Related Experiment Video
Updated: Jun 24, 2025
Dynamic Digital Biomarkers of Motor and Cognitive Function in Parkinson's Disease
Published on: July 24, 2019
The Parkinson's Disease Composite of Executive Functioning: A Measure for Detecting Cognitive Decline in Clinical
Christina B Young1, Brenna Cholerton1, Alena M Smith1
1From the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.
Background And Objectives:
Executive functioning is one of the first domains to be impaired in Parkinson disease (PD), and the majority of patients with PD eventually develop dementia. Thus, developing a cognitive endpoint measure specifically assessing executive functioning is critical for PD clinical trials. The objective of this study was to develop a cognitive composite measure that is sensitive to decline in executive functioning for use in PD clinical trials.
Methods:
We used cross-sectional and longitudinal follow-up data from PD participants enrolled in the PD Cognitive Genetics Consortium, a multicenter setting focused on PD. All PD participants with Trail Making Test, Digit Symbol, Letter-Number Sequencing, Semantic Fluency, and Phonemic Fluency neuropsychological data collected from March 2010 to February 2020 were included. Baseline executive functioning data were used to create the Parkinson's Disease Composite of Executive Functioning (PaCEF) through confirmatory factor analysis. We examined the changes in the PaCEF over time, how well baseline PaCEF predicts time to cognitive progression, and the required sample size estimates for PD clinical trials. PaCEF results were compared with the Montreal Cognitive Assessment (MoCA), individual tests forming the PaCEF, and tests of visuospatial, language, and memory functioning.
Results:
A total of 841 participants (251 no cognitive impairment [NCI], 480 mild cognitive impairment [MCI], and 110 dementia) with baseline data were included, of which the mean (SD) age was 67.1 (8.9) years and 270 were women (32%). Five hundred forty five PD participants had longitudinal neuropsychological data spanning 9 years (mean [SD] 4.5 [2.2] years) and were included in analyses examining cognitive decline. A 1-factor model of executive functioning with excellent fit (comparative fit index = 0.993, Tucker-Lewis index = 0.989, and root mean square error of approximation = 0.044) was used to calculate the PaCEF. The average annual change in PaCEF ranged from 0.246 points per year for PD-NCI participants who remained cognitively unimpaired to -0.821 points per year for PD-MCI participants who progressed to dementia. For PD-MCI, baseline PaCEF, but not baseline MoCA, significantly predicted time to dementia. Sample size estimates were 69%-73% smaller for PD-NCI trials and 16%-19% smaller for PD-MCI trials when using the PaCEF rather than MoCA as the endpoint.
Discussion:
The PaCEF is a sensitive measure of executive functioning decline in PD and will be especially beneficial for PD clinical trials.
More Related Videos
Related Concept Videos
01:24Parkinson's Disease: Treatment
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...
01:15Parkinson's Disease: Overview
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...