Cognitive Correlates of Mitochondrial Function in Older Adults

老年人线粒体功能的认知相关性

• 批准号: 10380587
• 负责人: Francesca Veanna Lopez
• 金额: $ 1.89万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-16 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10380587
• 关键词: Adenosine Triphosphate; Adult; Age; Aging; Alzheimer' s Disease; Apoptosis; Arizona; Back; Brain; Cell physiology; Clinical; Cognition; Cognitive; Cognitive aging; Consumption; Data; Dementia; Elderly; Energy Metabolism; Evidence based intervention; Florida; Funding; Goals; Grant; Hippocampus (Brain); Impaired cognition; Infrastructure; Lead; Learning; Left; Magnetic Resonance Spectroscopy; Mediating; Memory; Methods; Mitochondria; National Research Service Awards; Neurodegenerative Disorders; Neurons; Older Population; Outcome; Oxidative Stress; Participant; Pathogenesis; Performance; Phospholipid Metabolism; Phosphorus; Population; Process; Production; Protocols documentation; Public Health; Randomized Clinical Trials; Research Personnel; Resources; Respiration; Risk; Role; Sampling; Science; Short-Term Memory; Structure; Techniques; Temporal Lobe; Time; Training; United States; Universities; age related; base; clinically relevant; cognitive performance; cognitive task; executive function; experience; frontal lobe; health care service utilization; in vivo; indexing; innovation; inorganic phosphate; interest; neuroimaging; neuroinflammation; neuromechanism; non-demented; novel; potential biomarker

PROJECT SUMMARY/ABSTRACT As the population of adults ages beyond 65 years, one of the most pressing public health concerns is cognitive decline, transition to dementia, and utilization of health care resources. Thus, it is imperative to identify and characterize the contribution of specific neural mechanisms to non-normative cognitive decline with the goal of finding evidence-based interventions. Evidence suggests that mitochondrial efficiency and energy production decline with older age. The brain is reliant on mitochondria to carry out a host of vital cellular functions including energy metabolism, respiration, and apoptosis to maintain neuronal integrity. Clinically relevant, dysfunctional or damaged mitochondria have been implicated as central to the pathogenesis of neurodegenerative disease processes like Alzheimer’s disease. Phosphorous magnetic resonance spectroscopy (31-P MRS) is a unique, non-invasive, and powerful method for examining in vivo mitochondrial function. To date, only a handful of studies have used this approach to assess the relationship between markers of mitochondrial function and cognition, and findings have been mixed. The goal of the current study is to better understand the differential influence of mitochondrial function on cognition in older adults. Given that declines in executive function and memory are particularly sensitive to aging, the central hypothesis is that regional markers of mitochondrial function, namely adenosine triphosphate (ATP), will be differentially associated with domain-specific cognition across frontal and temporal regions. The proposed study aims to (1) concurrently examine markers of ATP function over frontal and temporal regions using a non-invasive, state-of-the-science neuroimaging technique, 31-P MRS, and (2) determine the relationship between regional 31-P MRS-based markers of ATP function and domain-specific cognition (i.e., executive, memory). Working hypotheses for the proposed study are (1) markers of temporal ATP function will be greater in concentration as compared to markers of frontal ATP function given the high energy consumption within temporal regions (e.g., hippocampus) and more rapid age-related declines in structure and function within frontal regions, (2) markers of frontal ATP function will be more strongly associated with executive function tasks relative to memory tasks, and (3) markers of temporal ATP function will be more strongly associated with memory tasks as compared to executive function tasks. Innovative features of the proposed study include (1) hypothesis guided focus on mitochondrial function in frontal and temporal regions, (2) the assessment of cognitive domains that rely upon intact structure-function within these regions, and (3) the use of novel, powerful, and non-invasive markers of in vivo ATP function. Findings from this study will increase current understanding of the applicability of 31-P MRS as a potential biomarker of mitochondrial function. Broadly, these findings have the potential to inform more nuanced distinctions between normal and abnormal aging processes.

项目摘要/摘要 随着成年人年龄超过65岁的人口，最紧迫的公共卫生问题之一是认知 衰落，向痴呆过渡以及医疗资源的利用。那是必须识别和 表征特定神经机制对非规范认知下降的贡献，目的是 寻找基于证据的干预措施。有证据表明线粒体效率和能源产生 随着年龄的增长而下降。大脑依靠线粒体来执行许多重要的细胞功能 能量代谢，呼吸和凋亡以维持神经元完整性。临床相关，功能失调或 线粒体受损是神经退行性疾病发病机理的核心 如阿尔茨海默氏病这样的过程。磷磁共振光谱（31-P MRS）是独特的， 非侵入性，有力的方法，用于检查体内线粒体功能。迄今为止，只有少数研究 已经使用这种方法来评估线粒体功能和认知标记之间的关系， 发现混合在一起。当前研究的目的是更好地了解 老年人认知方面的线粒体功能。鉴于执行功能和内存下降是 对衰老特别敏感，中心假设是线粒体功能的区域标记，即 三磷酸腺苷（ATP）将与跨额叶特定的域特异性认知有所不同 和临时区域。拟议的研究旨在（1）同时检查正面上ATP功能的标记 使用非侵入性，最先进的神经影像学技术，31-P MRS和（2）的临时区域 确定ATP功能的区域31-P MRS标记与域特异性的关系 认知（即执行，记忆）。拟议研究的工作假设是（1）临时ATP的标记 与额叶ATP功能的标记相比，浓度的功能将更高 临时区域（例如海马）内的消费和与年龄相关的更快的结构下降和 额叶区域内的功能，（2）正面ATP功能的标记将与执行 相对于内存任务的功能任务，（3）临时ATP功能的标记将更加强大 与执行功能任务相比，与内存任务相关联。拟议的创新特征 研究包括（1）假设指导着额叶和临时区域的线粒体功能的关注，（2） 评估依赖于这些区域内完整结构功能的认知领域，以及（3）使用 体内ATP功能的新颖，功能强大和非侵入性标记。这项研究的发现将增加电流 理解31-P MRS作为线粒体功能的潜在生物标志物的适用性。从广义上讲，这些 发现有可能告知正常和异常老化过程之间更细微的区别。

项目成果

Laterality of motor symptom onset and facial expressivity in Parkinson disease using face digitization.

• DOI: 10.1080/1357650x.2021.1946077
• 发表时间: 2022-01
• 期刊: Laterality
• 影响因子: 1.4
• 作者: Ratajska AM;Nisenzon AN;Lopez FV;Clark AL;Gokcay D;Okun MS;Bowers D
• 通讯作者: Bowers D

Early rapid eye movement sleep behavior disorder predicts incident cognitive impairment in Parkinson's disease across ages.

早期快速动眼睡眠行为障碍可预测不同年龄段帕金森病的认知障碍。

• DOI: 10.1016/j.parkreldis.2023.105392
• 发表时间: 2023
• 期刊: Parkinsonism & related disorders
• 影响因子: 4.1
• 作者: Kenney,LaurenE;Ratajska,AdriannaM;Lopez,FrancescaV;Marsiske,Michael;Bowers,Dawn
• 通讯作者: Bowers,Dawn

What does the Dementia Rating Scale-2 measure? The relationship of neuropsychological measures to DRS-2 total and subscale scores in non-demented individuals with Parkinson's disease.

• DOI: 10.1080/13854046.2021.1999505
• 发表时间: 2023-01
• 期刊: CLINICAL NEUROPSYCHOLOGIST
• 影响因子: 3.9
• 作者: Lopez, Francesca, V;Kenney, Lauren E.;Ratajska, Adrianna;Jacobson, Charles E.;Bowers, Dawn
• 通讯作者: Bowers, Dawn

Mapping Actuarial Criteria for Parkinson's Disease-Mild Cognitive Impairment onto Data-Driven Cognitive Phenotypes.

• DOI: 10.3390/brainsci12010054
• 发表时间: 2021-12-30
• 期刊: Brain sciences
• 影响因子: 3.3
• 作者: Kenney LE;Ratajska AM;Lopez FV;Price CC;Armstrong MJ;Bowers D
• 通讯作者: Bowers D