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Neuroanatomic connections link the olfactory and limbic systems potentially explaining an association between olfactory dysfunction and depression. Some previous studies have demonstrated that olfactory dysfunction is associated with increased depressive symptoms. However, these studies were cross-sectional and unable to establish which develops first. We used longitudinal data to determine if impaired odor identification increased subsequent depressive symptoms or vice versa. We assessed olfaction and depression in the National Social Life, Health, and Aging Project, a nationally representative, 15-year longitudinal study of older US adults. Olfaction was measured using a validated odor identification test (Sniffin' Sticks). Depressive symptoms were measured using a modified version of the validated Center for Epidemiological Studies Depression Scale. Multivariable logistic regression models examined the temporal relationships between developing olfactory dysfunction and depression while accounting for demographics, disease comorbidities, alcohol use, smoking, and cognition. Older adults with olfactory dysfunction had concurrent frequent depressive symptoms (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.00–1.43). Among healthy adults at baseline, those who had olfactory dysfunction were more likely to develop frequent depressive symptoms 5 or 10 years later (OR = 2.22, 95% CI = 1.13–4.37). Conversely, those with frequent depressive symptoms at baseline were not more likely to develop olfactory dysfunction 5 or 10 years later. We show for the first time that olfactory dysfunction predicts subsequent development of depression in older US adults. These data support screening for depression in older adults with chemosensory impairment and set the stage for disentangling the relationship between olfaction and depression. [ABSTRACT FROM AUTHOR]

Inflammation has been implicated in physical frailty, but its role in sensory impairment is unclear. Given that olfactory impairment predicts dementia and mortality, determining the role of the immune system in olfactory dysfunction would provide insights mechanisms of neurosensory decline. We analyzed data from the National Social Life, Health and Aging Project, a representative sample of home-dwelling older US adults. Plasma levels of 18 cytokines were measured using standard protocols (Luminex xMAP). Olfactory function was assessed with validated tools (n -butanol sensitivity and odor identification, each via Sniffin' Sticks). We tested the association between cytokine profiles and olfactory function using multivariate ordinal logistic regression, adjusting for age, gender, race/ethnicity, education level, cognitive function, smoking status, and comorbidity. Older adults with the IL-1Rahigh-IL-4low-IL-13low cytokine profile had worse n -butanol odor sensitivity (odds ratio [OR] = 1.61, 95% confidence interval [CI] 1.19–2.17) and worse odor identification (OR = 1.42, 95% CI 1.11–1.80). Proinflammatory, Th1, or Th2 cytokine profiles were not associated with olfactory function. Moreover, accounting for physical frailty did not alter the main findings. In conclusion, we identified a plasma cytokine signature—IL-1Rahigh-IL-4low-IL-13low—that is associated with olfactory dysfunction in older US adults. These data implicate systemic inflammation in age-related olfactory dysfunction and support a role for immune mechanisms in this process, a concept that warrants additional scrutiny. [ABSTRACT FROM AUTHOR]