Pharmaceutical companies and the NIH have invested heavily in a variety of 
potential disease-modifying therapies for Alzheimer's disease (AD) but 
unfortunately all double-blind placebo-controlled Phase III studies of these 
drugs have failed to show statistically significant results supporting their 
clinical efficacy on cognitive measures. These negative results are surprising 
as most of these medications have the capability to impact the biomarkers which 
are associated with progression of Alzheimer's disease. Areas covered: This 
contradiction prompted us to review all study phases of Intravenous 
Immunoglobulin (IVIG), Bapineuzumab, Solanezumab, Avagacestat and Dimebolin to 
shed more light on these recent failures. We critically analyzed these studies, 
recommending seven lessons from these failures which should not be overlooked. 
Expert commentary: We suggest a new methodology for future treatment research in 
Alzheimer's disease considering early intervention with more focus on cognitive 
decline as a screening tool, more sophisticated exclusion criteria with more 
reliance on biomarkers, stratification of subjects based on the rate of 
cognitive decline aiming less heterogeneity, and a longer study duration with 
periodic assessment of cognition and activities of daily living during the study 
and also after a washout period.