Summary Interventions that have even quite modest effects at the individual level could drastically reduce the future burden of dementia associated with Alzheimer's disease at the population level. ...In the past three decades, both pharmacological and lifestyle interventions have been studied for the prevention of cognitive decline or dementia in randomised controlled trials of individuals mostly aged older than 50–55 years with or without risk factors for Alzheimer's disease. Several trials testing the effects of physical activity, cognitive training, or antihypertensive interventions showed some evidence of efficacy on a primary cognitive endpoint. However, most of these trials had short follow-up periods, and further evidence is needed to confirm effectiveness and establish the optimum design or dose of interventions and ideal target populations. Important innovations in ongoing trials include the development of multidomain interventions, and the use of biomarker or genetic inclusion criteria. Challenges include the use of adaptive trial designs, the development of standardised, sensitive outcome measures, and the need for interventions that can be implemented in resource-poor settings.
...a substantial increase in long-term funding for multidisciplinary research programmes is absolutely essential to reduce the burden of individual suffering and the enormous societal cost of AD. In ...2015, almost 47 million people worldwide were estimated to be affected by dementia, and the numbers are expected to reach 75 million by 2030, and 131 million by 2050, with the greatest increase expected in low-income and middle-income countries.2 In 2012 and 2015, the World Health Organization (WHO) presented reports in which it acknowledged this trend--sometimes described in terms of a fast-growing epidemic--and concluded that AD and other dementias should be regarded as a global public health priority.3,4 Similar policy declarations have been made by the European Union5 (EU) and by some individual countries. Care for people with dementia is provided by several sectors in society, with the social-care (long-term care and home services) and informal-care (provided by non-professional caregivers) sectors accounting for the greatest proportion of costs--even greater than the cost of direct medical care.6 In cost-of-illness studies, total societal cost estimates for dementia in Europe in 2010 were between $238·6 billion6 and euro105·6 billion.7 The economic costs of caring for a growing number of people with AD and other dementias are formidable, but the combined economic and societal burden of dementia is more daunting still, corresponding to the aggregate burden of people with dementia and their next of kin.
During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, ...it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this “silent” stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.
Longitudinal data are data in which each variable is measured repeatedly over time. One possibility for the analysis of such data is to cluster them. The majority of clustering methods group together ...individual that have close trajectories at given time points. These methods group trajectories that are locally close but not necessarily those that have similar shapes. However, in several circumstances, the progress of a phenomenon may be more important than the moment at which it occurs. One would thus like to achieve a partitioning where each group gathers individuals whose trajectories have similar shapes whatever the time lag between them.
In this article, we present a longitudinal data partitioning algorithm based on the shapes of the trajectories rather than on classical distances. Because this algorithm is time consuming, we propose as well two data simplification procedures that make it applicable to high dimensional datasets.
In an application to Alzheimer disease, this algorithm revealed a "rapid decline" patient group that was not found by the classical methods. In another application to the feminine menstrual cycle, the algorithm showed, contrarily to the current literature, that the luteinizing hormone presents two peaks in an important proportion of women (22%).
The sustainability of health and social care systems is threatened by a growing population of older persons with heterogeneous needs related to multimorbidity, frailty, and increased risk of ...functional impairment. Since disability is difficult to reverse in old age and is extremely burdensome for individuals and society, novel strategies should be devised to preserve adequate levels of function and independence in late life. The development of mobility disability, an early event in the disablement process, precedes and predicts more severe forms of inability. Its prevention is, therefore, critical to impede the transition to overt disability. For this reason, the Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies (SPRINTT) project is conducting a randomized controlled trial (RCT) to test a multicomponent intervention (MCI) specifically designed to prevent mobility disability in high-risk older persons. SPRINTT is a phase III, multicenter RCT aimed at comparing the efficacy of a MCI, based on long-term structured physical activity, nutritional counseling/dietary intervention, and an information and communication technology intervention, versus a healthy aging lifestyle education program designed to prevent mobility disability in 1500 older persons with physical frailty and sarcopenia who will be followed for up to 36 months. The primary outcome of the SPRINTT trial is mobility disability, operationalized as the inability to walk for 400 m within 15 min, without sitting, help of another person, or the use of a walker. Secondary outcomes include changes in muscle mass and strength, persistent mobility disability, falls and injurious falls, disability in activities of daily living, nutritional status, cognition, mood, the use of healthcare resources, cost-effectiveness analysis, quality of life, and mortality rate. SPRINTT results are expected to promote significant advancements in the management of frail older persons at high risk of disability from both clinical and regulatory perspectives. The findings are also projected to pave the way for major investments in the field of disability prevention in old age.
Summary Background Prevention strategies are urgently needed to tackle the growing burden of Alzheimer's disease. We aimed to assess efficacy of long-term use of standardised ginkgo biloba extract ...for the reduction of incidence of Alzheimer's disease in elderly adults with memory complaints. Methods In the randomised, parallel-group, double-blind, placebo-controlled GuidAge clinical trial, we enrolled adults aged 70 years or older who spontaneously reported memory complaints to their primary-care physician in France. We randomly allocated participants in a 1:1 ratio according to a computer-generated sequence to a twice per day dose of 120 mg standardised ginkgo biloba extract (EGb761) or matched placebo. Participants and study investigators and personnel were masked to study group assignment. Participants were followed-up for 5 years by primary-care physicians and in expert memory centres. The primary outcome was conversion to probable Alzheimer's disease in participants who received at least one dose of study drug or placebo, compared by use of the log-rank test. This study is registered with ClinicalTrials.gov , number NCT00276510. Findings Between March, 2002, and November, 2004, we enrolled and randomly allocated 2854 participants, of whom 1406 received at least one dose of ginkgo biloba extract and 1414 received at least one dose of placebo. By 5 years, 61 participants in the ginkgo group had been diagnosed with probable Alzheimer's disease (1·2 cases per 100 person-years) compared with 73 participants in the placebo group (1·4 cases per 100 person-years; hazard ratio HR 0·84, 95% CI 0·60–1·18; p=0·306), but the risk was not proportional over time. Incidence of adverse events was much the same between groups. 76 participants in the ginkgo group died compared with 82 participants in the placebo group (0·94, 0·69–1·28; p=0·68). 65 participants in the ginkgo group had a stroke compared with 60 participants in the placebo group (risk ratio 1·12, 95% CI 0·77–1·63; p=0·57). Incidence of other haemorrhagic or cardiovascular events also did not differ between groups. Interpretation Long-term use of standardised ginkgo biloba extract in this trial did not reduce the risk of progression to Alzheimer's disease compared with placebo. Funding Ipsen.
The "frailty syndrome" (a geriatric multidimensional condition characterized by decreased reserve and diminished resistance to stressors) represents a promising target of preventive interventions ...against disability in elders. Available screening tools for the identification of frailty in the absence of disability present major limitations. In particular, they have to be administered by a trained assessor, require special equipment, and/or do not discriminate between frail and disabled individuals. Aim of this study is to verify the agreement of a novel self-reported questionnaire (the "Frail Non-Disabled" FiND instrument) designed for detecting non-mobility disabled frail older persons with results from reference tools.
Data are from 45 community-dwelling individuals aged ≥60 years. Participants were asked to complete the FiND questionnaire separately exploring the frailty and disability domains. Then, a blinded assessor objectively measured the frailty status (using the phenotype proposed by Fried and colleagues) and mobility disability (using the 400-meter walk test). Cohen's kappa coefficients were calculated to determine the agreement between the FiND questionnaire with the reference instruments. Mean age of participants (women 62.2%) was 72.5 (standard deviation 8.2) years. Seven (15.6%) participants presented mobility disability as being unable to complete the 400-meter walk test. According to the frailty phenotype criteria, 25 (55.6%) participants were pre-frail or frail, and 13 (28.9%) were robust. Overall, a substantial agreement of the instrument with the reference tools (kappa = 0.748, quadratic weighted kappa = 0.836, both p values<0.001) was reported with only 7 (15.6%) participants incorrectly categorized. The agreement between results of the FiND disability domain and the 400-meter walk test was excellent (kappa = 0.920, p<0.001).
The FiND questionnaire presents a very good capacity to correctly identify frail older persons without mobility disability living in the community. This screening tool may represent an opportunity for diffusing awareness about frailty and disability and supporting specific preventive campaigns.
Sarcopenia, the age-associated loss of skeletal muscle mass and function, has considerable societal consequences for the development of frailty, disability, and health care planning. A group of ...geriatricians and scientists from academia and industry met in Rome, Italy, on November 18, 2009, to arrive at a consensus definition of sarcopenia. The current consensus definition was approved unanimously by the meeting participants and is as follows: Sarcopenia is defined as the age-associated loss of skeletal muscle mass and function. The causes of sarcopenia are multifactorial and can include disuse, altered endocrine function, chronic diseases, inflammation, insulin resistance, and nutritional deficiencies. Although cachexia may be a component of sarcopenia, the 2 conditions are not the same. The diagnosis of sarcopenia should be considered in all older patients who present with observed declines in physical function, strength, or overall health. Sarcopenia should specifically be considered in patients who are bedridden, cannot independently rise from a chair, or who have a measured gait speed less that 1 m/s(-1). Patients who meet these criteria should further undergo body composition assessment using dual energy x-ray absorptiometry with sarcopenia being defined using currently validated definitions. A diagnosis of sarcopenia is consistent with a gait speed of less than 1 m·s(-1) and an objectively measured low muscle mass (eg, appendicular mass relative to ht(2) that is ≤ 7.23 kg/m(2) in men and ≤ 5.67 kg/m(2) in women). Sarcopenia is a highly prevalent condition in older persons that leads to disability, hospitalization, and death.
In older patients, hospitalization is often associated with new or worsening disability. This hospitalization-associated disability may be explained in part by the cumulative effect of aging, ...frailty, comorbidities, and illnesses that led to hospitalization but may also result from health care management issues and the hospital environment. Our objective was to determine the frequency, causes, and the preventability of disability induced by the processes of care or "iatrogenic disability."
A total of 503 patients, aged 75 years and older, hospitalized in the 105 medical and surgical units of Toulouse University Hospital between October 2011 and March 2012, with a minimal length of stay of 2 days, were included. Hospitalization-associated disability was defined as a loss of 0.5 points or more in the Katz Activity of Daily Living Score between the time of hospital admission and discharge. To determine the iatrogenic component of hospitalization-associated disability, an expert panel in geriatric medicine reviewed each medical chart using a standardized record review and identified precipitating iatrogenic adverse events resulting in functional decline.
Incidence of iatrogenic disability was 11.9% (95% confidence interval, 9.2%-15.1%). Of the 60 cases of iatrogenic disability, 49 (81.7%, 95% confidence interval, 69.6%-90.5%) were judged to be potentially preventable. The most common health management issues identified in patients with preventable iatrogenic disability were low mobilization by excessive bed rest (26.5%) and lack of physical therapist intervention (55.1%), overuse of diapers (49.0%), and transurethral urinary catheterization (30.6%).
The present study suggests that a significant proportion of hospitalization-associated disability may be induced by iatrogenic events, and that most of them are potentially preventable. Health care professionals need to be educated on the specific needs of elderly hospitalized patients and should consider hospitalization-associated disability as an outcome of care.
Introduction The minimum frequency of physical activity associated with reduced risk for onset of several chronic diseases is not well established. Therefore, this study examined, in a large sample ...of citizens from 16 European countries, the predictive value of physical activity frequency and intensity on the incidence of heart diseases, cerebrovascular diseases, diabetes, cancer of any subtype, breast cancer, and colon/rectum cancer. Methods Using data from the longitudinal Survey of Health, Ageing, and Retirement in Europe, the long-term associations of physical activity with incident diseases in people aged ≥50 years were investigated. Cox proportional hazard models adjusted for potential confounders were performed for each disease. Data were collected between 2004 and 2013 and analyzed in 2015. Results Compared with people who never do physical activity, those doing vigorous physical activity once a week had a reduced risk of developing heart diseases (hazard ratio=0.80; 95% CI=0.70, 0.91), whereas those doing moderate physical activity once a week had a reduced risk of developing diabetes (hazard ratio=0.80; 95% CI=0.68, 0.95) and cerebrovascular diseases (hazard ratio=0.73; 95% CI 0.58, 0.91). The magnitude of the associations increased with higher frequencies for both moderate and vigorous physical activity. Consistent results were obtained in sensitivity analyses. Conclusions Doing physical activity once a week, which is less than current recommendations in terms of frequency, is associated with reduced risk of developing cardiovascular diseases and diabetes among middle-aged and older adults.
PDF
