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)

• 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
• 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' 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

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.

美国正在衰老；婴儿潮一代现在是老年人。保持精神精神不仅对经济至关重要 生存，也出于生活质量。然而，认知衰老的病理生理学仍然不明确，差距 防止开发新颖的诊断，治疗或预防策略。该实验室已经确定 前扣带回皮层（ACC）是前注意系统的主要组成部分，作为主要的 区域显示出从年轻人到成年后期的代谢下降。这种下降与执行人员下降有关 诸如流利度之类的功能。 ACC从统计上调节年龄的增长与 言语流利性降低。无淀粉样蛋白，认知完整的长者表现出强大的高管，但助记符较小 缺陷。该项目将测试以下假设：ACC功能障碍在原来没有临床前阿尔茨海默氏症 疾病（AD）与与衰老和严重压力有关的氧化还原功能障碍有关，后者如 PTSD。使用NAD+/NADH比，将用7 T MRI/MRS测量氧化应激，这是一种开发的方法 最近这里。两个因素将包括：年龄（年轻人与年龄较大）和压力（健康与慢性活动 PTSD）。神经心理学测试和血浆磷酸-TAU181 [或217]将确认没有临床前AD 除了重新审视异常观察：缺乏与衰老相关的记忆障碍（逻辑记忆I＆ ii） - 通常被视为衰老的正弦物质。预期的结果是1）ACC经历氧化还原 与衰老和可能的情绪压力有关的压力； 2）增加ACC氧化还原应力将与 在没有临床前AD的情况下，ACC代谢下降；两者都将与行政人员下降更多相关 少有内存功能障碍； 3）ACC代谢或氧化还原状态可能是认知的生物标志物 在没有神经退行性的情况下衰老； 4）科学的前提和基础设施将使该领域有利 测试抗氧化剂疗法在预防或延迟认知衰老方面的潜力。如果成功，老化 美国人将在精神上保持敏锐的年份。由于ACC还参加了认知储备，因此 即使发生神经变性，二次预防也会延迟症状。