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

• 批准号: 10614897
• 负责人: Charles Chiedu Nwaokobia
• 金额: $ 9.83万
• 依托单位: EVON MEDICS, LLC
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10614897
• 关键词: Acute; Administrative Supplement; African American population; Aging; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Anabolism; Animals; Base of the Brain; Behavior Therapy; Behavioral; Black Populations; Brain; Brain region; Businesses; Caregiver Burden; Caring; Certification; Clinical; Clinical Research; Clinical Trials; Cognitive; Communities; Dementia; Development; Devices; Disease; Disease Progression; Early Intervention; Early identification; Educational Materials; Effectiveness; Emotional; Ensure; Entrepreneurship; Environment; Evaluation; Exposure to; Functional disorder; Future; Generations; Goals; Government; Health care facility; Healthcare; Hippocampus (Brain); Home; Human; Human Subject Research; Impaired cognition; Individual; Industry; Internships; Intervention; Intervention Studies; Intervention Trial; Investigation; Knowledge; Lead; Leadership; Marketing; Maryland; Medical; Mentors; Minority; Minority Groups; Modification; Multimedia; Neurosciences; Odors; Olfactory Cortex; Olfactory Pathways; Participant; Pathologic; Patient Recruitments; Patients; Performance; Persons; Phase; Phase II Clinical Trials; Phase III Clinical Trials; Plant Roots; Plants; Policies; Population; Prevention; Primary Health Care; Principal Investigator; Process; Provider; Psychophysics; Public Health; Randomized Clinical Trials; Recommendation; Recording of previous events; Regimen; Research; Research Personnel; Resources; Safety; Sampling; Site; Sleep disturbances; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Solid; Stimulant; Structure; System; Therapeutic; Therapeutic Intervention; Time; Training; Training Programs; Translating; Translations; Underrepresented Minority; United States; Universities; Ursidae Family; Visit; abeta accumulation; advanced dementia; apolipoprotein E-4; base; career; cerebral atrophy; cognitive function; cognitive training; cohort; comorbidity; computerized; cost; distrust; early phase clinical trial; effectiveness implementation study; efficacy study; entorhinal cortex; ethnic minority; experience; feasibility trial; follow-up; habituation; hands on research; health literacy; improved; innovation; intervention program; member; mild cognitive impairment; minority communities; minority student; neurofilament; novel; portability; prevent; preventive intervention; programs; recruit; research and development; research study; resilience; satisfaction; screening; skills; skills training; social stigma; stimulant use; success; therapeutic target; user-friendly

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