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.

Déclaration de conflit d'intérêts

RY, KCH and JRS are full-time employees and minor shareholders of Eli Lilly and Company. RY has received funds from Eli Lilly and Company for attending meetings and or/travel. JC has received research funding from NIH and Janssen. MCD has received research funding from NIH and Janssen; consulting fees from Roche; has participated on a Data Safety Monitoring Board or Advisory Board for the University of California, San Diego and has a spouse who is a full-time employee of Janssen. KK has received research funding from NIH and ADDF; consulting fees from Biogen; support for attending meetings and/or travel from Alzheimer’s Association; has participated on a Data Safety Monitoring Board or Advisory Board for Takeda; has a leadership or fiduciary role in other board, society, committee or advocacy group for Alzheimer’s Association (unpaid) and NIH and has received research materials from Avid Radiopharmaceuticals. CRJ Jr. has received research funding from NIH, the GHR Foundation, and the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic; participated on a Data Safety Monitoring Board or Advisory Board for Roche (unpaid); has served as a speaker for Eisai, and consulted for Biogen, but he receives no personal compensation from any commercial entity. SMZ has no conflicts of interest to declare. KAJ has received research funding from NIH; consulting fees from Novartis and has participated on a Data Safety Monitoring Board or Advisory Board for Cerveau (unpaid). PSA has received research funding from NIH, Alzheimer’s Association and Eli Lilly and Company for the A4 Trial; research agreements with Janssen, Eli Lilly and Company and Eisai; research funding from NIA, the Alzheimer’s Association and FNIH and consulting fees from Biogen, Roche, Merck, Abbvie, Immunobrain Checkpoint, Rainbow Medical and Shionogi. RAS has received research funding from NIH, Alzheimer’s Association and Eli Lilly and Company for the current study; research funding from Eli Lilly and Company, Janssen, NIA, Alzheimer’s Association; consulting fees from AC Immune, Acumen, Alnylam, Cytox, Janssen, JOMDD, Nervgen, Neuraly, Neurocentria, Oligomerix, Prothema, Renew, Shionogi, Vigil Neuroscience, Ionis, Biogen, Eisai and Roche; honoraria for Harvard HUBWeek Panel (2018), Japan JSNM (2018), Marc Diamond UT Southwestern Symposium (2019), University of Chicago DOM Weekly Grand Rounds Seminar Series (2020), Virtual Rhode Island IDeA Symposium (2020) and Virtual IMPACT-AD Course (2020) and support for attending meetings and/or travel from Duke Lectureship (2018), Alzheimer Research Roundtable (2018), ADPD Symposium (2019), University of Tokyo Roundtable (2019), Biogen: ARIA State of the Art meeting (2019), University of Pittsburgh Distinguished Scientist Lecture (2019), University of Cincinnati Lurie Lecture (2019), UC Irvine Distinguished Lecture on the Brain (2020), Virtual Rhode Island IDeA Symposium (2020), Adler Foundation Symposium San Diego (2020), UC Irvine Lecture (2020)