Patient-Reported Cognition in People with Multiple Sclerosis: Neuropsychological Correlates and its Association with Cardiorespiratory Fitness

Abstract

Cognitive impairment (CI) is a common manifestation of multiple sclerosis (MS). Physical activity and exercise training are promising approaches to address impairments and preserve function in people with MS; however, their potential effects on patient-reported cognition remain understudied. Patient-reported outcomes (PROs) may provide insight into the effects of MS and interventions that are not always detectable using objective assessments. The objectives of this thesis were to better understand: i) the neuropsychological utility and interpretation of cognitive PROs; and ii) the potential protective effects of maintaining physiological fitness (as a marker of physical activity and exercise) in people with MS. Study 1 examined associations between cognitive PROs/insight (i.e., self-awareness of deficit) and objective neuropsychological outcomes (cognitive performance, biomarkers of neuroaxonal degeneration) and putative confounds (e.g., depression, fatigue). Analyses found that, in participants with MS, cognitive PROs more strongly correlated with the most affected objective neuropsychological outcomes in comparison to less affected outcomes. In the MS group, insight was not related to depression or fatigue. These preliminary findings provide support for the use of cognitive PROs to monitor/screen for MS-related cognitive decline. Study 2 assessed the relationship between cardiorespiratory fitness (CRF) and cognitive PROs. Analyses found that higher CRF coincided with "overestimation" of CI in the MS group. There were no true CI underestimators in the MS sample, namely, persons with objectively measured CI who overestimate their cognitive function. This might explain why CI "overestimators" - who had unimpaired executive function - displayed the greatest biomarker evidence of neurodegeneration and slowest information processing speeds relative to participants with MS who accurately estimated/"underestimated" their CI. Because of this unique profile, the association that occurred exclusively in the MS sample between CRF and overestimation of CI was viewed as preliminary support for CRF being associated with heightened insight of the cognitive effects of MS. The presented findings offer some support for the use of cognitive PROs to assess cognitive functioning in MS. Physical activity, exercise training, and the related maintenance of CRF may represent an approach for preserving cognitive precursors to insight in MS. Research is needed to replicate study findings in larger, more diverse MS samples. Future studies should examine longitudinal associations between cognitive PROs/insight and other objective neuropsychological outcomes in people with MS. Research should attempt to identify other components of fitness related to insight and elucidate what features of physical activity/exercise training may contribute to the preservation of insight in people with MS.