Negative argument for debate with V. O. Emery for J Neural Transmission

Abstract

Alzheimer’s disease (AD) represents a major public health challenge. It is the most common cause of dementia, the worldwide prevalence of which will double every 20 years in the foreseeable future. It would be good if it were possible to treat AD early to diminish its impact, but current evidence does not support early intervention. Vitamin E was no more effective than placebo in a study of vitamin E and donepezil against placebo in mild cognitive impairment (MCI). Vitamin E is associated with a higher rate of haemorrhagic events than is placebo. Neither donepezil nor galantamine has been shown to be helpful in retarding progression from MCI to AD. Gingko biloba was ineffective in delaying the onset of AD in a large prospective trial involving over 6,000 participants. Gamma secretase inhibitors have not yet been shown to retard the progression of AD and they seem to have a high incidence of adverse effects, especially rashes. Antibody therapy has not yet been shown to be helpful in the treatment of established AD, let alone its prevention. Metalloproteinase modifiers such as PBT2 may be useful AD therapies, but current evidence gives no support to their immediate use in pre-symptomatic AD. No evidence can yet be adduced to support the use of antibody therapies in MCI or early AD. Thus, it is clear that the early treatment of AD cannot be justified as yet, no matter how desirable this goal may be. Treatment of established AD with cholinesterase inhibitors and memantine, coupled with referral of interested patients to evaluative drug trials, is the best we can do at present.