Cerebral amyloid angiopathy and amyloid load distribution detected on amyloid–positron emission tomography: A systematic review and meta-analysis

Introduction: There are limited data regarding the amyloid positron emission tomography (PET) imaging among patients with Cerebral Amyloid Angiopathy (CAA). We sought to assess the amyloid load distribution detected on amyloid-PET among CAA patients compared to patients with Alzheimer’s Disease (AD), patients with hypertension (HTN) related hemorrhage (ICH) and healthy controls (HC). Patients and methods: A systematic review and meta-analysis of published studies with available data on global and regional amyloid-PET uptake was conducted. Comparisons with respect to amyloid load distribution were investigated using random-effects models based on the ratio of mean (RoM) amyloid-PET uptake. RoM < 1 and RoM > 1 indicate lower and higher global or regional amyloid-PET uptake in CAA compared to another population, respectively. Results: We identified 16 cohorts, comprising 271 CAA patients (mean age: 72 years; women: 46%) versus 130 AD patients (mean age: 73 years; women: 44%), 180 patients with HTN-related ICH (mean age: 66 years; women: 36%) and 61 HC (mean age: 71 years; women: 46%) with available data on amyloid-PET. Global amyloid PET ratio differentiated CAA from AD [RoM: 0.93; 95% CI: 0.90–0.96; p < 0.0001], HTN-related ICH [RoM: 1.25; 95% CI: 1.20–1.31; p < 0.0001], and HC [RoM: 1.26; 95% CI: 1.23–1.29; p < 0.0001]. Occipital amyloid-PET uptake [RoM: 1.20; 95% CI: 1.15–1.26; p < 0.0001] was higher in CAA compared to HTN-related ICH, and Occipital-to-global [RoM: 1.05; 95% CI: 1.03–1.07; p < 0.0001] ratio of amyloid-PET uptake differentiated also CAA from AD. Conclusions: CAA is characterized by a distinct amyloid-PET burden and distribution compared to AD patients, patients with HTN-related ICH and HC. These findings may contribute to the design and conduct of future randomized controlled clinical trials, aiming to treat CAA at preclinical stages.