The US Food and Drug (FDA) requires acceptable outcome measures to approve a cognitive-enhancing medication for the treatment of mild cognitive impairment (MCI) in Parkinson's disease (PD). The FDA has indicated that the Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) is an acceptable combined cognitive-functional outcome for use in clinical trials; however, the CDR-SOB has not yet been validated for use in PD. This project will assess the validity of the CDR-SOB by comparing the scale to expert diagnosis in a cohort of 100 participants with PD at the University of Pennsylvania (UPenn).
We hypothesize that the CDR-SOB will demonstrate good criterion (compared with expert diagnosis) and convergent (compared with commonly-used global cognition screening instruments) validity in PD, indicating that it is appropriate for use in clinical trials of participants with PD-MCI for regulatory approval.
A group of 100 participants with PD with a mix of cognitive diagnoses (normal cognition, MCI and dementia)will be enrolled in the UPenn Udall Center. An expert rater will administer the CDR-SOB by over the course of one year. CDR-SOB scores will be statistically compared to expert consensus cognitive diagnosis based on more detailed clinical and cognitive assessments. CDR-SOB results will also be compared to scores on commonly-use global cognitive rating scales (the Montreal Cognitive Assessment and the Dementia Rating Scale-2). These findings will provide preliminary data on the validity of the CDR-SOB in those with PD.
Impact on Diagnosis/Treatment of Parkinson's Disease:
Although MCI in PD is common and recognized as a risk factor for future development of dementia, there are no medications approved for this stage of cognitive impairment. Verifying PD-MCI as an acceptable outcome measure will accelerate research to identify treatments for PD-MCI.
Next Steps for Development:
If we find positive preliminary evidence for CDR-SOB in PD, next steps will include testing both its short-term stability and its sensitivity to change over time, including responsiveness to cognitive-enhancing treatments.