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The Impact of Frailty on Neurological Diseases: Sex and Gender Matter
FRAILTY IS CHARACTERIZED by diminished biological reserve and reduced resistance to stressors. Frailty increases a person’ s vulnerability and can lead to poor health outcomes. Frailty speeds up the natural decline of aging and plays a role in neurological diseases, including multiple sclerosis( MS).
Both sex-specific biological determinants and gender-specific social and lifestyle determinants can affect the occurrence of frailty. This study examined sex- and genderspecific patterns at the intersection of frailty and neurological disease.
THE STUDY
Researchers conducted a structured(“ systematic”) review of published studies that examined frailty in the context of neurological diseases, from January 2000 to April 2025. In total, 42 studies were assessed. Each study was published in English and included participants with neurological conditions.
THE OUTCOME
People diagnosed with dementia, Parkinson’ s disease, those who had a prior stroke, or those with MS were more likely to be frail. For MS, studies reported 15 %– 60 % greater frequency of frailty in people with MS than that in age-matched, healthy populations.
The reported prevalence or frequency depends on the assessment tool used and the individual’ s disease progression. Frailty in people with MS was associated with older age, longer disease duration, greater disability, and progressive MS. Frailty was also linked to poorer walking performance, increased falls, hospitalization, slower recovery following relapses, and higher mortality. Women with frailty reported fatigue and depression more often than men, while men with frailty showed more rapid disease progression and worse outcomes.
Frailty can present differently between men and women. Standard frailty assessments may not capture frailty equally across sexes. Frailty screening should be put into routine neurological practice and should be sensitive in assessing both sex- and genderdifferences in the development of frailty and its impact.
Lorefice, L., & Pellecchia, M. T.( 2025). Frailty across neurological diseases: Why sex and gender matter. Annals of Neurology, 99( 2), 297 – 311. https:// doi. org / 10.1002 / ana. 78110
Can Ocrelizumab Slow Disease Progression in Older People with Primary Progressive MS
THE ORATORIO TRIAL revealed that ocrelizumab could slow disability progression in people with Primary Progressive Multiple Sclerosis( PPMS). However, that study excluded older people with more advanced disability. Subsequently, the ORATORIO-HAND study was designed to assess whether ocrelizumab could benefit older people with PPMS. The focus of the trial was on preserving arm function.
THE STUDY
This multicenter, double-blind, randomized, placebo-controlled Phase 3b trial included 1,013 people with PPMS across 22 countries. Participants were between 18 and 65 years old, although average age was only 47 – 48 years. They had moderate to severe disability; some participants were full-time bed users. Participants were randomly assigned to receive either
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