Aging and the neuropsychiatry of multiple sclerosis: a cross-sectional study

Aging in multiple sclerosis (MS) affects clinical and radiological disease activity. Yet, evidence is equivocal about the effects of aging on the neuropsychiatric sequelae of MS, including anxiety, depression, fatigue, and cognitive dysfunction. This study aimed to clarify how the neuropsychiatric symptoms of MS vary across ages. A consecutive cohort of 1194 people with MS (pwMS) underwent neuropsychological testing using the Minimal Assessment of Cognitive Function in MS, the Hospital Anxiety and Depression Scale sub-scales for anxiety (HADS-A) and depression (HADS-D), Modified Fatigue Impact Scale (MFIS), and the Perceived Deficits Questionnaire (PDQ) for cognitive complaints. Participants were stratified into age sub-groups: 18-29, 30-39, 40-49, 50-59 years. t-tests were undertaken to compare symptoms between the 18-29 and 50-59 sub-groups. Linear regression analyses, controlling for disability (Expanded Disability Status Scale; EDSS), sex, educational years, and high-efficacy disease-modifying therapy use, were used to evaluate whether age significantly predicted neuropsychiatric sequelae. Mean age was 42.15 years, 74.12% were female, and median EDSS was 2.00. Older pwMS had reduced HADS-A, PDQ, California Verbal Learning Test (CVLT), Brief Visuospatial Memory Test (BVMT), Symbol Digit Modalities Test (SDMT), and Delis-Kaplan Executive Function System (D-KEFS) scores, all p < 0.01. There were no age differences on the HADS-D, MFIS, Controlled Oral Word Association Test, Judgment of Line Orientation, or Paced Auditory Serial Addition Test. Controlling for covariates, older age independently predicted reduced HADS-A, CVLT, BVMT, SDMT, and D-KEFS scores, all p < 0.01. In summary, as pwMS age, anxiety declines and performance on learning, memory, processing speed, and executive function tests worsens.