Alzheimer's Disease: a Pharmacological Challenge.

The description of the symptoms and progression (Alzheimer. 1907) of the disease discussed in the present review has maintained, even after nearly a century, all its frightening power. Alzheimer’s disease (AD) is one of the various forms of age-correlated pathological deterioration of brain functions, collectively designated senile dementia (SD) (Cacabelos, 1989a; Wisniewski, 1989), bearing in mind that AD also occurs at ages for which the definition of presenile dementia (PSD) is more appropriate. A typical feature of the disease is its apparently harmless beginning, so much similar to other, less worrying cognition disturbances, once indicated as “organic brain syndrome” and now undergoing reclassification as “age-associated memory impairment” (AAMI). AAMI is commonly experi enced as a benign form of senescent forgetfulness, a condition where patients suffer from mild memory loss and some correlated psychologic and behavioural difficulties. While this situation, affecting many people beyond the age of 50, is susceptible of amelioration under external stimulation as well as pharmacological treatment, AD has characteristic downhill progression, in which, from the early signs of memory loss. the patients rapidly develop an increasing number of neurological and psychological svmptoms. Besides worsening memory loss, AD-affected people experience alterations in their motor abilities, and increasingly dramatic modifications of their presymptomatic persona, with progressive disorientation and inability to care for themselves. In the late phases of the disease, the AD victims are bedridden, doubly incontinent and severelv disturbed. with epileptic and/or myoclonic attacks. Death occurs as a consequence of pneurnonic or urinary tract infections, an average of 5—8 years after the first symptoms have been reported. We believe that everyone involved in brain sciences should do his or her best to try to tackle and stop the spreading of this illness. In fact, the social impact of AD, which is already significant in industrialized countries, is bound to become even larger in the future with the recognized trends in world population development. A few figures can help us grasp the magnitude of the problem. First of all, we must look to the proportion of elderly people in the population. In the fifties the worldwide population over 60 was about 214 million, but this number is expected to increase up to a staggering one billion by the year 2025. In terms of percentage, official data issued in 1988 indicated that people over 60 comprised about 9% of the world’s population in 1985, but the figure will grow to 15% by 2015. Owing to the different rates of growth, it is thought that AD and related diseases (also referred to as senile dementia of Alzheimer’s type, SDAT) will weight more in industrialized countries. For a number of reasons, including better conditions, lifestyle, health assistance and so on, Europe, USA, Japan, Australia and Russia (before the economic crisis) are areas in which the population is becoming older, while it will remain younger in Africa, South America and Asia. From this it follows that the incidence of SD will be higher in the former countries. Several authors state that the current incidence of SD in people over 65 ranks 5%, reaching 25% in people aged more than 85; more than 50% of these patients suffer from AD. Owing to such figures, it is not surprising to find that the total number of people already affected by AD in the USA adds up to 1.5—2 miflion people (or up to 4 million according to other authors). Likewise, it is not surprising to find that, with a number of ca 216000 new cases and ca 100000 victims per year, AD ranks fourth as a major cause of death, after heart disease, cancer and stroke (Wurtman, 1985; Muller, 1989; Porsolt, 1989; Smith, 1989; Rocca et aL, 1990; Hardy and Allsop, 1991; Blass and Khachaturian, 1992; Lehmann, 1992a). In terms of money, the cost of AD in the USA alone during the mid-eighties was ca 25 billion dollars per year, but according to recent reports (Lehmann, 1992a) the figure has already climbed to ca 55 billions. This makes AD one of the top ten most expensive diseases, both in terms of direct health care and in terms of social costs. Facing AD is therefore a matter of critical importance, and we can understand why much money and energy are being invested in attempts to elucidate the pathogenesis and, above all, in efforts to discover therapeutic solutions