# Temporal Dynamics of Subtle Cognitive Change: Validation of a User-Friendly Multidomain Digital Assessment Using an Alcohol Challenge

## TL;DR

A new digital cognitive test battery was validated for detecting subtle changes in brain function, using alcohol to simulate cognitive impairment in a controlled setting.

## Contribution

The study validates a user-friendly digital cognitive battery's sensitivity to subtle changes in cognitive performance over time.

## Key findings

- Alcohol-induced cognitive impairment was detected across multiple digital tasks and returned to baseline as alcohol levels declined.
- Digital tasks showed moderate to strong correlations with benchmark measures during peak intoxication.
- Practice effects were minimal within the condensed testing protocol.

## Abstract

Clinical trials in neurological and psychiatric indications are hampered by poor measurement fidelity in currently used “standardized” rating scales. Digital, repeatable tests that can be remotely administered offer a more fine-grained understanding of the patient’s clinical trajectory. Several such tools are being developed, but only a few have been validated in terms of their ability to discern and describe change over time—a critical element of clinical trials.

Four cognitive tasks from a digital battery (delivered via tablet) are administered at high frequency following an alcohol challenge to assess sensitivity to change. The tasks are novel, repeatable, and self-administered implementations of classic neurobehavioral paradigms.

Thirty healthy younger adults were assessed on 2 separate days, once under the influence of alcohol and once under a placebo, with order counterbalanced. Each day included 8 assessments. The tasks comprised novel, engaging implementations of the Digit Symbol Substitution Task (DSST), reaction time, N-back working memory, and visual associative/episodic memory, and were compared with benchmark measures. In-laboratory assessments were preceded by massed practice (3 sessions), and blood alcohol concentration was monitored throughout using a breathalyzer and a Visual Analog Scale.

Alcohol-related impairment was observed across multiple measures, followed by a return to baseline as blood alcohol concentration declined. A slight practice effect was noted between the first and second sessions for the digital DSST, along with a longer-term effect across the 2 days. Moderate to strong correlations between digital and benchmark measures were observed at peak intoxication.

Under alcohol challenge, this battery, along with benchmark standardized tests, demonstrates sensitivity to subtle changes in cognitive performance over time. Practice effects are minimal within this condensed protocol. Patient-friendly, repeatable tests administered via a digital platform, such as those in the current battery, warrant further investigation in the context of remote clinical studies that require methodological approaches capable of discerning and describing small changes over time. The availability of validated single tests or test batteries as sensitive tools that can be easily and frequently administered (eg, daily) would address a critical gap: the lack of descriptors with sufficient sensitivity, specificity, and reliability to detect cognitive changes over time in clinical trials of new therapies for neurological and psychiatric conditions.