Alzheimers disease clinical trials: past failures and future opportunities

Author(s): Roy Yaari & Ann Hake

Over a decade has elapsed since the US FDA has approved a medication for Alzheimer’s disease (AD) despite clinical trials of numerous agents over a wide array of mechanisms including neurotransmitter modulation and disease modifying therapy targeting amyloid and tau. The failures of clinical trials in AD may be due to inadequate understanding of mechanisms of action and/or poor target engagement; however, other factors could include inadequate study design, stage of AD along the continuum studied, inclusion of participants without Alzheimer’s pathology into clinical trials and limited power of endpoint measures. Future studies will need to carefully assess these possible shortcomings in design of upcoming trials, especially as the field moves toward studies of disease modifying agents (as opposed to symptomatic treatment) of AD and to patients that are very early in the disease spectrum.