Olfactory dysfunction predicts 5-year mortality in older adults

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.

Figure 1

A. Olfactory dysfunction and 5-year mortality in three age groups (ages 57–64, 65–74, and 75–85 years). B. Progressive increase in 5-year mortality with each additional error in odor identification (p<0.001 from one degree of freedom test for trend); from logistic regression as in Model C Table 2, with number of odor identification errors.

Figure 2. Odds for 5-year mortality for olfactory dysfunction compared to most common causes of death.

Odds ratios with 95% confidence intervals are displayed in forest plot format. Confidence intervals that do not cross the vertical dashed line (odds ratio  = 1) indicate statistical significance at the 0.05 level. Heart attack refers to myocardial infarction, whereas heart failure refers to congestive heart failure.

Figure 3. Effect of olfactory ability on the mean predicted probability of 5-year mortality, adjusting for age (A) and composite mortality risk score composed of all variables in Model C except olfaction (B).

At the 75^th percentile of composite mortality risk, anosmia increases the average probability of death to 0.39 from 0.16 for normal smellers.