Archives of Gerontology and Geriatrics

Volume 37, Issue 2 , September-October 2003, Pages 119-130

Olfactory identification in elderly Greek people in relation to memory and attention measures

Alexandra Economou 

            The University of Pennsylvania Smell Identification Test (UPSIT) and the Cross-Cultural Smell Identification Test (CC-SIT) were administered to nondemented Greek participants ranging in age from 49 to 88 years together with tests of verbal memory from the Wechsler Memory Scale-3rd Edition (WMS-III). The test scores of the sample administered the CC-SIT were compared with the test scores of the 12 analogous UPSIT items of the sample administered the UPSIT. The percent of individuals correctly identifying each of the odorants of the UPSIT and CC-SIT is reported, together with means and standard deviations (S.D.) of the total smell scores. UPSIT performance in both the full test and the 12 analogous items was associated with WMS-III Logical Memory I performance after accounting for the effects of age, education and gender. CC-SIT performance was associated with gender, score on the Beck Depression Inventory-II and Logical Memory I performance. The study shows that olfactory identification is associated with verbal memory in nondemented individuals after accounting for demographic variables.



Neurobiology of Aging

Volume 24, Issue 5 , September 2003, Pages 663-673

3-Nitrotyrosine immunoreactivity in olfactory receptor neurons of patients with Alzheimer's disease: implications for impaired odor sensitivity

M. L. Getchell, D. S. Shaha, S. K. Buch, D. G. Davis and T. V. Getchell

            Olfactory sensory function is impaired in patients with the diagnosis of probable Alzheimer's disease (AD) compared to elderly controls, and the olfactory epithelium (OE) of AD patients exhibits several pathological changes characteristic of the AD brain. To confirm that the populations from whom our postmortem tissues are obtained exhibit similar decrements in sensory function, threshold testing was performed; probable AD patients had significantly higher olfactory thresholds than controls. To determine if oxidative stress contributes to decreased olfactory function in AD, we localized 3-nitrotyrosine (3-NT) immunoreactivity in OE obtained postmortem from patients with neuropathologically confirmed AD and age-matched controls with brains free of significant neurodegenerative pathology. In AD patients, immunoreactivity was localized in olfactory receptor neurons (ORNs), including dendritic knobs where ion channels that participate in sensory transduction are located, suggesting a direct mechanism for olfactory impairment. In controls, immunoreactivity occurred in blood vessel endothelium, suggesting age-related vascular dysfunction. Immunohistochemistry for CD68, a macrophage scavenger receptor, demonstrated activated macrophages, a source of free radicals contributing to 3-NT formation, in the OE of AD patients but not controls. These results demonstrate increased oxidative stress and modification of ORN proteins that may contribute directly to olfactory impairment in AD patients.




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The cerebellum and olfaction in the aging brain: a functional magnetic resonance imaging study

Sally Ferdona and Claire Murphy, , a, b

            The present study investigated activation of distinct cerebellar regions as a result of olfactory stimulation in healthy young and elderly adults using functional magnetic resonance imaging (fMRI). Ten young and 10 elderly adults were imaged using a 1.5-TMR scanner. The odorant amyl acetate was delivered in 12-s on, 40-s off cycles. Throughout the scan participants responded with a button press at first detection of each stimulus interval followed by a second button press upon odorant extinction. Images were processed with AFNI software. Elderly participants showed significantly decreased cerebellar activation in both the superior semilunar lobule (Crus I) and the inferior semilunar lobule (Crus II), two of three previously identified regions of interest for odor processing, compared to young adults. Interestingly, both groups showed similar levels of activation in the third region of interest, the posterior quadrangular lobule (VI), although the elderly showed more variability than the young did. Previous research identifying this area to be involved in attention may reflect the possibility that elderly adults engaged in olfactory tasks may show more variability than young participants in the degree of attentional demands needed for these tasks as a result of decreased olfactory abilities.




Article in Press, Corrected Proof - Note to users

Functional brain imaging of olfactory processing in monkeys

J. M. Boyett-Andersona, D. M. Lyonsa, A. L. Reissa, b, c, A. F. Schatzberga, c and V. Menon, , a, b, c

            As a step toward bridging the gap between human and animal studies of olfactory brain systems, we report results from an fMRI study of olfaction in squirrel monkeys. High-resolution fMRI images at 3 T with 1.25 × 1.25 × 1.2 mm3 voxels were obtained covering the whole brain using an 8-cm-diameter birdcage coil and a gradient–echo spiral pulse sequence. Data were acquired from six sedated adult males using a standard block design. All fMRI data were spatially normalized to a common template and analyzed at the individual and group levels with statistical parametric and nonparametric methods. Robust odorant-induced activations were detected in several brain regions previously implicated in conscious human olfactory processing, including the orbitofrontal cortex, cerebellum, and piriform cortex. Consistent with human data, no stimulus intensity effects were observed in any of these regions. Average signal changes in these regions exceeded 0.6%, more than three times the expected signal change based on human fMRI studies of olfaction adjusting for differences in voxel size. These results demonstrate the feasibility of studying olfaction in sedated monkeys with imaging techniques commonly used at 3 T in humans and help promote direct comparisons between humans and nonhuman primates. Our findings, for example, provide novel support for the hypothesis that the cerebellum is involved in sensory acquisition. More broadly, this study suggests that olfactory processing in sedated monkeys and nonsedated humans shares similar neural substrates both within and beyond the primary olfactory system.



Neuropsychopharmacology (2002) 26 27-39.

Tracking the Cognitive Pharmacodynamics of Psychoactive Substances with Combinations of Behavioral and Neurophysiological Measures

Alan Gevins DSc, Michael E Smith Ph.D and Linda K McEvoy Ph.D; alan@eeg.com

            Many common pharmacological treatments have effects on cognitive ability. Psychometric task batteries used to characterize such effects do not provide direct information about treatment-related changes in brain function. Since overt task performance reflects motivation and effort as well as ability, behavioral measures alone may overestimate or underestimate the impact of a pharmacological intervention on brain function. Here we present a method that combines behavioral and neurophysiological measures in an attempt to detect the psychoactive effects of pharmacological treatments with greater sensitivity than that provided by behavioral measures alone. Initial application of the method is made to the data from a double blind, placebo-controlled, crossover study in which caffeine, diphenhydramine, and alcohol were used to alter the mental state of 16 healthy subjects at rest and while they performed low load and high load versions of a working memory task. For each intervention, more sensitive detection of drug or alcohol effects over a four hour period was obtained when EEG variables were included in multivariate analyses than when only behavioral variables were used. These initial results suggest that it can be useful to incorporate neurophysiological measures of brain activity into inferences concerning the acute impact of drugs on mental function, and demonstrate the feasibility of using multivariate combinations of behavioral and neurophysiological measures to sensitively characterize the pharmacodynamics of drug-induced changes in cognition.



Neuron, Vol 39, 991-1004, 11 September 2003

Intensity versus Identity Coding in an Olfactory System

Mark Stopfer, Vivek Jayaraman, and Gilles Laurent *  laurentg@caltech.edu

We examined the encoding and decoding of odor identity and intensity by neurons in the antennal lobe and the mushroom body, first and second relays, respectively, of the locust olfactory system. Increased odor concentration led to changes in the firing patterns of individual antennal lobe projection neurons (PNs), similar to those caused by changes in odor identity, thus potentially confounding representations for identity and concentration. However, when these time-varying responses were examined across many PNs, concentration-specific patterns clustered by identity, resolving the apparent confound. This is because PN ensemble representations changed relatively continuously over a range of concentrations of each odorant. The PNs' targets in the mushroom body—Kenyon cells (KCs)—had sparse identity-specific responses with diverse degrees of concentration invariance. The tuning of KCs to identity and concentration and the patterning of their responses are consistent with piecewise decoding of their PN inputs over oscillation-cycle length epochs.



Psychiatry Research

Volume 120, Issue 2 , 30 September 2003, Pages 155-164

A brief smell identification test discriminates between deficit and non-deficit schizophrenia

Nora Goudsmit, , a, Eliza Colemanb, Regine Anna Seckingera, Rachel Wolitzkya, Arielle D. Stanforda, Cheryl Corcorana, Raymond R. Goetza and Dolores Malaspinaa

            Evidence is accumulating that smell identification deficits (SID) and social dysfunction in schizophrenia may share a common pathophysiology. While most schizophrenia studies utilize the lengthy 40-item University of Pennsylvania Smell Identification Test (UPSIT) to assess smell identification ability, a brief 12-item smell identification test (B-SIT) has recently been constructed as a culturally neutral substitute for the UPSIT. By selecting the 12 items of the UPSIT from which the B-SIT was originally derived, we constructed a proxy for the B-SIT and compared the performance of 83 patients with schizophrenia to 69 normal subjects. We examined select properties of the B-SIT proxy in relation to the UPSIT to determine its efficacy for use in psychiatric populations. We considered the sensitivity of the B-SIT proxy and evaluated a cutoff score for identifying deficit syndrome schizophrenia (DS). The UPSIT and B-SIT proxy were significantly related in the patients (n=83, r=0.85, P=0.01) and in comparison subjects (n=69, r=0.83, P=0.01), and both measures similarly distinguished DS from non-deficit syndrome (non-DS) patients. The results of this study support the utility of the B-SIT for schizophrenia research and highlight the robustness of the relationship between SID and social dysfunction in schizophrenia.




Decrements in Volume of Anterior Ventromedial Temporal Lobe and Olfactory Dysfunction in Schizophrenia

Bruce I. Turetsky, MD; Paul J. Moberg, PhD; David R. Roalf, BA; Steven E. Arnold, MD; Raquel E. Gur, MD, PhD

Arch Gen Psychiatry. 2003;60:1193-1200.

            Context  Patients with schizophrenia exhibit olfactory deficits, but it is unclear whether these represent a specific abnormality. The link between olfactory impairments and regional brain abnormalities has yet to be established.  Objectives  To determine whether patients with schizophrenia exhibit volumetric deficits in the anterior ventromedial temporal lobe, the target for neuronal inputs from the olfactory bulb, and whether these are related to olfactory performance deficits.  Design  A cohort study of patients and healthy control subjects who underwent both 1-mm spoiled-gradient echo magnetic resonance imaging and behavioral tests of olfaction and memory. Setting  Schizophrenia Research Center at the University of Pennsylvania, Philadelphia.  Participants  Fifty-two patients with a DSM-IV diagnosis of schizophrenia and 38 healthy control subjects. Individuals were excluded for history of head trauma, significant substance abuse, and medical conditions affecting brain function or olfactory capacity.  Main Outcome Measures  Gray matter volumes of the left and right temporal poles and the perirhinal and entorhinal cortexes; olfactory threshold detection sensitivity and identification test scores; composite indexes of verbal and spatial memory ability.  Results  Patients had reduced volumes, relative to cranial size, in left (P = .003) and right (P = .01) perirhinal and left (P = .002) and right (P = .002) entorhinal cortexes, but not in the temporal pole. Perirhinal, but not entorhinal, cortical volume decrement was associated with decreased olfactory threshold sensitivity. Neither region was associated with impaired memory performance.  Conclusions  Patients with schizophrenia have reduced cortical volumes in brain regions that receive afferents directly from the olfactory bulb. Behavioral olfactory deficits are related to structural brain abnormalities in these regions.



Clinical Neuroscience Research

Volume 3, Issues 4-5 , December 2003, Pages 253-262

A review of the relevance and validity of olfactory bulbectomy as a model of depression

Andrew Harkin, , John P. Kelly and Brian E. Leonard

            Development of valid animal models for human affective disorder. Attempts have involved numerous approaches such as the exploitation of vulnerability factors for depression including maternal deprivation, exposure to psychophysiological stress or by pharmacological depletion of monoamines. However, no approach is perhaps so radical as the removal of a part of the brain as occurs in the olfactory bulbectomy (OB) model of depression. The ensuing behavioural symptoms also distinguish the OB model from other animal models of depression, in that it possesses significant face validity as a model of agitated depression. OB in rodents provokes behavioural changes that respond to chronic but not acute treatment with antidepressants thus mimicking the time-course of antidepressant action in the clinic. The persistent use and popularity of the model over the past 25 years is a testament to its utility in exploring the neurobiological mechanisms of antidepressant action, as well as the pathophysiology of major depression. In this review, the present status of the model is presented.