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AMYLOID-RELATED IMAGING ABNORMALITIES AND OTHER MRI FINDINGS IN A COGNITIVELY UNIMPAIRED POPULATION WITH AND WITHOUT CEREBRAL AMYLOID

R. Yaari, K.C. Holdridge, J. Choi, M.C. Donohue, K. Kantarci, C.R. Jack Jr, S.M. Zuk, J.R. Sims, K.A. Johnson, P.S. Aisen, R.A. Sperling

BACKGROUND: Screening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies provide a unique opportunity to compare magnetic resonance imaging (MRI) findings such as amyloid-related imaging abnormalities (ARIA) in cognitively unimpaired elderly with and without elevated cerebral amyloid. OBJECTIVES: To compare screening MRI findings, such as ARIA, in the cognitively unimpaired potential participants of a clinical trial with and without elevated cerebral amyloid. DESIGN: Cross-sectional analysis of structural MRI findings in screening data from the A4 and LEARN studies. SETTING: The A4 Study is a multi-center international clinical trial. The LEARN Study is a multi center observational study in the United States. PARTICIPANTS: Clinically normal older adults (65-85 years) with elevated cerebral amyloid (Aβ+; n = 1250, A4) and without elevated cerebral amyloid (Aβ-; n = 538, LEARN). MEASUREMENTS: Participants underwent florbetapir positron emission tomography for Aβ+/- classification. A centrally read 3T MRI to assess for study eligibility was conducted on study qualified MRI scanners. RESULTS: No ARIA-effusions (ARIA-E) was detected on screening MRI in the Aβ+ or Aβ- cohorts. At least one ARIA-H (microhemorrhages [MCH] or superficial siderosis [SS]) was present in 18% of the Aβ+ cohort compared with 8% in Aβ- (P < 0.001). In the Aβ+ cohort, approximately 2% of screening MRIs demonstrated MCH ≥4 compared with 0% in Aβ-. The presence of two apolipoprotein E ε4 (APOEε4) alleles (vs no ε4 alleles) in the Aβ+ cohort increased the odds for presence of MCH (odds ratio [OR] = 2.03; 95% CI, 1.23 to 3.27, P = 0.004). Cortical infarctions (4% vs 0%) and subcortical infarctions (10% vs 1%) were observed at statistically significantly higher prevalence in the Aβ+ cohort compared with Aβ- (P < 0.001). Females showed reduced odds of MCH in the Aβ+ cohort by a factor of 0.63 (95% CI, 0.47 to 0.84, P = 0.002). CONCLUSIONS: ARIA-E is rare in cognitively unimpaired Aβ+ and Aβ- populations prior to anti-amyloid drug intervention. ARIA-H in Aβ+ was greater than in Aβ- populations.

CITATION:
R. Yaari ; K.C. Holdridge ; J. Choi ; M.C. Donohue ; K. Kantarci ; C.R. Jack Jr ; S.M. Zuk ; J.R. Sims ; K.A. Johnson ; P.S. Aisen ; R.A. Sperling ; for the A4 Study Team ; (2022): Amyloid-Related Imaging Abnormalities and Other MRI Findings in a Cognitively Unimpaired Population With and Without Cerebral Amyloid. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2022.56

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