Clinical significance of amyloid positivity in patients with probable cerebral amyloid angiopathy markers

PurposeWe investigated the frequency and clinical significance of amyloid (A) positivity on PET in patients with cerebral amyloid angiopathy (CAA).MethodsWe recruited 65 patients who met the modified Boston criteria for probable CAA. All underwent amyloid PET, MRI, APOE genotyping and neuropsychological testing, and we obtained information on MRI markers of CAA and ischemic cerebral small-vessel disease (CSVD). We investigated the CAA/ischemic CSVD burden and APOE genotypes in relation to A positivity and investigated the effect of A positivity on longitudinal cognitive decline.ResultsAmong the 65 CAA patients, 43 (66.2%) showed A PET positivity (A+). Patients with A+ CAA had more lobar microbleeds (median 9, interquartile range 2-41, vs. 3, 2-8; P=0.045) and a higher frequency of cortical superficial siderosis (34.9% vs. 9.1%; P=0.025), while patients with A- CAA had more lacunes (1, 0-2, vs. 0, 0-1; P=0.029) and a higher frequency of severe white matter hyperintensities (45.5% vs. 20.9%; P=0.040). The frequency of epsilon 4 carriers was higher in A+ patients (57.1%) than in A- patients (18.2%; P=0.003), while the frequency of epsilon 2 carriers did not differ between the two groups. Finally, A positivity was associated with faster decline in multiple cognitive domains including language (P<0.001), visuospatial function (P<0.001), and verbal memory (P<0.001) in linear mixed effects models.ConclusionOur findings suggest that a significant proportion of patients with probable CAA in a memory clinic are A- on PET. A positivity in CAA patients is associated with a distinct pattern of CSVD biomarker expression, and a worse cognitive trajectory. A positivity has clinical relevance in CAA and might represent either advanced CAA or additional Alzheimer's disease neuropathological changes.