Multisensory, Motor, and Biomarker Changes in Aging and Preclinical Alzheimer's Disease

家长拨款摘要(RF1 AG066837) 阿尔茨海默病(AD)和其他导致认知障碍的原因正在成为日益严重的公共卫生问题 大量婴儿潮一代的老龄化，以及迎接未来的工人和设施短缺 阿尔茨海默病和其他痴呆患者的护理需求。与广告相关的大脑变化可能会发生数年或数十年 在症状出现之前，因此，在中年识别AD的高危人群是很重要的 提供充分的机会在可能延迟临床上有意义的 症状和丧失独立性。纵向研究表明，感觉(听觉、视觉、嗅觉) 运动障碍与认知障碍、痴呆症或AD的风险增加有关。这 项目是研究衰老对感觉功能(听觉、嗅觉、视觉和味觉)的影响以及 运动功能对中年人临床前阿尔茨海默病10年风险的影响。海狸水坝后代研究是一项 人群成年后代感觉和认知老化的纵向队列研究 听力损失流行病学研究队列。参与者(N=1536，平均年龄49岁)的数据 基线(2005-2008年)、5年随访(2010-2013年)和10年随访(2015-2013年)的储存血清样本 2017)考试将包括在内。三个时间点的储存样本将进行血清检测 淀粉样蛋白β40和β42(Aβ40，Aβ42)，血清总tau(TT)和神经丝轻链(NFL)； 阿尔茨海默氏症的病理、神经元损伤和神经变性。 将使用最小二乘多元线性回归模型和纵向线性混合效应模型 确定感觉和运动功能与AD和痴呆的其他传统危险因素是否相关 A-β、TT和NFL水平分别在基线和10年后发生变化。这个 生物标志物，Aβ，TT和NFL，以及黄斑神经节细胞内丛状层的厚度(MGCIPL)将是 应用于NIA-阿尔茨海默病协会AT(N)框架的修改以识别临床前阿尔茨海默病 以及中年的非阿尔茨海默氏症神经病理学。使用这个修改后的框架和传统认知 结果我们将确定衰老中的感觉和运动变化是否有助于10年风险预测模型 用于生物学上和功能上定义的临床前AD。最佳预测模型结果将扩展到 创建临床有用的风险评分。无症状中年人的风险评分是基于 实用的测试电池将在临床和研究环境中有用。

PARENT GRANT ABSTRACT (RF1 AG066837) Alzheimer’s disease (AD) and other causes of cognitive impairment are growing public health problems with the aging of the large baby boom generation and there is a shortage of workers and facilities to meet the future care needs of those with AD and other dementias. AD-related brain changes may occur years or decades before the onset of symptoms and, therefore, it is important to identify, in midlife, people at high risk for AD to provide ample opportunity to intervene when it may be possible to delay the onset of clinically significant symptoms and loss of independence. Longitudinal studies have shown that sensory (hearing, vision, olfaction) and motor impairments are associated with increased risk of cognitive impairment, dementia, or AD. This project is to study the impact of aging changes in sensory function (hearing, olfaction, vision, and taste) and motor function on the 10-yr risk of pre-clinical AD in middle-aged adults. The Beaver Dam Offspring Study is a longitudinal cohort study of sensory and cognitive aging in the adult offspring of the population-based Epidemiology of Hearing Loss Study cohort. Data from participants (N=1536, mean age 49 years) who have stored serum samples from the baseline (2005-2008), 5-yr follow-up (2010-2013) and 10-yr follow-up (2015- 2017) examinations will be included. Stored samples from the three time points will be assayed for serum amyloid β40 and β42 (Aβ40, Aβ42), serum total tau (TT) and neurofilament light chain (NfL); biomarkers of Alzheimer’s pathology, neuronal injury and neurodegeneration. Least squares multiple linear regression models and longitudinal linear mixed effects models will be used to determine if sensory and motor function and other traditional risk factors for AD and dementia are associated with levels of Aβ, TT and NfL at baseline and 10-year change, respectively, in these serum biomarkers. The biomarkers, Aβ, TT and NfL, and thickness of the macular ganglion cell inner plexiform layer (mGCIPL) will be applied to a modification of the NIA-Alzheimer’s Association AT(N) framework to identify preclinical Alzheimer’s and non-Alzheimer’s neuropathology in midlife. Using this modified framework and traditional cognitive outcomes we will determine if sensory and motor changes in aging contribute to 10-year risk prediction models for biologically and functionally defined preclinical AD. The best prediction model results will be extended to create clinically useful risk scores. Risk scores for asymptomatic middle-aged people which are based on practical test batteries will be useful in clinical and research settings.