Investigating Dopamine Replacement-Associated Fluctuations in Cognition and Mood in Cognitively Unimpaired Parkinson’s Disease

Mov Disord Clin Pract. 2025 Apr 25. doi: 10.1002/mdc3.70100. Online ahead of print.

ABSTRACT

BACKGROUND: Non-motor fluctuations, characterized by variability in mood and cognition, are prevalent in advanced Parkinson’s disease (PD), but less is known about these fluctuations in early PD.

OBJECTIVE: The objective was to characterize fluctuations in cognition and mood in early PD without cognitive impairment.

METHODS: Individuals with PD but without cognitive impairment were evaluated “on” and “off” dopaminergic medications for minimal clinically important differences (MCID) in depression, anxiety, and cognition. Multivariable logistic regression evaluated factors associated with medication-related fluctuations in anxiety, depression, and cognition.

RESULTS: Clinically meaningful fluctuations in anxiety were associated with dysautonomia (OR [odds ratio] 7.5) and female sex (OR 3.9). Fluctuations in Symbol Digit Modalities Test (SDMT), a measure of processing speed and executive function, were associated with dysautonomia (OR 2.82). Such an association was not found with depression or Stroop test.

CONCLUSIONS: Dysautonomia may influence fluctuations in anxiety and some aspects of cognition in cognitively unimpaired PD.

PMID:40276915 | DOI:10.1002/mdc3.70100