B. Vellas*, L.J. fitten**

Centre Alzheimer, département de Médecine Interne et Gérontologie Clinique, CHU Purpan Casselardit, 31300 Toulouse, France. **UCLA, Los Angeles USA.

It seems that 2002 brings a relative quiet in the fight against Alzheimer's disease (AD). It is a transitional period that should be used to consolidate the foundations necessary to the development of new advances (1).
The causes of the disease are still largely unknown in spite of the spectacular progress that has been achieved with regard to cellular and molecular pathophysiologic mechanisms recently described.
Currently we have at our disposal symptomatic treatments such as donepezil, galantamine, and rivastigmine, whose usefulness has been confirmed in numerous recent trials following several years of use. But the development of preventive, protective or curative treatments has encountered barriers and setbacks as evidenced by the recent discontinuation of the anti-amyloid vaccination trial. In a similar manner, the promise held out by secretase inhibitors and growth factors appears delayed, while the production of anti-amyloid antibodies offers a new hope, albeit a distant one at this time.
The clinical concept of Minimal Cognitive Impairment (MCI) awaits further clarification. Several important clinical trials attempting to delay the conversion of MCI into Alzheimer's disease are currently underway. These trials will contribute to our better understanding of the nature of MCI per se, in addition to evidencing the impact of several treatments (donepezil, galantamine, rivastigmine, cox-2 inhibitors, vitamine E, nootrtopic agents) on the onset of AD. Beside it's linkage to a pre-Alzheimer state, as described in memory clinics serving the cognitively impaired, MCI may also be linked to age-related cognitive decline of other causes such as cardio- and cerebrovascular disease, diabetes, general frailty and sensory deficits found commonly in the elderly population. The development of symptomatic treatments for these other potential causes of MCI seems equally opportune.
The modern era of AD treatment, which is now over 10 years old, witnessed an initial interest in the early stages of the illness. Most recently, however, concern has shifted more toward the advanced phases of the disease. Catalysts for this are several and include the recent encouraging results obtained by Feldman and his group using cholinesterase inhibitors in the treatment of severely demented subjects, and the approval given memantine by the European Commission for use in severe dementia. Another catalyst derives from the economics of the disease. Whereas a patient with MCI or very mild dementia may be seen two or three times a year in a follow-up clinic, one with severe disease will require multiple consultations and hospitalizations or institutionalization. In the United States, for example, the direct and indirect costs of treating and managing severe dementia are two to three-fold what they are for managing mild AD, and are even greater when compared to the cost of managing MCI. Finally, through recent research, we have been made more aware of the impact of severe disease on the quality of life of patients and caregivers alike, as well as the cost, in terms of personal suffering, that the illness exacts from its victims and their relatives.
Alzheimer prevention, nevertheless, should begin before the MCI stage, either at the level of the population at large or more specifically in populations of subjects older than 75 years who present with a cognitive complaint in the primary care sector and are thus at higher risk of developing the disease. Such is the rationale in the European pilot study of Egb761 and placebo on a population of 2800 subjects over the age of 75 to be followed for five years. Other similar studies on Egb761, estrogens and anti-inflammatories are currently under way in the United States.
The year 2002 is, therefore, a year of transition between the major advances of the last few years and the greater ones surely to come. This year should serve to better organize and realize international cooperation in the fight against AD. Networks of clinical research are currently being organized in Germany, France and Great Britain. Organizational progress is equally occurring at the European level with the creation of the European Alzheimer's Disease Consortium which met on April 3, 2002 in Geneva, Switzerland during a joint session with the American Alzheimer Disease Cooperative Study Group. Large cooperative studies on both sides of the Atlantic are expected. These will surely enhance the effectiveness of our fight against AD.

(1) Research and Practice in Alzheimer's Disease 2002. Serdi (Paris); Springer (New York).