Wisconsin longitudinal study: Initial lifetime's impact on Alzheimer's disease and related disorders (WLS-ILIAD)

摘要 这项应用的首要科学前提是评估社会优势的积累是如何 在整个生命过程中，逆境会影响阿尔茨海默病（AD）和相关疾病的风险和恢复力。 痴呆症（ADRD）。虽然社会科学和生物科学界对这一问题有着相当大的热情， 关于多方面疾病的社会生物学基础， 社会问题和健康的社会决定因素，有证据明确地将 * 终生 * 社会暴露与 AD/ADRD仍然有限。由于缺乏涵盖整个生命周期的数据， 当然，以及相对忽视性，特别是性别，如何塑造这些过程。我们解决 这些差距与国家情报局资助的R 01（AG 06073）的竞争性续期申请，题为“威斯康星州” 纵向研究-初始寿命对ADRD的影响（WLS-ILIAD）"，该研究开始跟踪AD和相关疾病， 2019年老年人队列中的痴呆发作，前瞻性收集的数据延伸到他们的出生 年在当前赠款周期（2018-2023年）内实现了约80%的回复率，更新后的项目 将继续评估参与者超过85岁的痴呆症。我们建议继续进行WLS-ILIAD 项目建立一个宝贵的和独特的全面的数据集，这将使我们-和我们更广泛的用户 基础-描述AD生物标志物、认知、社会、行为和风险参与者的医学概况 或者对痴呆症有抵抗力该提案的具体目标包括：目标1：我们将继续跟踪痴呆症 在使用严格的AD生物标志物的WLS队列中，当参与者年龄约为85-90岁时。和以前一样，数据将 供公众广泛使用。目的2：我们将在完整样本（n=~5000）中添加血浆AD生物标志物， 检查核心AD生物标志物是否可以预测和调节认知功能、AD风险或恢复力。淀粉样 将对200名参与者进行tau PET脑扫描和脑脊液（CSF）采集， 100次随访访视，以验证基于血液的生物标志物，并确定特定血液AD的临界点 生物标志物。目标3.研究积累的社会优势和逆境如何影响风险和复原力 针对痴呆症发作，注意性别/性别差异。这一目标侧重于两种形式的复原力。 第一个是对痴呆症的恢复力。不管潜在的病理学，归因于痴呆症的成本是 更高，预计到2050年，全球用于痴呆症的医疗保健支出将达到1.6万亿美元，因此， 决定因素是关键。第二种类型是没有临床症状或痴呆， 通过生前疾病生物标志物确定的AD病理学。目的4：利用AD生物标志物 在目标2中收集的数据，我们将对非裔美国人和土著参与者的大样本（n=468）进行折叠 参加了威斯康星州ADRC，分析早期生活的优势和逆境如何影响恢复力， 认知功能在AD病理的存在。这扩展了前一个赠款期关注的目标 早期生活对痴呆风险和恢复力的影响。

Abstract The overarching scientific premise of this application is to evaluate how the accumulation of social advantage and adversity over the full life course impacts risk and resilience against Alzheimer’s Disease (AD) and Related Dementias (ADRD). While there is considerable enthusiasm across the social and biological sciences regarding the sociobiological underpinnings of multifaceted diseases, including a growing research base on the social exposome and social determinants of health, evidence clearly linking *lifetime* social exposures to AD/ADRD remains limited. Existing work has been hampered by the paucity of data that covers the full life course, and relative inattention to how sex and, especially gender, may shape these processes. We address these gaps with the competing renewal application of an NIA-funded R01 (AG06073), entitled the “Wisconsin Longitudinal Study-Initial Lifetime’s Impact on ADRD (WLS-ILIAD)”, which began tracking AD and related dementia onset in 2019 among a cohort of older adults with prospectively collected data extending to their birth year. Having achieved an ~80% response rate during the current grant cycle (2018-2023), the renewed project would continue to assess for dementia as participants surpass age 85. We propose to continue the WLS-ILIAD project to build an invaluable and uniquely comprehensive dataset, which will allow us-and our broader user base-to characterize the AD biomarkers, cognitive, social, behavioral, and medical profile of participants at risk or resilient to dementia. The specific aims for this proposal include: Aim 1: We will continue to track dementia in the WLS cohort using rigorous AD biomarkers, when participants will be ~age 85-90. As before, data will be released for broad public use. Aim 2: We will add plasma AD biomarkers to the full sample (n=~5000) to examine whether core AD biomarkers predict and moderate cognitive function, AD risk, or resilience. Amyloid and tau PET brain scans, and cerebrospinal fluid (CSF) collection will be performed on 200 participants with 100 follow up visits to validate the blood-based biomarkers and identify cut points for specific blood AD biomarkers. Aim 3. Examine how accumulated social advantage and adversity influence risk and resilience against dementia onset, with attention to sex/gender differences. This aim focuses on two forms of resilience. The first is resilience to dementia. Regardless of underlying pathology, the costs attributable to dementia are high, with global health care spending on dementia projected to reach $1.6 trillion by 2050, so attention to its determinants are critical. The second type is the absence of clinical symptoms or dementia in the presence of AD pathology as established through antemortem disease biomarkers. Aim 4: Drawing on AD biomarkers collected in Aim 2, we will fold a large sample (n=468) of African American and Indigenous participants enrolled in the Wisconsin ADRC to analyze how early life advantage and adversity impact resilience in cognitive function in the presence of AD pathology. This extends the aims of the prior grant period’s attention to early life influences on dementia risk and resilience.