@article{uoadl:3498702,
    volume = "8",
    number = "1",
    journal = "JAMA NETWORK OPEN",
    keywords = "Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Apolipoprotein E4; Biomarkers; Cerebral Hemorrhage; Cross-Sectional Studies; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Plaque, Amyloid; Positron-Emission Tomography; amino acid; amyloid; amyloid beta protein; amyloid beta protein[1-42]; apolipoprotein E4; biological marker; amyloid beta protein; apolipoprotein E4; biological marker; age; aged; allele; Alzheimer disease; Article; brain hemorrhage; cerebrospinal fluid; cohort analysis; controlled study; cross-sectional study; female; homozygote; human; major clinical study; male; mild cognitive impairment; neuropathology; nuclear magnetic resonance imaging; outcome assessment; positron emission tomography; prevalence; risk factor; very elderly; Alzheimer disease; amyloid plaque; epidemiology; genetics; metabolism; middle aged; pathology; procedures",
    BIBTEX_ENTRY = "article",
    year = "2025",
    author = "Oomens, Julie E. and Van Gils, Veerle and Vos, Stephanie J. B. and Freeze, Whitney M. and Maserejian, Nancy N. and Curiale, Gioacchino and Gillis, Cai and Boada, Mercè and Van Der Flier, Wiesje M. and Hort, Jakub and Johnson, Sterling C. and Lleó, Alberto and Ramakers, Inez H. and Rodrigue, Karen M. and Sánchez-Juan, Pascual and Sarazin, Marie and Scarmeas, Nikolaos and Zetterberg, Henrik and Alcolea, Daniel and Barkhof, Frederik and Blennow, Kaj and Bottlaender, Michel and Den Braber, Anouk and Cerman, Jiří and Drake-Perez, Marta and Fortea, Juan and Handels, Ron and Ingala, Silvia and Jiménez-Bonilla, Julio F. and Karavasilis, Stratos and Lagarde, Julien and Legdeur, Nienke and Lorenzini, Luigi and Marquié, Marta and Moonen, Justine E. F. and Olivieri, Pauline and Orellana, Adelina and Ossenkoppele, Rik and Rivera-Rivera, Leonardo A. and Rodríguez-Rodriguez, Eloy and Ruiz Laza, Agustín and Teunissen, Charlotte E. and Tijms, Betty M. and Velonakis, Giorgos and Verhey, Frans R. J. and Visser, Pieter Jelle and Jansen, Willemijn J.",
    abstract = "Importance: Baseline cerebral microbleeds (CMBs) and APOE ϵ4 allele copy number are important risk factors for amyloid-related imaging abnormalities in patients with Alzheimer disease (AD) receiving therapies to lower amyloid-β plaque levels. Objective: To provide prevalence estimates of any, no more than 4, or fewer than 2 CMBs in association with amyloid status, APOE ϵ4 copy number, and age. Design, Setting, and Participants: This cross-sectional study used data included in the Amyloid Biomarker Study data pooling initiative (January 1, 2012, to the present [data collection is ongoing]). Data from 15 research and memory clinic studies were pooled and harmonized. Participants included individuals for whom data on age, cognitive status, amyloid status, and presence of CMBs were available. Data were analyzed from October 22, 2023, to April 26, 2024. Main Outcomes and Measures: The main outcomes were age, cognitive status, amyloid status and presence, location, and number of CMBs. Presence of amyloid pathology was determined based on 42 amino acid-long form of amyloid-β peptide (Aβ42) levels in cerebrospinal fluid or on amyloid-positron emission tomography. Presence and, in a subset, location (lobar vs deep) and number of CMBs were determined on magnetic resonance imaging (locally with visual rating). Results: Among 4080 participants included in the analysis, the mean (SD) age was 66.5 (8.9) years, and 2241 (54.9%) were female. A total of 2973 participants had no cognitive impairment (cognitive unimpairment [CU]), and 1107 had mild cognitive impairment (MCI) or AD dementia (ADD). One thousand five hundred and thirteen participants (37.1%) had amyloid pathology, 1368 of 3599 (38.0%) with data available were APOE ϵ4 carriers, and 648 (15.9%) had CMBs. In the CU group, amyloid pathology and APOE ϵ4 copy number were not associated with presence of any, no more than 4, or fewer than 2 CMBs but were associated with increased odds of lobar CMBs (odds ratio [OR] for amyloid, 1.42 [95% CI, 1.20-1.69], P <.001; OR for 2 vs 0 alleles, 1.81 [95% CI, 1.19-2.74], P =.006; OR for 1 vs 0 alleles, 1.10 [95% CI, 0.83-1.46], P =.49; and OR for 2 vs 1 allele, 1.64 [95% CI, 0.90-2.97], P =.11; overall P =.02). In the MCI-ADD group, amyloid pathology was associated with presence of any CMBs (OR, 1.51 [95% CI, 1.17-1.96], P =.002), no more than 4 CMBs (OR, 1.44 [95% CI, 1.18-1.82], P =.002), and fewer than 2 CMBs (OR 1.34 [95% CI, 1.03-1.74], P =.03) but not lobar CMBs. APOE ϵ4 copy number was associated with presence of any (OR for 2 vs 0 alleles, 1.72 [95% CI, 0.88-3.35], P =.11; OR for 1 vs 0 alleles, 0.78 [95% CI, 0.59-1.04], P =.09; and OR for 2 vs 1 allele, 2.20 [95% CI, 1.32-3.67], P =.002; overall P <.001) and no more than 4 CMBs (OR for 2 vs 0 alleles, 1.31 [95% CI, 0.64-2.68], P =.45; OR for 1 vs 0 alleles, 0.75 [95% CI, 0.54-1.04], P =.08; and OR for 2 vs 1 allele, 1.76 [95% CI, 0.97-3.19], P =.06; overall P =.03) but not with fewer than 2 or lobar CMBs. Prevalence estimates of CMBs ranged from 6% at 50 years of age in a non-APOE ϵ4 allele carrier with no amyloid pathology and no cognitive impairment to 52% at 90 years of age in an APOE ϵ4 homozygote carrier with amyloid pathology and cognitive impairment. Conclusions and Relevance: In this cross-sectional study of 4080 participants, prevalence estimates of CMBs were associated with amyloid status, APOE ϵ4 copy number, and age. CMB prevalence estimates may help inform safety evaluations for antiamyloid clinical trials.  ©2025 Oomens JE et al.",
    title = "Cerebral Microbleeds and Amyloid Pathology Estimates From the Amyloid Biomarker Study",
    doi = "10.1001/JAMANETWORKOPEN.2024.55571"
}