Operationalization of a frailty index in patients with multiple sclerosis: A cross-sectional investigation

Abstract

Background: Frailty is an age-related status of increased vulnerability to stressors caused by the accumulation of multiple health deficits. This construct may allow to capture the clinical complexity of patients with multiple sclerosis (MS). Objective: To investigate the relationship between frailty and the clinical manifestations of MS. Methods: Patients with MS were consecutively enrolled at five tertiary dedicated services. Disability and fatigue were assessed. The phenotypes of MS were also identified. Frailty was measured using a frailty index (FI), computed by cumulatively considering 42 age-related multidimensional health deficits. Results: Overall, 745 MS patients (mean age = 48.2 years, standard deviation = 11.7 years; women 68%) were considered. The median FI value was 0.12 (interquartile range = 0.05–0.19) and the 99th percentile was 0.40. FI scores were associated with MS disease duration, disability, fatigue, as well as with the number of previous disease-modifying treatments and current symptomatic therapies. A logistic regression analysis model showed that FI score was independently associated with the secondary progressive phenotype. Conclusion: Frailty is significantly associated with major characteristics of MS. The findings of the present cross-sectional investigation should be explored in future longitudinal studies.

Frailty in multiple sclerosis: A closer look at the deficit accumulation framework

“…For instance, Belvisi et al reported a surprisingly low FI in their study (median = 0.12, interquartile range = 0.05-0.19) which resembles the FI of a healthy control group (mean age = 61 ± 6.5) from another recently published report in MSJ and is about 50% lower than the FI value reported among people with MS. 3 Importantly, an FI of 0.12 is also below well-established cut-points indicative of frailty 4 and in disagreement with findings from a recent UK Biobank study, which concluded that MS was the top long-term disorder associated with frailty (15-fold higher risk compared to the non-MS population) in people aged 37-73 years old. 5 Therefore, we suggest that the FI designed by Belvisi et al 2 may underestimate the actual prevalence of frailty in the MS community and may reflect comorbidity rather than frailty.…”

“…The adopted FI was calculated in full accordance with a standard procedure that requires (1) to incorporate a critical mass (at least 30) of health deficits consisting of diseases, symptoms and signs (not constituting specific nosological entities), disabilities, and laboratory abnormalities; (2) that the considered deficits are age-related and cover multiple organs and systems; and (3) that deficits do not saturate too early or too late. 2 Since the main aim of our study was not to estimate the prevalence of frailty in MS patients, but rather to explore how frailty is associated with the main clinical manifestations of the disease (e.g., disability), the FI was designed to include items that would not overlap with those of the outcome measures (e.g., Expanded Disability Scale Status). Indeed, this might have prevented the unbiased investigation of the relationship between frailty and the phenotypic characteristics of MS.…”

“…We read with interest the recently published study by Belvisi et al, 2 who designed an FI based on routinely available clinical variables in a relatively large MS population ( n = 745). The authors’ operationalization of frailty relied predominantly on health deficits identified through the presence or absence of comorbid conditions and abnormal laboratory values (~70% of the included deficit items).…”

Are Neurophysiological Biomarkers Able to Discriminate Multiple Sclerosis Clinical Subtypes?

“…Previous studies in healthy subjects showed that age influences inhibitory-mediated mechanisms in motor [ 41 ] and sensory functions [ 42 , 43 , 44 ]. The mathematical model derived from our regression analysis also includes age as a factor in the formula predicting SPMS.…”

Response to “Frailty in multiple sclerosis: A closer look at the deficit accumulation framework”

“…We thank Zanotto et al for their interest in our paper "Operationalization of a frailty index in patients with multiple sclerosis: A cross-sectional investigation", in which we investigated the relationship between frailty and the clinical expression of multiple sclerosis (MS) in a large population of patients by applying a specifically designed Frailty Index (FI). 1 The reflections on the results obtained by measuring the individual degree of frailty through an FI cannot be separated from an accurate evaluation of (1) how the index was computed, and (2) to which population it was applied. The adopted FI was calculated in full accordance with a standard procedure that requires (1) to incorporate a critical mass (at least 30) of health deficits consisting of diseases, symptoms and signs (not constituting specific nosological entities), disabilities, and laboratory abnormalities; (2) that the considered deficits are age-related and cover multiple organs and systems; and (3) that deficits do not saturate too early or too late.…”