ALPHA 2 AGONIST PLUS A CHOLINESTERASE INHIBITOR IN ALZHEIMERS DISEASE

AD(阿尔茨海默病)的类胆碱疗法只遇到了 有限的成功。尽管有一小部分患者有适度的 胆碱酯酶抑制剂的临床显著改善，这 很难像L-多巴那样有效地治疗帕金森氏症或 甚至还有治疗精神分裂症的氟哌啶醇。显然，一个纯粹的问题是 AD心理治疗的胆碱能途径是AD不是 只是胆碱能缺乏症。阿尔茨海默病患者去甲肾上腺素缺乏的证据 来自研究表明LC神经元的损失，大多数 在有最大神经皮质斑块形成的受试者中很明显 并与痴呆症的严重程度相关。此外，去甲肾上腺素 大脑的几个区域的含量减少了，这种减少是 与智力退化的更严重程度有关， 阿尔茨海默病患者。因此，有令人信服的数据表明， 严格影响本病的症状和疗效 胆碱能途径。尽管开发了安全、更容易使用的 胆碱酯酶抑制剂，如雅理生，只治疗了一部分 患者的影响不大。对第三阶段数据的评估 Aricept的试验表明，62.3%的大量非 因此，对纯胆碱能治疗的应答者 因此，有必要开发替代方法。动物研究 提供令人信服的证据来支持这种替代办法， 尤其是能增强胆碱能和去甲肾上腺素能的药物 活动。因此，我们的总体目标是确定联合- 给予选择性α-2去甲肾上腺素受体激动剂， 使用乙酰胆碱酯酶抑制剂Aricept的金刚烷 临床上治疗阿尔茨海默病认知症状更有效 比单独使用Aricept更有效。我们建议治疗公元72年 受试者在14周的双盲、安慰剂对照的平行设计中， 方案，另加3周的安慰剂洗脱阶段。研究对象将 在认知和全局的衡量标准上相结合 功能正常。

Cholinomimetic therapies for AD (Alzheimer's disease) have met with only limited success. Although a sub-group of patients have a modest, albeit clinically significant improvement with cholinesterase inhibitors, this is hardly as a robust a treatment as L-dopa for Parkinson's disease or even haloperidol for schizophrenia. Clearly, one problem with a purely cholinergic approach to the psychotherapeutics of AD is that AD is not simply a cholinergic deficit. Evidence for a noradrenergic deficit in AD derives from studies which demonstrate a loss of LC neurons, most evident among subjects with the greatest neurocortical plaque formation and is correlated with severity of dementia. Furthermore, norepinephrine content in several brain areas is reduced and this reduction is associated with greater severity of intellectual deterioration among patients with AD. Thus, there are compelling data to indicate probably influence the symptoms of the disease and the efficacy of a strictly cholinergic approach. Despite the development of safe, easier to use cholinesterase inhibitors, such as Aricept, only a portion of treated patients have a modest effect. Evaluation of the data from Phase III trials of Aricept shows that 62.3% of substantial numbers of non- responders to a purely cholinergic approach to treatment therefore necessitate the need to develop alternative approaches. Animal studies provide convincing evidence to support such an alternative approach, particularly one which enhances both cholinergic and noradrenergic activity. Therefore, our overall aim to determine whether the co- administration of the selective alpha-2 noradrenergic receptor agonist, guanfacine, with the acetylcholinesterase inhibitor, Aricept, is clinically more effective in treating cognitive symptoms of Alzheimer's disease than administration of Aricept alone. We propose to treat 72 AD subjects in a 14 week double blind, placebo controlled, parallel design, protocol, with an additional 3 week placebo washout phase. Subjects will be treated with a combination on measures of cognitive and global functioning.