Document Type

Journal Article

Publication Title

Journal of Neurology




School of Medical and Health Sciences / Exercise Medicine Research Institute




Federal Cooperative Research centre for Mental Health (CRCMH) Perron Institute for Neurological and Translational Science University of Notre Dame Australia Richard Walter Gibbon Medical Research Scholarship Australian Government Research Training Program Scholarship


Bakeberg, M. C., Gorecki, A. M., Kenna, J. E., Jefferson, A., Byrnes, M., Ghosh, S., ... Anderton, R. S. (2021). Differential effects of sex on longitudinal patterns of cognitive decline in Parkinson’s disease. Journal of Neurology, 268(5), 1903-1912.


© 2021, The Author(s). Background: Cognitive impairment is an important and diverse symptom of Parkinson’s disease (PD). Sex is a purported risk variable for cognitive decline in PD, but has not been comprehensively investigated. Objectives: This cross-sectional and longitudinal study examined sex differences in global and domain-specific cognitive performance in a large PD cohort. Methods: Cognitive function was evaluated using the Addenbrooke’s Cognitive Examination in 392 people with PD (PwP) from the Australian Parkinson’s Disease Registry. The influence of sex on domain-specific cognitive performance was investigated using covariate-corrected generalised linear models. In a repeated measures longitudinal subset of 127 PwP, linear mixed models were used to assess the impact of sex on cognition over time, while accounting for covariates. Results: Cross-sectional-corrected modelling revealed that sex was significantly predictive of cognitive performance, with males performing worse than females on global cognition, and memory and fluency domains. Longitudinally, sex was significantly predictive of cognitive decline, with males exhibiting a greater reduction in global cognition and language, whereas females showed a greater decline in attention/orientation, memory and visuospatial domains, despite starting with higher baseline scores. At follow-up, a significantly higher proportion of males than females fulfilled criteria for mild cognitive impairment or PD dementia. Conclusions: Sex was revealed as a significant determinant of overall cognitive performance as well as specific cognitive domains, with a differential pattern of decline in male and female participants. Such sex-specific findings appear to explain some of the heterogeneity observed in PD, warranting further investigation of mechanisms underlying this sexual dimorphism.



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This work is licensed under a Creative Commons Attribution 4.0 License.

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