Clinical significance of amyloid β positivity in patients with probable cerebral amyloid angiopathy markers
We investigated the frequency and clinical significance of amyloid β (Aβ) positivity on PET in patients with cerebral amyloid angiopathy (CAA).
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.
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.
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.
KeywordsCerebral amyloid angiopathy Amyloid β Amyloid β PET
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).
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).
Compliance with ethical standards
Conflicts of interest
Role of the funder
The funders had no role in the design or conduct of the study; in the collection, management, analysis or interpretation of the data; in the preparation, review or approval of the manuscript; or in the decision to submit the manuscript for publication.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 22.McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–9.CrossRefGoogle Scholar
- 25.Kang Y, Na DL. Seoul Neuropsychological Screening Battery (SNSB). Incheon: Human Brain Research & Consulting Co; 2003.Google Scholar