Child Maltreatment and Risk for Mild Cognitive Impairment and Alzheimer's Disease

项目摘要/摘要 早年的逆境与各种负面后果有关，包括轻度认知风险。 损害(MCI)和阿尔茨海默病(AD)。然而，对两者之间关系的了解 儿童时期的逆境--特别是虐待和忽视儿童--以及认知能力下降和功能下降 成年是有限的。现有研究在很大程度上依赖于横断面研究和回溯性自我报告。 儿童期虐待的案例。虽然这些研究的结果是提示性的，确凿的证据表明 证实虐待儿童和认知功能减退与阿尔茨海默病并不存在，在文献上有很大差距。 对回溯性自我报告的依赖，特别是在人口老龄化或老龄化的情况下，会导致以下问题 该信息的可靠性和有效性。这项拟议的研究试图：(1)确定认知能力 在有记录的虐待史以及他们是否面临更高风险的成年人中，下降更快 对于MCI和AD；(2)检查从虐待儿童到增加MCI/AD风险的两条假设路径 通过(A)身体健康和心理社会风险因素和(B)生物标记物；(3)审查潜力 可修改和不可修改的风险因素，可保护受虐待儿童免受MCI/AD风险；以及(4) 使用儿童虐待的前瞻性报告和回顾报告比较MCI/AD的风险，并确定 老化样本中回溯性报告的可靠性和有效性。利用独特的前景 纵向研究，拟议的研究将使用现有的和新收集的数据从大样本 特征良好的高危个体，已被研究了30多年。这项研究有一个数字 克服了以前研究的许多局限性的重要方法优势；(1)长 定期随访(2020年估计平均年龄59岁)；(2)有记录的虐待和忽视儿童案件；(3)a 根据年龄、性别、种族/民族、 和儿童遭受虐待和忽视时的大致家庭社会阶层；(4)高已知风险率 两组中MCI/AD的因素；(5)允许解开以下问题的前瞻性纵向设计 病因和时间顺序；(6)多样化的样本，包括男性、女性、黑人和白人；(7) 参与者和采访者对研究的目的视而不见，避免了偏见问题；以及(8) 已经在几个时间点收集了关于调解人的数据。新的数据收集将包括 神经心理学电池使用NIH工具箱和NACC统一数据集的组件，抽血 测定载脂蛋白Eε4等位基因、表观遗传年龄、端粒长度和免疫功能，评估态度 促进老龄化和重新评估以前的指标，以及关于虐待儿童的回顾自我报告。 建议的研究比设计一项新的前瞻性纵向研究更具成本效益和可行性 有了这些元素。这项研究还将生成可供协作使用的数据档案 儿童期虐待对认知功能减退及MCI和AD风险的影响

PROJECT ABSTRACT/SUMMARY Early life adversities have been associated with a variety of negative outcomes, including risk for mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, knowledge about the relationship between childhood adversities – particularly child abuse and neglect – and cognitive decline and functioning in adulthood is limited. Existing research relies heavily on cross-sectional studies and retrospective self-reports of childhood maltreatment. While the results of these studies are suggestive, conclusive evidence linking verified child maltreatment and cognitive decline and AD does not exist, a significant gap in the literature. Reliance on retrospective self-reports, particularly with an aging or aged population, leads to questions about the reliability and validity of that information. The proposed research seeks to: (1) determine whether cognitive decline is more rapid in adults with documented maltreatment histories and whether they are at increased risk for MCI and AD; (2) examine two hypothesized pathways from child maltreatment to increased risk for MCI/AD through (a) physical health and psychosocial risk factors and (b) biological markers; (3) examine potential modifiable and non-modifiable risk factors that may protect maltreated children from risk for MCI/AD; and (4) compare risk for MCI/AD using both prospective and retrospective reports of child maltreatment and determine the reliability and validity of retrospective reports in an aging sample. Capitalizing on a unique prospective longitudinal study, the proposed research will use existing and newly collected data from a large sample of well-characterized, high-risk individuals that have been studied for over 30 years. This research has a number of important methodological advantages that overcome many of the limitations of previous research; (1) long term follow-up (estimated mean age 59 in 2020); (2) documented cases of child abuse and neglect; (3) a control group of children who were matched to the documented cases on the basis of age, sex, race/ethnicity, and approximate family social class at the time of the childhood abuse and neglect; (4) high rates of known risk factors for MCI/AD in both groups; (5) prospective longitudinal design that permits disentangling of issues of etiology and temporal sequence; (6) a diverse sample, including males, females, Blacks, and Whites; (7) participants and interviewers have been blinded to the purpose of the study, avoiding issues of bias; and (8) data on mediators has already been collected over several time points. The new data collection will include a neuropsychological battery using components of the NIH toolbox and NACC Uniform Data Set, a blood draw to determine APOE ε4 allele, epigenetic age, telomere length and immune function, assessment of attitudes towards aging and re-assessment of previous indicators, and retrospective self-reports of child maltreatment. The proposed research is more cost effective and feasible than designing a new prospective longitudinal study with these elements. This study will also generate a data archive that would be available for collaborative investigations of the effects of child maltreatment on cognitive decline and risk for MCI and AD.