INS NYC 2024 Program

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by chronic inflammation and neurodegeneration. Common symptoms include motor impairment, cognitive decline, and debilitating fatigue. Patient-reported outcomes such as the Patient-Determined Disease Steps (PDDS) are increasingly used to measure disease progression. Despite its frequent inclusion in studies of adults with MS, no studies have validated the PDDS in older adults. The current study sought to address this gap in knowledge. Specifically, we evaluated the validity of the PDDS as a measure of disease severity in older adults (age ≥60) with MS by examining its relationship with real-world disability symptoms and brain neuroimaging.

The sample consisted of 87 community-residing older adults (mean age=64.67±4.24; %female=65.5) enrolled in the “Brain Predictors of Mobility and Falls in Older Adults with Multiple Sclerosis” cohort study. Participants included in the analyses had physician-confirmed diagnoses of MS (%relapsing-remitting=59.8; mean disease duration=22.33±11.40 years), the ability to ambulate without assistance, and no symptom exacerbations for at least six months prior to testing. The PDDS, a self-reported ordinal scale (0- 8), was utilized to assess MS-related disability, with higher scores indicating greater disability. Lower extremity functioning was measured by Timed 25-foot Walk (T25FW) performance and total score on the Short Physical Performance Battery (SPPB). Fine motor dexterity was measured by the Nine-Hole Peg Test (9HPT). Executive functioning/cognitive processing speed were measured by the oral Symbol-Digit Modalities Test (SDMT). Fatigue was assessed using the Fatigue Severity Scale (FSS). To examine brain structure, participants underwent 3T MRI. Whole-brain white matter lesion load (WMLL) was calculated from 3D fluid-attenuated inversion recovery and T1 weighted images. Volume calculations for grey matter structures used validated automatic segmentation methods. Structures of interest were the thalamus, hippocampus, caudate, globus pallidus (GP), and putamen. Spearman correlations were used to examine associations between PDDS scores and all outcome variables, as well as continuous sociodemographic covariates. A chi-square test was used to determine whether scores differed by sex.

PDDS scores ranged from 0-5 (mean=2.18±1.77) and were positively skewed. Higher PDDS scores significantly correlated with worse outcomes on the following measures: T25FW (r_s = .664, p < .001), SPPB (r_s = -.54, p < .001), fine motor dexterity on the dominant-hand (r_s = .367, p < .001) and non-dominant hand (r_s = .263, p = .014), and fatigue (r_s = .383, p < .001). Additionally, higher PDDS scores correlated with lower grey matter volume in the left caudate (r_s = -.221, p = .039), right putamen (r_s = -.226, p = .035), and right hippocampus (r_s = -.255, p = .017). Associations with other brain regions, WMLL, SDMT, and sociodemographic variables were not significant.

This study was the first to demonstrate significant associations between PDDS scores and known indicators of MS disease progress in older adults. Corroborated by neuroimaging of key brain markers and clinical outcomes, these results support the use of the PDDS as a measure of disease severity in older adults with MS.