Lower recorded prevalence of Alzheimer’s disease in natalizumab-exposed older adults with multiple sclerosis: A hypothesis-generating observation

Adaptive immune mechanisms, including CD8 T cell-mediated neuroinflammation, are increasingly implicated in Alzheimer's disease. We examined whether exposure to natalizumab, an α4-integrin antagonist that restricts leukocyte trafficking into the central nervous system, was associated with Alzheimer's disease prevalence among older adults with multiple sclerosis. Using Epic Cosmos electronic health record data, we identified 875,226 individuals with MS, of whom 9095 had an Alzheimer's disease diagnosis after age 65 years. Alzheimer's disease prevalence differed significantly across disease-modifying therapies, with natalizumab-treated patients demonstrating the lowest prevalence (0.13%; 95% confidence interval: 0.10-0.17%). These findings demonstrate a lower recorded prevalence of late-life Alzheimer's disease among natalizumab-exposed patients; however, given the aggregated nature of the data, this observation should be considered descriptive and hypothesis-generating.