The global interest in the study of aging processes and age-related diseases is due to the rise in the elder’s proportion associated with an increased sanitary implication. Frailty constitutes a precise measurement of aging symptoms and it indicates a multidimensional syndrome of energy, physical ability, and cognition loss. This syndrome has been shown to be potentially preventable and could be reverted in its earlier stages. Thus, we conducted a retrospective study in Belgian elders (n = 124, aged 65 and over), classified according to their frailty status, in order to increase evidence related to frailty and to find parameters that could be used as early indicators.
The current study examined the relationship between frail status and cognitive function in Belgian elderly. We confirmed that physical frailty is correlated with a decline in cognitive functions, which support previous findings. Indeed, data from the Rush Memory and Aging study found that higher levels of frailty were associated with a faster rate of decline in all cognitive domains . Furthermore, the results of Wu et al. (2015) indicated that the appearance of memory impairment may indicate its association with higher frail status, suggesting that existing cognitive impairment is a risk factor for an additional frail decline . Also, it has been shown that cognitive function across all domains was significantly worse in frail participants than non-frail, with the exception of self-rated memory and processing speed. Weakness and walking speed were also linked to poorer cognition . However, our findings contradict some studies suggesting the absence of an association between memory decline and frailty [8, 23, 24]. This discrepancy could be explained by the size or the homogeneity of the samples in these studies [8, 23, 24].
Biological and psychological factors, including neuropathology, cardiovascular disease, inflammation, hormonal changes, nutrition, social vulnerability, and isolation have been suggested to explain the link between frailty and cognition . In the present study, we tried to find an explanation for this association. Thus, several biochemical measures, frail status assessments and neuropsychiatric assessment, including the Mini-Mental State Examination have been performed in a population of Belgian elderly patients.
Some biochemical measures were associated with frailty. In fact, frailty was associated with CRP and albumin levels. It is well known that serum albumin is the most abundant blood protein and used as a marker of nutritional status. Hypoalbuminemia can reflect complications in different systems in elderly subjects. Since frailty is related to dysfunction in several organs, that could explain the observed inverse association between albumin and frailty index in the study population. These data are in accordance with others studies demonstrating that low albumin concentrations were associated with higher frailty scores [26-28]. Recently, hypoalbuminemia was associated with chronic inflammation . In fact, chronic low-grade inflammation, is considered as a risk factor for the development of aging-related diseases, has been found to be associated with organ damage, muscle waste and chronic diseases, which all contribute to frailty . On the other hand, chronic inflammation appears as a consequence of chronic diseases such as atherosclerosis and Alzheimer dementia . This phenomenon has been linked to both frailty and cognitive function . Furthermore, several studies support the direct association between serum CRP levels and frailty in elders . In accordance, we found that elevated levels of CRP were associated with higher frailty scores in the study population.
Hypoalbuminemia has also been used as a marker of malnutrition . Hence, the observed correlation between frailty and albumin deficiency could reflect a poor nutritional status in the studied population, suggesting that malnutrition is associated with higher frailty. Nutritional deficiencies could reflect insufficient micronutrient intake. Knowledge about the relationship between micronutrient status and frailty could promote interventions to correct micronutrient deficiencies. Insufficient serum 25-hydroxyvitamin (25(OH)D) concentrations were associated with frailty status and measures of physical performance .
Contrary to the literature, we could not find an inverse correlation between Vitamin D and frailty score [6, 27, 33]. However, this is comparable to data of Schoufour et al. (2015) study,
conducted on elderly people with intellectual disabilities . Furthermore, the Vitamin D levels were higher in frail and severely frail patients compared to non-frail. This could be explained by the supplementation since sufficient 25(OH)D was considered crucial for the frailty prevention. Recently, it has been reported that among the hospitalized elders without Vitamin D supplementation, Vitamin D deficiency was prevalent suggesting a necessity to supplement Vitamin D in order to maintain desirable levels .
In addition, the multivariable model using logistic regression identified dementia, polypharmacy ≥ 5, living in nursing home, and decrease of ADL as significantly asssociated to frailty (P < 0.05). Thus, our study confirms the existence of an association between the prevalence of frailty and the number of drugs prescribed. Indeed, previous studies indicated that frail patients were likely to receive a higher number of drugs than non-frail ones [35, 36]. Also, it was reported that each additional drug was associated with frailty with an odds ratio > 1 [35, 37, 38]. The enhancement of the interactions and adverse reactions associated with each additional prescription could explain the effect of multiple drugs intake on frailty.
Also, in the Umegaki et al. (2019) study, the number of medications was associated with gait independently from the prescription of potentially inappropriate medications and from the Charlson Comorbidity Index . In addition, it has been shown that the effects of psychotropic medications could be implicated in the underlying mechanism of the association between polypharmacy and gait speed . However, this effect is still too small to fully explain it. In other hand, it has been demonstrated that patients with dementia used a higher number of medications [40-41]. However, others found no association between number of medications and dementia or even showed that patients with dementia use a lesser number of medications . This controversy is not surprising because the effects of the medications type are diverse. Herr et al. (2015) suggested that polypharmacy may be utile to identify older patients, whose health is more susceptible to deteriorate and then to carry out corrective actions with regard to physical activity, nutrition, and management of chronic diseases .
Furthermore, it has been described that polypharmacy is common in the elderly and that residents nursing homes are taking the highest number of drugs . Different studies have described higher prevalence of frailty in older adults living in nursing homes than in community based older adults [45-46]. Recently, it has been shown that frailty but not pre-frailty was associated with increased nursing homes admission. Indeed, among community-living participants, those who were frail had a three times higher risk to be admitted to a nursing home, than those who were non-frail .
The knowledge of the factors associated to frailty represent target conditions for programs and policies directed at reducing frailty in older population. Although, it is still unknown whether frailty risk accumulates or there is a required chain of events. It is also unknown if these factors identified precede or are the consequences of frailty. Indeed, the very complexity of the life course approach in the study of frailty should be considered to guide prevention actions. This would enhance the reliability of predictors factors of frailty in the early period (critical period) and could guide the preventives strategies
However, our study has some limitations related to the small sample size and limited duration of observation. Indeed, the majority of the studied population was already in a severely frail state. Thus, recrutement of frail patients at an early state could be of interest, would enhance the reliability of predictor’s factors of frailty in the early period, and could allow the timely implementation of preventive strategies.
Furthermore, since frailty development is a life-long process, this study needs to be completed with repeated measurements and examination of frailty over time, which could give us new informations about the evolution of individual trajectories along with the different state of frailty. Also, proving the effect of a restriction of polypharmacy to its truly appropriate need or a dose reduction of medication is another approach to study the association between polypharmacy and frailty.