Olfactory Dysfunction Predicts 5-Year Mortality in Older Adults

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.

[1]  D. Binder On the variances of asymptotically normal estimators from complex surveys , 1983 .

[2]  Michael Brauer,et al.  Associations of ambient air pollution with chronic obstructive pulmonary disease hospitalization and mortality. , 2013, American journal of respiratory and critical care medicine.

[3]  David W. Kern,et al.  Field Survey Measures of Olfaction , 2014, Field methods.

[4]  J. Sorkin,et al.  Serum albumin level and physical disability as predictors of mortality in older persons. , 1994, JAMA.

[5]  R. Moineddin,et al.  J-shapedness: an often missed, often miscalculated relation: the example of weight and mortality , 2014, Journal of Epidemiology & Community Health.

[6]  J. Mullol,et al.  Furthering the understanding of olfaction, prevalence of loss of smell and risk factors: a population-based survey (OLFACAT study) , 2012, BMJ Open.

[7]  Hideyuki Okano,et al.  In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus , 2000, Nature Medicine.

[8]  E. Pfeiffer A Short Portable Mental Status Questionnaire for the Assessment of Organic Brain Deficit in Elderly Patients † , 1975, Journal of the American Geriatrics Society.

[9]  J. Schwob,et al.  Neural regeneration and the peripheral olfactory system , 2002, The Anatomical record.

[10]  G. Beauchamp,et al.  Prenatal and postnatal flavor learning by human infants. , 2001, Pediatrics.

[11]  L. Fried,et al.  Frailty in older adults: evidence for a phenotype. , 2001, The journals of gerontology. Series A, Biological sciences and medical sciences.

[12]  R. Doty,et al.  Intranasal Administration of Neurotoxicants in Animals: Support for the Olfactory Vector Hypothesis of Parkinson’s Disease , 2011, Neurotoxicity Research.

[13]  N. Hays,et al.  The anorexia of aging in humans , 2006, Physiology & Behavior.

[14]  Anders Larsson,et al.  Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. , 2008, The New England journal of medicine.

[15]  G Bard Ermentrout,et al.  Intrinsic heterogeneity in oscillatory dynamics limits correlation-induced neural synchronization. , 2012, Journal of neurophysiology.

[16]  Kenneth M. Heilman,et al.  A brief olfactory test for Alzheimer's disease , 2013, Journal of the Neurological Sciences.

[17]  David A Bennett,et al.  Odor Identification and Progression of Parkinsonian Signs in Older Persons , 2008, Experimental aging research.

[18]  K. Flegal,et al.  Association of All-Cause Mortality With Overweight and Obesity Using Standard Body Mass Index Categories , 2012 .

[19]  David A Bennett,et al.  Olfactory Impairment in Presymptomatic Alzheimer's Disease , 2009, Annals of the New York Academy of Sciences.

[20]  G. Rettinger,et al.  Telomere Shortening Impairs Regeneration of the Olfactory Epithelium in Response to Injury but Not Under Homeostatic Conditions , 2011, PloS one.

[21]  D W Bates,et al.  Can comorbidity be measured by questionnaire rather than medical record review? , 1996, Medical care.

[22]  C. Henríquez-Roldán,et al.  Long-term Air Pollution Exposure Is Associated with Neuroinflammation, an Altered Innate Immune Response, Disruption of the Blood-Brain Barrier, Ultrafine Particulate Deposition, and Accumulation of Amyloid β-42 and α-Synuclein in Children and Young Adults , 2008, Toxicologic pathology.

[23]  S. Gustincich,et al.  Functional genomics reveals dysregulation of cortical olfactory receptors in Parkinson disease: novel putative chemoreceptors in the human brain. , 2013, Journal of neuropathology and experimental neurology.

[24]  Saskia le Cessie,et al.  Use of Framingham risk score and new biomarkers to predict cardiovascular mortality in older people: population based observational cohort study , 2009, BMJ : British Medical Journal.

[25]  Wendy Levinson,et al.  A study of sexuality and health among older adults in the United States. , 2007, The New England journal of medicine.

[26]  P. Hildebrandt,et al.  N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults. , 2005, JAMA.

[27]  R. Doty The olfactory vector hypothesis of neurodegenerative disease: Is it viable? , 2008, Annals of neurology.

[28]  P. Hildebrandt,et al.  N-Terminal Pro-Brain Natriuretic Peptide, C-Reactive Protein, and Urinary Albumin Levels as Predictors of Mortality and Cardiovascular Events in Older Adults , 2005 .

[29]  L. Ferrucci,et al.  Peripheral Blood Markers of Inflammation Predict Mortality and Functional Decline in High‐Functioning Community‐Dwelling Older Persons , 2002, Journal of the American Geriatrics Society.

[30]  E. Laumann,et al.  Sexuality: measures of partnerships, practices, attitudes, and problems in the National Social Life, Health, and Aging Study. , 2009, The journals of gerontology. Series B, Psychological sciences and social sciences.

[31]  E Guillibert,et al.  [Detecting alcoholism]. , 1984, Soins; la revue de reference infirmiere.

[32]  M. McClintock,et al.  Psychological Effects of Musky Compounds: Comparison of Androstadienone with Androstenol and Muscone , 2002, Hormones and Behavior.

[33]  L. Rosero-Bixby,et al.  Predicting mortality with biomarkers: a population-based prospective cohort study for elderly Costa Ricans , 2012, Population Health Metrics.

[34]  Yoshihito Niimura,et al.  Evolutionary dynamics of olfactory receptor genes in chordates: interaction between environments and genomic contents , 2009, Human Genomics.

[35]  Benoist Schaal,et al.  The Secretion of Areolar (Montgomery's) Glands from Lactating Women Elicits Selective, Unconditional Responses in Neonates , 2009, PloS one.

[36]  M. McClintock,et al.  Assessment of sensory function in the National Social Life, Health, and Aging Project. , 2009, The journals of gerontology. Series B, Psychological sciences and social sciences.

[37]  J. Tainmont A historical vignette (14). The anatomo-clinical method applied to ENT at the time of Jean Cruveilhier. , 2009, B-ENT.

[38]  C. O'muircheartaigh,et al.  Statistical design and estimation for the national social life, health, and aging project. , 2009, The journals of gerontology. Series B, Psychological sciences and social sciences.

[39]  R A Kronmal,et al.  Risk factors for 5-year mortality in older adults: the Cardiovascular Health Study. , 1998, JAMA.

[40]  Carole Ober,et al.  Paternally inherited HLA alleles are associated with women's choice of male odor , 2002, Nature Genetics.

[41]  E. Parati,et al.  Isolation and Characterization of Neural Stem Cells from the Adult Human Olfactory Bulb , 2000, Stem cells.

[42]  R. Suzman The National Social Life, Health, and Aging Project: an introduction. , 2009, The journals of gerontology. Series B, Psychological sciences and social sciences.

[43]  M. Makary,et al.  Frailty as a predictor of surgical outcomes in older patients. , 2010, Journal of the American College of Surgeons.

[44]  D. Roth,et al.  Body mass index, weight loss, and mortality in community-dwelling older adults. , 2007, The journals of gerontology. Series A, Biological sciences and medical sciences.

[45]  D. Qato,et al.  Racial and ethnic disparities in cardiovascular medication use among older adults in the United States , 2010, Pharmacoepidemiology and drug safety.

[46]  C. Seplaki,et al.  Predicting mortality from clinical and nonclinical biomarkers. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[47]  J. Ewing,et al.  Detecting alcoholism. The CAGE questionnaire. , 1984, JAMA.

[48]  Ageing, neurodegeneration, and olfactory and gustatory loss. , 2009, B-ENT.

[49]  L. Vosshall,et al.  An olfactory demography of a diverse metropolitan population , 2012, BMC Neuroscience.

[50]  G. Pham-Kanter,et al.  Measures of chronic conditions and diseases associated with aging in the national social life, health, and aging project. , 2009, The journals of gerontology. Series B, Psychological sciences and social sciences.

[51]  David W. Kern,et al.  Racial disparities in olfactory loss among older adults in the United States. , 2014, The journals of gerontology. Series A, Biological sciences and medical sciences.

[52]  C. Mueller,et al.  A new Procedure for the Short Screening of Olfactory Function Using Five Items from the “Sniffin’ Sticks” Identification Test Kit , 2006, American journal of rhinology.