Clinical manifestations

Presentation and course

	• Clinically significant olfactory loss is common in the elderly but is frequently unrecognized, in part because deficits typically begin insidiously and accumulate gradually over decades.
	• Self-reported olfactory impairment significantly underestimates prevalence rates obtained by olfactory testing.
	• The elderly have higher olfactory thresholds, perceive suprathreshold odors less intensely, and are less able to discriminate odors or to recognize and identify common odors.
	• Because chemosensory impairment is so prevalent among the elderly, many elderly people complain that food lacks flavor (hypogeusia).

Clinically significant olfactory loss is common in the elderly, but is frequently unrecognized, in part because deficits typically begin insidiously and accumulate gradually over decades: indeed, self-reported olfactory impairment significantly underestimates prevalence rates obtained by olfactory testing (32; 27; 24).

There are major alterations of olfactory processing in advanced age with substantial losses in odor memory and odor identification performance (28). The elderly have higher olfactory thresholds, perceive suprathreshold odors less intensely, and are less able to discriminate odors or to recognize and identify common odors (02; 10). Age-related losses in olfaction are heterogeneous and are more likely to involve sensitivity to heavier molecules (44).

Because chemosensory impairment is so prevalent among the elderly, many elderly people complain that food lacks flavor (hypogeusia) (14). Loss of smell (hyposmia), distortions (dysosmia), and hallucinations (phantosmia) are common in the elderly; most distortions of smell resolve over time, although this may take years (12).

Olfactory impairment impacts quality of life for elderly individuals. Individuals with worse olfactory function are more likely to report loneliness (06). Olfactory dysfunction predicts subsequent development of depression in older adults in the United States (16). Olfactory impairment in older adults is associated with lower body weight and greater weight loss, decreased sexual motivation, and emotional satisfaction (39; 43).

Prognosis and complications

For patients with olfactory dysfunction, the prognosis depends primarily on etiology and on the degree of residual function, but also secondarily on gender, parosmia (distortion of the sense of smell), smoking habits, and age (20; 19). Male gender, initial presence of parosmia, smoking, and older age are negative prognostic factors (19; 38).

In some elderly patients, hyposmia may be an early ("preclinical") marker for the subsequent development of overt neurodegenerative disease. For example, impaired olfaction is associated with the later development of Parkinson disease and with increased likelihood of either incidental Lewy bodies or neuronal loss in the substantial nigra or locus coeruleus (11; 40).

Impaired olfaction adversely affects quality of life, psychological and physical health, and the enjoyment of eating, and it contributes to hypogeusia, impaired appetite, weight loss, frailty, and depression in elderly patients (21; 12). In addition, it may pose a safety risk as affected individuals may not smell smoke or gas leaks and are less likely to recognize that food has spoiled.

Biological basis

	• Age-related losses of smell (presbyosmia) are common in the elderly and result from normal aging, certain diseases (especially Alzheimer disease, Parkinson disease, and dementia with Lewy bodies), medications, surgical interventions, and prior environmental exposures, including tobacco use.
	• The majority of the age-related functional declines of the chemosenses are attributable to accumulated insults to the sensory system, smoking, medications, and comorbid disease.
	• Age-related loss of olfaction (presbycusis) does not share a common etiologic factor with age-related losses in other sensory modalities when assessed with objective measures.

Etiology and pathogenesis

Age-related losses of smell (presbyosmia) are common in the elderly and result from normal aging, certain diseases (especially Alzheimer disease, Parkinson disease, and dementia with Lewy bodies), medications, surgical interventions, and prior environmental exposures, including tobacco use (14; 12; 17; 18; 32; 25; 29; 27; 22).

The components of age-related losses of smell related to aging per se are relatively small (but significant), whereas most of the age-related functional declines of the chemosenses are attributable to accumulated insults to the sensory system, smoking, medications, and comorbid disease (20; 32; 25; 29).

Under normal conditions, adult stem cells reconstitute the olfactory neuroepithelium in response to cell loss. Aging-related inflammatory changes in stem cells of the olfactory epithelium may contribute to presbyosmia by disrupting normal epithelial homeostasis (35). Basal stem cells of the olfactory epithelium of presbyosmic individuals exhibit increased expression of genes involved in the response to cytokines, stress, or the regulation of proliferation and differentiation (35). In a culture model, cytokine exposure drove increased TP63, a transcription factor that prevents stem cell differentiation in the olfactory epithelium (35).

Part of the decline in olfactory abilities with age results from degeneration of the olfactory bulb: the number of mitral cells and glomeruli in the olfactory bulb decline markedly with age, at an approximate rate of 10% per decade, so that less than 30% of these elements remain by the ninth and tenth decades (31). Functional imaging shows significantly lower activation among the elderly in brain regions receiving primary olfactory projections (ie, piriform cortex, entorhinal cortex, and amygdala) (04).

In animal models, spatio-temporally restricted caspase activation occurs in neural structures required for olfaction (05). Caspase is activated in an age-dependent manner in specific subsets of olfactory receptor neurons and apparently plays a role in the regulation of cell death (05).

Age-related loss of olfaction (presbycusis) does not share a common etiologic factor with age-related losses in other sensory modalities when assessed with objective measures (03). Therefore, presbycusis is not associated with age-related losses in other sensory modalities (03). However, elderly individuals who experience a loss of smell may generalize this to their assessments of their functional abilities with other sensory modalities (03). Therefore, subjective measures should be combined with objective sensory threshold measurements when evaluating sensory dysfunction in the elderly (03).

Epidemiology

	• Olfactory senescence starts by the fifth decade and accelerates with advancing years, preferentially involving pleasant odors.
	• Smell identification ability declines markedly after the seventh decade: major olfactory impairment is present in about one third to one half of those aged 65 to 80 years and in some two thirds to four fifths of those over 80 years of age.
	• Factors associated with an increased prevalence of olfactory impairment in the elderly include race (ie, African American and Hispanic), male gender, current smoking, medications, medication polypharmacy, cumulative exposure to toxic fumes, prior head trauma, and comorbid conditions.

The prevalence of olfactory impairment increases with age. Olfactory senescence starts by the fifth decade and accelerates with advancing years, preferentially involving pleasant odors (14; 10; 38). Smell identification ability declines markedly after the seventh decade: major olfactory impairment is present in about one third to one half of those aged 65 to 80 years, and in some two thirds to four fifths of those over 80 years of age (14; 08; 10; 32; 26).

Race (ie, African American and Hispanic), male gender, current smoking, medications, medication polypharmacy, cumulative exposure to toxic fumes, prior head trauma, comorbid conditions (eg, nasal congestion, upper respiratory tract infection, sinusitis, systemic viral illness, epilepsy, cerebrovascular disease, and neurodegenerative diseases), and lower education are associated with an increased prevalence of olfactory impairment in the elderly (42; 18; 32; 34; 33; 37; 38; 30; 36; 22; 45; 07). The relative resilience to age-related olfactory decline in women may be due to their profuse olfactory network connectivity (30).

In the US National Health and Nutrition Examination Survey (NHANES, 2013-2014), participants aged 70 to 80 years with vitamin D insufficiency (20 to 30 ng/mL) had a higher prevalence of smell and taste impairment (01). Vitamin D insufficiency may have a significant role in age-related smell impairment in adults aged 40 years or older and in age-related taste impairment in the elderly aged 70 to 80 years (01).

Prevention

Odor identification and odor detection threshold in healthy community-dwelling elderly who exercised regularly for more than 1 year (for at least 30 minutes more than 3 times per week) were significantly higher than those for non-exercisers (46). Both odor threshold and odor identification among those who exercised by practicing tai chi, dancing, or running were significantly better than among those who exercised by walking or who did not exercise (46).

In the US National Health and Nutrition Examination Survey (NHANES, 2013-2014), participants aged 70 to 80 years with vitamin D insufficiency (20 to 30 ng/mL) had a higher prevalence of smell and taste impairment (01). Vitamin D insufficiency may have a significant role in age-related smell impairment in adults aged 40 years or older and in age-related taste impairment in the elderly aged 70 to 80 years (01).

Differential diagnosis

Associated or underlying disorders

Disorders of olfaction in the elderly can be conveniently divided into conductive, sensorineural, and central disorders, where (1) conductive disorders involve transmission of the sensory stimuli to the sensory receptors (usually, but not always, by impeding transmission), (2) sensorineural disorders involve dysfunction of the sensory receptors or conduction of signals from the sensory receptors to the brain, and (3) central disorders involve dysfunction of processing of sensory information within the central nervous system, and particularly within the brainstem and cerebrum.

Conductive hyposmia (depending on the author or circumstance, “conductive” is sometimes stated conversely as “obstructive”) occurs if there are impediments to conveyance of odorants to the olfactory neuroepithelium (eg, upper respiratory infection, chronic rhinosinusitis, nasal polyposis). Sensorineural disorders involve the receptors themselves (“sensory”) or the afferent neural pathways involving the respective cranial nerves, tracts, or central processing centers of the brain (collectively “neural”). In addition to presbyosmia, other common causes of sensorineural hyposmia in the elderly include tobacco smoking, drug toxicity, head injury, hypothyroidism, and post-viral disorders (following an influenza-like infection). Common causes of central hyposmia in the elderly include Parkinson disease and dementia with Lewy bodies, but other neurodegenerative disorders are also associated with loss of smell. In general, conductive loss of olfaction is more likely to be remediable (ie, to result in significantly improved function) than is a sensorineural or central loss (41).

Diagnostic workup

	• Elderly patients with hyposmia should undergo a focused history and examination that addresses particularly the sense of smell, the nasal passages, and the nervous system.
	• Office testing of smell can include well-standardized, commercially available tests (eg, University of Pennsylvania Smell Identification Test or UPSIT) or crude approaches utilizing identification of a few readily available odorants (eg, oil of wintergreen, oil of cloves).
	• The UPSIT is a forced-choice olfactory discrimination test utilizing microencapsulated odorants in standardized "scratch 'n sniff” booklets.
	• A history of head trauma, past and current tobacco smoking, and medications should be reviewed for potential contributing causes to olfactory dysfunction.

Elderly patients with hyposmia should undergo a focused history and examination that addresses particularly the sense of smell, the nasal passages, and the nervous system. Office testing of smell can include well-standardized, commercially available tests (eg, University of Pennsylvania Smell Identification Test or UPSIT) or crude approaches utilizing identification of a few readily available odorants (eg, oil of Wintergreen, oil of cloves) (13; 15; 09). More complicated odor identification and detection tests are also available but are rarely practical outside of specialized diagnostic laboratories (09). The UPSIT is a forced-choice olfactory discrimination test utilizing micro-encapsulated odorants in standardized "scratch 'n sniff” booklets. UPSIT scores are standardized by gender and age and can be used to identify degrees of hyposmia and some malingerers. Irritant substances, such as ammonia, are sometimes employed when psychogenic or malingered anosmia is a consideration because such substances are perceived via trigeminal afferent pathways rather than through the olfactory system.

A history of head trauma, past and current tobacco smoking, and medications should be reviewed for potential contributing causes to olfactory dysfunction. Thyroid dysfunction should be excluded with thyroid-stimulation hormone (TSH) and free T4 assays. Patients with evidence of a conductive olfactory disturbance may warrant CT imaging of the paranasal sinuses or otolaryngologic referral or both. Patients with neurologic signs or symptoms need further evaluation to exclude neurodegenerative disorders and, rarely, structural lesions of the cribriform plate or basal forebrain. Neuroimaging is recommended in patients with dementia and in those with asymmetric or unilateral hyposmia not attributable to conductive hyposmia. Patients without conductive hyposmia and without evidence of neurologic signs of symptoms most likely have presbyosmia, although early neurologic disease is possible. Periodic re-examination may help identify cases of early neurodegenerative disease (eg, Alzheimer disease, Parkinson disease, dementia with Lewy bodies).

Management

	• There is no established treatment for presbyosmia, and, in general, sensorineural and central causes of hyposmia are seldom correctable.
	• Smokers should be advised to quit smoking, and further counseling and pharmacologic managements should be employed as necessary to facilitate cessation.
	• Patients should be counseled regarding safety issues and the use of proper monitoring devices for smoke and natural gas.

There is no established treatment for presbyosmia, and, in general, sensorineural and central causes of hyposmia are seldom correctable (23); nevertheless, advances in the understanding of olfactory neuron physiology, olfactory tissue maintenance, and regeneration have suggested new potential therapeutic targets (23). Sinonasal disease should be treated when present. Smokers should be advised to quit smoking and further counseling and pharmacologic managements should be employed as necessary to facilitate cessation. Patients should be counseled regarding safety issues and the use of proper monitoring devices for smoke and natural gas; this is particularly important for those who are living alone. In addition, the effects of hyposmia on gustation and appetite should be assessed, and, if necessary, a dietary consult should be obtained; in some cases, dietary supplements or flavor enhancers may prove beneficial.