Traditional Cognitive Tests Miss Early Changes in Parkinson’s

Standardized cognitive tests showed limited sensitivity to early cognitive changes in Parkinson’s disease (PD), according to research recently published in Psychopharmacology Bulletin. ¹ In their study, researchers found only minor declines in the working memory of Parkinson’s patients over a five-year period compared to healthy controls, with no significant differential rates of change detected in other cognitive domains.

Standardized tests can detect some changes, but they may not be fully sensitive to all early cognitive changes in Parkinson’s disease. This has implications for PD clinical trial outcome selection and study design, according to the authors.

About the Study

The Parkinson’s Progression Markers Initiative (PPMI) is a multicenter longitudinal investigation to comprehensively characterize PD motor and non-motor symptom progression². Participants completed cognitive testing at baseline and yearly follow-up evaluations over a 5-year span.  The battery included standardized measures of memory, visuospatial functions, processing speed, working memory and verbal fluency.  Complete datasets were obtained from 253 newly diagnosed PD patients and 134 healthy controls. Within the PD cohort, potential mild cognitive impairment (MCI) was identified in 84 individuals at baseline.

Change over time was similar between PD and controls on all but two tests. . One was a processing speed test, and researchers determined that the performance was a function of motor decline. The other was working memory.

Working memory–assessed by the letter-number sequencing (LNS) task–deteriorated slightly faster in PD patients compared to healthy controls.  The PD patients with potential MCI performed worse than PD-normal patients at baseline but did not show faster cognitive decline. One possibility is that the working memory decline may be related to dopamine depletion in fronto-striatal systems.

Implications for Further Research

Working memory measures may be sensitive to early cognitive changes in PD. This suggests that working memory tests (e.g., LNS) may be more likely than tasks from other domains to detect treatment effects in trials aimed at slowing or preventing cognitive decline in early PD, the authors note. Moreover, because patients with potential MCI at baseline did not show a more rapid decline, it may not be necessary to screen participants based on cognitive deficits at the outset.

In a statement accompanying the release of the study², lead author Travis Turner, PhD, Senior Clinical Director, Movement Disorders at WCG, elaborated on this, suggesting that researchers developing disease-modifying or neuroprotective interventions for PD should not use these tests as outcomes in clinical trials because they are not sensitive to the early subjective changes often reported by patients.

“I am hoping [this research] can be used for industry trials that I really want to succeed. I’m a PD researcher, so if a drug comes along that slows or stops its progression, I want reliable outcome measures that are sensitive to that effect.”

Travis Turner, PhD | Senior Clinical Director, Movement Disorders, WCG

Future investigations will explore the sensitivity of these tests to structural changes observed on neuroimaging and their correlation with clinician ratings of cognition and other non-motor PD symptoms.

References:

1. Turner TH, Lench DH, Adams R, Wilson S, Marsicano C, Rodriguez-Porcel F. Are Standardized Tests Sensitive to Early Cognitive Change in Parkinson’s Disease? Psychopharmacol Bull. 2023;53(1):19-29.
2. Parkinson Progression Marker Initiative. The Parkinson Progression Marker Initiative (PPMI). Progress in Neurobiology. 2011;95(4):629 635. https://doi.org/10.1016/j.pneurobio.2011.09.005
3.  New study challenges the idea that early Parkinson’s Disease causes cognitive dysfunction.  Medical University of South Carolina press release via EurekAlert! April 18, 2023 https://www.eurekalert.org/news-releases/986746