The Convergence: Integrating Blood Biomarker Tests and Digital Cognition to Accelerate Alzheimer’s Research

The Imperative for Biomarker-Driven Trials

While the reliance on clinical opinion and the high cost and invasiveness of more definitive pathophysiological evidence (via PET scans or CSF analysis from lumbar puncture) have historically defined AD diagnosis, this landscape is rapidly changing.

As Dr. Braunstein noted, dementia is a clinical phenotype, not the underlying disease. In fact, up to 39% of early dementia due to AD cases are misdiagnosed in primary care settings in the absence of biomarker data.

This diagnostic inconsistency drives a need for molecular characterization to ensure proper management, including treatment.

• BBM tests as Confirmatory Tools
  Blood tests, such as the PrecivityAD2™ test can measure analytes like Aβ42/40 and p-tau217/np-tau217 (known as %p-tau217), which can provide high diagnostic accuracy (over 90%) in confirming presence of brain amyloid pathology. These offer a less invasive and more accessible alternatives to CSF & PET for early diagnosis and monitoring.
• Targeting the Treatment Window
  This is critical because effective disease-modifying therapies have been approved by various global regulatory bodies, but their success depends on identifying patients early, while they are still within the appropriate “treatment window”. If diagnosis is delayed by months, or even years (up to two years in some systems), patients can miss the opportunity for intervention.

DCAs: Scaling Precision in Functional Assessment

While BBM tests can excel at confirming presence of AD pathology, clinical trials require objective, longitudinal measures of functional change – the impact of the disease. This is where DCAs provide essential value, tackling the systematic shortage of specialists and the bottleneck in memory care.

Dr. Cormack highlighted that to address the millions of people concerned about memory, assessment needs to be deployed at scale.

• Feasibility and Compliance
  Data shows that remote, digital cognitive assessments are not only scalable and accessible, but maintain high compliance and engagement over prolonged periods, even in patients with mild cognitive impairment (MCI) or mild AD.
• Sensitivity to Biology
  Modern DCAs are designed to be sensitive not just to the clinical phenotype, but also to the underlying biology. Certain tasks are able to selectively activate the hippocampus, an area particularly impaired in MCI and AD, and are statistically sensitive to AD-related biomarkers like hippocampal volume, CSF amyloid, and tau. Furthermore, the evidence shows that DCAs are able to predict functional decline over 24 months.

A Blueprint for Integration

The AI Mind project provides a powerful, real-world example of this convergence in a longitudinal setting. As Dr. Hatlestad-Hall described, the study combines high-density EEG (neurophysiology), CANTAB® DCAs (behaviour/function), and BBMs (pathology) across multiple European cohorts.

Preliminary insights from this study, based on unpublished data, reveal the complex, but measurable, relationships essential for clinical trial design:

• Plasma p-tau217 levels were already dependent on APOE ε4 status at the baseline MCI stage.
• Performance on a classic verbal memory test was negatively correlated with plasma p-tau217 levels.
• Higher p-tau217 load at baseline appeared related to time-dependent cognitive decline, with higher quartile groups showing an average drop in performance after their second visit on tests like Pattern Recognition Memory (PRM).

This combination of tools offers a path to investigate functional trajectories in relation to biomarker evolution, providing the objective data drug developers need to manage trial risk and confirm treatment efficacy.

Precision Medicine for AD: Unifying Pathology and Function

The unified approach of precise pathology confirmation (BBM tests) and objective, scalable functional measurement (DCAs) positions CNS drug developers to transition AD care from a reactive model to a preventive one. This precision is the key to optimizing drug development, ensuring trial cohorts are appropriately enriched, and validating efficacy endpoints, ultimately helping to accelerate the delivery of life-changing treatments.