# Positron Emission Tomography in Cerebral Amyloid Angiopathy: A Scoping Review
## 4 Discussion
A systematic review and meta-analysis reported that in patients with AD, the prevalence of CAA was 48% when determined by pathology, but only 22% whenidentified using imaging techniques. Similarly, in the general population, CAA prevalence was reported as 23% by pathology and 7% by imaging [6; 53]. These discrepancies highlight the limitations of current amyloid PET tracers, which are not specific to vascular amyloid deposits. The inability to distinguish between vascular and parenchymal amyloid deposits remains a critical challenge in accurately diagnosing CAA. Amyloid PET imaging has significant clinical applications in the management of CAA. First, it provides prognostic information by identifying patients who are at risk of recurrent hemorrhages or progressive cognitive decline. Higher amyloid burdens have been correlated with more severe disease phenotypes and poorer outcomes. Second, amyloid PET enhances the differentiation of CAA from other amyloid-related disorders, such as Alzheimer's disease, especially when MRI findings are inconclusive. For example, the occipital-predominant amyloid deposition seen in CAA is distinct from the more diffuse patterns typically observed in AD. This distinction can guide clinical decision-making and inform therapeutic strategies. Finally, amyloid PET imaging is being used to evaluate the effectiveness of emerging therapies targeting amyloid-beta. Clinical trials investigating amyloid-reducing agents rely on imaging markers, including PET, to assess treatment efficacy. In AD patients, there is reliable pathological information on the accuracy of in vivo [18F]forbetapir PET and histopathology [54; 55]. Most data come from studies on end-of-life subjects with advanced disease, in which autopsy is anticipated shortly after PET imaging, and with the specific goal of demonstrating efficacy. Unfortunately, these studies have a selection bias, considering only patients at the extreme ends of the \(\beta\)-amyloid spectrum (either no or frequent neuritic plaque densities, according to CERAD criteria [56]), limiting the applicability of the proposed high test sensitivity and specificity. In both AD and AA, patients that are candidates for functional imaging are those in the early stages of disease development with borderline \(\beta\)-amyloid pathology, as well as patients with preserved cognition. The GE067-026 trial demonstrated 91% sensitivity and 90% specificity of [18F]flutmetamol PET by a majority read for the presence of moderate or frequent plaques [57]. The probability of an abnormal [18F]flutmetamol scan increased with neocortical plaque density and AD diagnosis. The majority of PET assessments accurately reflected the amyloid plaque burden, in 90% of cases. Although tracer retention was best associated with amyloids in neuritic plaques, amyloid in diffuse plaques and CAA best explained three [18F]flutmetamol positive cases with mismatched (sparse) neuritic plaque burden. Advanced cortical atrophy was associated with the seven false negative [18F]flutmetamol images. The interpretation of images from pathologically equivocal cases was associated with low reader confidence and inter-reader agreement. Our results provide supporting evidence that amyloids in neuritic plaque burdens are the primary form of \(\beta\)-amyloid pathology detectable with [18F]flutmetamol PET imaging. Interestingly, a retrospective study on probable CAA patients categorized as having CSS or not focused on the atrophy pattern [32]. In this study, ten patients with probable CAA were cSS-negative and negative for amyloids on PET imaging. In addition, the cSS+ group exhibited an AD-like atrophy pattern, involving the precuneus, posterior cingulate, parietotemporal, superior frontal, and medial temporal areas, suggesting that a subgroup of patients with probable CAA reflects a CAA phenotype that shares pathologic hallmarks with AD, providing insight into the CAA-to-AD continuum.