When a Parkinson’s disease (PD) diagnosis is made, the focus is often on the cardinal motor symptoms. However, there are a number of important non-motor symptoms that accompany the disease, including cognitive impairment.
Cognitive symptoms have long been recognized as associated with PD. Measures such as the MDS-UPDRS or the PDQ-39 have always included items that assess aspects of attention, memory, and other cognitive domains.
More recently, with the FDA’s Patient-Focused Drug Development Initiative, a PD patient meeting was held, and cognitive impairment was one of the most frequently mentioned symptoms (Voice of the Patient Report, April 2016).
Cognition is therefore prominent not only in the clinical assessment of PD, but in the major impacts that patients themselves experience.
Given the importance to patients and the various ways PD can manifest, categories of cognitive impairment associated with parkinsonism have been identified and studied:
- Parkinson’s disease Mild Cognitive Impairment (PD-MCI) is typically a multidomain presentation, with impairment in executive function, visuospatial function, and other impacts in addition to memory impairment.
- Parkinson’s disease dementia (PDD) is diagnosed when a patient has had a PD diagnosis for a significant period prior to cognitive decline. PDD is highly relevant, as 80% of PD patients may develop PDD.
- It is also important to remember that a PD diagnosis in and of itself often includes cognitive decline and thus is an area an increasing number of clinical trials are evaluating.
[PARKINSON’S DISEASE WEBINAR]
This blog summarizes a presentation that outlines key considerations in designing and conducting Parkinson’s disease clinical trials in a manner that enables heightened decision making. (Watch the full presentation here.)
5 Questions to Guide Cognitive Assessment Selection in PD Clinical Trials
Whether a clinical trial is assessing PD, PD-MCI, or PDD, at present, there is little consensus in terms of the assessments that should be employed to evaluate cognitive decline. Some papers suggest 30+ different options (Litvan et al, Mov Discord 2012), but there could easily be as many as 50 assessments that are useful to consider when planning a trial of this nature.
With so many possibilities it can be challenging to select assessments for PD trials. That said, there are several considerations that can help determine which route to take. Here we outline 5 questions that can help narrow down the choices.
- What licensing and translation efforts will be required?
Understanding the needed copyright permissions and associated license fees is a key factor in determining which scales to use. This process can require a fair amount of planning, and unanticipated delays from license holders can be a factor. Furthermore, consider whether a standardized test manual with scoring guidance exists to help guide administration. Additionally, consider the availability of translations and cultural adaptations, or how complicated and costly translations would be to complete.
- Is normative data available?
The availability of normative data varies considerably across different tests. Education corrections are particularly challenging and need to be researched thoroughly.
- What test versions should I use?
Test versions can differ greatly. As one example, we often see reference to an effective test called the Digit Symbol Substitution Test. This test has 6 commonly used versions, and each requires different approaches and results in different data outputs.
- How difficult will it be for raters to administer the test properly?
Many of the assessments used in PD trials are complex neuropsychological tests and can be particularly challenging to administer. There are many scale options that pose significant challenges to raters; particularly as typical raters in Phase 2 or 3 studies will have had less experience, if any, with these assessments. This means teams must also consider how robust of a rater training program will be necessary for the scales selected. Learn more about Cogstate’s rater training services for PD trials here.
- Should I add central monitoring to validate appropriate administration?
In addition to making sure raters are well trained on these complex scales, teams also need to consider adding a central monitoring program to ensure scale administration is done properly. These programs can range from little to no monitoring, to reviewing in great detail all forms and audio recorded test administrations submitted by the raters.
Digital Cognitive Assessments in PD Populations
In addition, digital assessments have been widely used to study cognition in PD. Computerized tests can have advantages over paper and pencil assessments including:
- Objective and standardized administration with automated scoring
- Tests are brief and repeatable
- Unaffected by language or culture
- High usability and acceptability to participants
- Minimal motor response demands, and without graphomotor responding
Cogstate digital tests can be organized into batteries that assess the cognitive domains affected by PD. Battery recommendations for PD studies vary depending on the stage of the disease and the study’s focus area, but below is one example using Cogstate digital assessments.
Example PD Cognitive Battery
- International Shopping List Tests [Verbal Learning]
- Detection Test [Psychomotor Function / Processing Speed]
- Identification Test [Attention]
- One Card Learning Test [Visual Learning]
- One Back Test [Working Memory]
- Two Back Test [Working Memory]
- Groton Maze Learning Test [Executive Function]
- iDSSTm [Processing Speed/Attention]
Talk to Our Team
Cogstate helps sponsors gather high quality data in PD trials by providing sensitive and reliable computerized cognitive testing, as well as supporting rater training, central monitoring, and eCOA for the full range of clinical outcome assessments including motor function, quality of life, cognition, depression, suicidality, symptom severity, and sleep.
We invite you to contact us to learn more.