Objective: To define how sex affects worsening of cognition and instrumental activities of daily living (IADLs) in a heterogeneous cohort of people with Parkinson’s disease (PwPD) with and without mild cognitive impairment (PD-MCI).

Background: Sex has been shown to affect prevalence and progression of symptoms in PwPD, such as cognitive deficits. Sex differences have been associated with different trajectories in worsening of cognitive domains, but reports are inconsistent. For example, males with Parkinson’s disease demonstrate worse cognitive performance, especially in the memory, executive (fluency) and attention domains, compared to females. In de-novo PwPD, differences in the course of cognitive decline could not be detected by stratification of person’s cognitive status.

Method: 164 non-demented PwPD were assessed twice with a mean interval of 3.8±0.8 years. All participants completed a comprehensive neuropsychological battery and the Pfeffer Functional Activities Questionnaire (FAQ), allowing for the differentiation of cognitive (FAQc) and motor (FAQm) influences on IADLs. Age-corrected composite domain (attention, executive functions, memory, visuospatial abilities, and language) and total scores were calculated from respective z-scores. For the cognitive and FAQ scores and the Montreal Cognitive Assessment (MoCA), annual changes were derived from coefficients of linear mixed models (LMMs), including a three-way interaction of cognitive baseline status (PD-MCI vs. normal cognition=PD-CN)*sex*time. Disease duration, motor severity (MDS-UPDRS-III), education years, and levodopa equivalent daily dose were included as covariates.

Results: At baseline, 36.3% of males and 33.9% of females had PD-MCI (p=0.87). Compared to females and PwPD with PD-CN, males with PD-MCI showed more pronounced worsening in the FAQc, FAQm and FAQ total (three-way interaction, p≤0.001). Regarding cognitive performance, PD-MCI vs. PD-CN scored lower in all cognitive domains and the MoCA, at both visits (p<0.05). Males had lower MoCA scores at both visits (p=0.03). Apart from that, no significant main effects of sex and three-way interactions of baseline cognitive status*sex*time could be identified.

Conclusion: In PD-MCI, sex affects worsening of IADLs assessed by the FAQ, as well as global cognition assessed by the MoCA, but not cognitive domain scores.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/does-sex-affect-worsening-of-cognitive-and-iadl-functions-in-pd-with-and-without-pd-mci/