Abstract
Several hundred clinical trials of initially promising drugs have failed to produce meaningful clinical improvement of Alzheimer's disease (AD), which is probably because there are at least 25 biochemical pathways known to be aberrant that underpin the disease, and unless there is a single drug that addresses all or most of them, even promising drugs if given alone are unlikely to succeed. Because so many pathways are potentially at fault, it is quite possible that no treatment might succeed. However, because amnestic mild cognitive impairment (aMCI) often precedes AD and, assuming that those with aMCI who progress to AD commence with insufficient risk factors for AD but accrue them later, then it is likely that fewer pathways need addressing in aMCI than in AD to either prevent progression of aMCI to AD or effect its reversion. Published reports show that eight drugs, that is, dantrolene, erythropoietin, lithium, memantine, minocycline, piracetam, riluzole, and silymarin, address many of the pathways underlying MCI and AD. Among those eight drugs, combinations between either two or three of them have combined nonoverlapping actions that benefit enough of the approximately 25 pathways at fault so that their convergent efficacy has the potential to prevent aMCI from progressing to AD. The combinations should be subjected to a clinical trial in persons with aMCI to establish their safety and efficacy.