Jané F
Hospital de la Santa Creu i Sant Pau, Departamento de Farmacología y Psiquiatría, Universidad Autónoma de Barcelona.
Rev Neurol. 1995 Jan-Feb;23(119):103-7.
Alzheimer's disease (AD) is the commonest cause of dementia. Although its ethology is unknown, there is increasing evidence in support of the view that an abnormal degradation of the amyloid precursor protein (APP), perhaps influenced by a number of genetic, tisular or environmental factors, may be the primary cause of the many biochemical and morphological disorders that exist in the associative areas of the brain of these patients. Histopathologically it can be shown by the presence of extracellular senile plaques, intraneuronal fibrilar tangles and neuronal loss. There is no specific pharmacological treatment at present to prevent the disease or its development, in spite of the numerous and diverse drugs studied. Many of these studies are methodologically inadequate. The attempt of activating the cholinergic system has deserved special attention. A reversible inhibitor of acetylcholinesterase, tacrine, has been approved in the United States and other countries for the symptomatic treatment of mild to moderate AD, but its use still arises many questions. Different drug and non drug related interventions may be of great value in the care of these patients, and may influence the specific pharmacological treatments. The complexity and heterogeneity of AD and the multiple factors which may take part in its evolution make it necessary to place special attention on the methodological aspects of the clinical trials with new drugs for the treatment of this disease.
阿尔茨海默病(AD)是痴呆最常见的病因。尽管其病因不明,但越来越多的证据支持这样一种观点,即淀粉样前体蛋白(APP)的异常降解,可能受多种遗传、组织或环境因素影响,可能是这些患者大脑联合区域存在的许多生化和形态学紊乱的主要原因。在组织病理学上,可通过细胞外老年斑、神经元内纤维缠结和神经元丢失来证实。尽管研究了众多不同的药物,但目前尚无预防该病或其发展的特异性药物治疗方法。其中许多研究在方法上并不充分。激活胆碱能系统的尝试值得特别关注。一种乙酰胆碱酯酶可逆抑制剂他克林,已在美国和其他国家被批准用于轻至中度AD的对症治疗,但其使用仍存在许多问题。不同的药物和非药物相关干预措施在这些患者的护理中可能具有重要价值,并且可能影响特异性药物治疗。AD的复杂性和异质性以及可能参与其演变的多种因素,使得有必要特别关注用于治疗该疾病的新药临床试验的方法学方面。