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。保持头脑敏锐不仅对经济至关重要