ArticleJournal of neurology2026
Sex differences in disease trajectories of sporadic creutzfeldt-jakob disease: a registry-based cohort study.
Article in Journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundSporadic Creutzfeldt-Jakob disease (sCJD) is characterized by marked clinical heterogeneity. Established determinants of this variability include age at onset, PRNP codon 129 polymorphism, and prion conformational strains, whereas the contribution of sex remains unclear. We assessed whether sex influences age at onset, clinical phenotype, survival, and disease trajectories.
methodsIn this retrospective, registry-based cohort study, we included 599 definite/probable RT-QuIC-supported sCJD cases (313 females, 286 males). Demographic and clinical features at onset and case notification were compared between sexes. Sex-related differences in the overall clinical profile were assessed using FDR-corrected univariate analyses and hierarchical logistic regression models. Time to bedridden state, akinetic mutism and death were analysed using Kaplan-Meier and Cox models adjusted for age at onset and PRNP Codon 129 genotype.
resultsAge at onset did not differ by sex. Females had longer disease duration. FDR-corrected univariate analyses identified higher frequencies of mood disorders at disease onset and of falls, anxiety disorders, mood disorders, and dystonia at case notification in females. Hierarchical models adjusted for established disease modifiers supported an overall sex-related difference in the clinical profile, although no individual clinical coefficient remained significant after FDR correction. Time to bedridden state was longer in females than in males (5 vs 3 months). Male sex was independently associated with faster progression to bedridden state (HR
conclusionsSex is associated with clinical heterogeneity and disease progression in sCJD, with females showing longer survival, slower progression to bedridden state and differences in early clinical features, further refining the characterization of the disease's natural history.
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