Clinical Amyloid positivity Prediction Score (CAPS) shows excellent accuracy in the COMPASS‐ND cohort

BACKGROUND: CAPS is a simple clinical tool developed by the authors on a small Canadian cohort (n =48) with diagnosed clinical Alzheimer's Disease (AD) to help clinicians predict amyloid positivity (Aβ+) (Lahiri et al, 2024). We now wished to validate CAPS on a different but similar cohort. The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study is a national Canadian observational study of participants clinically diagnosed with a range of neurodegenerative disorders, including Alzheimer's syndrome and therefore presents an ideal validation opportunity. METHODS: Patients with a clinical diagnosis of AD, including Subjective Cognitive Impairment (SCI) Mild Cognitive Impairment (MCI) and dementia, and known amyloid status (based on decreased csf amyloid-beta 42 levels), from the COMPASS-ND cohort were included. Demographic and clinical variables were compared between Aβ+ and Aβ-subgroups, following the same framework as in Lahiri et al, 2023. CAPS was assigned as follows: cognitive decline >2 points/year on Mini Mental State Examination (MMSE)= 1 point, NPI-Q ≥2 = 2 points, and high white matter burden (WMH)= 0 points. A total CAPS score ≥2 was considered indicative of amyloid positivity. RESULTS: Total 86 patients fulfilled the inclusion criteria. There were no differences between the subgroups based on age, sex, and duration of illness. Aβ+ people had higher NPI-Q scores (2 vs 0.5, p =0.005) and a lower baseline MMSE score (26.5 vs 28, p =0.009). The frequency of dementia, characterized by restriction of ADLs, was found to be higher in them (p <0.001). High WMH on brain MRI was reported more frequently in the Aβ- subgroup (50% vs 33.8%, p <0.001), as their cognitive decline is likely driven by non-amyloid pathologies (mostly vascular). The frequency of people with a CAPS score of 2 or higher is significantly higher in the Aβ+ subgroup as compared to their Aβ- peers (72.1% vs 55.6%, p <0.001). CAPS ≥2 demonstrated an overall accuracy of 85.7%, sensitivity of 72.1%, and specificity of 99.9% in predicting Aβ+ status. CONCLUSION: This is a second and larger Canadian cohort, where CAPS was found to demonstrate excellent accuracy in distinguishing between Aβ+ and Aβ- subgroups. This approach allows clinicians to largely predict amyloid positivity prior to obtaining biomarkers.

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