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.

美国正在老龄化；婴儿潮一代现在是老年人。保持头脑敏锐不仅是经济上的关键 生存更是为了生活质量。然而，认知老化的病理生理学仍不明确，这是一个空白。 防止出现新的诊断、治疗或预防策略。这个实验室已经确定了 前扣带回皮质(ACC)是前注意系统的主要组成部分 从年轻到成年后期表现出代谢衰退的区域。这一下降与高管人数的下降有关 流畅等功能。Acc在年龄增长与年龄增长之间的关系中起统计中介作用 语言流畅度下降。不含淀粉样蛋白、认知功能完好的老年人执行力强，但记忆力较差 赤字。该项目将检验这样一种假设，即没有临床前阿尔茨海默病的老年人的ACC功能障碍 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，后者见 创伤后应激障碍。氧化应激将用7T MRI/MRS使用NAD+/NADH比率进行测量，这是一种开发的方法 最近在这里。两个因素将包括：年龄(年轻与年长)和压力(健康与慢性运动 创伤后应激障碍)。神经心理测试和血浆磷酸化tau181[或217]将确认临床前AD的存在 以及重温不同寻常的观察：没有与衰老相关的记忆损害(逻辑记忆I和 二)--通常被视为衰老的必要条件。预期的结果是：1)ACC经历氧化还原 压力与衰老有关，可能与情绪压力有关；2)增加ACC氧化还原压力将与 在没有临床前阿尔茨海默病的情况下ACC代谢下降；两者都将与执行力下降更相关 3)ACC代谢或氧化还原状态可作为认知功能的生物标志物 在没有神经退化的情况下老化；以及4)科学前提和基础设施将使该领域保持平衡 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，则老化 美国人将在更长的时间里保持头脑敏锐。由于ACC也参与认知储备， 即使发生神经变性，二级预防也会延缓症状。