URBAn Native Elders (URBANE): Risk and Protective Factors for Alzheimer's and Related Dementias

摘要：阿尔茨海默病及相关疾病（ADRD）是美国人日益关注的公共卫生问题 印第安人和阿拉斯加原住民（AI/AN），但AI/AN在ADRD研究中的代表性严重不足。为 例如，国家阿尔茨海默氏症协调中心数据库，这是有影响力的ADRD的重要资源 研究，包括31，000名成年人中的162名AI/AN（0.5%）。这是一个令人不安的排除，因为AI/AN具有很高的 许多ADRD风险因素的负担，包括高血压、2型糖尿病、创伤性脑损伤、血管性脑损伤 创伤（VBI）和中风。美国印第安人脑血管疾病及其后果（CDCAI）研究， 由我们的研究小组进行的，是唯一一项前瞻性队列研究， 认知功能，ADRD和VBI在任何美国本土人群。在第一波考试中，CDCAI收集了 在818老年AI/AN生活在保留在3个主要的农村，地理区域;第二波考试是 正在进行中CDCAI在AI/AN的ADRD风险因素和生物标志物方面产生了开创性的发现; 33%的样本 显示出VBI的证据，男性甚至更高。然而，该队列并不能代表全国AI/AN人群 因为72%的人工智能/人工智能现在居住在城市地区。城市A/AN代表了一个基本上不存在的“无形部落” 从健康研究。一个可能的解释是，城市环境具有独特的风险和保护性， 概况，包括加剧与年龄相关的认知能力下降的生活方式因素，以及保护因素，如 更好地获得急症和专科护理，并接受更高水平的教育。因此，我们提出了一项新的研究， URBAN Native Elders（URBANE），在具有广泛地理分布的大型城市AI/AN队列中复制CDCAI 表示.我们将在5个地理位置不同的大都市招募1，200名年龄在55岁及以上的男性和女性 有大量AI/AN人口的地区。数据收集将包括所有参与者的MRI， 所有种族人群中与ADRD相关的等位基因。我们将扩大CDCAI协议，以反映国家的- 艺术成像和神经心理学评估。我们将使用CDCAI建立的协议来估计 基于一次检查的可能的ADRD。结果分析将建立认知障碍的基线患病率。 损伤、可能的ADRD和VBI及其与临床、遗传、神经影像学、行为和 生活方式风险和保护因素。重要的是，这项横向研究将为未来的研究奠定基础。 ADRD的纵向研究。我们的具体目标是：量化可能的ADRD和VBI的程度， 通过大脑MRI定义，并确定它们与城市不同样本中认知功能的关联。 AI/AN长老。2)评价传统风险因素与可能的ADRD之间的关联，并评价 VBI对选定风险因素的潜在介导作用。3)在探索性分析中，评估以下方面的潜在差异： 我们的主要协会按性别;并评估教育和获得医疗保健作为潜在的保护因素 老年VBI患者的认知障碍和可能的ADRD。

ABSTRACT: Alzheimer’s disease and related disorders (ADRD) is a growing public health concern for American Indian and Alaska Native (AI/ANs) people, but AI/ANs are profoundly underrepresented in ADRD research. For example, the National Alzheimer’s Coordinating Center database, an important resource for influential ADRD studies, includes just 162 AI/ANs out of 31,000 adults (0.5%). This is a troubling exclusion, since AI/ANs have high burdens of many ADRD risk factors, including hypertension, type 2 diabetes, traumatic brain injury, vascular brain injury (VBI), and stroke. The Cerebrovascular Disease and its Consequences in American Indians (CDCAI) study, conducted by our research group, is the only prospective cohort study with longitudinal data for rigorous evaluation of cognitive function, ADRD, and VBI in any US Native population. In its first wave of exams, CDCAI collected data on 818 elderly AI/ANs living on reservations in 3 primarily rural, geographic regions; the second wave of exams is underway. CDCAI is yielding seminal findings on ADRD risk factors and biomarkers in AI/ANs; 33% of the sample showed evidence of VBI, with men even higher. Yet the cohort is not representative of the national AI/AN population because 72% of AI/ANs now reside in urban areas. Urban A/ANs represent an “invisible tribe” that is largely absent from health research. One likely explanation is that urban environments feature distinctive risk and protective profiles, including lifestyle factors that exacerbate age-related cognitive decline, and protective factors such as better access to acute and specialty care and higher levels of education. Accordingly, we propose a novel study, URBan Native Elders (URBANE), to replicate CDCAI in a large cohort of urban AI/ANs with broad geographic representation. We will recruit 1,200 men and women ages 55 and older in 5 geographically diverse metropolitan areas with large AI/AN populations. Data collection will include MRI for all participants, and genetic testing for alleles associated with ADRD in the all-races population. We will expand CDCAI protocols to reflect state-of-the- art imaging and neuropsychological assessments. We will use protocols established by the CDCAI to estimate probable ADRD based on a single exam. The resulting analyses will establish the baseline prevalence of cognitive impairment, probable ADRD, and VBI and their associations with clinical, genetic, neuroimaging, behavioral, and lifestyle risk and protective factors. Of importance, this cross-sectional study will lay the foundation for future longitudinal research on ADRD. Our Specific Aims are to: Quantify the extent of probable ADRD and VBI as defined by brain MRI, and determine their associations with cognitive functioning in a diverse sample of urban AI/AN elders. 2) Evaluate associations between conventional risk factors and probable ADRD, and evaluate potential mediation of selected risk factors by VBI. 3) In an exploratory analysis, evaluate potential differences in our primary associations by sex; and evaluate education and access to healthcare as potential protective factors for cognitive impairment and probable ADRD in elders with VBI.