Cognitive Aging Trajectories in Survivors of Trauma

痴呆症和认知衰退的前驱阶段共同影响着大约25%-30%的老年人 在美国(美国)。创伤后应激障碍(PTSD)的发病率增加了111% 任何类型的痴呆症的风险，即使在控制了潜在的混杂因素后，如创伤性脑 损伤(TBI)。因此，创伤后应激障碍可能是早期预防认知功能减退和潜能的重要靶点。 进展为痴呆症。大多数关于创伤后应激障碍和认知的研究都采用了横断面研究设计 没有检查重要的潜在影响因素(例如，性别和APOE4携带者状态)，在 我们对创伤后应激障碍对认知功能纵向轨迹的影响的基本理解。 此外，尽管创伤后应激障碍在女性中更为普遍，但大多数关于创伤后应激障碍和认知的研究 在男人身上进行。这项建议具有及时的公共卫生重要性，因为大流行前的终生流行率 在美国，创伤后应激障碍的发病率为6%，但大流行后的流行病学调查结果表明， 在年轻人中约有32%。新冠肺炎事件也导致了无创伤后应激障碍症状 符合《精神疾病诊断和统计手册》第5版(DSM-5)标准A。因此， 我们理解创伤后应激障碍对认知老化影响的关键研究差距包括：1)前瞻性 其中时间顺序和认知减退率可以在以下背景下评估的研究 2)检验性别和载脂蛋白4携带者状态对创伤后应激障碍 创伤后应激障碍状态和认知能力下降；3)了解标准A在确定 创伤后应激障碍与认知功能衰退的关系。AIMS 1和2将利用来自 国家阿尔茨海默氏症协调中心(NACC)。在55岁以上的成年人中，多层次建模和 交互作用分析将确定创伤后应激障碍状态对创伤后应激障碍的轨迹、速度和时间顺序的影响 特定领域的认知能力下降，并将测试性别和载脂蛋白4携带者状态作为潜在的影响修饰物。为 目标3，男性和女性参与者，年龄65岁以上，有或没有创伤标准A，将被招募并 多元回归将用于明确阐明创伤后应激障碍的严重程度(标准B至E)是否与 在不符合标准A的情况下具有认知功能。该K01奖项将在以下方面提供培训和指导 健康老龄化，认知老化，创伤后应激障碍的性别特定健康影响，创伤后应激障碍的神经心理学，纵向 研究设计，先进的统计和推动PI成为具有专业知识的独立调查员 在创伤应激和生物心理社会因素对认知老化的影响方面，重点关注性别和 与NIA《2020-2025年战略方向》的目标B-3、B-4和F-4保持一致。

Dementia and the prodromal stages of cognitive decline, together, affect approximately 25-30% of older adults across the United States (U.S.). Posttraumatic Stress Disorder (PTSD) has been linked to a 111% increased risk of developing dementia of any type, even after controlling for potential confounders such as traumatic brain injury (TBI). Therefore, PTSD may be an important target for early prevention of cognitive decline and potential progression to dementia. Most studies on PTSD and cognition have used a cross-sectional study design and have not examined important potential effect modifiers (e.g., sex and APOE4 carrier status), leaving a gap in our fundamental understanding of the effect of PTSD on longitudinal trajectories of cognitive functioning. Further, although PTSD is more prevalent in women, most research on PTSD and cognition has been conducted in men. This proposal is of timely public health importance, as the pre-pandemic lifetime prevalence of PTSD in the U.S. was 6%, but post-pandemic epidemiological findings have indicated a rise to approximately 32% among young adults. COVID-19 events have also resulted in PTSD symptoms without meeting Diagnostics and Statistical Manual of Mental Disorders, 5th edition (DSM-5) Criterion A. Therefore, critical research gaps in our understanding of the effect of PTSD on cognitive aging include: 1) prospective investigation wherein temporal sequencing and rate of cognitive decline can be evaluated in the context of PTSD, 2) testing the potential modifying effects of sex and APOE4 carrier status on the relationship between PTSD status and cognitive decline and, 3) understanding whether Criterion A is necessary when determining the relationship between PTSD and cognitive decline. Aims 1 and 2 will leverage existing data from the National Alzheimer's Coordinating Center (NACC). In adults aged 55+ years, multilevel modeling and interaction analyses will determine the impact of PTSD status on trajectories, rate, and temporal sequence of domain-specific cognitive decline and will test sex and APOE4 carrier status as potential effect modifiers. For Aim 3, men and women participants, aged 65+, with and without Criterion A trauma, will be recruited and multiple regression will be used to unambiguously clarify if PTSD severity (Criteria B through E) is associated with cognitive functioning without meeting Criterion A. This K01 award will provide training and mentorship in aging health, cognitive aging, sex-specific health effects of PTSD, neuropsychology of PTSD, longitudinal study design, and advanced statistics and propel the PI to become an independent investigator with expertise in the effects of traumatic stress and biopsychosocial factors on cognitive aging, with a sex-specific focus and in alignment with Goals B-3, B-4, and F-4 of NIA’s Strategic Directions 2020-2025.