To examine the association between odor identification deficits and future mortality in a multiet... more To examine the association between odor identification deficits and future mortality in a multiethnic community cohort of older adults. Participants were evaluated with the 40-item University of Pennsylvania Smell Identification Test (UPSIT). Follow-up occurred at 2-year intervals with information on death obtained from informant interviews and the National Death Index. During follow-up (mean 4.1 SD 2.6 years), 349 of 1169 (29.9%) participants died. Participants who died were more likely to be older (p < 0.001), male (p < 0.001), have lower UPSIT scores (p < 0.001), and have a diagnosis of dementia (p < 0.001). In a Cox model, the association between lower UPSIT score and mortality (Hazard Ratio 1.07 per point interval, 95%CI 1.05 to 1.08, p<0.001) persisted after controlling for age, gender, education, ethnicity, language, modified Charlson medical comorbidity index, dementia, depression, alcohol abuse, head injury, smoking, Body Mass Index, vision and hearing impair...
The effects of age, sex, and handedness on olfaction have not been adequately addressed with odor... more The effects of age, sex, and handedness on olfaction have not been adequately addressed with odor-stimulated functional MR imaging studies. We sought to determine the effect of age on functional MR imaging experiments performed with odor stimulation. Five right-handed subjects with a mean age of 73 years and five right-handed subjects with a mean age of 24 years underwent gradient-echo echo-planar functional MR imaging using binasal olfactory stimulation. Imaging parameters included 3000/30 (TR/TE) and a 5-mm section thickness in a 6-minute sequence with 30 seconds of pulsed odorants alternating with 30 seconds of room air. The data were normalized to a standard atlas, and individual and group statistical parametric maps (SPMs) were generated for each task. The SPMs were thresholded for a P < .01, and the volumes of activation and distribution of cluster maxima were compared for the two groups. Analysis of the group SPMs revealed activated voxels in the frontal lobes, perisylvian...
To evaluate the sites of injury in patients with posttraumatic olfactory deficits and to compare ... more To evaluate the sites of injury in patients with posttraumatic olfactory deficits and to compare damage with findings on clinical olfactory tests. Twenty-five patients with posttraumatic olfactory dysfunction were examined by means of olfactory testing, endoscopy, and MR imaging. MR surface-coil scans through the olfactory bulbs and tracts and head-coil scans of the temporal lobes were evaluated. Quantitative and qualitative gradings of damage to the olfactory bulbs, tracts, subfrontal region, hippocampus, and temporal lobes were compared with results on tests of odor identification, detection, memory, and discrimination. Twelve patients were anosmic, eight had severe impairment, and five were mildly impaired. Injuries to the olfactory bulbs and tracts (88% of patients), subfrontal region (60%), and temporal lobes (32%) were found, but these did not correlate well with individual olfactory test scores. Volumetric analysis showed that patients without smell function had greater volum...
To determine the locations and extent of activation in areas of the brain at functional magnetic ... more To determine the locations and extent of activation in areas of the brain at functional magnetic resonance (MR) imaging with olfactory stimulation and to determine whether accommodation or amplification of brain activation occurs with sequential olfactory stimulation. Five adult men with normal senses of smell underwent multisection, gradient-echo, echo-planar imaging according to a blood-oxygen-level-dependent experimental paradigm. Odorants that nearly exclusively stimulate the olfactory system and odorants that stimulate the olfactory and trigeminal nerves were compared by using repetitive imaging procedures. Activation with olfactory nerve-mediated odorants was demonstrated in the orbitofrontal cortex (Brodmann area 11) with a right-sided predominance. Mild cerebellar stimulation was also observed. With repeated testing, overall activation with olfactory nerve-mediated odorants declined. Odorants that also stimulated the trigeminal nerve produced additional cingulate, temporal, ...
Olfactory dysfunction in patients with schizophrenia has been a topic of increasing interest, wit... more Olfactory dysfunction in patients with schizophrenia has been a topic of increasing interest, with deficits in odor identification, detection threshold sensitivity, discrimination, and memory being reported. Despite increasing knowledge, controversy has existed about possible differential deficits among olfactory tests as well as the influences of gender, smoking, and medication status on olfactory measures. To help elucidate some of this controversy,
To determine the predictive utility of baseline odor identification deficits for future cognitive... more To determine the predictive utility of baseline odor identification deficits for future cognitive decline and the diagnosis of Alzheimer disease (AD) dementia. In a multiethnic community cohort in North Manhattan, NY, 1,037 participants without dementia were evaluated with the 40-item University of Pennsylvania Smell Identification Test (UPSIT). In 757 participants, follow-up occurred at 2 years and 4 years. In logistic regression analyses, lower baseline UPSIT scores were associated with cognitive decline (relative risk 1.067 per point interval; 95% confidence interval [CI] 1.040, 1.095; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), and remained significant (relative risk 1.065 per point interval; 95% CI 1.034, 1.095; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) after including covariates. UPSIT, but not Selective Reminding Test-total immediate recall, predicted cognitive decline in participants without baseline cognitive impairment. During follow-up, 101 participants transitioned to AD dementia. In discrete time survival analyses, lower baseline UPSIT scores were associated with transition to AD dementia (hazard ratio 1.099 per point interval; 95% CI 1.067, 1.131; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), and remained highly significant (hazard ratio 1.072 per point interval; 95% CI 1.036, 1.109; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) after including demographic, cognitive, and functional covariates. Impairment in odor identification was superior to deficits in verbal episodic memory in predicting cognitive decline in cognitively intact participants. The findings support the cross-cultural use of a relatively inexpensive odor identification test as an early biomarker of cognitive decline and AD dementia. Such testing may have the potential to select/stratify patients in treatment trials of cognitively impaired patients or prevention trials in cognitively intact individuals.
Whether Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp... more Whether Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD) influences suprathreshold changes in perceived odor intensity is unknown. In patients with Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease, patients with schizophrenia, and the elderly, such perception is reportedly normal. If generally true, this could reflect a core element of the olfactory system insulated to some degree from age- and disease-related pathological conditions. Odor intensity ratings for pentyl acetate were obtained from 29 early-stage PD patients when on and off dopamine-related medications (DRMs) and from 29 matched controls. The ratings were significantly attenuated at the higher odorant concentrations, with the degree of attenuation associated with overall olfactory dysfunction. Ratings were higher on the right than on the left side of the nose of both patients and controls. No associations with DRMs, Unified Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Disease Rating Scale (UPDRS) scores, or striatal dopamine transporter imaging were found. Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD) influences suprathreshold estimates of perceived odor intensity, negating the notion that such perception might be spared in this disease. No association with dopaminergic processes was apparent.
The influences of feedback and ascending and descending trial sequences on the ability of 135 col... more The influences of feedback and ascending and descending trial sequences on the ability of 135 college-aged subjects to detect phenyl ethyl alcohol odorant concentrations ranging from 10-9 to 10-5.5 v/v were examined in a two-alternative forced-choice test paradigm. At the highest concentrations, ascending trial sequences produced better performance than descending trial sequences; the reverse was true at the lowest concentrations.
The purpose of this study was to define the primary sites of injury in patients with posttraumati... more The purpose of this study was to define the primary sites of injury in patients with posttraumatic anosmia and hyposmia with magnetic resonance (MR) imaging and to determine if these sites correlated with the results of psychophysical olfactory tests. Thirty-six patients with subjective loss in olfaction after head trauma underwent volumetric MR studies of the olfactory bulbs and tracts and temporal lobes. Pearson correlations were computed between olfactory bulb and tract and temporal lobe volumes and the patients&#39; scores on tests of odor identification (including the University of Pennsylvania Smell Identification Test [UPSIT]), detection, and memory. Analysis of variance was used to compare volumes of the control subjects and the posttraumatic patients. The olfactory bulbs and tracts (32 [89%] of 36 patients), the subfrontal lobes (22 [61%] of 36 patients), and the temporal lobes (11 [31%] of 36 patients) showed the highest incidence of posttraumatic encephalomalacia. Left olfactory bulb and tract volumes showed a statistically significant correlation with left and total UPSIT scores. A statistically significant difference (P &lt; .001) was found in the right and left olfactory bulb and tract volumes between anosmic and hyposmic patients and between posttraumatic patients and control subjects. Olfactory bulb and tract damage may correlate with deficits in odor identification. Olfactory bulb and tract and frontal lobe encephalomalacia coexist in many patients.
The chronic health effects associated with sustained exposures to high concentrations of air poll... more The chronic health effects associated with sustained exposures to high concentrations of air pollutants are an important issue for millions of megacity residents and millions more living in smaller urban and rural areas. Particulate matter (PM) and ozone (O3) concentrations close or above their respective air quality standards during the last 20 years affect 24 million people living in the Mexico City Metropolitan Area (MCMA). Herein we discuss PM and O3 trends in MCMA and their possible association with the observed central nervous system (CNS) effects in clinically healthy children. We argue that prenatal and postnatal sustained exposures to a natural environmental exposure chamber contribute to detrimental neural responses. The emerging picture for MCMA children shows systemic inflammation, immunodysregulation at both systemic and brain levels, oxidative stress, neuroinflammation, small blood vessel pathology, and an intrathecal inflammatory process, along with the early neuropathological hallmarks for Alzheimer and Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s diseases. Exposed brains are briskly responding to their harmful environment and setting the bases for structural and volumetric changes, cognitive, olfactory, auditory and vestibular deficits and long term neurodegenerative consequences. We need to improve our understanding of the PM pediatric short and long term CNS impact through multidisciplinary research. Public health benefit can be achieved by integrating interventions that reduce fine PM levels and pediatric exposures and establishing preventative screening programs targeting pediatric populations that are most at risk. We fully expect that the health of 24 million residents is important and blocking pediatric air pollution research and hiding critical information that ought to be available to our population, health, education and social workers is not in the best interest of our children.
It is well established that olfactory dysfunction has significant implications for safety, nutrit... more It is well established that olfactory dysfunction has significant implications for safety, nutrition, and quality of life. The more reliable standardized tests of olfactory function, such as the University of Pennsylvania Smell Identification Test (UPSIT), assess odor identification ability. Unfortunately, cultural factors can influence such tests, as a number of odors are not universally recognized. In this study, a Portuguese language version of the UPSIT was administered to an age- and sex-stratified prospective sample of 1820 Brazilian subjects. Normative data were developed for a subset of 1578 subjects who reported having no difficulties smelling or tasting. Individuals with a history of head trauma or, in the case of those over the age of 64 years, Mini-Mental State Examination Scores <24, were excluded from analysis. As in other populations, the test scores were significantly influenced by age and sex. The median overall difference between the North American and Brazilian...
Despite the fact that clinical otolaryngologists are often presented with complaints of olfactory... more Despite the fact that clinical otolaryngologists are often presented with complaints of olfactory dysfunction, they have limited means to diagnose these problems. A major reason has been the lack of a clinically-useful and reliable quantitative test of olfactory function. Recent work at our Clinical Research Center has resulted in the development of such a test. This test--the University of Pennsylvania Smell Identification Test (UPSIT)--can be self-administered and uses microencapsulated odorants which are released by scratching standardized odor-impregnated test booklets. As indicated in this paper, studies have demonstrated that the UPSIT can identify most malingerers and is sensitive to age, gender, smoking habits, and a wide variety of olfactory disorders. A description of this new test, along with some of its applications, is presented.
The development of the 12-item Cross-Cultural Smell Identification Test (CC-SIT), based upon item... more The development of the 12-item Cross-Cultural Smell Identification Test (CC-SIT), based upon items from the University of Pennsylvania Smell Identification Test (UPSIT), is described. In developing this test, the authors initially selected UPSIT items that are familiar to most persons from North American, European, South American, and Asian cultures. The CC-SIT was then administered to 198 people ranging in age from 5 to 96 years, and the the test scores were compared to analogous items from UPSITs administered to 198 age-, sex-, race-, and smoking-habit-matched control subjects. Since the pattern of test scores did not differ for the two groups, the authors developed normative data for the 12-item test using equivalent UPSIT items sampled from a database containing UPSIT scores for 3760 subjects. Norms are provided for determining the percentile ranks of a given patient&#39;s score as a function of age and gender. The CC-SIT provides, for the first time, a self-administered means for reliably assessing olfactory function in less than 5 minutes.
To determine the sensitivity, specificity, and positive and negative predictive value of response... more To determine the sensitivity, specificity, and positive and negative predictive value of responses to the following questionnaire statements in detecting taste loss: &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;I can detect salt in chips, pretzels, or salted nuts,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;I can detect sourness in vinegar, pickles, or lemon,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;I can detect sweetness in soda, cookies, or ice cream,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;I can detect bitterness, in coffee, beer, or tonic water.&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; Responses to an additional item, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;I can detect chocolate in cocoa, cake or candy,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; was examined to determine whether patients clearly differentiate between taste loss and flavor loss secondary to olfactory dysfunction. A total of 469 patients (207 men, mean age = 54 years, standard deviation = 15 years; and 262 women, mean age = 54 years, standard deviation = 14 years) were administered a questionnaire containing these questions with the response categories of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;easily,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;somewhat,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;not at all,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; followed by a comprehensive taste and smell test battery. The questionnaire items poorly detected bona fide taste problems. However, they were sensitive in detecting persons without such problems (i.e., they exhibited low positive but high negative predictive value). Dysfunction categories of the University of Pennsylvania Smell Identification Test (UPSIT) were not meaningfully related to subjects&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; responses to the questionnaire statements. Both sex and age influenced performance on most of the taste tests, with older persons performing more poorly than younger ones and women typically outperforming men. Although it is commonly assumed that straight-forward questions concerning taste may be useful in detecting taste disorders, this study suggests this is not the case. However, patients who specifically report having no problems with taste perception usually do not exhibit taste dysfunction. The difficulty in detecting true taste problems by focused questionnaire items likely reflects a combination of factors. These include the relatively low prevalence of taste deficits in the general population and the tendency of patients to confuse…
To determine whether radiation alters taste function and structure. Prospective, longitudinal stu... more To determine whether radiation alters taste function and structure. Prospective, longitudinal study. Testing prior to starting radiation, and 2 weeks, 2 months, and 6 months after completing radiation. Relative to controls, patients had lower taste identification test scores for bitter, salty, and sour tastes. Sour taste also showed a significant group-by-time interaction (P = .03). Taste pores were decreased in the irradiated group, with a significant group-by-time interaction (P = .03). Head and neck cancer patients have decreased taste function, and radiation adversely affected sour taste and taste pores.
To examine the association between odor identification deficits and future mortality in a multiet... more To examine the association between odor identification deficits and future mortality in a multiethnic community cohort of older adults. Participants were evaluated with the 40-item University of Pennsylvania Smell Identification Test (UPSIT). Follow-up occurred at 2-year intervals with information on death obtained from informant interviews and the National Death Index. During follow-up (mean 4.1 SD 2.6 years), 349 of 1169 (29.9%) participants died. Participants who died were more likely to be older (p < 0.001), male (p < 0.001), have lower UPSIT scores (p < 0.001), and have a diagnosis of dementia (p < 0.001). In a Cox model, the association between lower UPSIT score and mortality (Hazard Ratio 1.07 per point interval, 95%CI 1.05 to 1.08, p<0.001) persisted after controlling for age, gender, education, ethnicity, language, modified Charlson medical comorbidity index, dementia, depression, alcohol abuse, head injury, smoking, Body Mass Index, vision and hearing impair...
The effects of age, sex, and handedness on olfaction have not been adequately addressed with odor... more The effects of age, sex, and handedness on olfaction have not been adequately addressed with odor-stimulated functional MR imaging studies. We sought to determine the effect of age on functional MR imaging experiments performed with odor stimulation. Five right-handed subjects with a mean age of 73 years and five right-handed subjects with a mean age of 24 years underwent gradient-echo echo-planar functional MR imaging using binasal olfactory stimulation. Imaging parameters included 3000/30 (TR/TE) and a 5-mm section thickness in a 6-minute sequence with 30 seconds of pulsed odorants alternating with 30 seconds of room air. The data were normalized to a standard atlas, and individual and group statistical parametric maps (SPMs) were generated for each task. The SPMs were thresholded for a P < .01, and the volumes of activation and distribution of cluster maxima were compared for the two groups. Analysis of the group SPMs revealed activated voxels in the frontal lobes, perisylvian...
To evaluate the sites of injury in patients with posttraumatic olfactory deficits and to compare ... more To evaluate the sites of injury in patients with posttraumatic olfactory deficits and to compare damage with findings on clinical olfactory tests. Twenty-five patients with posttraumatic olfactory dysfunction were examined by means of olfactory testing, endoscopy, and MR imaging. MR surface-coil scans through the olfactory bulbs and tracts and head-coil scans of the temporal lobes were evaluated. Quantitative and qualitative gradings of damage to the olfactory bulbs, tracts, subfrontal region, hippocampus, and temporal lobes were compared with results on tests of odor identification, detection, memory, and discrimination. Twelve patients were anosmic, eight had severe impairment, and five were mildly impaired. Injuries to the olfactory bulbs and tracts (88% of patients), subfrontal region (60%), and temporal lobes (32%) were found, but these did not correlate well with individual olfactory test scores. Volumetric analysis showed that patients without smell function had greater volum...
To determine the locations and extent of activation in areas of the brain at functional magnetic ... more To determine the locations and extent of activation in areas of the brain at functional magnetic resonance (MR) imaging with olfactory stimulation and to determine whether accommodation or amplification of brain activation occurs with sequential olfactory stimulation. Five adult men with normal senses of smell underwent multisection, gradient-echo, echo-planar imaging according to a blood-oxygen-level-dependent experimental paradigm. Odorants that nearly exclusively stimulate the olfactory system and odorants that stimulate the olfactory and trigeminal nerves were compared by using repetitive imaging procedures. Activation with olfactory nerve-mediated odorants was demonstrated in the orbitofrontal cortex (Brodmann area 11) with a right-sided predominance. Mild cerebellar stimulation was also observed. With repeated testing, overall activation with olfactory nerve-mediated odorants declined. Odorants that also stimulated the trigeminal nerve produced additional cingulate, temporal, ...
Olfactory dysfunction in patients with schizophrenia has been a topic of increasing interest, wit... more Olfactory dysfunction in patients with schizophrenia has been a topic of increasing interest, with deficits in odor identification, detection threshold sensitivity, discrimination, and memory being reported. Despite increasing knowledge, controversy has existed about possible differential deficits among olfactory tests as well as the influences of gender, smoking, and medication status on olfactory measures. To help elucidate some of this controversy,
To determine the predictive utility of baseline odor identification deficits for future cognitive... more To determine the predictive utility of baseline odor identification deficits for future cognitive decline and the diagnosis of Alzheimer disease (AD) dementia. In a multiethnic community cohort in North Manhattan, NY, 1,037 participants without dementia were evaluated with the 40-item University of Pennsylvania Smell Identification Test (UPSIT). In 757 participants, follow-up occurred at 2 years and 4 years. In logistic regression analyses, lower baseline UPSIT scores were associated with cognitive decline (relative risk 1.067 per point interval; 95% confidence interval [CI] 1.040, 1.095; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), and remained significant (relative risk 1.065 per point interval; 95% CI 1.034, 1.095; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) after including covariates. UPSIT, but not Selective Reminding Test-total immediate recall, predicted cognitive decline in participants without baseline cognitive impairment. During follow-up, 101 participants transitioned to AD dementia. In discrete time survival analyses, lower baseline UPSIT scores were associated with transition to AD dementia (hazard ratio 1.099 per point interval; 95% CI 1.067, 1.131; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), and remained highly significant (hazard ratio 1.072 per point interval; 95% CI 1.036, 1.109; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) after including demographic, cognitive, and functional covariates. Impairment in odor identification was superior to deficits in verbal episodic memory in predicting cognitive decline in cognitively intact participants. The findings support the cross-cultural use of a relatively inexpensive odor identification test as an early biomarker of cognitive decline and AD dementia. Such testing may have the potential to select/stratify patients in treatment trials of cognitively impaired patients or prevention trials in cognitively intact individuals.
Whether Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp... more Whether Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD) influences suprathreshold changes in perceived odor intensity is unknown. In patients with Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease, patients with schizophrenia, and the elderly, such perception is reportedly normal. If generally true, this could reflect a core element of the olfactory system insulated to some degree from age- and disease-related pathological conditions. Odor intensity ratings for pentyl acetate were obtained from 29 early-stage PD patients when on and off dopamine-related medications (DRMs) and from 29 matched controls. The ratings were significantly attenuated at the higher odorant concentrations, with the degree of attenuation associated with overall olfactory dysfunction. Ratings were higher on the right than on the left side of the nose of both patients and controls. No associations with DRMs, Unified Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Disease Rating Scale (UPDRS) scores, or striatal dopamine transporter imaging were found. Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD) influences suprathreshold estimates of perceived odor intensity, negating the notion that such perception might be spared in this disease. No association with dopaminergic processes was apparent.
The influences of feedback and ascending and descending trial sequences on the ability of 135 col... more The influences of feedback and ascending and descending trial sequences on the ability of 135 college-aged subjects to detect phenyl ethyl alcohol odorant concentrations ranging from 10-9 to 10-5.5 v/v were examined in a two-alternative forced-choice test paradigm. At the highest concentrations, ascending trial sequences produced better performance than descending trial sequences; the reverse was true at the lowest concentrations.
The purpose of this study was to define the primary sites of injury in patients with posttraumati... more The purpose of this study was to define the primary sites of injury in patients with posttraumatic anosmia and hyposmia with magnetic resonance (MR) imaging and to determine if these sites correlated with the results of psychophysical olfactory tests. Thirty-six patients with subjective loss in olfaction after head trauma underwent volumetric MR studies of the olfactory bulbs and tracts and temporal lobes. Pearson correlations were computed between olfactory bulb and tract and temporal lobe volumes and the patients&#39; scores on tests of odor identification (including the University of Pennsylvania Smell Identification Test [UPSIT]), detection, and memory. Analysis of variance was used to compare volumes of the control subjects and the posttraumatic patients. The olfactory bulbs and tracts (32 [89%] of 36 patients), the subfrontal lobes (22 [61%] of 36 patients), and the temporal lobes (11 [31%] of 36 patients) showed the highest incidence of posttraumatic encephalomalacia. Left olfactory bulb and tract volumes showed a statistically significant correlation with left and total UPSIT scores. A statistically significant difference (P &lt; .001) was found in the right and left olfactory bulb and tract volumes between anosmic and hyposmic patients and between posttraumatic patients and control subjects. Olfactory bulb and tract damage may correlate with deficits in odor identification. Olfactory bulb and tract and frontal lobe encephalomalacia coexist in many patients.
The chronic health effects associated with sustained exposures to high concentrations of air poll... more The chronic health effects associated with sustained exposures to high concentrations of air pollutants are an important issue for millions of megacity residents and millions more living in smaller urban and rural areas. Particulate matter (PM) and ozone (O3) concentrations close or above their respective air quality standards during the last 20 years affect 24 million people living in the Mexico City Metropolitan Area (MCMA). Herein we discuss PM and O3 trends in MCMA and their possible association with the observed central nervous system (CNS) effects in clinically healthy children. We argue that prenatal and postnatal sustained exposures to a natural environmental exposure chamber contribute to detrimental neural responses. The emerging picture for MCMA children shows systemic inflammation, immunodysregulation at both systemic and brain levels, oxidative stress, neuroinflammation, small blood vessel pathology, and an intrathecal inflammatory process, along with the early neuropathological hallmarks for Alzheimer and Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s diseases. Exposed brains are briskly responding to their harmful environment and setting the bases for structural and volumetric changes, cognitive, olfactory, auditory and vestibular deficits and long term neurodegenerative consequences. We need to improve our understanding of the PM pediatric short and long term CNS impact through multidisciplinary research. Public health benefit can be achieved by integrating interventions that reduce fine PM levels and pediatric exposures and establishing preventative screening programs targeting pediatric populations that are most at risk. We fully expect that the health of 24 million residents is important and blocking pediatric air pollution research and hiding critical information that ought to be available to our population, health, education and social workers is not in the best interest of our children.
It is well established that olfactory dysfunction has significant implications for safety, nutrit... more It is well established that olfactory dysfunction has significant implications for safety, nutrition, and quality of life. The more reliable standardized tests of olfactory function, such as the University of Pennsylvania Smell Identification Test (UPSIT), assess odor identification ability. Unfortunately, cultural factors can influence such tests, as a number of odors are not universally recognized. In this study, a Portuguese language version of the UPSIT was administered to an age- and sex-stratified prospective sample of 1820 Brazilian subjects. Normative data were developed for a subset of 1578 subjects who reported having no difficulties smelling or tasting. Individuals with a history of head trauma or, in the case of those over the age of 64 years, Mini-Mental State Examination Scores <24, were excluded from analysis. As in other populations, the test scores were significantly influenced by age and sex. The median overall difference between the North American and Brazilian...
Despite the fact that clinical otolaryngologists are often presented with complaints of olfactory... more Despite the fact that clinical otolaryngologists are often presented with complaints of olfactory dysfunction, they have limited means to diagnose these problems. A major reason has been the lack of a clinically-useful and reliable quantitative test of olfactory function. Recent work at our Clinical Research Center has resulted in the development of such a test. This test--the University of Pennsylvania Smell Identification Test (UPSIT)--can be self-administered and uses microencapsulated odorants which are released by scratching standardized odor-impregnated test booklets. As indicated in this paper, studies have demonstrated that the UPSIT can identify most malingerers and is sensitive to age, gender, smoking habits, and a wide variety of olfactory disorders. A description of this new test, along with some of its applications, is presented.
The development of the 12-item Cross-Cultural Smell Identification Test (CC-SIT), based upon item... more The development of the 12-item Cross-Cultural Smell Identification Test (CC-SIT), based upon items from the University of Pennsylvania Smell Identification Test (UPSIT), is described. In developing this test, the authors initially selected UPSIT items that are familiar to most persons from North American, European, South American, and Asian cultures. The CC-SIT was then administered to 198 people ranging in age from 5 to 96 years, and the the test scores were compared to analogous items from UPSITs administered to 198 age-, sex-, race-, and smoking-habit-matched control subjects. Since the pattern of test scores did not differ for the two groups, the authors developed normative data for the 12-item test using equivalent UPSIT items sampled from a database containing UPSIT scores for 3760 subjects. Norms are provided for determining the percentile ranks of a given patient&#39;s score as a function of age and gender. The CC-SIT provides, for the first time, a self-administered means for reliably assessing olfactory function in less than 5 minutes.
To determine the sensitivity, specificity, and positive and negative predictive value of response... more To determine the sensitivity, specificity, and positive and negative predictive value of responses to the following questionnaire statements in detecting taste loss: &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;I can detect salt in chips, pretzels, or salted nuts,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;I can detect sourness in vinegar, pickles, or lemon,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;I can detect sweetness in soda, cookies, or ice cream,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;I can detect bitterness, in coffee, beer, or tonic water.&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; Responses to an additional item, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;I can detect chocolate in cocoa, cake or candy,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; was examined to determine whether patients clearly differentiate between taste loss and flavor loss secondary to olfactory dysfunction. A total of 469 patients (207 men, mean age = 54 years, standard deviation = 15 years; and 262 women, mean age = 54 years, standard deviation = 14 years) were administered a questionnaire containing these questions with the response categories of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;easily,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;somewhat,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;not at all,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; followed by a comprehensive taste and smell test battery. The questionnaire items poorly detected bona fide taste problems. However, they were sensitive in detecting persons without such problems (i.e., they exhibited low positive but high negative predictive value). Dysfunction categories of the University of Pennsylvania Smell Identification Test (UPSIT) were not meaningfully related to subjects&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; responses to the questionnaire statements. Both sex and age influenced performance on most of the taste tests, with older persons performing more poorly than younger ones and women typically outperforming men. Although it is commonly assumed that straight-forward questions concerning taste may be useful in detecting taste disorders, this study suggests this is not the case. However, patients who specifically report having no problems with taste perception usually do not exhibit taste dysfunction. The difficulty in detecting true taste problems by focused questionnaire items likely reflects a combination of factors. These include the relatively low prevalence of taste deficits in the general population and the tendency of patients to confuse…
To determine whether radiation alters taste function and structure. Prospective, longitudinal stu... more To determine whether radiation alters taste function and structure. Prospective, longitudinal study. Testing prior to starting radiation, and 2 weeks, 2 months, and 6 months after completing radiation. Relative to controls, patients had lower taste identification test scores for bitter, salty, and sour tastes. Sour taste also showed a significant group-by-time interaction (P = .03). Taste pores were decreased in the irradiated group, with a significant group-by-time interaction (P = .03). Head and neck cancer patients have decreased taste function, and radiation adversely affected sour taste and taste pores.
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