Diagnosis of Alzheimer's disease and related dementia among people with multiple sclerosis: Large cohort study, USA

Background: Alzheimer's disease and related dementia (ADRD) and multiple sclerosis (MS) are two neurodegenerative diseases with some shared pathophysiological characteristics. While the salient attribute of ADRD is a progressive decline in cognitive function, MS is mainly known for causing physical weakness, vision loss, and muscle stiffness. Progressive cognitive decline, however, is not uncommon among MS patients, and many case reports of MS were indicative of ADRD coexistence. Due to a lack of large epidemiological studies on this topic, we aimed to examine time to diagnosis of and adjusted hazard for ADRD using administrative claims data, comparing adults with and without MS. Methods: Using 2007-2017 private claims data from Optum Clinformatics Data Mart in the U.S., we identified adults (45+) with a MS diagnosis (n = 6151) as well as adults without MS for comparison (n = 916,143). We propensity score matched people with MS with those without (n = 6025) using age, sex, race/ethnicity, chronic conditions including cardiometabolic, psychologic, and musculoskeletal, U.S. Census Division, and socioeconomic variables. In addition to incidence estimates of ADRD diagnosis compared at 4-years, survival models were utilized to quantify unadjusted, fully adjusted, and adjusted propensity-matched hazard ratios. Results: Unmatched data revealed that incidence of early-onset ADRD diagnosis was 7 times higher among adults 45-64 years old with MS (1.4%) compared to those without (0.2%); among older adults (65+) with MS, incident ADRD was 4.0% compared to 3.3% among those without MS. Adjusted survival models indicated that adults with MS had a substantially high risk for early-onset ADRD diagnosis (among 45-64 years old: unmatched hazard ratio (HR): 4.25 (95% CI: 3.40 -5.32), matched HR: 4.49 (95% CI:2.62-7.69); among 65+ years old: unmatched HR: 1.39 (95% CI: 1.22, 1.58), matched HR: 1.26 (1.04, 1.54)). Conclusions: Individuals with MS had a greater incidence of and risk for early- and late-onset ADRD diagnosis compared to those without MS. It is not clear whether this greater risk is due to an accelerated dementia risk or at least partially due to clinical misdiagnosis. Advancements in the development of clinical and imaging biomarkers should be more commonly used in clinical settings to facilitate future research on this topic.

Automated summary

This study compared the time to diagnosis and adjusted hazard for Alzheimer's disease and related dementia (ADRD) between adults with and without multiple sclerosis (MS) using administrative claims data. The results showed that individuals with MS had a higher incidence and risk for early-onset ADRD diagnosis compared to those without MS.