Alzheimer's Association Gives Largest-Ever Research Grant

Pauline Anderson

March 11, 2014

The Alzheimer's Association has announced the largest ever research grant — $8 million over 4 years — to support the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study, which will follow participants who are free of elevated amyloid in the brain at baseline. The study's aim is to determine what biological changes are related to cognitive decline, including possible later amyloid accumulation or increases in tau levels.

The first of its kind, LEARN will be a companion study to the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, which is investigating whether antiamyloid treatments block build-up of amyloid and slow or prevent AD in asymptomatic individuals with no known genetic risk mutations but with some amyloid in their brain.

The goal of both of these "ground-breaking" projects is to "jump-start" the development of new detection methods, treatment, and prevention strategies for AD, Maria Carrillo, PhD, the Association's vice president of medical and scientific relations, said in a press release.

Perplexing Variations

The goal of the LEARN subcomponent of A4 is to help shed light on perplexing individual variations in disease progression.

"Although research suggests that older people with elevated amyloid-β build-up are at increased risk of cognitive decline, there is a critical need to demonstrate a differential rate of clinical decline between amyloid-positive and amyloid-negative individuals on a standardized set of clinical outcomes," said Reisa Sperling, MD, professor, neurology, Harvard Medical School, Boston, Massachusetts, and co–principal investigator for the A4 trial, who received the grant.

"LEARN will attempt to confirm the important expectation that the cognitive outcomes used in the A4 study's treatment arms do, in fact, manifest amyloid-related cognitive decline at a faster rate. We will also learn a great deal about the nonamyloid drivers of cognitive decline to facilitate future trials aimed at other age-related brain processes."

The A4 prevention study will screen 3000 older individuals with positron emission tomography (PET) amyloid imaging to identify 1000 people with elevated levels of amyloid-β. This group will be randomly assigned into 2 groups: active treatment or placebo. The A4 study will incorporate novel cognitive measures, including computerized memory tests and self-assessment of memory function using an iPad, that might detect the earliest subtle changes.

Five hundred of the 2000 persons not randomly assigned in A4 will be matched to the 2 treatment groups and followed in the natural history LEARN observational cohort. The LEARN study will follow participants for 36 months, with clinical and cognitive testing every 6 months running parallel to the A4 treatment study.

In making the announcement, the Alzheimer's Association said that part of the grant will fund the use of a new, as-yet-unnamed "cutting-edge" tau imaging agent for PET scans in both the A4 and LEARN studies. This pilot substudy will include 150 participants: 100 from the A4 study and 50 from the LEARN study.

This study aims in part to clarify the role of tau in tracking progression toward AD dementia. In particular, study investigators hope to determine whether tau is suitable as a biological marker of disease progression from the preclinical to the early symptomatic stages of AD, and to investigate whether the build-up of tau is altered in response to antiamyloid treatments.


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