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

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.

• Authors: Hyemin Jang, Young Kyoung Jang, Hee Jin Kim, David John Werring, Jin San Lee, Yeong Sim Choe, Seongbeom Park, Juyeon Lee, Ko Woon Kim, Yeshin Kim, Soo Hyun Cho, Si Eun Kim, Seung Joo Kim, Andreas Charidimou, Duk L Na, Sang Won Seo
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 46 Issue 6 Pg. 1287-1298 (Jun 2019) ISSN: 1619-7089 [Electronic] Germany
• PMID: 30937462 (Publication Type: Journal Article)

Chemical References

• Amyloid beta-Peptides
• ApoE protein, human
• Apolipoproteins E
• Biomarkers

Topics

• Aged
• Aged, 80 and over
• Amyloid beta-Peptides (genetics)
• Apolipoproteins E (genetics)
• Biomarkers (metabolism)
• Cerebral Amyloid Angiopathy (diagnostic imaging)
• Cerebral Hemorrhage (diagnostic imaging)
• Cognition
• Cognition Disorders (diagnostic imaging)
• Female
• Genotype
• Humans
• Image Processing, Computer-Assisted
• Linear Models
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Neuropsychological Tests
• Positron-Emission Tomography
• Prospective Studies
• White Matter (diagnostic imaging)