The LEARN study a multicenter, observational study will that will evaluate the rate of cognitive change in approximately 500 clinically normal older individuals who "screen-fail" for the A4 trial on the basis of their screening PET imaging not demonstrating evidence of elevated amyloid accumulation (Aβ negative) but meet all other A4 study eligibility criteria. This study will leverage the A4 infrastructure and maximize the data acquired in screening a large number of well-characterized older adults for the A4 trial. The LEARN observational cohort will provide a critical comparison group for the A4 placebo arm, and future trials in preclinical AD. Although accumulating longitudinal data suggest that older individuals with elevated Aβ burden are at increased risk of cognitive decline, it is important to demonstrate a differential rate of clinical decline between Aβe ("Aβ elevated") and Aβne ("Aβ not elevated") individuals on a standardized set of clinical outcomes. Over 2000 well-characterized, highly motivated older volunteers will "screen fail" for the A4 trial. The LEARN study will follow 500 of these individuals, matched as closely as possible to the two treatment arms, in this observation cohort. The LEARN study may selectively recruit from a specific range of SUVr that fall below the threshold for "elevated amyloid" in order to support analyses of the relationship of baseline SUVr to subsequent cognitive change and amyloid accumulation. The observational cohort will be followed for 384 weeks with identical clinical/cognitive testing performed every 24 weeks, running parallel to the A4 treatment study and open label extension.
Study Type
OBSERVATIONAL
Enrollment
538
University of Alabama, Birmingham
Birmingham, Alabama, United States
Banner Alzheimer's Institute
Phoenix, Arizona, United States
Banner Sun Health Research Institute
Sun City, Arizona, United States
University of California, Irvine
Irvine, California, United States
University of Southern California
Los Angeles, California, United States
Change from Baseline of the ADCS Preclinical Alzheimer Cognitive Composite (ADCS-PACC) to Week 240
Time frame: 4.5 years
Change from Baseline in Cognitive Function Index (CFI) to Week 240
Time frame: 4.5 years
Change from Baseline in Mean Composite Summary Uptake Value Ratio (SUVr) to Week 240
Time frame: 4.5 years
Change from Baseline in Cerebral Spinal Fluid (CSF) Tau Biomarkers to Week 240
Time frame: 4.5 years
Change from Baseline of Cerebrospinal Fluid (CSF) Concentrations of Amyloid Beta (Abeta) to Week 240
Time frame: 4.5 years
Change from Baseline of Volumetric Magnetic Resonance Imaging (vMRI) to Week 240
Time frame: 4.5 years
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University of California, Los Angeles
Los Angeles, California, United States
VA Palo Alto HSC / Stanford School of Medicine
Palo Alto, California, United States
Yale University School of Medicine
New Haven, Connecticut, United States
Georgetown University
Washington D.C., District of Columbia, United States
Howard University
Washington D.C., District of Columbia, United States
...and 30 more locations