Contributors:
Kaycee Sink, MD, MAS (Chief Medical Officer)
Svenja Wacker, PhD (Neuropsychology Science Director)
Alzheimer’s disease (AD) research and clinical trials rely heavily on a range of cognitive assessment tools to measure disease progression and treatment efficacy. One of the most widely used tools in clinical research for assessing cognitive function in Alzheimer’s disease patients is the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog). Since its development in the 1980s by Rosen et al.*, the ADAS-Cog has become a cornerstone in clinical trials, helping researchers evaluate the effectiveness of potential treatments.
The ADAS-Cog was created to evaluate the severity of cognitive symptoms in AD. It is a performance outcome (PerfO) measure where participants complete tasks within a structured battery of cognitive tests administered by a trained rater. ADAS-Cog is considered a gold standard tool in AD clinical trials due to its regulatory acceptance by agencies like the FDA.
Based upon decades of experience utilizing the ADAS-Cog in global AD clinical trials, Cogstate scientific leaders share thoughts on three key questions about utilizing the ADAS-Cog in clinical research.
What are the advantages of using the ADAS-Cog in clinical research?
The ADAS-Cog covers multiple cognitive domains including processing speed, memory, visual-spatial construction, orientation, and language. It has been widely used and extensively validated, making it easy to compare outcomes and data across studies. It is also relatively sensitive to cognitive changes in mild to moderate stages of Alzheimer’s dementia. Additional versions of the ADAS-Cog with added items have been developed for use in earlier stages of disease (i.e. ADAS-Cog13 and ADAS-Cog14)
What challenges and considerations should clinical trial teams be aware of when using the ADAS-Cog?
In addition to the strengths of the ADAS-Cog, there are key nuances that should be considered prior to implementing the scale in a global trial. The limited number of alternate forms can lead to practice effects in long-term trials inflating scores and affecting data accuracy. Unlike scales such as the CDR, the ADAS-Cog does not incorporate measurement of cognitive changes in daily functioning. Administration can take 30 to 60 minutes, which can be burdensome for participant and study sites.
In addition, the ADAS-Cog requires well-trained, experienced raters to administer and score correctly. Even small errors can compromise data quality and affect the detection of drug effects.
“Careful selection of experienced raters is vital when choosing to include the ADAS-Cog in your clinical trial,” says Svenja Wacker, PhD, Science Director and Licensed Neuropsychologist. “Your rater certification program should include comprehensive training methods with plenty of hands-on practice and guided feedback from clinical experts to assure valid data that you can use to reliably make decisions about your drug.”
Lastly, more than 30 modified versions of the ADAS-Cog exist that can be utilized to best meet the specific requirements of a trial. Modifications including reduced or expanded battery of different combinations of subtests or altered scoring methodology may improve the performance of the ADAS-Cog but can limit between-study comparison.
Can the ADAS-Cog be administered remotely?
Some subtests of the ADAS-Cog lend themselves to remote administration, while other sections require in-person interaction or considerable modification which complicates remote administration and may compromise validity.
Wrapping Up
The ADAS-Cog is widely regarded as an industry standard scale in AD trials because of its high sensitivity, coverage of multiple cognitive domains, and extensive validation. However, the scale presents several limitations that should be considered when deciding to include it in the endpoint strategy for your study.
- This blog is part of a series exploring the individual scales reviewed in our Alzheimer’s Disease Clinical Trial Endpoint Guide. Access the full guide here.
- Interested in learning more? We are happy to discuss endpoint selection with your team in more depth. Contact us today.
