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Accepted for/Published in: JMIR Formative Research

Date Submitted: Nov 4, 2024
Open Peer Review Period: Nov 4, 2024 - Dec 30, 2024
Date Accepted: May 28, 2025
(closed for review but you can still tweet)

The final, peer-reviewed published version of this preprint can be found here:

Association of a Brief Computerized Cognitive Assessment With Cholinergic Neurotransmission: Assessment Validation Study

Attarha M, De Figueiredo Pelegrino A, Ouellet L, Toussaint PJ, Grant SJ, Van Vleet T, de Villers-Sidani E

Association of a Brief Computerized Cognitive Assessment With Cholinergic Neurotransmission: Assessment Validation Study

JMIR Form Res 2025;9:e68374

DOI: 10.2196/68374

PMID: 40622012

PMCID: 12257569

A brief computerized cognitive assessment correlates with cholinergic neurotransmission: An assessment validation study

  • Mouna Attarha; 
  • Ana De Figueiredo Pelegrino; 
  • Lydia Ouellet; 
  • Paule-Joanne Toussaint; 
  • Sarah-Jane Grant; 
  • Thomas Van Vleet; 
  • Etienne de Villers-Sidani

ABSTRACT

Background:

Computerized cognitive assessments are most often validated against standard neuropsychological measures with limited validation against biological indices of brain health.

Objective:

To evaluate whether a self-administered computerized cognitive assessment can predict cholinergic neurotransmission using the vesicular acetylcholine transporter ligand [18F]fluoroethoxybenzovesamicol (FEOBV) and positron-emission tomography (PET).

Methods:

In a retrospective analysis, we report baseline data from the Improving Neurological Health in Aging via Neuroplasticity-based Computerized Exercise (INHANCE) trial. The current study provides normative data for healthy older adults aged 65 and above. We evaluate the predictive validity of the Double Decision cognitive assessment (from the BrainHQ assessment platform) by examining its association with tracer binding in the anterior cingulate cortex, as measured by FEOBV-PET. We also assess concurrent validity with neuropsychological performance using standardized measures of executive function and global cognition.

Results:

The intent-to-treat population from the INHANCE trial analyzed in this study included 92 healthy adults with a mean age of 71.9 years (SD = 4.86; range 65-83), the majority of whom were female (66%, 61/92), with an average of 16.45 years of education (SD = 3.40; range 9-27). The Double Decision assessment predicted FEOBV binding in the anterior cingulate cortex, explaining 8% of the variance; and was associated with neuropsychological performance measures. The assessment was sensitive to age and was not influenced by education level or gender. Psychometric properties supported its usability and the assessment showed an average completion time of 3 minutes (SD 1.12).

Conclusions:

We present the first brief, self-administered computerized cognitive assessment capable of predicting cholinergic network health. This tool is scalable and accessible to any individual with an internet-connected device, offering a practical and cost-efficient approach to cognitive screening. The findings provide valuable insights into brain health, particularly for early detection of cognitive decline, and hold significant potential for broad applications across both clinical and non-clinical contexts. Clinical Trial: https://clinicaltrials.gov/study/NCT04149457


 Citation

Please cite as:

Attarha M, De Figueiredo Pelegrino A, Ouellet L, Toussaint PJ, Grant SJ, Van Vleet T, de Villers-Sidani E

Association of a Brief Computerized Cognitive Assessment With Cholinergic Neurotransmission: Assessment Validation Study

JMIR Form Res 2025;9:e68374

DOI: 10.2196/68374

PMID: 40622012

PMCID: 12257569

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