Abstract
BackgroundCognitive 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.ObjectivesThis cross-sectional and longitudinal study examined sex differences in global and domain-specific cognitive performance in a large PD cohort.MethodsCognitive 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.ResultsCross-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.ConclusionsSex 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.
Highlights
Cognitive impairment is an often devastating and debilitating non-motor symptom of Parkinson’s disease (PD) [1, 2]
Upwards of 40% of people with Parkinson’s disease (PwP) develop some form of cognitive impairment, with a subset progressing from mild cognitive impairment (MCI) to a more severe Parkinson’s disease dementia (PDD) [1]
Some prior studies have been purely cross sectional in nature [5, 9, 10, 12, 17,18,19], while longitudinal studies have not examined the sex-specific differences in various cognitive domains [20], or have not focussed primarily on elucidating the impact of sex on cognition [32]
Summary
Cognitive impairment is an often devastating and debilitating non-motor symptom of Parkinson’s disease (PD) [1, 2]. Studies examining demographic and clinical factors have identified increasing age, lower education levels, increasing disease duration, and motor symptom severity, among others, as contributing to susceptibility of cognitive impairment in PD [5]. Of these factors, patient sex influences disease risk [6, 7], but the presentation of several non-motor symptoms [8,9,10]. 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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