Abstract Details

An accurate non-invasive diagnosis of CAA, an age-related small vessel disease, characterised by progressive deposition of amyloid β in the cerebrovascular wall, is important for clinical decision-making, as well as research in the field. Yet, the diagnostic accuracy and validity of key MRI markers and molecular markers of the disease remain (paradoxically) poorly studied.

We synthesized evidence on the accuracy of different diagnostic approaches for cerebral amyloid angiopathy (CAA), including the clinical-MRI based Boston criteria, amyloid-PET and core CSF biomarkers.

In a systematic literature search, we identified case-control studies with data relevant for sensitivity/specificity of the Boston criteria, amyloid PET positivity and core CSF biomarkers in symptomatic CAA patients vs. different comparison groups, as applicable. Using a hierarchical (multilevel) logistic regression model we calculated pooled diagnostic test accuracy.

Five studies had data on the Boston criteria v.1.5 (n=123): the pooled sensitivity and specificity for probable CAA diagnosis was 73.1% (95% CI, 45%-90.1%) and 86% (95% CI, 41.4%-98.1%), respectively. Thirteen amyloid-PET studies (211 CAA, 181 controls) were included in the meta-analysis. The overall pooled sensitivity of amyloid-PET for CAA diagnosis was 80% (95%CI: 67%-84%) and specificity was 82% (95%CI: 71%-86%). Seven studies (153 CAA, 185 Alzheimer’s disease patients), provided data on core CSF biomarkers (Aβ40, Aβ42, t-tau, and p-tau). Aβ40 demonstrated the best overall performance for CAA diagnosis vs Alzheimer’s disease with 80% (95%CI: 68%-83%) pooled sensitivity and 68% (95%CI: 59%-74%) specificity. The core CSF pattern characteristic of CAA was low Aβ40, with intermediate t-tau/p-tau levels (higher than healthy controls, but lower than Alzheimer’s disease) (p < 0.0001 for all comparisons).

Amyloid-PET and specific CSF patterns of Aβ40, t-tau, and p-tau have moderate-to-good diagnostic accuracy for CAA diagnosis and might supplement the Boston criteria in certain clinical settings (such an approach will be presented at the meeting).