The influences of age on olfaction: a review

Richard L Doty, Vidyulata Kamath, Richard L Doty, Vidyulata Kamath

Abstract

Decreased olfactory function is very common in the older population, being present in over half of those between the ages of 65 and 80 years and in over three quarters of those over the age of 80 years. Such dysfunction significantly influences physical well-being and quality of life, nutrition, the enjoyment of food, as well as everyday safety. Indeed a disproportionate number of the elderly die in accident gas poisonings each year. As described in this review, multiple factors contribute to such age-related loss, including altered nasal engorgement, increased propensity for nasal disease, cumulative damage to the olfactory epithelium from viral and other environmental insults, decrements in mucosal metabolizing enzymes, ossification of cribriform plate foramina, loss of selectivity of receptor cells to odorants, changes in neurotransmitter and neuromodulator systems, and neuronal expression of aberrant proteins associated with neurodegenerative disease. It is now well established that decreased smell loss can be an early sign of such neurodegenerative diseases as Alzheimer's disease and sporadic Parkinson's disease. In this review we provide an overview of the anatomy and physiology of the aging olfactory system, how this system is clinically evaluated, and the multiple pathophysiological factors that are associated with its dysfunction.

Keywords: Alzheimer's disease; Parkinson's disease; age; anatomy; neurodegeneration; olfaction; physiology; psychophysics.

Figures

Figure 1
Figure 1
(A) Cross-section of the human olfactory epithelium. Four main types of cells can be discerned: bipolar receptor cells (arrows point to largely denuded cilia at dendritic knobs); c, cell body, microvillar cells (m), sustentacular cells (s), and basal cells (b); bg, Bowman's gland; lp, lamina propria; n, collection of axons within an ensheathing cell; d, degenerating cell; bs, basal cell undergoing mitosis. Photo courtesy of Dr. David Moran, Longmont, Colorado. (B) A transition zone between the human olfactory epithelium (bottom) and the respiratory epithelium (top). Arrows signify two examples of olfactory receptor cell dendrites with cilia that have been cut off. Bar = 5 μm. From Menco and Morrison (2003), with permission. Copyright©2003, Marcel Dekker, Inc.
Figure 2
Figure 2
Schematic drawing of the major layers of the olfactory bulb and the interactions between the different types of bulbar cells. Abbreviations: G, granule cells; M, mitral cells; T, tufted cells. Note that the largely GABAergic granule cells send projections into the mitral cell and external plexiform layers, and that some small cells extend projections into more than one glomerulus. Reprinted with permission from Duda (2010), with permission. Copyright©2010, Elsevier B.V.
Figure 3
Figure 3
The 40-item University of Pennsylvania Smell Identification Test (UPSIT). This test is comprised of four booklets, each containing 10 microencapsulated (“scratch and sniff”) odors which are released by a pencil tip. The examinee is required to provide an answer on each test item (see columns on last page of each booklet) even if no odor is perceived or the perceived odor does not smell like one of the response alternatives (i.e., the test is forced-choice). This test has been administered to hundreds of thousands of subjects and is available in 15 different language versions. Photograph courtesy of Sensonics International, Haddon Heights, New Jersey USA. Copyright©2013, Sensonics International.
Figure 4
Figure 4
Scores on the University of Pennsylvania Smell Identification Test (UPSIT) as a function of age and gender in a large heterogeneous group of subjects. Numbers by data points indicate sample sizes. From Doty et al. (1984a), with permission. Copyright©1984, American Association for the Advancement of Science.
Figure 5
Figure 5
The Self-administered Computerized Olfactory Testing System (SCOTS). This modern olfactometer allows for self-administration of olfactory threshold tests, among other types of tests, and automatically calculates the threshold value based upon subject responses. This system eliminates administrator error in the presentation of test stimuli and provides exacting control of stimulus duration, inter-stimulus intervals, and other factors. Photograph courtesy of Sensonics International, Haddon Heights, New Jersey USA. Copyright©2013, Sensonics International.
Figure 6
Figure 6
Test scores for men and women on a 12-item odor discrimination/memory test as a function of age. Note age-related decline in performance and the fact that women outperform men at all ages. Data are collapsed over 0-, 30- and 60-s delay intervals. From Choudhury et al. (2003), with permission. Copyright©2003, Oxford University Press.
Figure 7
Figure 7
Magnitude estimates given to six concentrations of amyl butyrate after adjustment for number usage by the employment of a cross-modal matching procedure. Each age group was comprised of 10 men and 10 women. The younger group ranged in age from 18 to 25 years, and the older group from 65 to 85 years. From Stevens et al. (1982), with permission. Copyright©1982, ANKHO International, Inc.
Figure 8
Figure 8
Air-dilution olfactometer used to present pulses of odorants into a purified and humidified airstream directed through nares of a subject. This device ensures that the odor event-related potentials (OERPs) are not confounded by somatosensory artifacts due to alterations in stimulus pressure, temperature, or other factors. Photo courtesy of the University of Pennsylvania Smell and Taste Center, Philadelphia, PA.
Figure 9
Figure 9
Olfactory event-related potentials obtained from 12 younger (mean age: 24 years) and 12 older (mean age: 71 years) subjects using normal breathing or breathing after being trained to close the palate to minimize airflow from the mouth (velopharyngeal closure). Note the smaller amplitude and longer latency responses in the older group. From Thesen and Murphy (2001), with permission. Copyright©2001, Elsevier Science B.V.
Figure 10
Figure 10
Mean (s.e.m.) sniff magnitude ratios obtained from the Sniff Magnitude Test as a function of age. Sample size = 137 subjects, 74% of whom were female. From Frank et al. (2006), with permission. Copyright©2006, American Medical Association.
Figure 11
Figure 11
Left: left and right halves of the cribriform plate of a 25-year-old female in superior view. Right: left half of cribriform plate of a 66-year-old male in superior view. Note the difference in size and number of patent foramina that transmit cranial nerve I between the young and old cribriform plates. Anterior is toward top. From Kalmey et al. (1998), with permission. Copyright©1998, Wiley-Liss, Inc.
Figure 12
Figure 12
Respiratory epithelium in the olfactory region of the adult human. Top: ciliated and goblet cell-containing respiratory epithelium has invaded degenerated olfactory neuroepithelium (between arrows). Arrows indicate junction of respiratory and olfactory epithelia (HandE, × 100). Middle: gland-like invagination (between arrows) of respiratory epithelium into the lamina propria (HandH, × 200). Bottom: gland-like respiratory epithelium with large lumina in the lamina propria (HandE, × 1000). From Nakashima et al. (1984), with permission. Copyright©1984, American Medical Association.
Figure 13
Figure 13
Olfactory functional magnetic resonance imaging (fMRI) activation maps from 11 younger (left; mean age = 23.9 years) and 8 older (right; mean age = 66.4 years) persons to lavender and spearmint odors. Note greater activation in the younger subjects. From Wang et al. (2005), with permission. Copyright©2005, Gerontological Society of America.

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