Favaro Massimo, Longo Chiara, Ottaviani Donatella, Dodich Alessandra, Papagno Costanza
Center for Mind/Brain Sciences CIMeC, University of Trento, Rovereto, Italy.
Department of Neurology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy.
Brain Behav. 2025 Aug;15(8):e70737. doi: 10.1002/brb3.70737.
Sex-based differences in cognitive and behavioral symptoms have been previously reported in Parkinson's disease (PD), as well as the effects of motor lateralization and phenotypes at onset. However, no studies investigated the interaction between these variables.
We aimed to evaluate whether sex differences interact with motor phenotype and lateralization at the onset of cognitive and neurobehavioral symptoms.
Data from 304 PD patients (119 women and 185 men) were retrospectively examined, including comprehensive neurologic, neuropsychological, and neurobehavioral assessments. MANCOVAs on tests divided based on the results of a principal component analysis were performed to compare cognitive and behavioral performance, considering sex, motor phenotype at onset, and onset lateralization as grouping variables. Analyses were also performed on a subsample of patients (n = 200) in which subgroups were balanced in terms of motor and demographic features.
Significant sex effects were found, with females showing higher performance compared to males in verbal long-term memory (p = 0.00003), social cognition (p = 0.0001), and naming tasks (p = 0.03009). Significant interactions between motor phenotype and sex were found: rigid-akinetic (RA) females showed higher performance than other groups in a verbal memory task (p = 0.0183), and tremor-dominant (TD) females made more errors than the other groups in an inhibitory control task (p = 0.03853). Interestingly, RA females performed better on verbal learning than tremor-dominant (TD) males (p = 0.00911), suggesting that sex effects overcome motor phenotype in this cognitive function. No significant interactions were found between sex and lateralization at onset concerning cognitive variables. However, patients with right-sided onset, in particular females, self-reported higher levels of behavioral symptoms.
These results emphasize the complex relationship between demographic and PD motor features in delineating the clinical phenotype, which should be considered in designing patient-tailored strategies for disease monitoring and intervention.
先前已有报道称帕金森病（PD）存在基于性别的认知和行为症状差异，以及运动偏侧化和发病时表型的影响。然而，尚无研究调查这些变量之间的相互作用。
我们旨在评估性别差异是否与认知和神经行为症状发作时的运动表型及偏侧化相互作用。
回顾性分析了304例PD患者（119名女性和185名男性）的数据，包括全面的神经学、神经心理学和神经行为评估。基于主成分分析结果对测试进行多变量协方差分析，以比较认知和行为表现，将性别、发病时的运动表型和发病偏侧化作为分组变量。还对一组患者亚样本（n = 200）进行了分析，这些亚组在运动和人口统计学特征方面是平衡的。
发现了显著的性别效应，女性在言语长期记忆（p = 0.00003）、社会认知（p = 0.0001）和命名任务（p = 0.03009）方面的表现高于男性。发现运动表型与性别之间存在显著相互作用：强直少动型（RA）女性在言语记忆任务中的表现高于其他组（p = 0.0183），震颤为主型（TD）女性在抑制控制任务中的错误比其他组更多（p = 0.03853）。有趣的是，RA女性在言语学习方面的表现优于震颤为主型（TD）男性（p = 0.00911），这表明在这种认知功能中性别效应克服了运动表型。在发病时的性别与偏侧化之间，未发现与认知变量相关的显著相互作用。然而，右侧发病的患者，尤其是女性，自我报告的行为症状水平较高。
这些结果强调了人口统计学和PD运动特征在描绘临床表型方面的复杂关系，在设计针对患者的疾病监测和干预策略时应予以考虑。
