Effectiveness of a primary care based multifactorial intervention to improve frailty parameters in the elderly: a randomised clinical trial: rationale and study design

The concept of frailty has long been associated with advancing age although only recently has it been specifically defined as a medical syndrome [1‐4]. Disability, comorbidity, malnutrition, biological changes, cognitive impairment, dependency needs, and demands for social services are directly age-related; age, however, as an isolated criterion is not enough to identify vulnerability [5].

Despite considerable discussion, frailty remains to be systematically defined [6]. There is evidence that it increases proportionally to an accumulation of deficits [7]; acute problems -falls, fractures, and infections-, progressive loss of autonomy, and psychosocial limitations all lead to disability and a higher risk of hospitalization, institutionalization, and death [8, 9].

There is no agreement on a valid evaluation model for both research and clinical approaches [10], and some authors differentiate between physical and cognitive frailty [11]. The standard clinical proposal is that which has been presented by Fried et al. who identify someone as having a frail phenotype when three or more of the following components are presented [3]: unintentional weight loss (4.5 kg (=10 lbs) in the past year), self-reported exhaustion (two positive questions of Center for Epidemiologic Studies Depression Scale (CES-D)), weakness, slow walking speed, and low levels of physical activity. Such a definition would be mainly related to physical frailty. For rapid frailty screening of a community-living elderly population these five criteria, however, do not represent a pragmatic approach [10]. Avila-Funes et al. proposed a review to slightly modify Fried’s measurements in order to strengthen the predictive validity of the concept [12], with variable results [13, 14]. In addition, Gill et al. introduced two tests of physical ability strongly associated with disability development and progression: the Rapid-Gait Test and the Stand-Up Test [15]. Other useful batteries of physical performance, such as the Short Physical Performance Battery (SPPB) from Guralnik, can also be found as predictors of old age disability [16, 17].

Sarcopenia is linked to physical frailty and is a key feature of this condition in older people [18]. In fact, a non-negligible proportion of elderly individuals are moderately affected by this it [19]. Sarcopenia is related to loss of muscle mass and muscle strength, strong predictors of adverse health outcomes [20] and death [21, 22].

Epidemiological studies have linked physical frailty and cognitive impairment: frailty increases the risk of cognitive decline and cognitive impairment increases the risk of frailty, therefore, both dimensions would benefit from being addressed [23, 24].

Identifying interventions to prevent or delay the loss of autonomy is currently a public health priority for the successful management of the ageing [25, 26]. Multidimensional home interventions have revealed some benefits, although conclusions are inconsistent and seem to be dependent on factors such as the provider’s experience, access to monitoring, and duration of the follow-up program [15].

A comprehensive geriatric assessment, followed by a multidimensional intervention on disability risk factors -medical, functional, psychological, and environmental problems- through disease management and health promotion in a low-risk elderly population, succeeds in reducing institutionalization and the risk of falls, delaying disabled functional decline, and improving physical performance. The effects, however, are not statistically significant [27‐29].

Strategies involving mass screening in Primary Care to apply preventive approaches based on healthy ageing advice, long-term exercise programs, assistance devices including home telecare kits [30], and environmental modifications can reduce falls [31]. Nevertheless, when considered separately, these methods have no impact on reducing disability [32].

Exercise programs improve strength, aerobic capacity, balance, and function [33, 34], but these benefits depend on long-term adherence, extended training, and exercise-related behaviours acquired in early life. The most promising strategies to increase physical activity in the elderly are those which provide appropriate written advice and generate feelings of fun and satisfaction [35].

Recent surveys have put forward new strategies for the management of sarcopenia to slow down the decline of muscle features: resistance training in combination with adequate protein and energy intake and, additionally, treatment of vitamin D deficiency [36, 37].

Nutritional interventions alone show weak correlation with health improvement in the vulnerable, elderly population. However, dietary advice in association with protein supplementation intake seems to have some effects on sarcopenia, inducing muscle hypertrophy, accelerating weight gain in undernourished older people [38], and reducing fractures [39]. There is a lack of evidence, however, concerning its effects on mortality and hospital admission rates [40].

Findings from cognitive training studies show positive effects. Memory training can aid maintaining long-term improvement in performance [41, 42].

Exercise also leads to enhanced cognitive functioning and psychological well-being in frail, older adults [43]. Aerobic exercise has shown effects on some measures of cognitive function, without consistency for all values [44].

There are few randomized, controlled trials concluding that cognitive interventions, plus complementary physical exercise, can produce significant global improvements in cognitive function, and quality of life, and delay the onset of disability [45].

What about medication use in frail, older adults? The rates of adverse drug events are higher in the elderly population, as many of them have comorbidities, multiple drug prescriptions, and deteriorated physical and cognitive impairment [46]. In the previous decade, deprescribing, based on clinical and ethical criteria, has been defended as an option for managing chronic conditions, avoiding adverse effects, and improving patient outcomes. Polypharmacy has been independently associated with an increase of mortality in the elderly [47], indeed, several multifaceted interventional studies have demonstrated that medication review has a positive effect on reducing mortality, hospital admissions and falls, and enhances quality of life [48].

Such a wide range of interrelated factors gives weight to our proposal to conduct a multifactorial intervention aimed at non-disabled, i.e. frail, elderly individuals. Our objective is to focus on this population whose health status still permits some positive modifications in the inevitable evolution from frailty to dependence so that by preventing home confinement or institutionalization, older people can stay active and live by themselves in the community.

Our study is addressed at evaluating the effectiveness of a multifactorial intervention to improve frailty parameters and prevent disability in patients 65 years or older. Improvements in physical performance, muscle strength, nutritional status, and cognitive performance are expected, as well as a reduction in the incidence of new complications such as falls, fractures, hospital admissions, and worsening of ADL scales, all of which are related to the appearance of disability [33, 34]. Tackling frailty in a multifaceted manner will also diminish adverse outcomes such as inclusion in a home-care program, institutionalization or death.

In the field of preventive geriatrics, studies have shown that exercise training has clinical benefits inducing positive physiologic changes in muscle and function while multi-nutrient supplementation alone, without concomitant exercise, does not reduce muscle weakness or physical frailty [61].

The innovation of our study lies in regard to the follow-up and evaluation of a multifaceted strategy focused on different risk factors: physical decline, cognitive impairment, nutritional status, and polypharmacy. Previous series have provided a certain degree of evidence about improvement with these interventions on only an individual basis.

The greatest limitation of this study could proceed from the lack of agreement in the scientific community with respect to the definition of frailty and the most suitable measurements to gauge it. Including non- frail subjects (non-homogeneous risk state) could affect generalizability. The initial inclusion criterion, the low specificity Barber Questionnaire, has been included in this study because it was the first frailty test to be used in our clinical records. It has been also complemented, however, with other inclusion criteria such as the TGUGT. Participants scoring lower than 10 seconds or higher than 30 are excluded as they are considered either too frail or not frail enough to benefit from the intervention. The exclusion of more severely affected frail patients, because of their poor physical or cognitive condition, may limit external validity. Nevertheless, the random distribution of our patients to both groups guarantees comparability. Also, additional information about potential confounders (comorbidity, sensory impairment, and social risk) and the use of other parameters and tests of frailty are expected to solve the possible selection bias and help to further characterize the study population. Losses to follow-up are minimized through contacting the participants by telephone.

If evidence of a multi-strategy composed of physical exercise and a cognitive workshop, along with nutritional support and medication review, is achieved as an effective approach, a future implementation should be considered as a Frail-Community Prevention Program for the elderly to prevent or delay disability.