Because we don't fully understand the pathology yet or the sequence of events in the pathophysiology, we may be intervening too late to see positive results.

– Edilio Borroni, PhD
Hoffman LaRoche, Basel, Switzerland

It may be that research is focusing on only 1 or 2 variables when Alzheimer's disease is a multimodal disease, and unless we look into all variables, which is not easy, we are missing the boat.

– Silvia Panitch, MD
Lakeview Integrative Medicine, Chicago, IL

I guess we don't understand yet what amyloid aggregation is really all about. Maybe now with imaging it will be easier, but it is still a question of timing and specificity. I hope that the research with familial Alzheimer's disease will help us understand the mechanisms of the disease because our working hypothesis could be wrong and that may be why we don't see results yet in clinical trials.

– Voyko Kavcic, PhD
Wayne State University, Detroit, MI

In patients with severe disease, there are caregiver burdens that make it more likely that patients will drop out of a trial and it is difficult to get sites to enroll patients with late-stage disease, who may be aggressive or aggravated with highly variable behavior.

– Brian Reynolds, PhD
ClinSearch Resources, Cary, NC

By using behavioral symptoms, it's hard to tell if we are late or early in the disease. Maybe when we have a reliable biomarker to accurately diagnose Alzheimer's disease, it will get easier. For example in diabetes, we use glucose levels to define the presence and subtypes of the disease. If we had a validated biomarker, we could better identify whether an agent is working or not.

– Harold Komiskey, PhD
Philadelphia College of Osteopathic Medicine, Suwanee, GA

So far, we have treated amyloid accumulation only after clinical symptoms appear and that may be too late. Newer trials that are treating amyloid accumulation earlier, before people have clinical symptoms, may give us better results.

– Ging-Yuek Robin Hsiung, MD, MHSc
University of British Columbia, Vancouver, Canada