Mixed pathologies and neural reserve: Implications of complexity for Alzheimer disease drug discovery

Alzheimer disease (AD) is among the most common causes of dementia worldwide. Approved medications for the symptoms of AD dementia have marginal benefit, and no new therapies have been approved in more than a dozen years. There are no approved treatments for the prevention of AD dementia. The lack of robust therapeutics comes despite intense efforts by the public and private research community to discover them. There have been about 450 failed clinical trials on www.clinicaltrials.gov since the last drug approval by the Food and Drug Administration With changing demographics forecasting a marked increase in the number of persons with AD and other dementias worldwide, and with extraordinary attendant costs of care and toll on individuals and families, countries around the globe are investing substantial capital to stimulate basic and translational research in the hopes of developing new therapeutics for the treatment and prevention of AD and other dementia.