A systems-biology clinical trial of a personalized multimodal lifestyle intervention for early Alzheimer's disease.
A systems-biology clinical trial of a personalized multimodal lifestyle intervention for early Alzheimer's disease.
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DOI：
10.1002/trc2.12191
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Roach JC
中科院分区：
文献类型：
--
作者：
McEwen SC;Merrill DA;Bramen J;Porter V;Panos S;Kaiser S;Hodes J;Ganapathi A;Bell L;Bookheimer T;Glatt R;Rapozo M;Ross MK;Price ND;Kelly D;Funk CC;Hood L;Roach JC
目前迫切需要开发针对阿尔茨海默病（AD）患者的有效干预治疗方法。AD是多种相互作用的功能失调生物系统数十年复杂相互作用的结果，目前尚未完全阐明。流行病学研究已经将几种可改变的生活方式因素与AD发病率的增加联系起来。由于单一疗法未能预防或改善AD，因此干预性研究应部署多种有针对性的干预措施，以解决导致AD的功能失调系统。这项随机对照试验（RCT）将在60名轻度认知障碍（MCI）和早期AD患者（年龄50岁以上，淀粉样蛋白阳性）中检查12个月个性化、多模式生活方式干预的疗效。两组都接受了数据驱动的生活方式建议，旨在针对与AD相关的多个系统性途径。一组人在没有指导的情况下接受这些个性化的建议。另一组接受个性化的建议，包括健康指导、饮食咨询、运动训练、认知刺激和营养补充剂。我们收集临床、蛋白质组学、代谢组学、神经影像学和遗传学数据，以推动系统生物学分析。我们将研究对认知和海马体积的影响。该研究的总体目标是纵向跟踪与AD有关的生物系统，以揭示干预期间这些系统之间的动态，以了解治疗反应的差异。我们已经制定并实施了一项针对早期AD患者的个性化多模式干预方案。我们于2019年9月开始招募;我们已经招募了我们目标的三分之一（60人中的20人），保留率为95%，合规率为86%。这项研究提出了一个范式转变，设计多模式，生活方式干预，以减少认知能力下降，以及如何阐明生物系统的目标。解释个体轨迹的机制或因果基础以及多组学变量之间相互作用的分析工作将为未来假设的设计和有效精准医学试验的开发提供信息。
There is an urgent need to develop effective interventional treatments for people with Alzheimer's disease (AD). AD results from a complex multi‐decade interplay of multiple interacting dysfunctional biological systems that have not yet been fully elucidated. Epidemiological studies have linked several modifiable lifestyle factors with increased incidence for AD. Because monotherapies have failed to prevent or ameliorate AD, interventional studies should deploy multiple, targeted interventions that address the dysfunctional systems that give rise to AD. This randomized controlled trial (RCT) will examine the efficacy of a 12‐month personalized, multimodal, lifestyle intervention in 60 mild cognitive impairment (MCI) and early stage AD patients (aged 50+, amyloid positivity). Both groups receive data‐driven, lifestyle recommendations designed to target multiple systemic pathways implicated in AD. One group receives these personalized recommendations without coaching. The other group receives personalized recommendations with health coaching, dietary counseling, exercise training, cognitive stimulation, and nutritional supplements. We collect clinical, proteomic, metabolomic, neuroimaging, and genetic data to fuel systems‐biology analyses. We will examine effects on cognition and hippocampal volume. The overarching goal of the study is to longitudinally track biological systems implicated in AD to reveal the dynamics between these systems during the intervention to understand differences in treatment response. We have developed and implemented a protocol for a personalized, multimodal intervention program for early AD patients. We began enrollment in September 2019; we have enrolled a third of our target (20 of 60) with a 95% retention and 86% compliance rate. This study presents a paradigm shift in designing multimodal, lifestyle interventions to reduce cognitive decline, and how to elucidate the biological systems being targeted. Analytical efforts to explain mechanistic or causal underpinnings of individual trajectories and the interplay between multi‐omic variables will inform the design of future hypotheses and development of effective precision medicine trials.
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影响因子：
5
作者：
COHEN, S;KAMARCK, T;MERMELSTEIN, R
通讯作者：
MERMELSTEIN, R
DOI：
10.1016/j.jalz.2011.03.005
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
McKhann GM;Knopman DS;Chertkow H;Hyman BT;Jack CR Jr;Kawas CH;Klunk WE;Koroshetz WJ;Manly JJ;Mayeux R;Mohs RC;Morris JC;Rossor MN;Scheltens P;Carrillo MC;Thies B;Weintraub S;Phelps CH
通讯作者：
Phelps CH
影响因子：
14
作者：
Langbaum, Jessica B.;Hendrix, Suzanne B.;Reiman, Eric M.
通讯作者：
Reiman, Eric M.
影响因子：
48
作者：
Barnes, Deborah E.;Yaffe, Kristine
通讯作者：
Yaffe, Kristine
影响因子：
3.2
作者：
Barclay, Alan Winston;Flood, Victoria Mary;Mitchell, Paul
通讯作者：
Mitchell, Paul