Antioxidant clinical trials in mild cognitive impairment and Alzheimer's disease - challenges and perspectives.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder representing the most common form of dementia and the most feared highly disabling age-related condition of our time. Hallmarks of AD include a dramatically increasing number of cases due to prospected demographics and the absence of a cure. AD is incurable as it escapes the formula "one disease, one mechanism, one drug". AD has a multifaceted pathophysiology only in part uncovered. Even the proven chronological primacy of free radical-related damage in AD-related neurodegeneration has not yield successful oxidative stress - lowering trial designs. As a consequence, clinical trials of antioxidants in AD have brought largely negative conclusions. The aims of this review are to discuss 1. rationale for antioxidant trials, 2. reasons for failure of antioxidants in AD therapy, 3. potential preventive benefits of natural nutrition against AD onset and 4. the enormous relevance of detecting and treating AD risk factors as long as possible prior to AD manifestation.