Vascular Cerebral Damage in Frail Older Adults: The AMImage Study

International audienceFrailty has been associated with increased risk of adverse-health related outcomes including cognitive impairment. However, little is know about the pathogenesis relating frailty to cognitive decline. Therefore, the main objective of this study was to investigate the association between vascular cerebral damage and frailty. Cross-sectional study involving 176 community-dwelling participants aged 67-86 years, participating in the AMImage Study, an ancillary neuro-imaging project of the AMI cohort, a French prospective cohort including older farmers living in rural areas. Frailty was defined as proposed by Fried. 3T magnetic resonance imaging (MRI) examination was performed with anatomical, diffusion, and fluid-attenuated inversion recovery sequences. The evaluation included the assessment of white matter hyperintensities (WMH) volumes and of microstructural white matter integrity through exploration of diffusion tensor imaging (DTI) parameters. The analyses showed that WMH volumes were higher in frail persons compared with nonfrail subgroup. Frail participants presented DTI modifications in extensive areas of white matter. In comparison with nonfrail subgroup, frail participants showed a strong association between WMH volumes and DTI changes. These results show that subclinical cerebrovascular damage is present in the frail older person, which could support the hypothesis that frailty is a prodromal state of central nervous system vascular injury

Comparative effectiveness in multiple sclerosis: A methodological comparison

Background: In the absence of evidence from randomised controlled trials, observational data can be used to emulate clinical trials and guide clinical decisions. Observational studies are, however, susceptible to confounding and bias. Among the used techniques to reduce indication bias are propensity score matching and marginal structural models. Objective: To use the comparative effectiveness of fingolimod vs natalizumab to compare the results obtained with propensity score matching and marginal structural models. Methods: Patients with clinically isolated syndrome or relapsing remitting MS who were treated with either fingolimod or natalizumab were identified in the MSBase registry. Patients were propensity score matched, and inverse probability of treatment weighted at six monthly intervals, using the following variables: age, sex, disability, MS duration, MS course, prior relapses, and prior therapies. Studied outcomes were cumulative hazard of relapse, disability accumulation, and disability improvement. Results: 4608 patients (1659 natalizumab, 2949 fingolimod) fulfilled inclusion criteria, and were propensity score matched or repeatedly reweighed with marginal structural models. Natalizumab treatment was associated with a lower probability of relapse (PS matching: HR 0.67 [95% CI 0.62-0.80]; marginal structural model: 0.71 [0.62-0.80]), and higher probability of disability improvement (PS matching: 1.21 [1.02 -1.43]; marginal structural model 1.43 1.19 -1.72]). There was no evidence of a difference in the magnitude of effect between the two methods. Conclusions: The relative effectiveness of two therapies can be efficiently compared by either marginal structural models or propensity score matching when applied in clearly defined clinical contexts and in sufficiently powered cohorts

Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis

Background and purpose: This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS). Methods: We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow-up ≥ 1 year, and Expanded Disability Status Scale (EDSS) score ≥ 3, with ≥1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12-month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics. Results: Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45–0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41–0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09–1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity. Conclusions: DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age