Multiple Sclerosis and The Risk of Dementia: A Real-World, Nationwide Cohort Study

Ting-An Chen¹Sung-Tao Li²Wu-Chien Chien³Chi-Hsiang Chung⁴Fang-Jung Wan²Ta-Chuan Yeh²Yi-Wei Yeh²Nian-Sheng Tzeng^2*

• ¹Tri-Service General Hospital Department of Psychiatry, Taipei City, Taiwan
• ²Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
• ³College of Public Health, National Defense Medical University, Taipei, Taiwan
• ⁴National Defense Medical University, Taipei City, Taiwan

ABSTRACT Background Multiple sclerosis (MS) is a chronic autoimmune and neurodegenerative disease that often causes cognitive impairment. This study aimed to investigate the association between MS and the risk of dementia in a large, nationwide Taiwanese cohort and to examine the potential impact of Disease-modifying drugs (DMDs) on the dementia incidences. Methods We conducted a population-based cohort study using Taiwan's National Health Insurance Research Database (NHIRD) between 2000–2015. Adults aged ≥20 years with a diagnosis of MS (n = 10,525) were matched 1:3 by age, sex, index date, and healthcare utilization to non-MS controls (n = 31,575). Dementia diagnoses were confirmed ≥1 year after the MS diagnosis. The Fine and Gray competing risks model was applied so as to estimate the sub-distribution hazard ratios (SHRs) for dementia, adjusting for the demographic, socioeconomic, and clinical covariates. Subgroup, sensitivity, and DMD-use analyses were performed. Results During the follow-up, the cumulative incidence of dementia was higher in the MS cohort (739.97 per 100,000 person-years) than in the controls (343.95 per 100,000 person-years; log-rank p < 0.001). MS was associated with an almost five-fold increased risk of dementia (adjusted SHR = 4.919, 95% CI: 4.329–5.743, p < 0.001). An elevated risk of dementia persisted after excluding the cases diagnosed within the first year and first five years. Vascular and autoimmune comorbidities further increased the risk of dementia. The usage of the DMDs, including interferon-β-1a, interferon-β-1b, natalizumab, and teriflunomide was associated with the reduced risk of other degenerative dementias, and the teriflunomide was also linked to a lower Alzheimer's risk of disease. Conclusions MS is an independent and potent risk factor for dementia in the Taiwanese population, from the NHIRD records. The findings underscore the importance of the early cognitive monitoring, the comprehensive comorbidity management, and the optimal pharmacologic intervention. The DMD usage may be associated with a reduced risk of dementia, thereby warranting further prospective investigation.