Aging, PTSD, and the Anterior Cingulate Cortex (ACC)

衰老、创伤后应激障碍 (PTSD) 和前扣带皮层 (ACC)

基本信息

批准号：
10587057
负责人：
JOSE V PARDO
金额：
--
依托单位：
MINNEAPOLIS VA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10587057
关键词：
Acceleration Accounting Adenine Adult Aerobic Exercise Age Age-associated memory impairment Aging Alzheimer&apos s Disease American Amyloid Anterior Antioxidants Apoptosis Area Atrophic Attention Behavior Disorders Biochemical Pathway Biological Markers Biology Brain Brain Diseases Buffers Cell Aging Cell Respiration Chronic Chronic Post Traumatic Stress Disorder Clinical Clinical Trials Cognition Cognition Disorders Cognitive Cognitive aging Cognitive deficits Cysteine DNA Damage DNA Methylation DNA Repair Data Deposition Development Diet Dinucleoside Phosphates Discipline Disease Drug Metabolic Detoxication Economics Elderly Emotional Stress Environment Exposure to Functional disorder Future Generations Gluconeogenesis Glutathione Health Health behavior Human Impaired cognition Impairment Inflammation Infrastructure Intervention Laboratories Lipids Magnetic Resonance Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Measures Medial Mediating Medical Memory Memory impairment Mental disorders Metabolic Metabolic dysfunction Metabolism Methods Modeling NADH NADP Nerve Degeneration Neurodegenerative Disorders Neuropsychological Tests Nicotine Occipital lobe Outcome Oxidants Oxidation-Reduction Oxidative Phosphorylation Oxidative Stress Pathologic Pathway interactions Patients Pellagra Performance Persons Pharmacologic Substance Plasma Play Post-Traumatic Stress Disorders Prevention Prevention strategy Proteins Psyche structure Quality of life Reactive Oxygen Species Regulation Research Research Priority Risk Factors Role Secondary Prevention Severities Signal Transduction Sirtuins Site Stress Symptoms System Telomere Shortening Temporal Lobe Testing Therapeutic Trauma Universities Veterans Visit Work aerobic glycolysis aging brain antioxidant therapy baby boomer cingulate cortex cofactor cognitive change cognitive reserve combat endophenotype epigenetic marker executive function glucose metabolism human old age (65+)in vivo indexing interest ketogenesis lipid biosynthesis mitochondrial dysfunction neuronal excitability nicotinamide-beta-riboside nicotine use novel novel diagnostics oxidation pre-clinical prevent rehabilitation strategy response stress disorder stress management tau Proteins therapeutic target verbal young adult

项目摘要

America is aging; baby boomers are now seniors. Staying mentally astute is essential not only for economic survival but also for quality of life. Yet, the pathophysiology of cognitive aging remains ill-defined, a gap preventing development of novel diagnostic, therapeutic, or preventive strategies. This laboratory has identified the anterior cingulate cortex (ACC), the major component of the anterior attention system, as the principal region showing metabolic decline from young to late adulthood. This decline correlates with declining executive functions such as fluency. The ACC mediates statistically the relationship between increasing age and decreasing verbal fluency. Amyloid-free, cognitively intact elders show robust executive but lesser mnemonic deficits. This project will test the hypothesis that ACC dysfunction in the elderly free of preclinical Alzheimer’s disease (AD) is associated with redox dysfunction related to aging and severe stress, the latter as seen in PTSD. Oxidative stress will be measured with 7 T MRI/MRS using the NAD+/NADH ratio, a method developed here recently. Two factors will include: AGE (younger vs. older) and STRESS (healthy vs. chronic active PTSD). Neuropsychological testing and plasma phospho-tau181 [or 217] will confirm absence of preclinical AD as well as revisit the unusual observation: absence of aging-related memory impairment (Logical Memory I & II) —typically viewed as the sine qua non for aging. The anticipated outcomes are 1) the ACC undergoes redox stress related to aging and possibly emotional stress; 2) increasing ACC redox stress will correlate with declining ACC metabolism in the absence of preclinical AD; both will correlate more with declining executive and less with memory dysfunction; 3) ACC metabolism or redox status may serve as a biomarker for cognitive aging in the absence of neurodegeneration; and 4) scientific premise and infrastructure will poise the field to test the potential of antioxidant therapies in preventing or delaying cognitive aging. If successful, aging American would remain mentally sharp for more years. Since the ACC also participates in cognitive reserve, secondary prevention would delay symptoms even if neurodegeneration occurs.

美国正在老龄化；婴儿潮一代现在已是老年人，保持头脑敏锐不仅对经济至关重要。然而，认知衰老的病理生理学仍然不明确，存在差距。该实验室已确定阻止新的诊断、治疗或预防策略的发展。前扣带皮层 (ACC) 是前注意系统的主要组成部分，从年轻到成年晚期新陈代谢下降的区域与执行力下降相关。 ACC 介导了年龄增长与流利度等功能之间的关系。无淀粉样蛋白、认知能力完整的老年人表现出较强的执行力，但记忆力较差。该项目将检验无临床前阿尔茨海默病的老年人中 ACC 功能障碍的假设。疾病（AD）与衰老和严重压力相关的氧化还原功能障碍有关，后者见于氧化应激将使用 NAD+/NADH 比率（一种开发的方法）通过 7 T MRI/MRS 进行测量。最近，两个因素包括：年龄（年轻与年长）和压力（健康与长期活跃）。 PTSD）。神经心理学测试和血浆磷酸化 tau181 [或 217] 将证实不存在临床前 AD。以及重新审视不寻常的观察结果：不存在与衰老相关的记忆障碍（逻辑记忆 I 和 II) —通常被视为老化的必要条件预期结果是 1) ACC 发生氧化还原。与衰老相关的压力和可能的情绪压力；2) ACC 氧化还原压力的增加与在没有临床前 AD 的情况下 ACC 代谢下降；两者都与执行能力下降更相关。记忆功能障碍较少；3) ACC 代谢或氧化还原状态可以作为认知的生物标志物没有神经退行性变的情况下的衰老；4）科学前提和基础设施将使该领域做好准备测试抗氧化疗法在预防或延缓认知衰老方面的潜力，如果成功的话，衰老。由于 ACC 也参与了认知储备，美国人将在未来几年保持思维敏锐。即使发生神经退行性变，二级预防也会延迟症状。