Development and Evaluation of Computerized Olfactory Training Program (COT) for Cognitive Decline in Early Alzheimer's Disease
针对早期阿尔茨海默病认知衰退的计算机嗅觉训练计划 (COT) 的开发和评估
基本信息
- 批准号:10614897
- 负责人:
- 金额:$ 9.83万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-30 至 2023-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdministrative SupplementAfrican American populationAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease diagnosisAlzheimer&aposs disease pathologyAlzheimer&aposs disease related dementiaAlzheimer&aposs disease riskAmyloidAmyloid beta-ProteinAnabolismAnimalsBase of the BrainBehavior TherapyBehavioralBlack PopulationsBrainBrain regionBusinessesCaregiver BurdenCaringCertificationClinicalClinical ResearchClinical TrialsCognitiveCommunitiesDementiaDevelopmentDevicesDiseaseDisease ProgressionEarly InterventionEarly identificationEducational MaterialsEffectivenessEmotionalEnsureEntrepreneurshipEnvironmentEvaluationExposure toFunctional disorderFutureGenerationsGoalsGovernmentHealth care facilityHealthcareHippocampus (Brain)HomeHumanHuman Subject ResearchImpaired cognitionIndividualIndustryInternshipsInterventionIntervention StudiesIntervention TrialInvestigationKnowledgeLeadLeadershipMarketingMarylandMedicalMentorsMinorityMinority GroupsModificationMultimediaNeurosciencesOdorsOlfactory CortexOlfactory PathwaysParticipantPathologicPatient RecruitmentsPatientsPerformancePersonsPhasePhase II Clinical TrialsPhase III Clinical TrialsPlant RootsPlantsPoliciesPopulationPreventionPrimary Health CarePrincipal InvestigatorProcessProviderPsychophysicsPublic HealthRandomized Clinical TrialsRecommendationRecording of previous eventsRegimenResearchResearch PersonnelResourcesSafetySamplingSiteSleep disturbancesSmall Business Innovation Research GrantSmall Business Technology Transfer ResearchSolidStimulantStructureSystemTherapeuticTherapeutic InterventionTimeTrainingTraining ProgramsTranslatingTranslationsUnderrepresented MinorityUnited StatesUniversitiesUrsidae FamilyVisitabeta accumulationadvanced dementiaapolipoprotein E-4basecareercerebral atrophycognitive functioncognitive trainingcohortcomorbiditycomputerizedcostdistrustearly phase clinical trialeffectiveness implementation studyefficacy studyentorhinal cortexethnic minorityexperiencefeasibility trialfollow-uphabituationhands on researchhealth literacyimprovedinnovationintervention programmembermild cognitive impairmentminority communitiesminority studentneurofilamentnovelportabilitypreventpreventive interventionprogramsrecruitresearch and developmentresearch studyresiliencesatisfactionscreeningskillsskills trainingsocial stigmastimulant usesuccesstherapeutic targetuser-friendly
项目摘要
ABSTRACT
We propose to evaluate and optimize the portable, home-based product – the Computerized Olfactory Training
Program (COT) – as a disease modifying intervention for prevention of progressive cognitive decline and
progressive dementia in early Alzheimer's Disease (AD). The COT uses validated neuroprotective olfactory
stimulants to intensely engage the primary and secondary olfactory cortices, with stimulation parameters that
overcome olfactory habituation, paired with computerized olfactory cognitive training tasks that synergistically
enhance the same brain regions; with the goal of increasing structural and functional resilience to AD
progression. Phase I research and development met or exceeded stated technical milestones: COT
intervention led to increased olfactory and cognitive functions 6 and 12 months later in ApoE4 carriers with mild
cognitive impairment and early dementia. Among completers of 12-month follow-up visit, COT blunted
trajectory in shrinkage of the entorhinal cortex and the hippocampus. Furthermore, the acute effects of odorant
molecules in the COT in regulating sleep disruptions and emotional reactivity adds to a potential value of COT
for treatment of behavioral dysfunctions in advanced AD. Alzheimer’s disease is a major public health crisis
both in the United States and worldwide. Hitherto, no therapeutic has demonstrated significant effectiveness in
modifying progression from early stages to advanced stages of AD. Most putative disease modifying
therapeutics targeting various steps of amyloid biosynthesis and amyloid beta (Aβ) accumulation have either
failed to reverse cognitive decline or worsened cognitive decline in Phase III clinical trials. However,
neuroscience evidence that AD pathology progresses early, over several decades in the olfactory brain
regions, before emergence of progressive, irreversible cognitive decline and dementia, as well as experimental
and clinical findings that olfactory compromise accelerates the progression of AD, provide solid premise for
targeting olfactory structure and function in the modification of AD progression. The success of use of enriched
odor environment in reducing aggregation of pathological neurofilaments in animals spurred high hopes for
translation of olfactory training (OT) into treatment of AD in humans. Unfortunately, lack of innovative
approaches to sustain olfactory engagement sufficiently to influence functional and structural plasticity in
clinical populations, hindered the translation of OT into an AD intervention. We built an innovative olfactory
treatment delivery system for home use; established a proprietary regimen of safe neuroprotective plant
odorant extracts and stimulation parameters that overcome odorant habituation in the primary olfactory cortex;
and created a synchronized App to simultaneously administer olfactory cognitive training tasks that
synergistically target the same brain regions being stimulated by the odorants. This breakthrough product, the
COT showed excellent promise in reversing cognitive decline in our Phase I SBIR. Key technical objectives of
this Phase II project are to: (1) demonstrate COT efficacy for prevention of brain atrophy and cognitive decline
in a powered randomized clinical trial of early dementia; (2) validate its safety; (3) further configure the platform
for user-friendliness, portability for home use, acceptability and marketing; and (4) explore new indications for
treating behavioral disturbances in people with moderate to advanced dementia, in an effort to reduce care-
giver burden. Upon completion of Phase II, we will be poised to expand the research to Phase III efficacy
study, or an implementation study of effectiveness in the real-world setting through commercial partnerships
developed over the course of this project. To the best of our knowledge, this will be the first evaluation of a
home-based, scalable, computerized, chemosensory-based brain stimulation for disease modification in AD.
摘要
我们建议评估和优化便携式,家庭为基础的产品-电脑嗅觉训练
计划(COT)-作为一种疾病修饰干预措施,用于预防进行性认知衰退,
早期阿尔茨海默病(AD)中的进行性痴呆。COT使用经过验证的神经保护嗅觉
刺激物强烈地接合初级和次级嗅觉皮层,刺激参数
克服嗅觉习惯化,配合计算机化的嗅觉认知训练任务,
增强相同的大脑区域;目的是增加对AD的结构和功能弹性
进展第一阶段的研究和开发达到或超过了规定的技术里程碑:COT
干预导致轻度ApoE 4携带者在6个月和12个月后的嗅觉和认知功能增加,
认知障碍和早期痴呆。在12个月随访访视的完成者中,COT变钝
内嗅皮层和海马体萎缩的轨迹。此外,气味剂的急性效应
COT中调节睡眠中断和情绪反应的分子增加了COT的潜在价值
用于治疗晚期AD的行为功能障碍。阿尔茨海默病是一个重大的公共卫生危机
无论是在美国还是全世界。迄今为止,没有任何治疗方法在以下方面表现出显著的有效性:
改变AD从早期到晚期的进展。大多数假定的疾病修饰
针对淀粉样蛋白生物合成和淀粉样蛋白β(Aβ)积累的各个步骤的治疗剂具有以下任一种
在III期临床试验中未能逆转认知能力下降或使认知能力下降恶化。然而,在这方面,
神经科学证据表明,AD病理学在嗅觉脑中早期发展,持续数十年
在出现进行性、不可逆的认知衰退和痴呆之前,
嗅觉损害加速AD进展的临床研究结果,
在AD进展的调节中靶向嗅觉结构和功能。成功使用浓缩的
气味环境在减少动物病理性神经丝聚集方面的作用激发了人们对
将嗅觉训练(OT)转化为人类AD的治疗。遗憾的是,缺乏创新
维持嗅觉参与足以影响功能和结构可塑性的方法,
临床人群,阻碍了OT转化为AD干预。我们建立了一个创新的嗅觉
家庭使用的治疗输送系统;建立了安全的神经保护植物的专有方案
克服初级嗅觉皮层中气味习惯化的气味提取物和刺激参数;
并创建了一个同步应用程序,同时管理嗅觉认知训练任务,
协同地靶向被气味刺激的相同大脑区域。这个突破性的产品,
COT在我们的I期SBIR中显示出很好的逆转认知下降的前景。关键技术目标
该II期项目的目的是:(1)证明COT预防脑萎缩和认知能力下降的疗效
在早期痴呆症的有效随机临床试验中;(2)验证其安全性;(3)进一步配置平台
用户友好性、家庭使用的便携性、可接受性和营销;以及(4)探索新的适应症,
治疗中度至晚期痴呆症患者的行为障碍,以减少护理-
给予者的负担在第二阶段完成后,我们将准备将研究扩展到第三阶段疗效
研究,或通过商业伙伴关系在现实世界环境中的有效性实施研究
在这个项目的过程中发展起来。据我们所知,这将是第一次评估一个
基于家庭的、可扩展的、计算机化的、基于化学传感器的脑刺激用于AD中的疾病修饰。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Charles Chiedu Nwaokobia其他文献
Charles Chiedu Nwaokobia的其他文献
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{{ truncateString('Charles Chiedu Nwaokobia', 18)}}的其他基金
Development and Evaluation of Portable Compendium of Psychophysical and Physiological Tests for Alzheimer's Disease and Related Dementias (ADRD)
阿尔茨海默病和相关痴呆症(ADRD)便携式心理物理和生理测试纲要的开发和评估
- 批准号:
10699349 - 财政年份:2023
- 资助金额:
$ 9.83万 - 项目类别:
The Development and Evaluation of Enhanced Digital-Chemosensory-Based Olfactory Training for Remote Management of Substance Use Disorders (EDITOR)
用于药物使用障碍远程管理的增强型数字化学感应嗅觉训练的开发和评估(编辑)
- 批准号:
10794665 - 财政年份:2023
- 资助金额:
$ 9.83万 - 项目类别:
The Development and Evaluation of Enhanced Digital-Chemosensory-Based Olfactory Training for Remote Management of Substance Use Disorders (EDITOR)
用于药物使用障碍远程管理的增强型数字化学感应嗅觉训练的开发和评估(编辑)
- 批准号:
10741580 - 财政年份:2022
- 资助金额:
$ 9.83万 - 项目类别:
The Development and Evaluation of Enhanced Digital-Chemosensory-Based Olfactory Training for Remote Management of Substance Use Disorders (EDITOR)
用于药物使用障碍远程管理的增强型数字化学感应嗅觉训练的开发和评估(编辑)
- 批准号:
10469912 - 财政年份:2022
- 资助金额:
$ 9.83万 - 项目类别:
Development and Evaluation of Computerized Chemosensory-Based Orbitofrontal Networks Training for Treatment of Pain (CBOT-P)
用于治疗疼痛的计算机化化学感应眼眶额网络训练 (CBOT-P) 的开发和评估
- 批准号:
10547925 - 财政年份:2022
- 资助金额:
$ 9.83万 - 项目类别:
Development and Evaluation of Computerized Olfactory Training Program (COT) for Cognitive Decline in Early Alzheimer's Disease (AD)
针对早期阿尔茨海默病 (AD) 认知衰退的计算机嗅觉训练计划 (COT) 的开发和评估
- 批准号:
10574428 - 财政年份:2018
- 资助金额:
$ 9.83万 - 项目类别:
Development and Evaluation of Computerized Olfactory Training Program (COT) for Cognitive Decline in Early Alzheimer's Disease (AD)
针对早期阿尔茨海默病 (AD) 认知衰退的计算机嗅觉训练计划 (COT) 的开发和评估
- 批准号:
10399659 - 财政年份:2018
- 资助金额:
$ 9.83万 - 项目类别:
Development and Evaluation of Computerized Olfactory Training Program (COT) for Cognitive Decline in Early Alzheimer's Disease (AD)
针对早期阿尔茨海默病 (AD) 认知衰退的计算机嗅觉训练计划 (COT) 的开发和评估
- 批准号:
10256329 - 财政年份:2018
- 资助金额:
$ 9.83万 - 项目类别:
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