Application of a clinical scale for predicting Aβ-positivity in a multicentre Canadian dementia cohort: A necessity in the era of amyloid targeting treatment

Abstract

Background: Clinical Amyloid positivity Prediction Score (CAPS) is a clinical tool developed on a small Canadian cohort with clinical Alzheimer’s Disease (AD) to help predict amyloid-beta (Aβ) positivity. The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study is a national Canadian observational study of participants clinically diagnosed with various neurodegenerative disorders, including Alzheimer’s syndrome, making it an ideal platform to validate CAPS on an independent but similar cohort of participants.

Methods: Participants from the COMPASS-ND cohort with Subjective Cognitive Impairment (SCI), Mild Cognitive Impairment (MCI) or dementia due to AD, and a known Aβ status were included. CAPS was assigned to the individuals as follows: cognitive decline of >2 points/year on the Mini-Mental State Examination (MMSE) = 1-point, Neuropsychiatric Inventory Questionnaire (NPI-Q) ≥2 = 2 points, and low Fazekas score (0 or 1) = 1 points. A total CAP score ≥ 2 was considered indicative of Aβ positivity.

Results: Total 86 participants fulfilled the inclusion criteria. Aβ + individuals had higher NPI-Q scores (2 vs 0.5, p = 0.005) and a lower baseline MMSE score (26.5 vs 28.0, p = 0.009). High WMH on brain MRI was reported more frequently in the Aβ- subgroup (50.0% vs 33.8%, p < 0.001). The frequency of people with a CAPS score of ≥2 is significantly higher in the Aβ + subgroup (75% vs 50%, p < 0.001). CAPS demonstrated a reasonable predictive value in this cohort, with 67% accuracy, and 73% sensitivity.

Conclusion: This validation study in a larger Canadian cohort showed that CAPS demonstrated reasonable accuracy in distinguishing between Aβ + and Aβ- subgroups.

Plain Language Summary

The question we studied: Brain deposit of amyloid or Aβ, a harmful protein, is known as the main cause of Alzheimer’s Disease (AD). The Clinical Amyloid Positivity Prediction Score (CAPS) helps doctors estimate the likelihood that a patient has Aβ buildup in the brain, using fewer tests and simpler information than usually required. However, the original version of this tool was created with a relatively small number of people. The goal of this study was to check whether the CAPS tool works well in a similar, but larger, group of Canadian people.

How we studied it: We compared basic personal and medical information between people diagnosed with AD who had Aβ buildup (Aβ+; an accumulation of plaque in the brain) and those who did not (Aβ–).

What we found: With this new and larger group of people, we found that the CAPS tool was very effective at distinguishing between Aβ+ and Aβ- subgroups.

Why it matters: As new treatments that target Aβ become available, tools like CAPS could play an important role in identifying which people diagnosed with AD may qualify for these therapies or need specialist referral—without relying on invasive or expensive testing.