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.

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

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

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