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. 2021 May;268(5):1903-1912.
doi: 10.1007/s00415-020-10367-8. Epub 2021 Jan 5.

Differential effects of sex on longitudinal patterns of cognitive decline in Parkinson's disease

Megan C Bakeberg  1   2 , Anastazja M Gorecki  1   3 , Jade E Kenna  1   2 , Alexa Jefferson  1 , Michelle Byrnes  1   2 , Soumya Ghosh  1   2 , Malcolm K Horne  4   5 , Sarah McGregor  5 , Rick Stell  1   2 , Sue Walters  1 , Paola Chivers  6   7 , Samantha J Winter  1   6 , Frank L Mastaglia  1   2 , Ryan S Anderton  8   9   10
Affiliations

Differential effects of sex on longitudinal patterns of cognitive decline in Parkinson's disease

Megan C Bakeberg et al. J Neurol. 2021 May.

Abstract

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.

Keywords: Cognitive decline; Domain specific; Longitudinal; Parkinson’s disease; Sex.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Participants classified as MCI (a) and PDD (b) over time, corrected for age at assessment and age at onset. Kaplan–Meier curves depicting the effect of sex on the proportion of participants classified as MCI (c) and PDD (d). % percentage, MCI mild cognitive impairment, PDD Parkinson’s disease dementia
See this image and copyright information in PMC

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