Poor sense of smell and the health of older adults

项目摘要/摘要 多达四分之一的美国老年人嗅觉差，大多数人都没有意识到这种感觉障碍 的。我们和其他人发现，嗅觉不良是痴呆症和帕金森氏症的重要早期症状 (PD)，并有力地预测了死亡率的加速。其他人也推测，嗅觉不佳会对 营养、安全性和生活质量，但在很大程度上缺乏严格的实证数据。我们最新的分析 研究显示，痴呆症、帕金森病和体重减轻加在一起，只能解释大约30%的嗅觉不良相关的过度反应 老年人死亡率上升，导致死亡率上升的很大一部分潜在原因仍不清楚。 因此，拟议的项目旨在利用通过廉价、 通过回答两个具有临床意义的新问题，方便、非侵入性的嗅觉测试：1)什么 不良的健康后果可能预示着老年人的嗅觉不良，此外 神经退行性疾病？2)嗅觉差是衰老加速的标志吗？我们将广泛利用 来自健康ABC和ARIC的前瞻性数据-神经认知研究-以社区为基础 具有可比人群、研究设计和数据收集的混血儿队列。据我们所知，建议的 这项研究将是迄今为止规模最大的，将经过客观测试的嗅觉和纵向评估相结合。 年龄65岁的8,630名美国成年人的健康状况，其中56.6%的女性和27.6%的非裔美国人≥ 评估性和种族影响。我们假设，作为早期的标记和/或因素，嗅觉障碍 老年人意味着患多种重大疾病的风险增加，包括但不限于痴呆症和帕金森病(AIM) 1)，身体、肺和认知/精神功能下降，以及虚弱(目标2)，它与 年龄加速的表观遗传标记(目标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症、帕金森病和其他与以下因素相关的不良健康后果的关系 嗅觉差。这些目标得到了我们严格的已公布和未公布的初步数据的支持，以及 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。科学的严谨性是由大量的样本和精心收集的健康数据保证的， 精心计划的统计分析、研究结果的交叉验证、战略性的汇集分析，以及非常 经验丰富的跨机构研究团队。我们创新的建议分析和预测结果将 除了痴呆症，极大地提高了对嗅觉不良对老年人健康意味着什么的理解 和帕金森病，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情况的风险，为识别处于危险中的情况提供信息 新的干预试验，并最终改善老年人的健康和存活率。

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.