Tariot Pierre N
Memory Disorders Center, Banner Alzheimer's Disease Institute, Phoenix, AZ 85006, USA.
J Clin Psychiatry. 2006;67 Suppl 3:15-22; quiz 23.
Because of the mild symptomatology associated with its earlier stages, Alzheimer's disease (AD) is most commonly diagnosed in an intermediate to late stage of progression. Patients with moderate to severe AD at diagnosis have already experienced appreciable losses in cognition and functioning. However, such patients may still benefit greatly from the use of antidementia agents such as cholines-terase inhibitors (ChEIs) and the N-methyl-D-aspartate (NMDA) receptor open-channel antagonist memantine. Monotherapy regimens involving a ChEI or memantine have been shown to slow the progression of cognitive symptoms in patients with moderate to severe AD, although memantine is currently the only agent approved for use in this setting. Furthermore, combination therapy involving memantine and a ChEI has been shown to yield increased cognitive benefits relative to ChEI monotherapy, a result that is believed to be attributable to the distinct therapeutic mechanisms associated with NMDA receptor open-channel antagonists and ChEIs. Nonetheless, recent findings indicate that the therapeutic effects of these antidementia agents are not limited to cognition. For example, emerging data highlight the efficacy of ChEIs and memantine, used either alone or in combination, in improving outcomes related to patient functioning and behavior, 2 domains that may have a great deal of significance for patients and caregivers. Furthermore, recent clinical trial data suggest that antidementia agents may significantly delay nursing home placement, a unique endpoint that can be tremendously distressing to patients with AD and their caregivers. Thus, it is clear that the ChEIs and memantine provide substantial benefits that extend across the spectrum of symptoms of AD, improving outcomes for those who are affected, either directly or indirectly, by this debilitating condition.
由于阿尔茨海默病（AD）早期阶段症状较为轻微，其最常于病情进展的中晚期被诊断出来。诊断时患有中度至重度AD的患者已经在认知和功能方面出现了明显衰退。然而，这类患者使用抗痴呆药物（如胆碱酯酶抑制剂（ChEIs）和N-甲基-D-天冬氨酸（NMDA）受体开放通道拮抗剂美金刚）仍可能受益匪浅。尽管美金刚是目前唯一被批准用于此情况的药物，但涉及ChEI或美金刚的单药治疗方案已被证明可减缓中度至重度AD患者认知症状的进展。此外，与ChEI单药治疗相比，美金刚与ChEI联合治疗已被证明能带来更大的认知益处，这一结果被认为归因于NMDA受体开放通道拮抗剂和ChEIs相关的不同治疗机制。尽管如此，最近的研究结果表明，这些抗痴呆药物的治疗效果并不局限于认知方面。例如，新出现的数据突出了ChEIs和美金刚单独或联合使用在改善与患者功能和行为相关结局方面的疗效，这两个领域对患者及其护理人员可能具有重大意义。此外，最近的临床试验数据表明，抗痴呆药物可能会显著延迟入住养老院的时间，这是一个独特的终点，对AD患者及其护理人员来说可能极其痛苦。因此，很明显，ChEIs和美金刚提供了广泛的益处，涵盖了AD的各种症状，改善了直接或间接受这种衰弱病症影响的人群的结局。
