Digit Symbol Substitution Test (DSST): New Digital Version is Sensitive and Low-burden Option for Global Alzheimer’s Disease Trials

April 6, 2023

In Alzheimer’s Disease (AD) clinical trials, cognition is a key outcome that is measured to evaluate the efficacy of potential treatments. A test paradigm used commonly to assess cognition in both early and symptomatic AD is the Digit Symbol Substitution Test (DSST).  The DSST is used to measure attention, processing speed and executive function. These cognitive domains are particularly relevant as they are important for everyday activities such as driving and both occupational and independent living skills.

Conventional versions of the DSST use paper-and-pencil methods and were developed for use in educated, English-speaking adults in developed countries. In general, Cogstate digital cognitive tests have been developed for use in varied cultural, linguistic, and educational contexts. Continuing with this approach, a digital version of the DSST, called the DSST-Meds, has now been created and validated.

A recent study published in the Journal of Clinical and Experimental Neuropsychology reports the outcome of one of the first validation studies of the DSST-Meds. Data show the utility and validity of the test for measuring cognitive dysfunction in early AD, applied in global and varied contexts.

How is the DSST-Meds Test Different?

All DSST versions require participants to complete the test under a time limitation where they must process information about abstract geometric designs and pair these with numbers using a response grid that they mark with responses. The Cogstate DSST is novel in that rather than requiring individuals match symbols to numbers, they must match images of different medicines with weekdays.

Like many conventional neuropsychological test paradigms, DSST tests utilize stimulus material consisting of numbers and abstract, geometric figures.  This introduces cultural bias to tests limiting their application in studies and clinical settings with culturally and linguistically diverse people, and in global clinical trials. It would be inappropriate to interpret low test scores from culturally and diverse groups as suggesting cognitive impairment.

The Cogstate DSST-Meds version of the test retains the well-validated DSST paradigm but, it replaces abstract stimuli with ecologically relevant and cross-culturally applicable images of medications and replaces numbers with dates. Medication management is a familiar, universal, and relevant activity for members of most cultural groups, including older individuals and those with some degree of cognitive impairment.

In addition, despite it being a relatively simple test, the conventional paper-and-pencil versions of the DSST require test administrators have considerable experience with application and scoring. Errors in scoring the DSST are common, especially when the test has been administered to people with cognitive impairment. By contrast, DSST-Meds provides standardized administration with automatic scoring, thus eliminating variances related to differences in experience or manual scoring. And, given its functionality, the DSST-Meds does not require an expert neuropsychologist rater.

Furthermore, as with other Cogstate tests, the DSST-Meds can be administered in both supervised and unsupervised (remote) settings, make it an option for decentralized clinical trials.


  • The Cogstate Digital DSST-Symbols has been included in 12 clinical trials across Ph 1 and Ph 2 research, supporting indications including Alzheimer’s Disease, Narcolepsy, and Safety.
  • The Cogstate DSST-Meds version has been included in 5 clinical trials across Pilot, Ph 1, Ph2, and Ph3 research, supporting indications including Alzheimer’s Disease, MCI, Parkinson’s Disease, and Safety.

Published Validation Results for the DSST-Meds

Careful validation of psychometric properties of the DSST-Meds was important to ensure that modification of test stimuli did not interfere with the validity of the test paradigm itself.

In the recent study, Williamson and colleagues showed that performance on the Cogstate DSST-Meds and Cogstate DSST-Symbols tests were associated strongly with performance on the WAIS coding test in cognitively unimpaired older adults and in adults with early symptomatic Alzheimer’s disease. Thus, the DSST-meds showed strong construct validity.

A second study compared the sensitivity of the DSST-meds and the WAIS coding test to cognitive impairment associated with mild AD. This study confirmed that both test paradigms were sensitive to AD related cognitive impairment, although the magnitude of this was greater on the DSST-Meds test than on the WAIS coding test. Thus, the DSST-meds had a strong criterion validity.

A self-paced shaping strategy was developed to teach the rules and requirements of the DSST-Meds to individuals being assessed. This Learn module allowed individuals to complete the test in an unsupervised context. A third study from Williamson and colleagues found that AD-related impairment in performance detected in individuals taking the DSST-meds in an unsupervised context was equivalent to that when it was given in a supervised manner.  Thus, performance on the DSST-meds as equivalent between supervised and unsupervised contexts of use.

Data from the studies indicate the modification of the DSST paradigm to reference a meaningful activity of daily life did NOT compromise the test’s theoretical and psychometric integrity, validity, or sensitivity to detect AD-related cognitive impairment. Furthermore, the data confirm the DSST-Meds is suitable for remote administration and “decentralized trial friendly.”

The DSST-Meds should be considered a useful, well-validated and low-burden tool for inclusion in global Alzheimer’s Disease clinical trials to measure cognition in preclinical, prodromal, and clinical patient groups.


Source: Williamson, M., Maruff, P., Schembri, A., Cummins, H., Bird, L., Rosenich, E., & Lim, Y. Y. (2023). Validation of a digit symbol substitution test for use in supervised and unsupervised assessment in mild Alzheimer’s disease. Journal of Clinical and Experimental Neuropsychology, 1–12.

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