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 The aims are supported by our rigorous published and unpublished preliminary data, and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.