Poor sense of smell and the health of older adults

项目总结/摘要 多达四分之一的美国老年人嗅觉差，这是一种大多数人都没有意识到的感官障碍。 的.我们和其他人发现嗅觉差是痴呆症和帕金森病的一个重要早期症状 (PD)，并稳健地预测加速死亡率。其他人也推测，嗅觉差会对 营养、安全和生活质量，但在很大程度上缺乏严格的经验数据。我们最新的分析 痴呆、帕金森病和体重减轻加在一起只能解释约30%的嗅觉不良相关过度 老年人的死亡率增加，导致这种死亡率增加的大部分潜在原因仍然未知。 因此，拟议的项目旨在利用预测和信息能力， 通过回答两个新颖且具有临床意义的问题，简单且无创的嗅觉测试：1）什么 不良的健康后果可能是老年人嗅觉不良的潜在预兆，此外， 神经退行性疾病2)嗅觉差是加速衰老的标志吗？我们将广泛利用 来自健康ABC和ARIC神经认知研究的前瞻性数据-成熟的基于社区的 具有可比人群、研究设计和数据收集的双盲队列。据我们所知， 这项研究将是迄今为止规模最大的一项研究，将客观测试的嗅觉和纵向评估相结合， 8，630名年龄≥65岁的美国成年人的健康结局，包括56.6%的女性和27.6%的非洲裔美国人， 评估性别和种族的影响。我们假设，作为一个早期标志物和/或贡献者，嗅觉差， 老年人意味着多种主要疾病的风险增加，包括但不限于痴呆和PD（目的 1），身体，肺，认知/精神功能下降，虚弱（目的2），它与 年龄加速的表观遗传标记（Aim 3）。根据我们的初步发现，我们进一步假设， 性别和种族可能会改变痴呆、PD和其他不良健康结果之间的关系， 嗅觉差这些目标得到了我们严格的已发表和未发表的初步数据的支持， 一个由流行病学家、生物统计学家和临床研究人员组成的多学科团队，具有良好的跟踪记录 富有成效的合作。大样本量、精心收集的健康数据， 精心计划的统计分析，研究结果的交叉验证，策略性的汇总分析，以及一个非常 经验丰富的多机构研究团队。我们创新的分析和预测结果将 除了痴呆症之外，还大大促进了对嗅觉不良对老年人健康的理解 和PD，因此可能有助于将老年临床范式转向评估老年人的嗅觉， 临床访问，以监测和更好地预测即将发生的疾病的风险， 新的干预性试验，并最终改善老年人的健康和生存。

PROJECT SUMMARY/ABSTRACT Up to a quarter of older US adults have a poor sense of smell, a sensory impairment which most are unaware of. We and others found that poor olfaction is an important early symptom of dementia and Parkinson’s disease (PD), and robustly predicts accelerated mortality. Others also speculate that poor olfaction adversely affects nutrition, safety, and quality of life, but rigorous empirical data are largely lacking. Our most recent analysis revealed that dementia, PD, and weight loss combined explained only ~30% of poor olfaction-associated excess mortality in older adults, leaving a large portion of the potential causes of such increased mortality still unknown. The proposed project thus aims to leverage the predictive and informational power available via inexpensive, facile, and noninvasive olfaction testing, by answering two novel and clinically-significant questions: 1) What adverse health outcomes can a poor sense of smell in older adults potentially herald, in addition to neurodegenerative diseases? 2) Is poor olfaction a marker of accelerated aging? We will exploit extensive prospective data from the Health ABC and ARIC-Neurocognitive studies – well-established community-based biracial cohorts with comparable populations, study design, and data collection. To our knowledge, the proposed study will be the largest to date, combining the objectively-tested sense of smell and longitudinally assessed health outcomes in 8,630 US adults aged ≥65 years, including 56.6% women and 27.6% African Americans to assess sex and racial influences. We hypothesize that, as an early marker and/or contributor, poor olfaction in older adults signifies elevated risk of multiple major diseases, including but not limited to dementia and PD (Aim 1), declines in physical, pulmonary, and cognitive/mental functions, and frailty (Aim 2), and it is associated with epigenetic markers of age acceleration (Aim 3). Based on our preliminary findings, we further hypothesize that sex and race may modify the relationships of dementia, PD, and other adverse health outcomes associated with a poor sense of smell. The aims are supported by our rigorous published and unpublished preliminary data, and a multidisciplinary team of epidemiologists, biostatisticians, and clinical researchers with a proven track record of productive collaborations. Scientific rigor is assured by large sample sizes, meticulously collected health data, carefully planned statistical analyses, cross-validation of study findings, strategized pooled analyses, and a very experienced multi-institutional research team. Our innovative proposed analyses and predicted results will significantly advance understanding of what poor olfaction means for the health of older adults, besides dementia and PD, and may thus help shift the geriatric clinical paradigm toward assessing olfaction in the elderly during clinical visits, to monitor and better anticipate risks of impending conditions, to inform the identification of at-risk populations for novel interventional trials, and ultimately to improve the health and survival of older adults.