations for supplementation. This review aims at reporting the current knowledge of vitamin D supplementation in NH and proposing recommendations adapted to the specificities of this institutional setting. DESIGN: Current literature on vitamin D supplementation for NH residents was narratively presented and discussed by the French Group of Geriatrics and Nutrition. RESULT: Vitamin D supplementation is a safe and well-tolerated treatment. Most residents in NH have vitamin D insufficiency, and would benefit from vitamin D supplement. However, only few residents are actually treated. Current specific and personalized protocols for vitamin D supplementation may not be practical for use in NH settings (e.g., assessment of serum vitamin D concentrations before and after supplementation). Therefore, our group proposes a model of intervention based on the systematic supplementation of vitamin D (1,000 IU/day) since the patient's admission to the NH and throughout his/her stay without the need of a preliminary evaluation of the baseline levels. Calcium should be prescribed only in case of poor dietary calcium intake. CONCLUSION: A population-based rather than individual-based approach may probably improve the management of vitamin D insufficiency in the older population living in NH, without increasing the risks of adverse health problems. The clinical relevance and cost effectiveness of this proposal should be assessed under NH real-world conditions to establish its feasibility.

Designing Phase II B trials in sarcopenia: the best target population.

Despite the existing limitations and controversies regarding the definition of sarcopenia and its clinical consequences, the current scientific evidence strongly suggests that muscle decline is a primary determinant of the disabling process (and likely of other major health-related events). In fact, the muscle loss (in terms of mass as well as strength) occurring with aging has been growingly associated with mobility impairment and disability in older persons. Unfortunately, current evidence is mainly from observational studies. Times are mature to begin testing interventions aimed at modifying the sarcopenia process through the design and development of specific clinical trials. Considering the emergence of many promising interventions towards this age-related condition (e.g., physical exercise [in particular, resistance training], testosterone, antioxidant supplementations), the need for Phase II trial designs is high. In the present report, we discuss which are the major issues related to the design of Phase II clinical trials on sarcopenia with particular focus on the participant's characteristics to be considered as possible inclusion and exclusion criteria.

Homocysteine-lowering treatment in coronary heart disease.

Homocysteine (Hcy) is a sulphur-containing amino acid product of methionine's metabolism. Hyperhomocysteinemia (HHcy) is considered an independent risk factor for cardiovascular (CV) disease, at least in high-risk patients. In fact, evidence indicates that although mild HHcy may be regarded as a minor risk factor for CHD in low-risk patients, it can play a role in triggering new events in patients with known CHD, also by interacting with the "classical" CV risk factors. This is of much interest because HHcy represents a correctable risk factor, inasmuch vitamin supplementation as has been shown to effectively lower total homocysteine plasma levels (tHcy). While case-control and cross-sectional studies have consistently demonstrated an association of HHcy with CV disease, prospective studies have given conflicting results. Moreover, the effect of the homocysteine-lowering treatment in preventing CV events is still under debate. Thus, it remains unclear which patients should be screened for HHcy and which ones should be treated to lower tHcy. In this paper we shall report and discuss knowledge on the potential role of HHcy in the development of CHD and on the benefits due to tHcy-lowering treatment with vitamins.

A new model of integrated home care for the elderly: impact on hospital use.

The objective of the present study was to examine the effect of a home care program based on comprehensive geriatric assessment-Minimum Data Set for Home Care-and case management on hospital use/cost of frail elderly individuals. We determined all hospital admissions and days spent in hospital during the first year since the implementation of the home care program, and compared them to the rate of hospitalization that the same patients had experienced in the year preceding the implementation of such program. Following the implementation of this program, there was a significant reduction of the number of hospitalizations (pre 44% vs. post 26%, P < 0.001), associated with a reduction of hospital days, both at the individual patient level and for each admission. In conclusion, an integrated home care program based on the implementation of a comprehensive geriatric assessment instrument guided by a case manager has a significant impact on hospitalization and is cost-effective.