A Randomized Controlled Trial of Electroconvulsive Therapy plus Usual Care versus Simulated-ECT plus Usual Care for the Acute Management of Severe Agitation in Alzheimer's Dementia (ECT-AD)

摘要 阿尔茨海默氏痴呆症（AD）是最普遍的衰老神经退行性疾病，影响认知， 情绪和行为。躁动是一种常见的行为综合征，经常出现在中期 到晚期AD，其特征是精神活动过度、攻击性、易怒、大喊大叫、抵抗 关心和失眠。激动和相关行为障碍的不良后果是 相当大，包括生活质量受损，认知能力下降加速， 机构化，发病率和死亡率增加。躁动也增加了看护者的负担， 包括压力和有害的健康后果。然而，尽管煽动的破坏性影响 对于患者和护理者，目前的治疗方法仅具有适度的功效。行为管理策略 被广泛使用，但仅在轻度病例中有效。抗精神病药，最常用的一类 用于治疗痴呆症的激越和精神病的药物，在对照研究中显示了混合的结果 并与发病率和死亡率升高有关。因此，显然需要改进 干预，特别是对于AD中的严重激越。 电休克治疗（ECT）是一种安全有效的干预措施，用于治疗晚期严重心境障碍。 生活，包括抑郁症并发精神病，躁狂症或紧张症。对不良认知的担忧 然而，ECT的效果限制了ECT在治疗伴有激越的痴呆症中的临床应用。两个回顾性 我们小组进行的前瞻性研究支持ECT治疗AD患者的安全性和有效性 和严重的焦虑因此，ECT可能是治疗AD严重激越的有效方法。我们 提出一个五个地点，随机，单盲，对照临床试验，以确定安全性和有效性 ECT加常规治疗与模拟ECT（S-ECT）加常规治疗200例住院患者的比较 患有中度至重度阶段AD、可能的阿尔茨海默病类型（基于NIA-AA标准）的个体， 并伴有严重的焦虑受试者将随机接受（1）ECT治疗3周（最多9次ECT 治疗）加常规护理（UC），定义为标准行为治疗和药物治疗，或（2）模拟 ECT（S-ECT）加UC。将使用Cohen-Mansfield激越量表（CMAI）测量主要疗效。 安全性参数包括谵妄的每日评估（意识模糊评估方法，CAM）、认知 （严重损伤成套测验，SIB-8）和严重不良事件。为期12周的随访包括每月一次 评估以探索搅拌减少的稳定性。

ABSTRACT Alzheimer's dementia (AD), the most prevalent neurodegenerative disease of aging, affects cognition, emotion, and behavior. Agitation is a common behavioral syndrome that frequently emerges during middle to late stage AD and is characterized by psychomotor hyperactivity, aggression, irritability, yelling, resistance to care, and insomnia. The untoward consequences of agitation and related behavioral disturbances are considerable and include impaired quality of life, accelerated cognitive decline, heightened risk of institutionalization, and increased morbidity and mortality. Agitation also increases caregiver burden, including stress and deleterious health consequences. However, despite the damaging impact of agitation on the patient and caregiver, current treatments have only modest efficacy. Behavior management strategies are widely employed, but effective only in mild cases. Antipsychotics, the most commonly used class of medication for agitation and psychosis in dementia, have demonstrated mixed results in controlled studies and are associated with elevated morbidity and mortality. Thus, there is a clear need for improved interventions, particularly for severe agitation in AD. Electroconvulsive Therapy (ECT) is a safe and effective intervention for severe mood disorders in later life, including depression complicated by psychosis, mania or catatonia. Concerns regarding adverse cognitive effects of ECT, however, have limited ECT's clinical use in treating dementia with agitation. Both retrospective and prospective studies conducted by our group support the safety and efficacy of ECT in patients with AD and severe agitation. ECT, therefore, may represent an effective treatment of severe agitation in AD. We propose a five-site, randomized, single-blind, controlled clinical trial to determine the safety and efficacy of ECT plus usual care compared with Simulated ECT (S-ECT) plus usual care in 200 hospitalized individuals with moderate to severe stage AD , probable Alzheimer's type (based on NIA-AA criteria), complicated by severe agitation. Subjects will be randomized to either (1) ECT for three weeks (up to 9 ECT treatments) plus usual care (UC), defined as standard behavioral therapy and pharmacotherapy or (2) Simulated ECT (S-ECT) plus UC. Primary efficacy will be measured with the Cohen-Mansfield Agitation Inventory (CMAI). Safety parameters include daily assessment of delirium (Confusion Assessment Method, CAM), cognition (Severe Impairment Battery, SIB-8) and serious adverse events. A 12-week follow-up includes monthly assessments to explore stability of agitation reduction.