Mindfulness and guided imagery for depressed family caregivers of patients with Alzheimer’s disease and related dementias: clinical outcomes and neural mechanisms

阿尔茨海默病和相关痴呆症患者的家庭照顾者是一个弱势群体，由于压力增加，身体和心理并发症的风险增加。值得注意的是，报告心理压力的照顾者比非照顾者面临更大的过早死亡风险，而没有压力的照顾者不会分享这种风险。死亡率增加、免疫力降低和抑郁增加--所有这些都出现在阿尔茨海默病家庭成员的照顾者身上--表明照顾压力干扰了正常的生物衰老过程。照顾者的心理症状也增加了痴呆症亲属住院的风险。因此，开发能够降低照顾者压力和减少抑郁的干预措施，并了解改善的神经机制是至关重要的。照顾者中央冥想和意象疗法(CMIT)是一项为期4周的团体正念和引导意象团体疗法干预，旨在减少抑郁和压力等负面心理症状，促进健康老龄化。它被设计为一种短暂的干预，以适应照顾者繁忙的日程安排。CMIT提供了实用的放松和正念技巧，有助于个人内心的平静，也改善了参与者对患有痴呆症的亲人的看法。这些好处加在一起，可能会随着照顾者年龄的增长而增强他们的精神和社会功能。我们从对患有阿尔茨海默病和相关痴呆症的家庭成员的抑郁照顾者进行的一项小型对照试验(N=20)中获得了可行性数据，证明了相对于放松控制条件，CMIT在减少照顾者抑郁方面的巨大效果，并在照顾者的子集(N=8)中提供了初步证据，表明CMIT可能影响大脑结构和功能的变化。有了这笔R21拨款，我们将对50名抑郁的照顾者进行随机、对照、单盲的临床试验，并获得神经成像，以确定照顾者相对于支持组的改善机制。我们假设，与支持组相比，CMIT在减少照顾者抑郁方面有更大的效果，并且CMIT的参与者而不是支持组的参与者将表现出大脑结构和功能的变化。这些假设将根据我们的具体目标进行检验：(1)确定CMIT相对于支持组治疗阿尔茨海默病和相关痴呆患者照顾者抑郁症状的有效规模，(2)确定与干预前后改善相关的大脑回路，(3)确定CMIT治疗4周后照顾者抑郁的改善是否与脑结构变化相关。这些实验可能有助于建立一种新的、简短的治疗照顾者抑郁的方法，并了解改善的神经机制，以帮助指导未来的研究。

Family caregivers of patients with Alzheimer’s disease and related dementias are a vulnerable population at increased risk of physical and psychological complications due to increased stress. Notably, caregivers who report psychological stress are at a greater risk of early death relative to non-caregivers, whereas unstressed caregivers do not share this risk. Increased mortality, lower immunity, and increased depression – all of which are found in caregivers of family members with Alzheimer’s disease – indicate that caregiving stress interferes with the process of normal biological aging. Psychological symptoms in caregivers also increase the risk of institutionalization of the relative with dementia. It is therefore crucial to develop interventions that can lower caregiver stress and reduce depression, and to understand neural mechanisms of improvement. Central Meditation and Imagery Therapy for Caregivers (CMIT) is a 4-week group mindfulness and guided imagery group therapy intervention that aims to reduce negative psychological symptoms such as depression and stress, and promote healthy aging. It was designed as a brief intervention to fit with caregivers’ busy schedules. CMIT provides practical relaxation and mindfulness techniques that aid with individual peace of mind, and also improve perspective taking with participants’ loved ones with dementia. These benefits combined may bolster caregivers’ mental and social functioning as they age. We obtained feasibility data from a small, controlled trial of CMIT (N = 20) with depressed caregivers of family members with Alzheimer’s disease and related dementias, that demonstrated a large effect of CMIT relative to a relaxation control condition on reducing caregiver depression, and provided preliminary evidence in a subset of caregivers (N = 8) that CMIT may effect structural and functional brain changes. With this R21 grant, we will conduct a randomized, controlled, single-blind pilot clinical trial of 50 depressed caregivers, and obtain neuroimaging to determine mechanisms of caregiver improvement relative to a support group. We hypothesize that CMIT will have moderately greater effects on reducing caregiver depression than a support group, and that participants in CMIT but not the support group will demonstrate changes in brain structure and function. These hypotheses will be tested with our Specific Aims: (1) Determine an effect size of CMIT for the treatment of depression symptoms in caregivers with Alzheimer’s disease and related dementias relative to a support group, (2) Identify brain circuits that correlate with improvement from pre to post intervention, (3) Determine whether structural brain changes are associated with improvement of caregiver depression with CMIT over 4 weeks. These experiments may help to establish a new, brief therapy for caregiver depression and understand neural mechanisms of improvement to help guide future research.