Project 1 - Cognitive Function and Dementia

项目1：认知功能和痴呆-摘要 阿尔茨海默病和相关痴呆症（ADRD）的最大影响可能是在低- 中等收入国家（LMIC）。特别是撒哈拉以南非洲，预计将遇到一个戏剧性的 痴呆症患病率增加，越来越需要对ADRD进行严格的基于人群的研究， 这一区域南非的健康、老龄化和痴呆症：一项纵向研究（HAALSI） 老年痴呆症的流行病学问题。我们实施与全球协调一致的措施， 健康与退休研究（HRS）和协调认知评估协议（HCAP）网络， 使痴呆症及其风险因素的跨国比较成为可能。项目1（认知功能和 痴呆症）利用我们的深度表型HAALSI阿金库尔队列，以确定潜在的因果途径 认知轨迹，并将经过充分验证的神经心理学评估应用于全国代表 sample.这些数据将提供南非痴呆症患病率的第一个国家估计。我们这样做 通过在四个重叠的群组中紧密协调的工作。我们最初的HAALSI阿金库尔队列 包括5059名年龄≥40岁的受访者，我们收集了三波数据;此次更新将 增加两个额外的波浪。HAALSI-HCAP Agincourt（n = 700）是一个丰富的子队列，增加了详细的 ADRD的神经心理学测试、神经影像学和血液生物标志物;此次更新增加了一项额外的 HAALSI-HCAP Agincourt波（第3波）。我们建议进行一项新的、具有全国代表性的研究， 男性和女性（加上伴侣）以及HAALSI-HCAP全国调查（n = 624）。项目1有三个目标。要求1 重点是描述轻度认知障碍（MCI）和痴呆症的发病率和进展， 与Agincourt-HCAP富集队列中神经变性和ADRD神经病理学的关系。我们研究 脑老化的磁共振成像（MRI）标记物的纵向变化，并结合血浆 ADRD的标志物（即，Ab、p-tau、NfL、GFAP）来评估与痴呆症状的关联。在目标2中， 完善和验证HAALSI全球认知筛查、HAALSI-HCAP和HAALSI痴呆算法， 南非全国痴呆症调查。我们与项目4合作， HAALSI-HCAP波生成痴呆症和MCI的全国患病率估计。在目标3中，我们检查 社会因素的影响，包括教育质量和社会联系的新指标， 参与者的认知功能和变化轨迹。我们探索特殊教育的非正式教育经验， 在南非社会迅速变化的背景下的相关性，包括自学识字和 子女受教育程度对老年父母认知的影响。优化所有四个队列（HAALSI Agincourt， HAALSI-HCAP Agincourt，HAALSI National，HAALSI-HCAP National），我们确定了不同的生物和社会 南非影响晚年认知功能的疾病。HAALSI提供了丰富的、协调良好的数据 更好地了解ADRD的可变因素，并为全球预防战略提供信息。

Project 1: Cognitive Function and Dementia—Abstract The greatest impact of Alzheimer’s disease and related dementias (ADRD) is likely to be experienced in low- and middle-income countries (LMICs). Sub-Saharan Africa, in particular, is projected to encounter a dramatic increase in dementia prevalence and there is a growing need for rigorous population-based studies of ADRD in this region. Health, Aging and Dementia in South Africa: A Longitudinal Study (HAALSI) addresses core issues in dementia epidemiology in older South Africans. We implement measures harmonized with the global Health and Retirement Study (HRS) and Harmonized Cognitive Assessment Protocol (HCAP) networks to enable cross-national comparisons of dementia and its risk factors. Project 1 (Cognitive Function and Dementia) leverages our deeply phenotyped HAALSI Agincourt cohort to identify causal pathways underlying cognitive trajectories and applies well-validated neuropsychological assessments to a nationally representative sample. These data will provide the first national estimates of dementia prevalence in South Africa. We do this through tightly coordinated work across four overlapping cohorts. Our original HAALSI Agincourt cohort comprised 5059 respondents ≥40 years of age, for whom we collected three waves of data; this renewal will add two additional waves. HAALSI-HCAP Agincourt (n≈700) is an enriched subcohort that adds detailed neuropsychological testing, neuroimaging, and blood biomarkers of ADRD; this renewal adds one additional wave of HAALSI-HCAP Agincourt (wave 3). We propose to field a new, nationally representative study of 4500 men and women (plus partners) and a HAALSI-HCAP National survey (n≈624). Project 1 has 3 aims. Aim 1 focuses on characterizing the incidence and progression of mild cognitive impairment (MCI) and dementia in relation to neurodegeneration and ADRD neuropathology in the enriched Agincourt-HCAP cohort. We examine longitudinal change in magnetic resonance imaging (MRI) markers of brain aging and incorporate plasma markers of ADRD (i.e., Ab, p-tau, NfL, GFAP) to assess associations with dementia symptoms. In Aim 2, we refine and validate the HAALSI Global Cognitive Screen, HAALSI-HCAP, and HAALSI dementia algorithms for South African nationwide surveys of dementia. We collaborate with Project 4 to conduct a baseline National HAALSI-HCAP wave to generate national prevalence estimates for dementia and MCI. In Aim 3, we examine the impact of social factors, including novel indicators of educational quality and social connection on participants’ cognitive function and change trajectories. We explore informal educational experiences of special relevance in the context of rapid social changes in South Africa, including self-taught literacy and effects of children’s educational attainment on cognition in older parents. Optimizing all four cohorts (HAALSI Agincourt, HAALSI-HCAP Agincourt, HAALSI National, HAALSI-HCAP National) we identify distinct biological and social conditions that affect late-life cognitive function in South Africa. HAALSI provides rich, well-harmonized data to better understand modifiable factors in ADRD and inform global prevention strategies.