Impaired Odor Identification Research Articles

Odor Identification and Progression of Parkinsonian Signs in Older Persons

The authors tested the hypothesis that difficulty in identifying odors, a common finding in Parkinson's disease, is associated with more rapid progression of parkinsonian signs in 743 community-dwelling older people without dementia or Parkinson's disease at study onset. Odor identification ability was assessed at baseline with the 12-item Brief Smell Identification Test (mean = 9.0 correct, SD = 2.1), and parkinsonism was assessed annually for up to 5 years with a modified version of the Unified Parkinson's Disease Rating Scale. In an analysis adjusted for age, sex, and education, lower odor identification score was related to higher level of global parkinsonism at baseline (p < .001) and more rapid progression of global parkinsonism on follow-up (p = .002). This result mainly reflected an association of odor identification with worsening parkinsonian gait. The results suggest that impaired odor identification is associated with more rapid progression of parkinsonism in old age, particularly parkinsonian gait disturbance.

Impaired odor identification might help predict onset of Parkinson's disease

Impaired odor identification might help predict onset of Parkinson's disease

Olfactory Identification and Incidence of Mild Cognitive Impairment in Older Age

Mild cognitive impairment (MCI) is often a precursor to Alzheimer disease, but knowledge about factors that predict its development is limited. To test the hypothesis that impaired odor identification is related to increased risk of incident MCI. Longitudinal cohort study. Academic research. Subjects were 589 community-dwelling older persons without cognitive impairment at study baseline, at which time odor identification was assessed using the 12-item Brief Smell Identification Test (mean +/- SD score, 9.3 +/- 1.9). Incidence of MCI and rate of decline in cognitive function. During annual observation of up to 5 years, 177 subjects developed MCI. In a proportional hazards model adjusted for age, sex, and education, odor identification score predicted development of MCI (relative risk, 1.15; 95% confidence interval, 1.07-1.23), with risk increased by 50% in persons with below-average (score of 8 [25th percentile]) compared with above-average (score of 11 [75th percentile]) odor identification scores. Results were not substantially changed in subsequent analyses that controlled for level of cognitive function or disability, presence of stroke, or smoking status at baseline or that required MCI to persist for at least 1 year. Impaired odor identification was also associated with a lower level of global cognition at baseline and with more rapid decline in episodic memory, semantic memory, and perceptual speed. Among older persons without manifest cognitive impairment, difficulty in identifying odors predicts subsequent development of MCI.

Presentation of Alzheimer's disease in patients with and without olfactory deficits

Odor identification deficits are frequently reported in Alzheimer's disease (AD) but are not universal. This study examines differences in clinical presentation in AD patients with and without odor identification impairments. Ninety patients with probable AD were administered an odor identification test as part of a neuropsychological evaluation. Variables examined included demographic information, cognitive and behavioral measures, dementia severity, neuroimaging findings, and aspects of clinical history. Defining the groups with a median split, olfactory impaired and olfactory intact patients were mostly similar, though patients with impaired odor identification performance were more likely to be male, less likely to have a family history of dementia, and had worse visuospatial functioning. The differences noted raise the possibility of a clinical subtype of the disease.

Odor Identification and Decline in Different Cognitive Domains in Old Age

The authors examined the association of odor identification with rate of decline in different cognitive systems. Participants are 481 older persons from the Rush Memory and Aging Project. At baseline, the Brief Smell Identification Test was administered. At annual intervals for up to 3 years, a battery of 19 cognitive tests was administered from which previously established composite measures of 5 cognitive domains were derived. In mixed-effects models adjusted for age, sex, and education, lower odor identification score was associated with lower function at baseline in each cognitive domain. Lower score was also associated with more rapid decline in perceptual speed (estimate = 0.015, SE = 0.006, p = 0.013) and episodic memory (estimate = 0.012, SE = 0.006, p = 0.030) but not with rate of decline in semantic memory, working memory, or visuospatial ability. Thus, on average, a person with a low odor identification score (6, 10th percentile) declined more than twice as rapidly in perceptual speed and episodic memory as a person with a high score (11, 90th percentile). Results were unchanged in subsequent analyses that controlled for cigarette smoking or clinically diagnosed stroke. The results indicate that impaired odor identification in old age is associated with impaired global cognition and more rapid decline in perceptual processing speed and episodic memory.

Olfactory identification and WAIS-R performance in deficit and nondeficit schizophrenia

Introduction: An expanding database supports the notion that the deficit syndrome (DS) is a discrete condition within schizophrenia and recent data argues that Smell Identification Deficits (SID) may have a primary relationship with its pathophysiology. If so, then the relationship of University of Pennsylvania Smell Identification Test (UPSIT) scores with other neurocognitive measures in DS patients may point to the neural substrate of the deficit syndrome. Method: We examined the relationship of UPSIT scores and Wechsler Adult Intelligence Scale-Revised (WAIS-R) performance in 46 DSM-IV schizophrenia patients. The Schedule for the Deficit Syndrome (SDS) interview was used to subgroup the sample into 13 DS and 33 nondeficit syndrome (NDS) patients. Results: DS and NDS groups had similar mean ages, age of onset, and GAF scores, but DS patients had fewer years of education. DS and NDS patients also did not differ in full scale, verbal or performance IQ or in any WAIS-R subtest. However, UPSIT scores were significantly worse in the DS patients, most of whom met criteria for a clinically meaningful olfactory impairment. In DS patients, UPSIT scores were significantly correlated with Performance IQ, Block Design, and Object Assembly, all of which are associated with complex visual–motor organizational function thought to be mediated by parietal circuitry. UPSIT scores in NDS patients were significantly related with Vocabulary, Similarities, and Digit Symbol subtests, which are indicative of verbal functioning. Conclusion: These preliminary data support previous findings suggesting that in addition to frontal neuropsychological abnormalities, DS patients may have greater performance impairments on tasks associated with parietal functioning. Our findings furthermore suggest that the parietal circuitry may be a conspicuous substrate for impaired odor identification ability in these patients. The lesser abnormalities in UPSIT ability in NDS patients may be attributed to verbal ability. These data are preliminary and further investigations with larger samples are needed to support our findings.

Physiologic impairment of olfactory stimulus processing in schizophrenia

Background Behavioral studies of olfaction have demonstrated impairments in the ability to detect and identify odors in patients with schizophrenia. These deficits appear to be independent of either symptom severity or other cognitive impairment. Only limited efforts have been made to investigate the neurophysiologic substrate of these olfactory abnormalities. This article reports the first examination of olfactory electrophysiologic responses in patients with schizophrenia. Methods Olfactory event-related potential responses to three different concentrations of hydrogen sulfide were recorded in a sample of 21 patients and 20 healthy control subjects. Odors were presented via an olfactometer to ensure there was no associated trigeminal nerve stimulation. Results Patients exhibited abnormalities in the amplitudes of the N1 and P2 components of the olfactory evoked potential, and delayed latency of the P2. The N1 abnormality, which denotes primary olfactory cortex activity, was related to impaired odor detection threshold sensitivity; the P2 abnormality was related to impaired odor identification. Conclusions These data indicate the presence of a primary physiologic impairment in the olfactory cortex underlying behavioral olfactory deficits seen in patients with schizophrenia. This is consistent with postmortem and in vitro studies suggesting abnormalities in olfactory receptor neurons. Understanding the nature of these physiologic olfactory impairments could offer clues to the basic neuropathology of this disorder.

Severe Dysosmia Is Specifically Associated with Alzheimer-Like Memory Deficits in Nondemented Elderly Retirees

Objectives: To determine whether or not (1) impaired olfactory function is associated with impaired memory on neuropsychological testing in healthy retirees, and if so then (2) whether memory impairment is most consistent with a mesiotemporal rather than frontal system disorder. Methods: 173 independent residents of a continuing care retirement community were studied. Subjects completed the University of Pennsylvania Smell Identification Test (UPSIT) and a battery of both general and specific cognitive measures that included the Mini-Mental State Examination (MMSE) and the Executive Interview (EXIT25). Subjects were examined twice over 3 years. Results: UPSIT performance was normal in 21% and in the ‘anosmic’ range in 25% of subjects. Anosmic UPSIT performance was associated with significantly worse performance on all cognitive tests. However, only short-term verbal memory was independently associated with UPSIT-defined anosmia. This association remained significant after adjusting for the other cognitive and sociodemographic variables. The memory deficits of anosmic subjects were qualitatively consistent with a cortical type (type 1) dementing illness such as Alzheimer’s disease (AD). Over time, UPSIT-defined ‘anosmic’ cases suffered significantly greater declines on both the MMSE and the EXIT25, independently of baseline age, gender and MMSE score. Conclusions: Impaired odor identification in individuals without overt dementia is associated with an AD-like memory impairment and an increased rate of cognitive decline. The comorbid association of these deficits is consistent with the known hierarchical spread of preclinical AD pathology and may be a specific indicator of future clinical AD dementia.

Loss of Olfactory Function in Dementing Disease

Alzheimer’s (AD) patients show neuropathological changes in areas of the brain central to olfactory processing, suggesting the theoretical importance and potential diagnostic utility of investigating functional changes in olfaction in these patients. Persons with Down’s Syndrome who live to the fourth decade develop neuropathological changes in the brain similar to those found in AD. A series of investigations have been conducted to assess olfaction function in both patients with Alzheimer’s disease and persons with Down’s Syndrome. Functional testing included olfactory threshold, odor identification, odor similarity judgements, odor recognition memory, odor recall, odor fluency. Both Alzheimer’s patients and persons with Down’s Syndrome showed significant impairment in olfactory function, with some measures showing more impairment than others in the early stages of the disease process. Longitudinal investigation of several of the measures indicated decreased function over time consonant with falling DRS scores. Normal controls who tested positive for the APOE4 allele showed impaired odor identification compared to those who were allele negative. Patients with Huntington’s Disease showed olfactory functional impairments, although the degree of impairment differed from the cortical dementias for some of these tasks. The sensitvity and specificity of these assessments will be discussed in relation to analogous assessments in other sensory modalities.

Contribution of medial versus lateral temporal-lobe structures to human odour identification.

To investigate possible distinct contributions of different temporal-lobe structures to odour identification, the University of Pennsylvania Smell Identification Test was administered monorhinally to seizure-free patients who had undergone one of three types of temporal-lobe resection practised in three different institutions for surgical treatment of epilepsy. The resections were neocorticectomy (Dublin), selective amygdalohippocampectomy (Zurich), or anterior temporal-lobe resection with encroachment on amygdala and hippocampus (Montreal). Resections, analysed from MRI scans, showed unexpected encroachment on medial structures in most patients of the neocorticectomy groups, and largest amygdala and hippocampal resections in the amygdalohippocampectomy groups. Impaired odour identification was observed in all patient groups, irrespective of surgical approach, with greatest impairment in the nostril ipsilateral to the resection. The finding of deficits in all three surgical groups suggests that damage in the anterior temporal area, perhaps in piriform cortex, is sufficient to disrupt performance on this task; it may be that function is disrupted in the medial temporal-lobe region by disconnection when the periamygdaloid area is damaged, even when amygdala and hippocampus are left intact. An alternative explanation for our results is that damage in any one of these areas disrupts a complex network involving several distinct temporal-lobe structures.

Biological markers and diagnostic investigations in Alzheimer's disease

The diagnosis of Alzheimer's disease (AD) is based on numerous clinical, neuroradiological, neurophysiological, and neuropsychological evaluations, but a definitive diagnosis can only be established at autopsy or by brain biopsy. Because the need for a simple and accurate diagnostic marker is increasing as new drug treatments emerge, intensive research to identify diagnostic markers is now in progress. Computer tomography and magnetic resonance imaging are being used to compare linear and volumetric measurements of brains for patients with AD and normal controls. Functional imaging techniques, such as single photon emission computer tomography and positron emission tomography, are being used to identify possible disease-related changes in regional blood flow, glucose metabolism, and receptor activities. Elevated tau-protein concentrations or reduced levels of beta-amyloid precursor protein in the cerebrospinal fluid; mutations on chromosomes 14, 19, and 21; the presence of the Apo-epsilon-4 allele; and impaired odor identification are also being evaluated as possible markers.

The nature and course of olfactory deficits in Alzheimer's disease

The aim of this study was to determine the specific nature and course of olfactory deficits in Alzheimer's disease. Previous studies had noted impaired odor identification, but there was no unanimity about the presence of odor detection deficits. Odor identification was tested in 55 patients with Alzheimer's disease and 57 elderly control subjects by using the University of Pennsylvania Smell Identification Test. Odor detection was assessed in 46 subjects with Alzheimer's disease and 40 control subjects by using a forced-choice threshold test with geraniol as the odorant. Significant deficits in olfactory identification were present in subjects who were in the earliest stages of cognitive impairment, and these deficits increased as Alzheimer's disease progressed. There was some overlap in individual smell identification test scores between cognitively impaired patients and normal elderly subjects. On the other hand, odor detection deficits did not appear until Alzheimer's disease was relatively advanced. Smell identification test scores were correlated with Mini-Mental State scores, but geraniol detection was not. Odor identification is impaired early in Alzheimer's disease and may be more influenced by cognitive status than is acuity of odor detection, which is not altered until later in the disorder. The pattern of hyposmia in Alzheimer's disease suggests that the disorder may not "begin in the nose," as has been theorized previously. Further refinement of olfactory testing may be useful in the diagnostic evaluation of early dementia.

Olfactory identification deficits in HIV infection

Impaired odor identification is described in a number of CNS disorders, and human immunodeficiency virus (HIV) infects the CNS in a large percentage of patients. To evaluate whether impaired olfaction may indicate CNS disease, the authors measured odor identification in patient groups defined along a continuum of progressive immunodeficiency and in a comparison group. Most of the 42 HIV-infected patients in the study were outpatients in a clinic specializing in treatment of HIV-infected individuals. The comparison subjects were 37 healthy age- and sex-matched individuals who were recruited from hospital and medical school personnel. Ten of the patients were HIV-seropositive but had no symptoms, 24 had clinical evidence of immunocompromise, and eight had HIV dementia. All subjects were given the University of Pennsylvania Smell Identification Test, which presents common odorants and requires the subject to identify the odor from a four-item word list. The data were analyzed by using analysis of variance after arc-sine transformation and Scheffé post hoc analysis. All patients scored significantly lower on the Smell Identification Test than did the comparison subjects. The patients with HIV dementia had significantly lower scores than did the other two groups of patients. Clinically, impaired olfaction might serve as a marker of early CNS HIV involvement. Future studies should attempt to match comparison and experimental populations for socioeconomic status and HIV risk behavior.