Alcohol Research Center-Treatment and Implications -Targeting the Shared Substrates of Alcohol Misuse and Cognitive Impairment: Accelerated rTMS for Older Adults with Alcohol Use Disorder

酒精研究中心-治疗和影响-针对酒精滥用和认知障碍的共同基础：针对患有酒精使用障碍的老年人的加速 rTMS

• 批准号: 10712839
• 负责人: HOWARD C. BECKER
• 金额: $ 36.39万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10712839
• 关键词: Abstinence; Acceleration; Adherence; Aftercare; Age; Alcohol abuse; Alcohol consumption; Alcohols; Alzheimer' s disease related dementia; Back; Biological Markers; Brain; Clinical assessments; Cognition; Cognitive; Consumption; DSM-V; Dementia; Dose; Double-Blind Method; Elderly; Epidemiology; FDA approved; Functional Magnetic Resonance Imaging; Future; Goals; Heavy Drinking; Impaired cognition; Impairment; Individual; Infrastructure; Intervention; Left; Liquid substance; Measures; Mental Depression; Neurocognitive; Parietal; Participant; Patient Self-Report; Patients; Pattern; Pharmaceutical Preparations; Phase; Prefrontal Cortex; Randomized, Controlled Trials; Research Personnel; Rest; Rewards; Risk; Risk Factors; Sampling; Schedule; Treatment Protocols; United States National Institutes of Health; Urine; Vascular Cognitive Impairment; Woman; Work; addiction; alcohol misuse; alcohol research; alcohol use disorder; amnestic mild cognitive impairment; brain magnetic resonance imaging; carbohydrate-deficient transferrin; cognitive control; cognitive enhancement; cognitive performance; combat; craving; dementia risk; drinking; early onset; executive function; follow-up; improved; indexing; innovation; meetings; mild cognitive impairment; neurocognitive disorder; neurodegenerative dementia; neuropsychiatry; noninvasive brain stimulation; novel; phase I trial; pilot trial; primary outcome; recruit; repetitive transcranial magnetic stimulation; symptomatic improvement; timeline; treatment center; treatment duration

SUMMARY/ABSTRACT Alcohol misuse is a risk factor for early onset cognitive impairment, contributing to 10% of early onset dementia, with risk corresponding to amount consumed. Epidemiological estimates indicate 10-24% of those with current alcohol use disorder (AUD) meet criteria for dementia while 9-22% of those with dementia abuse alcohol. Furthermore, AUD appears to increase vulnerability particularly in women with a near three-fold increased risk of dementia. Furthermore, continued drinking risks worsening cognitive decline and dementia progression, while worsening cognitive impairment contributes to drinking escalation. Notably, there exists no intervention targeting the intersection of alcohol misuse and cognitive dysfunction in older adults. It is unclear whether alcohol-related impairments and structural brain changes represent classical Alzheimer's Disease and Related Dementias (ADRD) neurodegenerative patterns. Despite the unclear etiopathogenesis, there is emerging evidence that repetitive transcranial magnetic stimulation (rTMS) to upregulate executive/cognitive control circuitry can improve cognition in ADRD, and separately reduce heavy drinking in AUD. Our long-term objective is to optimize rTMS for simultaneous mitigation of both drinking and cognitive dysfunction in older adults towards breaking this cycle and thwarting progression to dementia. We propose to build upon our Charleston Alcohol Research Center (P50AA010761) expertise and infrastructure to expand recruitment to older adults (60-85 years) with AUD and cognitive impairment (DSM-5 Mild Neurocognitive Disorder). Participants (N=30) will receive high-dose accelerated rTMS: a recent innovation that reduces treatment burden, is FDA-approved for treatment of depression, and most importantly demonstrates rapid symptom improvements. Participants will receive 10 sessions of intermittent theta burst rTMS (iTBS-rTMS) to left dorsolateral prefrontal cortex (individualized to functional network connectivity) for 5 days/week for 1-week. All will undergo clinical assessments and resting-state fMRI at pre-treatment, at 1-week post-treatment, and 4- week follow up. We will use established primary outcomes for ADRD trials (ADCOMS; NIH Toolbox-Cognition Battery, Fluid Composite) and primary outcomes for AUD trials (self-report drinking (timeline follow back) and craving along with urine ethylglucorinide (ETG) and carbohydrate deficient transferrin (CDT) biomarkers). We hypothesize that iTBS-rTMS will enhance cognitive performance in AUD+MCI, as indexed in improved fluid cognition, as well as enhance frontal-parietal connectivity (Aim1) and that iTBS-rTMS will result in fewer heavy drinking and more abstinence days, and lower craving, ETG and CDT as well as enhanced connectivity between the frontal-parietal and reward networks (Aim 2). Findings will guide a follow-up double blind, randomized controlled trial of rTMS for AUD and MCI with 1-year longitudinal follow up to assess durability of staving off heaving drinking and cognitive decline.

摘要/摘要 酗酒是早发性认知障碍的一个危险因素，导致 10% 的早发性痴呆症， 风险与消耗量相对应。流行病学估计表明 10-24% 的人目前患有 酒精使用障碍 (AUD) 符合痴呆症标准，而 9-22% 的痴呆症患者滥用酒精。 此外，澳元似乎会增加脆弱性，尤其是女性，风险增加近三倍 痴呆症。此外，持续饮酒可能会加剧认知能力下降和痴呆症进展，而 认知障碍的恶化会导致饮酒量增加。值得注意的是，不存在针对 老年人酒精滥用和认知功能障碍的交叉点。 目前尚不清楚与酒精相关的损伤和大脑结构变化是否代表典型的阿尔茨海默病 疾病及相关痴呆 (ADRD) 神经退行性模式。尽管发病机制尚不清楚， 有新的证据表明重复经颅磁刺激（rTMS）可以上调 执行/认知控制电路可以改善 ADRD 中的认知，并分别减少 ADRD 中的酗酒 澳元。我们的长期目标是优化 rTMS 以同时缓解饮酒和认知障碍 老年人的功能障碍打破了这个循环并阻止了痴呆的进展。 我们建议以查尔斯顿酒精研究中心 (P50AA010761) 的专业知识和基础设施为基础 将招募范围扩大到患有 AUD 和认知障碍的老年人（60-85 岁）（DSM-5 轻度 神经认知障碍）。参与者 (N=30) 将接受高剂量加速 rTMS：一项最新创新， 减轻治疗负担，经 FDA 批准用于治疗抑郁症，最重要的是证明 症状快速改善。参与者将接受 10 次间歇性 theta 突发 rTMS (iTBS-rTMS) 课程 左背外侧前额皮质（根据功能网络连接进行个性化），每周 5 天，持续 1 周。 所有患者都将在治疗前、治疗后 1 周和 4-4 小时接受临床评估和静息态 fMRI 周跟进。我们将使用 ADRD 试验的既定主要结果（ADCOMS；NIH Toolbox-Cognition 电池、流体复合材料）和 AUD 试验的主要结果（自我报告饮酒（时间线追踪）和 渴望与尿液乙基葡萄糖苷（ETG）和碳水化合物缺乏转铁蛋白（CDT）生物标志物一起）。我们 假设 iTBS-rTMS 将增强 AUD+MCI 的认知表现，如液体改善所表明的 认知，以及增强额顶叶连接（目标 1），并且 iTBS-rTMS 将导致更少的重 饮酒和更多的禁欲日，降低渴望，ETG 和 CDT 以及增强之间的联系 额顶叶和奖励网络（目标 2）。研究结果将指导后续双盲、随机 针对 AUD 和 MCI 的 rTMS 对照试验，并进行 1 年纵向随访，以评估回避的持久性 酗酒和认知能力下降。