Amyloid-Related Imaging Abnormalities and Other MRI Findings in a Cognitively Unimpaired Population With and Without Cerebral Amyloid

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.