Sex differences for cognitive decline in progressive supranuclear palsy

Abstract

Introduction: Cognitive dysfunction is a core clinical feature of progressive supranuclear palsy (PSP), with executive function being most markedly affected. In other neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, there are a growing number of reports demonstrating that cognition is differentially impacted in men and women. In PSP, however, the sex differences in cognitive decline have yet to be fully characterized.

Methods: Data were obtained from the TAUROS trial for 139 participants with mild-to-moderate PSP (62 women, 77 men). Sex differences in longitudinal change in cognitive performance were evaluated with linear mixed models. Exploratory subgroup analyses assessed whether sex differences varied by baseline executive dysfunction, PSP phenotype, or baseline age.

Results: In the primary whole group analyses, there were no sex differences for change in cognitive performance. Among participants with normal executive function at baseline, men declined more severely on executive function and language tests. Among the PSP-Parkinsonism subgroup, men declined more severely on category fluency. Across people aged≥65, men had a worse decline on category fluency, whereas across people aged <65, women had a worse decline on DRS construction.

Conclusion: In people with mild-to-moderate PSP, there are no sex differences in cognitive decline. However, the rate of cognitive decline may differ for women and men based on the level of baseline executive dysfunction, PSP-phenotype and age. Further studies are needed to clarify how sex differences in PSP clinical progression vary by disease stage and to examine the contributions of co-pathology to these observed sex differences.

Keywords: Cognition; Executive function; Progressive supranuclear palsy; Sex differences.