Hollister L, Gruber N
Department of Psychiatry and Behavioural Sciences, University of Texas Houston Health Science Center, USA.
Drugs Aging. 1996 Jan;8(1):47-55. doi: 10.2165/00002512-199608010-00008.
Alzheimer's disease is a devastating illness that will become more common as the population ages. Although clinical diagnosis of the illness is not certain without histological examination of the brain, and misdiagnosis may occur, broad working criteria to help diagnose the likely presence of Alzheimer's disease are available. Thoughtful clinical evaluation improves diagnostic accuracy, and appropriately diagnosed patients are critical for involvement in research into new antidementia agents. Essential to the discovery of new drugs is careful measurement of illness response. A variety of scales--some aimed at patients, others at their caregivers, and yet others for clinicians--assess Alzheimer's disease severity, progression, symptom response, and quality of life. Of note, patient response is not the only measurement of treatment benefit today. Growing interest is also being placed on tracking the possible amelioration of caregiver 'burden'. This burden refers to the psychological, physical, and material costs of providing care for an Alzheimer's patient over long periods of time. A number of scales and questionnaires have been developed and are occasionally used. Many drugs have been tried in Alzheimer's disease, but very few have produced any benefit, and this is often modest. Ergoloid mesylates, initially thought to be effective, are now considered of little value. The cholinomimetic drugs, especially the acetylcholinesterase inhibitor tacrine, have provided a very modest benefit, slowing the progression of the illness for a number of months. No cognitive improvement has been noted with the various nootropic agents such as piracetam. Early studies with levacecarnine (acetyl-L-carnitine), a substance that facilitates the use of fatty acids, memantidine, the dimethyl derivative of amantidine, and the calcium channel blocker nimodipine, have shown some promise, but require larger, more rigorous studies. As mentioned above, documenting effects in individual patients is crucial; examining for potential benefit to caregivers is a growing part of research design. Current treatment efforts will become more sophisticated as a deeper understanding of the neurobiology of Alzheimer's disease develops. For the immediate future, the goal is not cure but slowing of the disease process. Achieving this limited goal would have a substantial impact on the financial and human costs of the illness.
阿尔茨海默病是一种毁灭性的疾病,随着人口老龄化,它将变得更加常见。虽然没有对大脑进行组织学检查就无法确定该病的临床诊断,而且可能会发生误诊,但已有广泛的工作标准来帮助诊断阿尔茨海默病的可能存在情况。细致的临床评估可提高诊断准确性,而诊断恰当的患者对于参与新型抗痴呆药物的研究至关重要。发现新药的关键在于仔细衡量疾病反应。多种量表——有些针对患者,有些针对其照护者,还有些供临床医生使用——可评估阿尔茨海默病的严重程度、进展情况、症状反应及生活质量。值得注意的是,患者反应并非如今衡量治疗益处的唯一指标。人们也越来越关注追踪照护者负担可能得到的改善情况。这种负担指的是长期照料阿尔茨海默病患者所产生的心理、身体和物质成本。现已开发出一些量表和问卷,偶尔会使用。许多药物都曾在阿尔茨海默病治疗中进行试验,但很少有药物产生任何益处,而且这种益处往往不大。最初认为有效的甲磺酸双氢麦角毒碱,如今被认为价值不大。拟胆碱药物,尤其是乙酰胆碱酯酶抑制剂他克林,带来了非常有限的益处,可使疾病进展延缓数月。诸如吡拉西坦等各种促智药未显示出认知改善效果。早期对左卡尼汀(乙酰 - L - 肉碱)、金刚烷胺的二甲基衍生物美金刚以及钙通道阻滞剂尼莫地平的研究已显示出一些希望,但需要更大规模、更严谨的研究。如上所述,记录个体患者的疗效至关重要;考察对照护者的潜在益处正日益成为研究设计的一部分。随着对阿尔茨海默病神经生物学的深入理解,当前的治疗努力将变得更加精细。在不久的将来,目标不是治愈该病,而是减缓疾病进程。实现这一有限目标将对该病的经济和人力成本产生重大影响。