The Aging Brain and the Cognition-Mobility Interface in Clinically Normal Older Adults

临床正常老年人的大脑老化和认知-移动界面

• 批准号: 9280827
• 负责人: Neelesh K Nadkarni
• 金额: $ 15.38万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9280827
• 关键词: Affect; Aging; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Amyloid deposition; Amyloidosis; Area; Award; Blood Vessels; Brain; Brain Pathology; Brain imaging; Brain region; Canada; Cessation of life; Clinical; Cognition; Cognitive; Complement; Consultations; Corpus striatum structure; Dementia; Deoxyglucose; Deposition; Disease; Doctor of Philosophy; Early Diagnosis; Elderly; Executive Dysfunction; Exercise; Fellowship; Functional disorder; Gait; Geriatrics; Hospitals; Human; Image; Impairment; Internal Medicine; Intervention; Knowledge; Ligands; Link; Locomotion; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Medical; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentorship; Microvascular Dysfunction; Motor; Musculoskeletal Equilibrium; Nerve Degeneration; Neurology; Neuropsychology; Neurosciences; Parietal; Pathologic; Pathologic Processes; Pathology; Performance; Physicians; Positron-Emission Tomography; Process; Proteins; Protocols documentation; Reaction Time; Recruitment Activity; Research; Research Activity; Research Personnel; Residencies; Risk; Risk Factors; Science; Scientist; Severities; Short-Term Memory; Stress Tests; Synapses; Task Performances; Testing; Time; Training; Training Activity; United States; Universities; Walking; White Matter Hyperintensity; Work; adverse outcome; age related; aging brain; base; burden of illness; cerebral amyloidosis; cognitive performance; cognitive task; design; disability; executive function; falls; functional decline; functional disability; glucose metabolism; gray matter; insight; motor control; multidisciplinary; multimodality; neuroadaptation; neuroimaging; neuron loss; novel; patient oriented research; prevent; processing speed; programs; public health relevance; rate of change; resilience; response; skills; statistics; stem; uptake

 DESCRIPTION (provided by applicant):This Mentored Patient-Oriented Research Career Development Award (K23) application is designed to enable the candidate, Neelesh Nadkarni, MD, PhD, FRCPC, to become an independent investigator through the study of the influence of three major brain pathologies (amyloidosis, neurodegeneration and small-vessel disease) on the cognition-mobility interface in older adults. Dr. Nadkarni is a licensed practicing geriatricia with residency and fellowship training acquired in the United States and Canada in internal medicine, geriatric medicine, geriatric and cognitive neurology, and hospital medicine. Dr. Nadkarni also completed a PhD in medical sciences and neurosciences following completion of his clinical training. This K23 award will train Dr. Nadkarni to develop research skills in the application of advanced neuroimaging to study brain amyloidosis and neurodegeneration and enhance his knowledge of small-vessel disease imaging. It will also train him to develop the cognition-mobility interface (COMBINE) through the refinement of a protocol of dual-tasks (gait- cognition tasks). The K23 research application will test the hypothesis that amyloidosis, neurodegeneration and small-vessel disease are related to the COMBINE, which can predict impending cognitive and/or mobility decline in clinically normal older adults (defined here as those without cognitive or mobility impairment). This application is based on the premise that in clinically normal older adults, progressive functional impairment stemming from cognitive or mobility decline is a continuum that commences with deficits in cognition and/or mobility. Concurrent performance of cognitive tasks while walking assesses the COMBINE, which can serve as "stress tests" of the brain. Pathological age-related disease burden in brain regions important to cognitive or mobility processes, can manifest as deficits in the COMBINE in clinically normal older adults. This study will quantify amyloidosis by measuring Pittsburgh B ligand retention on Positron Emission Tomography (PET), small-vessel disease by determining volume of white matter hyperintensities on magnetic resonance imaging (MRI), and neurodegeneration by measuring fluoro-2-deoxy-glucose uptake on PET. The study will evaluate the relationships between the three pathologies affecting the COMBINE in 120 cognitively normal older adults, who will be recruited from an ongoing longitudinal study of brain amyloid deposition (RF1 AG025516; PI: Klunk). The findings from this research can provide new insights into mechanisms and clinical approaches for early detection of cognitive and mobility decline in older adults, ultimately leading to novel targets for interventions to prevent adverse outcomes of aging. This K23 training and research application involves a stellar multidisciplinary team of experts in dementia, PET and MRI neuroimaging, neuropsychology, locomotion measurement, statistics, cognitive and motor aging, postural control and geriatrics. This team of renowned leaders is committed to provide the candidate with mentorship and consultation on a regular basis through the entire duration of this award. The K23 related training and research activities will be conducted at the University of Pittsburgh which is ideally suited to undertake this work. This K23 award will ultimately enable the geriatrician-candidate to become an independent investigator conducting patient-oriented research and a leader in brain aging and the cognition-mobility interface.

 描述（由申请人提供）：这个指导以患者为导向的研究职业发展奖（K23）应用程序旨在使候选人，医学博士，博士，FRCPC，通过研究三种主要的大脑病理（淀粉样变性，神经变性和小血管疾病）对老年人认知移动界面的影响，成为一名独立的研究者。Nadkarni博士是一位有执照的老年医学执业医师，在美国和加拿大接受了内科、老年医学、老年和认知神经学以及医院医学方面的住院医师和研究员培训。Nadkarni博士在完成临床培训后还获得了医学和神经科学博士学位。该K23奖项将培训Nadkarni博士发展高级神经成像应用的研究技能，以研究脑淀粉样变性和神经变性，并提高他对小血管疾病成像的了解。它还将训练他通过改进双重任务（步态-认知任务）的协议来开发认知-移动接口（联合收割机）。K23研究应用将测试淀粉样变性、神经变性和小血管疾病与COMBINE相关的假设，COMBINE可以预测临床正常老年人（此处定义为没有认知或移动障碍的老年人）即将发生的认知和/或移动能力下降。本申请基于以下前提：在临床正常的老年人中，由认知或移动性下降引起的进行性功能障碍是一个连续体，始于认知和/或移动性缺陷。步行时同时执行认知任务评估了联合收割机，这可以作为大脑的“压力测试”。对认知或移动过程重要的脑区域中的病理性年龄相关疾病负担可以表现为临床正常老年人中的组合缺陷。本研究将通过正电子发射断层扫描（PET）测量匹兹堡B配体保留来量化淀粉样变性，通过磁共振成像（MRI）确定白色高信号体积来量化小血管疾病，通过PET测量氟-2-脱氧葡萄糖摄取来量化神经变性。该研究将在120名认知正常的老年人中评估影响联合收割机的三种病理之间的关系，这些老年人将从正在进行的脑淀粉样蛋白沉积纵向研究（RF 1 AG 025516; PI：Klunk）中招募。这项研究的发现可以为早期检测老年人认知和活动能力下降的机制和临床方法提供新的见解，最终导致干预措施的新目标，以防止衰老的不良后果。这个K23培训和研究应用涉及痴呆症，PET和MRI神经成像，神经心理学，运动测量，统计学，认知和运动衰老，姿势控制和老年病学的专家组成的多学科团队。这支由知名领导人组成的团队致力于在整个奖项期间定期为候选人提供指导和咨询。K23相关的培训和研究活动将在匹兹堡大学进行， 适合从事这项工作。这个K23奖项最终将使老年医学候选人成为一名独立的研究人员，进行以患者为导向的研究，并在大脑老化和认知移动接口的领导者。