Amyloid-PET burden and regional distribution in cerebral amyloid angiopathy: a systematic review and meta-analysis of biomarker performance.

Introduction We performed a meta-analysis to synthesise current evidence on amyloid-positron emission tomography (PET) burden and presumed preferential occipital distribution in sporadic cerebral amyloid angiopathy (CA). Methods In a PubMed systematic search, we identified case-control studies with extractable data on global and occipital-to-global amyloid-PET uptake in symptomatic patients with CA (per Boston criteria) versus control groups (healthy participants or patients with non-CAA deep intracerebral haemorrhage) and patients with Alzheimer's disease. To circumvent PET studies' methodological variation, we generated and used 'fold change', that is, ratio of mean amyloid uptake (global and occipital-to-global) of CA relative to comparison groups. Amyloid-PET uptake biomarker performance was then quantified by random-effects meta-analysis on the ratios of the means. A ratio >1 indicates that amyloid-PET uptake (global or occipital/global) is higher in CA than comparison groups, and a ratio <1 indicates the reverse. Results Seven studies, including 106 patients with CA (>90% with probable CA) and 138 controls (96 healthy elderly, 42 deep intracerebral haemorrhage controls) and 72 patients with Alzheimer's disease, were included. Global amyloid-PET ratio between patients with CA and controls was above 1, with an average effect size of 1.18 (95% CI 1.08 to 1.28; p<0.0001). Occipital-to-global amyloid-PET uptake ratio did not differ between patients with CA versus patients with deep intracerebral haemorrhage or healthy controls. By contrast, occipital-to-global amyloid-PET uptake ratio was above 1 in patients with CA versus those with Alzheimer's disease, with an average ratio of 1.10 (95% CI 1.03 to 1.19; p=0.009) and high statistical heterogeneity. Conclusions Our analysis provides exploratory actionable data on the overall effect sizes and strength of amyloid-PET burden and distribution in patients with CA, useful for future larger studies.