Abstract
Prediction of mortality has focused on disease and frailty, although antecedent biomarkers may herald broad physiological decline. Olfaction, an ancestral chemical system, is a strong candidate biomarker because it is linked to diverse physiological processes. We sought to determine if olfactory dysfunction is a harbinger of 5-year mortality in the National Social Life, Health and Aging Project [NSHAP], a nationally representative sample of older U.S. adults. 3,005 community-dwelling adults aged 57–85 were studied in 2005–6 (Wave 1) and their mortality determined in 2010–11 (Wave 2). Olfactory dysfunction, determined objectively at Wave 1, was used to estimate the odds of 5-year, all cause mortality via logistic regression, controlling for demographics and health factors. Mortality for anosmic older adults was four times that of normosmic individuals while hyposmic individuals had intermediate mortality (p<0.001), a “dose-dependent” effect present across the age range. In a comprehensive model that included potential confounding factors, anosmic older adults had over three times the odds of death compared to normosmic individuals (OR, 3.37 [95%CI 2.04, 5.57]), higher than and independent of known leading causes of death, and did not result from the following mechanisms: nutrition, cognitive function, mental health, smoking and alcohol abuse or frailty. Olfactory function is thus one of the strongest predictors of 5-year mortality and may serve as a bellwether for slowed cellular regeneration or as a marker of cumulative toxic environmental exposures. This finding provides clues for pinpointing an underlying mechanism related to a fundamental component of the aging process.
Highlights
Olfaction is a critical, if underappreciated, component of human physiology
The weighted 5-year mortality rate among the analytic sample was 12.5%, consistent with what would be expected based on the Social Security Administration (SSA) life tables[37]
39% of older adults with anosmia were dead at Wave 2, 19% of those with hyposmia and only 10% of those with normal olfaction (p,0.001), a dose-dependent pattern seen in all age groups (Figure 1A)
Summary
Potentially less dependent on olfaction than many other mammals [1], humans still rely on this ancestral system which plays an essential role in health and behavior. Normal olfactory function depends on cellular regeneration of the olfactory neuroepithelium, bulb and hippocampus [10,11,12], a capacity impaired by telomere shortening which is a hallmark of aging in many systems [13]. Olfactory dysfunction presages major neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease, assessed both clinically and post-mortem, and even mild cognitive impairment [17,18,19]. Given that olfaction has multiple roles and relies on peripheral and central cell regeneration, we hypothesized that olfactory dysfunction could be an early integrative indicator of impending death
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