Abstract
Purpose
We investigated the frequency and clinical significance of amyloid β (Aβ) positivity on PET in patients with cerebral amyloid angiopathy (CAA).
Methods
We 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 Aβ positivity and investigated the effect of Aβ positivity on longitudinal cognitive decline.
Results
Among the 65 CAA patients, 43 (66.2%) showed Aβ PET positivity (Aβ+). Patients with Aβ+ 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 Aβ− 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 ε4 carriers was higher in Aβ+ patients (57.1%) than in Aβ− patients (18.2%; P = 0.003), while the frequency of ε2 carriers did not differ between the two groups. Finally, Aβ 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.
Conclusion
Our findings suggest that a significant proportion of patients with probable CAA in a memory clinic are Aβ− on PET. Aβ positivity in CAA patients is associated with a distinct pattern of CSVD biomarker expression, and a worse cognitive trajectory. Aβ positivity has clinical relevance in CAA and might represent either advanced CAA or additional Alzheimer’s disease neuropathological changes.
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Acknowledgments
S.W.S. receives funding from the Brain Research Program through the National Research Foundation of Korea (2016M3C7A1913844), the Korea Government (MSIP) through the National Research Foundation of Korea grant (2017R1A2B2005081), and the Research of Korea Centers for Disease Control and Prevention (2018-ER6203-01).
Funding
This research was funded by the Brain Research Program through the National Research Foundation of Korea (2016M3C7A1913844), the Korea Government (MSIP) through the National Research Foundation of Korea grant (2017R1A2B2005081), and the Research of Korea Centers for Disease Control and Prevention (2018-ER6203-01).
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Jang, H., Jang, Y.K., Kim, H.J. et al. Clinical significance of amyloid β positivity in patients with probable cerebral amyloid angiopathy markers. Eur J Nucl Med Mol Imaging 46, 1287–1298 (2019). https://doi.org/10.1007/s00259-019-04314-7
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DOI: https://doi.org/10.1007/s00259-019-04314-7