A review of sex differences in neurodegeneration and psychological comorbidities in MS and related disorders.

Abstract

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are chronic neuroinflammatory conditions that disproportionately affect women, with a 2:1 ratio in MS and up to 8.9:1 in NMOSD. Cognitive impairment is one of the earliest and most debilitating symptoms of MS, while mood disorders are common and significantly impact the quality of life and disease prognosis. Understanding sex differences in disease progression, particularly the potential differences in the mechanisms behind disability, is critical for advancing patient care. This review synthesizes current knowledge of sex-specific differences in MS and NMOSD, with a focus on neuroinflammation and neurodegeneration, as well as cognitive symptoms, and psychiatric comorbidities. The current state of research highlights the role of hormonal changes over the patient lifespan, such as estrogen and testosterone, as well as their role in modulating neuroinflammatory responses and subsequent neurodegeneration. Lastly, we discuss implications for disease monitoring and furthering knowledge in the field with a sex-specific lens, including recommendations for evaluating sex differences and personalized care in MS and NMOSD.