Shared and distinct effects of cognitive performance and mood on cognition-dependent instrumental activities of daily living in Parkinson’s disease

Background

Cognitive impairment in Parkinson’s disease (PD) significantly affects patients’ ability to perform instrumental activities of daily living (IADLs). However, neuropsychiatric symptoms, which are highly prevalent in PD, may also contribute to functional impairments. In this study, we investigated the independent contributions of cognitive and neuropsychiatric symptoms to functional impairments and tested whether mood mediates cognition–function associations.

Methods

We examined 104 patients from the Quebec Parkinson Network and replicated analyses in a sample of 144 patients from an independent online cohort. Participants completed the Penn Parkinson’s Daily Activities Questionnaire (PDAQ), a validated patient-reported measure designed to capture cognition-dependent IADLs, standard cognitive tests (executive function, attention, working memory), and neuropsychiatric questionnaires (apathy, depression, impulsivity, and anhedonia). Regression models tested the independent and combined effects of cognition and neuropsychiatric symptoms on PDAQ; mediation analyses explored mechanistic pathways.

Results

Both cognitive performance and neuropsychiatric symptoms were independently associated with PDAQ scores and the proportion of variance explained by neuropsychiatric symptoms was comparable to that explained by cognitive performance. Furthermore, depression and impulsivity partially confounded the relationship between cognitive performance and PDAQ and impulsivity partially mediated this relationship. The independent associations between neuropsychiatric symptoms and PDAQ were replicated in the replication sample.

Conclusion

These results indicate that impairments in cognitive IADLs reflect contributions of both cognition and neuropsychiatric changes and suggest that trials using measures of IADLs as an outcome measure should also carefully assess and control for neuropsychiatric symptoms.

Plain language summary

People with Parkinson’s disease often experience difficulties with everyday activities that rely on cognitive skills, such as organizing tasks, following instructions, or managing finances. These difficulties are usually linked to cognitive problems, but Parkinson’s disease is also commonly associated with mood and behavioral symptoms, including depression, apathy, and impulsivity. It is not well understood how much these symptoms contribute to problems with daily functioning compared to that of cognitive functions.

In this study, we examined the relationship between cognitive performance, mood symptoms, and daily functioning in two groups of people with Parkinson’s disease. Participants completed cognitive tests, questionnaires assessing mood and behavior, and the Penn Parkinson’s Daily Activities Questionnaire, which was designed to measure daily activities that depend on cognitive abilities. We found that both cognitive difficulties and mood symptoms were independently associated with worse daily functioning. Mood symptoms explained a similar amount of difficulty in daily activities as cognitive test performance. Depression and impulsivity partly confounded the relationship between cognitive impairment and daily functioning, and impulsivity also appeared to be one pathway through which cognitive difficulties affected everyday activities. Most findings were replicated in an independent group of participants.

These results indicate that difficulties in cognition-dependent daily activities in Parkinson’s disease reflect contributions from both cognitive impairment and mood or behavioral changes. Studies and clinical trials that use daily functioning as an outcome measure should therefore assess and account for mood symptoms to better understand whether changes in daily functioning are driven by cognitive improvement, changes in mood, or both.