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1.
Hum Mol Genet ; 31(23): 4055-4074, 2022 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-35796562

RESUMEN

NADK2 encodes the mitochondrial form of nicotinamide adenine dinucleotide (NAD) kinase, which phosphorylates NAD. Rare recessive mutations in human NADK2 are associated with a syndromic neurological mitochondrial disease that includes metabolic changes, such as hyperlysinemia and 2,4 dienoyl CoA reductase (DECR) deficiency. However, the full pathophysiology resulting from NADK2 deficiency is not known. Here, we describe two chemically induced mouse mutations in Nadk2-S326L and S330P-which cause severe neuromuscular disease and shorten lifespan. The S330P allele was characterized in detail and shown to have marked denervation of neuromuscular junctions by 5 weeks of age and muscle atrophy by 11 weeks of age. Cerebellar Purkinje cells also showed progressive degeneration in this model. Transcriptome profiling on brain and muscle was performed at early and late disease stages. In addition, metabolomic profiling was performed on the brain, muscle, liver and spinal cord at the same ages and on plasma at 5 weeks. Combined transcriptomic and metabolomic analyses identified hyperlysinemia, DECR deficiency and generalized metabolic dysfunction in Nadk2 mutant mice, indicating relevance to the human disease. We compared findings from the Nadk model to equivalent RNA sequencing and metabolomic datasets from a mouse model of infantile neuroaxonal dystrophy, caused by recessive mutations in Pla2g6. This enabled us to identify disrupted biological processes that are common between these mouse models of neurological disease, as well as those processes that are gene-specific. These findings improve our understanding of the pathophysiology of neuromuscular diseases and describe mouse models that will be useful for future preclinical studies.


Asunto(s)
Hiperlisinemias , Distrofias Neuroaxonales , Animales , Ratones , Humanos , NAD/genética , Distrofias Neuroaxonales/genética , Distrofias Neuroaxonales/metabolismo , Modelos Animales de Enfermedad , Expresión Génica , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Proteínas Mitocondriales/genética , Fosfolipasas A2 Grupo VI/genética
2.
Neuroscience ; 559: 8-16, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39179019

RESUMEN

Olfactory dysfunction is an early sign of such neurodegenerative diseases as Parkinson's (PD) and Alzheimer's (AD), and is often present in Mild Cognitive Impairment (MCI), a precursor of AD. Understanding neuro-temporal relationships, i.e., functional connectivity, between olfactory eloquent structures in such disorders, could shed light on their basic pathophysiology. To this end, we employed region-based analyses using resting-state functional magnetic resonance imaging (rs-fMRI) obtained from cognitively normal (CN), MCI, and PD patients with cognitive impairment (PD-CogImp). Using machine learning (linear and ensemble learning), we determined whether the identified functional patterns could classify abnormal function from normal function. Olfaction, as measured by objective testing, was found to be most strongly associated with diagnostic status, emphasizing the fundamental association of this primary sensory system with these conditions. Consistently lower functional connectivity was observed in the PD-CogImp cohort compared to the CN cohort among all identified brain regions. Differences were also found between PD-CogImp and MCI at the level of the orbitofrontal and cingulate cortices. MCI and CN subjects had different functional connectivity between the posterior orbitofrontal cortex and thalamus. Regardless of study group, males showed significantly higher connectivity than females in connections involving the orbitofrontal cortex. The logistic regression model trained using the top discriminatory features revealed that caudate was the most involved olfaction-related brain structure (accuracy = 0.88, Area under the Receiver operator characteristic curve of 0.90). In aggregate, our study demonstrates that resting functional connectivity among olfactory eloquent structures has potential value in better understanding the pathophysiology of several neurodegenerative diseases.


Asunto(s)
Disfunción Cognitiva , Imagen por Resonancia Magnética , Enfermedad de Parkinson , Humanos , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Anciano , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/diagnóstico por imagen , Persona de Mediana Edad , Descanso/fisiología , Aprendizaje Automático , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Trastornos del Olfato/fisiopatología , Trastornos del Olfato/diagnóstico por imagen , Vías Olfatorias/fisiopatología , Vías Olfatorias/diagnóstico por imagen , Mapeo Encefálico/métodos
3.
Chem Senses ; 36(4): 405-10, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21310764

RESUMEN

When an odorant is presented to one side of the nose and air to the other, the ability to localize which side received the odorant depends upon trigeminal nerve stimulation. It has been shown that performance on this lateralization task increases as stimulus concentration increases. In this study, we determined the influences of stimulus volume and sex on the ability to localize each of 8 odorants presented at neat concentrations: anethole, geraniol, limonene, linalool, menthol, methyl salicylate, phenyl ethanol, and vanillin. At a low stimulus volume (11 mL), only menthol was localized at an above-chance level. At a high stimulus volume (21 mL), above-chance localization occurred for all odorants except vanillin. Women were significantly better than men in localizing menthol. Stimuli rated as most intense were those that were most readily localized. The detection performance measures, as well as rated intensity values, significantly correlated with earlier findings of the trigeminal detectability of odorants presented to anosmic and normosmic subjects. This study suggests that differences in stimulus volume may explain some discrepant findings within the trigeminal chemosensory literature and supports the concept that vanillin may be a "relatively pure" olfactory stimulus.


Asunto(s)
Mucosa Nasal/metabolismo , Odorantes , Olfato , Adulto , Femenino , Humanos , Masculino , Odorantes/análisis , Factores Sexuales , Nervio Trigémino/metabolismo , Adulto Joven
4.
Gene Ther ; 17(6): 799-804, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20237508

RESUMEN

Adverse events linked to perturbations of cellular genes by vector insertion reported in gene therapy trials and animal models have prompted attempts to better understand the mechanisms directing viral vector integration. The integration profiles of vectors based on MLV, ASLV, SIV and HIV have all been shown to be non-random, and novel vectors with a safer integration pattern have been sought. Recently, we developed a producer cell line called CatPac that packages standard MoMLV vectors with feline leukemia virus (FeLV) gag, pol and env gene products. We now report the integration profile of this vector, asking if the FeLV integrase and capsid proteins could modify the MoMLV integration profile, potentially resulting in a less genotoxic pattern. We transduced rhesus macaque CD34+ hematopoietic progenitor cells with CatPac or standard MoMLV vectors, and determined their integration profile by LAM-PCR. We obtained 184 and 175 unique integration sites (ISs) respectively for CatPac and standard MoMLV vectors, and these were compared with 10 000 in silico-generated random IS. The integration profile for CatPac vector was similar to MoMLV and equally non-random, with a propensity for integration near transcription start sites and in highly dense gene regions. We found an IS for CatPac vector localized 715 nucleotides upstream of LMO-2, the gene involved in the acute lymphoblastic leukemia developed by X-SCID patients treated by gene therapy using MoMLV vectors. In conclusion, we found that replacement of MoMLV env, gag and pol gene products with FeLV did not alter the basic integration profile. Thus, there appears to be no safety advantage for this packaging system. However, considering the stability and efficacy of CatPac vectors, further development is warranted, using potentially safer vector backbones, for instance those with a SIN configuration.


Asunto(s)
Técnicas de Transferencia de Gen/efectos adversos , Vectores Genéticos/efectos adversos , Células Madre Hematopoyéticas/virología , Integrasas/genética , Virus de la Leucemia Felina/genética , Virus de la Leucemia Murina de Moloney/genética , Integración Viral , Animales , Cápside , Proteínas de la Cápside/genética , Virus de la Leucemia Felina/metabolismo , Macaca mulatta , Transducción Genética
5.
Oral Dis ; 16(3): 221-32, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19732354

RESUMEN

Practitioners of oral medicine frequently encounter patients with complaints of taste disturbance. While some such complaints represent pathological processes specific to the gustatory system, per se, this is rarely the case. Unless taste-bud mediated qualities such as sweet, sour, bitter, salty, umami, chalky, or metallic are involved, 'taste' dysfunction inevitably reflects damage to the sense of smell. Such 'taste' sensations as chicken, chocolate, coffee, raspberry, steak sauce, pizza, and hamburger are dependent upon stimulation of the olfactory receptors via the nasopharynx during deglutition. In this paper, we briefly review the anatomy, physiology, and pathophysiology of the olfactory system, along with means for clinically assessing its function. The prevalence, etiology, and nature of olfactory disorders commonly encountered in the dental clinic are addressed, along with approaches to therapy and patient management.


Asunto(s)
Trastornos del Olfato/diagnóstico , Percepción Olfatoria/fisiología , Olfato/fisiología , Humanos , Trastornos del Olfato/fisiopatología , Trastornos del Olfato/terapia , Neuronas Receptoras Olfatorias/fisiología , Gusto/fisiología
6.
Small ; 5(10): 1213-21, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19263430

RESUMEN

Common 2D cell cultures do not adequately represent the functions of 3D tissues that have extensive cell-cell and cell-matrix interactions, as well as markedly different diffusion/transport conditions. Hence, testing cytotoxicity in 2D cultures may not accurately reflect the actual toxicity of nanoparticles (NPs) and other nanostructures in the body. To obtain more adequate and detailed information about NP-tissue interactions, we here introduce a 3D-spheroid-culture-based NP toxicology testing system. Hydrogel inverted colloidal crystal (ICC) scaffolds are used to create a physiologically relevant and standardized 3D liver tissue spheroid model for in vitro assay application. Toxicity of CdTe and Au NPs are tested in both 2D and 3D spheroid cultures. The results reveal that NP toxic effects are significantly reduced in the spheroid culture when compared to the 2D culture data. Tissue-like morphology and phenotypic change are identified to be the major factors in diminishing toxicity. Acting as an intermediate stage bridging in vitro 2D and in vivo, our in vitro 3D cell-culture model would extend current cellular level cytotoxicity to the tissue level, thereby improving the predictive power of in vitro NP toxicology.


Asunto(s)
Nanopartículas/toxicidad , Esferoides Celulares/efectos de los fármacos , Pruebas de Toxicidad , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Coloides , Cristalización , Formazáns , Humanos , Cinética , L-Lactato Deshidrogenasa/metabolismo , Hígado/citología , Hígado/efectos de los fármacos , Hígado/ultraestructura , Esferoides Celulares/citología , Esferoides Celulares/ultraestructura , Sales de Tetrazolio , Células Tumorales Cultivadas
7.
Science ; 190(4221): 1316-8, 1975 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-1239080

RESUMEN

Men and women estimated (by the method of magnitude estimation) the pleasantness and intensity of the odors of vaginal secretions sampled from consecutive phases of 15 ovulatory menstrual cycles of four women. On the average, secretions from preovulatory and ovulatory phases were slightly weaker and less unpleasant in odor than those from menstrual, early luteal, and late luteal phases. However, considerable variation in odor patterns was present across cycles from the same donor, as well as across cycles from different donors. These results indicate that human vaginal odors change slightly in both pleasantness and intensity during the menstrual cycle, but do not support the notion that such odors are particularly attractive to humans in an in vitro test situation.


Asunto(s)
Menstruación , Odorantes/análisis , Vagina/metabolismo , Animales , Femenino , Fase Folicular , Humanos , Fase Luteínica , Feromonas
8.
Science ; 226(4681): 1441-3, 1984 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-6505700

RESUMEN

Smell identification ability was measured in 1955 persons ranging in age from 5 to 99 years. On the average, women outperformed men at all ages, and nonsmokers outperformed smokers. Peak performance occurred in the third through fifth decades and declined markedly after the seventh. More than half of those 65 to 80 years old evidenced major olfactory impairment. After 80 years, more than three-quarters evidenced major impairment. Given these findings, it is not surprising that many elderly persons complain that food lacks flavor and that the elderly account for a disproportionate number of accidental gas poisoning cases each year.


Asunto(s)
Envejecimiento , Olfato/fisiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Umbral Sensorial , Factores Sexuales , Fumar
9.
J Clin Endocrinol Metab ; 48(6): 912-8, 1979 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-447797

RESUMEN

A procedure is presented which overcomes most of the conceptual and statistical problems associated with the combining of data from heterogeneous menstrual cycles for graphical or statistical analyses. This procedure is based upon an initial normalization of the raw data to eliminate extraneous between-cycle variability, followed by the assignment of the data to a set of discrete cycle phases using a weighted-average technique. The efficacy of this procedure is compared to that of seven other published categorization methods by examining the proportion of variance accounted for and the P values from analyses of variance computed for 17 beta-estradiol and olfactory sensitivity measures. A major advantage of the proposed procedure is that it allows for the grouping of data from entire cycles (including menses) on the same figure without exhibiting points from heterogeneous sectors of individual cycles and without changing the sample size as distance from the midcycle LH surge increases. Thus, this procedure provides equal sample sizes for all phases of the cycle, allowing repeated-measures parametric statistical analyses to be performed. Data are presented which suggest that the categorization of menstrual cycle data without carefully established cycle phases can lead to quite erroneous conclusions.


Asunto(s)
Menstruación , Periodicidad , Adolescente , Adulto , Temperatura Corporal , Estradiol/sangre , Estrona/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Hormona Luteinizante/sangre , Métodos , Odorantes , Progesterona/sangre , Olfato
10.
J Clin Endocrinol Metab ; 82(1): 247-50, 1997 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8989268

RESUMEN

The discovery of variably decreased olfactory ability in Type Ia pseudohypoparathyroidism (PHP), a syndrome in which generalized hormone resistance is associated with deficiency of the alpha chain of the stimulatory guanine nucleotide-binding protein (Gs alpha) of adenylyl cyclase, has been used to support the hypothesis that Gs alpha plays a major role in human olfactory transduction. However, only a limited number of olfactory tests have been administered to such patients, and these patients have other problems that might cause or contribute to their olfactory dysfunction, including an unusual constellation of skeletal and developmental deficits termed Albright hereditary osteodystrophy (AHO). In this study, we administered tests of odor detection, identification, and memory to (i) 13 patients with Type Ia PHP; (ii) 8 patients with Type Ib PHP; (iii) 7 patients with pseudopseudohypoparathyroidism (PPHP); and (iv) 3 sets of normal controls matched to these groups on the basis of age, gender, and smoking history. Although we confirm that PHP Type Ia patients evidence olfactory dysfunction, we also demonstrate that (i) patients with Type Ib PHP, who have no AHO, no generalized hormone resistance, and normal Gs alpha activity, also evidence olfactory dysfunction relative to matched controls; and (ii) patients with PPHP, who have AHO, no generalized hormone resistance, and deficient Gs alpha protein activity, have relatively normal olfactory function. These observations do not support the hypothesis that the olfactory dysfunction associated with PHP is the result of generalized Gs alpha protein deficiency and imply that other mechanisms (e.g. ones associated with PTH or PTHrP resistance) are responsible for the olfactory deficits of this disorder.


Asunto(s)
Proteínas de Unión al GTP/deficiencia , Seudohipoparatiroidismo/fisiopatología , Olfato/fisiología , Adulto , Femenino , Humanos , Masculino , Memoria , Odorantes , Receptores Odorantes/fisiología
11.
Neurobiol Aging ; 18(2): 163-7, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9258893

RESUMEN

In the present study we assessed olfactory identification ability using the University of Pennsylvania Smell Identification Test (UPSIT) in 16 elderly patients with schizophrenia (ES), 20 patients with a diagnosis of probable Alzheimer's disease (AD), and 20 healthy elderly controls (EC). Both patient groups exhibited marked deficits in UPSIT performance relative to controls. ES and AD patients with similar levels of general cognitive impairment did not differ on the UPSIT, suggesting that the two disorders may share a common dysfunction in olfactory brain regions. While there have been recent reports of greater olfactory impairment in males, neither patient group exhibited significant gender differences on the UPSIT.


Asunto(s)
Enfermedad de Alzheimer/psicología , Psicología del Esquizofrénico , Olfato/fisiología , Anciano , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Caracteres Sexuales
12.
Am J Psychiatry ; 155(9): 1288-90, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9734558

RESUMEN

OBJECTIVE: The authors' goal was to compare the size and linear density of Purkinje cells in the cerebellar vermis of subjects with and without schizophrenia. METHOD: Blocks of alcohol-fixed cerebellar vermis were dissected at autopsy from the brains of 14 elderly patients with schizophrenia and 13 elderly subjects with no history of neuropsychiatric illness. The blocks of vermis were sectioned and stained with 1% cresyl violet. The linear density and cross-sectional area of Purkinje cells were measured by using computer-assisted image analysis. The subjects with schizophrenia had been assessed with clinical rating scales within 1 year prior to death. RESULTS: The average cross-sectional areas of Purkinje cells of the patients with schizophrenia were significantly smaller (by 8.3%) than those of the subjects without neuropsychiatric illness. No difference in Purkinje cell linear density was observed between the two groups. Significant correlations were seen between Purkinje cell size and scores on the Mini-Mental State, the Brief Psychiatric Rating Scale, and the antipsychotic drug dose. CONCLUSIONS: These data indicate cerebellar involvement in schizophrenia; they are also consistent with reports of reduced neuronal size in other brain regions of patients with schizophrenia. These findings support a model of wide-spread central nervous system abnormality in schizophrenia.


Asunto(s)
Cerebelo/citología , Células de Purkinje/citología , Esquizofrenia/diagnóstico , Anciano , Antipsicóticos/uso terapéutico , Autopsia , Recuento de Células , Tamaño de la Célula , Cerebelo/patología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Células de Purkinje/patología , Esquizofrenia/patología
13.
Am J Psychiatry ; 154(7): 1016-8, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9210756

RESUMEN

OBJECTIVE: The authors examined the relationship between deficits in olfactory identification and duration of illness in young and elderly patients with schizophrenia. METHOD: Olfactory identification performance of 38 patients with schizophrenia and 40 normal subjects was compared by using the University of Pennsylvania Smell Identification Test. RESULTS: The schizophrenic patients demonstrated olfactory deficits relative to the comparison group, and the elderly schizophrenic patients displayed a greater magnitude of olfactory deficit than the younger patients. Independent of normal aging effects and cognitive deficit, patients with schizophrenia showed a strong relationship between olfactory identification scores and duration of illness, which suggests that olfactory abilities decline progressively over the course of the disorder. CONCLUSIONS: In contrast to other neuropsychological measures that have been reported to be stable over the course of illness, olfactory identification abilities deteriorate steadily in patients with schizophrenia, even for those with relatively recent onset.


Asunto(s)
Esquizofrenia/diagnóstico , Trastornos de la Sensación/diagnóstico , Olfato/fisiología , Adolescente , Adulto , Factores de Edad , Anciano , Envejecimiento/fisiología , Discriminación en Psicología/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Odorantes , Trastornos del Olfato/diagnóstico , Esquizofrenia/fisiopatología , Trastornos de la Sensación/fisiopatología , Umbral Sensorial , Factores Sexuales , Factores de Tiempo
14.
Am J Psychiatry ; 157(5): 828-30, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10784482

RESUMEN

OBJECTIVE: The authors' goal in this study was to compare the size of olfactory bulbs of patients with schizophrenia and those of healthy subjects. METHOD: Magnetic resonance imaging scans of olfactory bulbs were obtained from 26 patients with schizophrenia and 22 healthy comparison subjects. A reliable region of interest procedure was used to measure olfactory bulb volume. RESULTS: Patients exhibited 23% smaller bilateral bulb volume than comparison subjects, independent of acute clinical, demographic, or treatment measures. Bulb volume correlated with odor detection sensitivity in healthy subjects but not in patients with schizophrenia. CONCLUSIONS: Patients with schizophrenia exhibit structural olfactory deficits as well as functional olfactory deficits. The olfactory system may be a model system in which to study the neurobiology of the disorder.


Asunto(s)
Bulbo Olfatorio/anatomía & histología , Esquizofrenia/diagnóstico , Adulto , Discriminación en Psicología/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Odorantes , Bulbo Olfatorio/fisiología , Bulbo Olfatorio/fisiopatología , Esquizofrenia/fisiopatología , Umbral Sensorial/fisiología , Olfato/fisiología
15.
J Comp Neurol ; 218(2): 159-73, 1983 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-6886069

RESUMEN

Horseradish peroxidase (HRP) was injected in relatively massive amounts to cover most, or portions, of opercular striate cortex in four macaques. Absence of transcallosal or circumventricular labelling, plus discrete and consistent retrograde labelling in other areas in the four cases, assured the validity and specificity of the observations. Numerous labelled cells in regions directly bordering striate cortex, however, were excluded from the analysis because of the possibility of uptake consequent to physical diffusion. With this exception, all labelled cells were counted at roughly 2-mm intervals for one case with extensive unilateral injection of HRP. Even excluding the closely circumstriate population, the totals indicate that more than 30% of the afferent input to striate cortex arises from nongeniculate sources. Four areas of neocortex together make up about one-fourth of the total afferents: superior temporal sulcus 17.1%; inferior occipital area, 6.1%; intraparietal sulcus, 0.4%; and parahippocampal gyrus, 0.3%. Other areas projecting to striate cortex include claustrum, pulvinar, nucleus paracentralis, raphé system, locus coeruleus, and the nucleus basalis of Meynert. Cells of the latter were particularly striking with their very heavy uptake of HRP, and, even in cases of minimal effective injection, were scattered throughout an extensive area from the posterior edge of the globus pallidus passing rostrally beyond the chiasm and into the nucleus of the diagonal band. On the basis of their distribution and known cholinergic affinity, it is argued that this group also includes the cells labelled in and around lateral hypothalamus and cerebral peduncle, and that as a whole the group constitutes a cholinergic counterpart of the diffusely projecting monoaminergic systems. It seems possible that the basalis projection at first follows a fornical-subcallosal pathway to reach striate cortex via callosoperforant fibers.


Asunto(s)
Corteza Visual/anatomía & histología , Vías Aferentes/anatomía & histología , Animales , Ganglios Basales/anatomía & histología , Mapeo Encefálico , Diencéfalo/anatomía & histología , Cuerpos Geniculados/anatomía & histología , Macaca mulatta , Mesencéfalo/anatomía & histología , Puente/anatomía & histología , Telencéfalo/anatomía & histología , Núcleos Talámicos/anatomía & histología
16.
Arch Neurol ; 55(1): 84-90, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9443714

RESUMEN

BACKGROUND: Olfactory deficits in Alzheimer's disease (AD) and idiopathic Parkinson's disease (PD) have been well established. OBJECTIVE: To clarify and review the literature by evaluating the evidence for olfactory deficits in 3 olfactory domains, including odor identification, recognition, and detection threshold. DATA SOURCES: A literature search of English-language studies of olfaction in AD, PD, and healthy controls was conducted via online databases (PsycInfo and MEDLINE) and reference lists from review articles. STUDY SELECTION: To meet selection criteria for meta-analysis, each study required a control group and complete and usable data. This review yielded 26 publications of olfactory identification, recognition, and/or detection threshold. Because of the inclusion of more than 1 relevant study of olfaction in several of these publications (eg, both identification and threshold assessed), 43 studies were ultimately appropriate for meta-analysis. DATA EXTRACTION: Effect sizes were calculated for each study by expressing differences between patient and control group means in SD units (Cohen's d). DATA SYNTHESIS: Extremely large effect sizes were shown across all tasks in both AD and PD groups. Both between-group analyses using the Mann-Whitney U test and within-group analyses using Friedman 2-way analysis of variance did not reveal any significant differences (all P > .30). CONCLUSIONS: As expected, severe deficits were found for both patients with AD and PD in each of the 3 olfactory domains relative to controls. However, no discriminating olfactory deficits were seen between patient groups or among the 3 measured olfactory domains, suggesting a similar disturbance in olfactory function between patients with AD and PD.


Asunto(s)
Enfermedad de Alzheimer/complicaciones , Enfermedad de Parkinson/complicaciones , Olfato , Adulto , Anciano , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/fisiopatología , Modificador del Efecto Epidemiológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/fisiopatología
17.
Arch Neurol ; 54(9): 1131-40, 1997 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9311357

RESUMEN

BACKGROUND: The ability to smell is commonly altered by head trauma (HT). However, the nature, prevalence, prognosis, and etiology of such alterations are poorly understood. OBJECTIVES: To quantitatively determine the degree of olfactory function in patients with HT-related chemosensory complaints and to examine the influences of age, sex, HT severity, time since HT, and other variables on such function. Also, to use quantitative magnetic resonance imaging (MRI) to establish whether and to what degree damage to the olfactory bulbs and tracts, frontal lobes, and temporal lobes occurs. PATIENTS AND METHODS: Two hundred sixty-eight patients with HT from the University of Pennsylvania Smell and Taste Center, Philadelphia, were administered a quantitative odor identification test, a depression inventory, and a medical history questionnaire; 66 were retested after individual test-retest periods ranging from 1 month to 13 years. The volume of olfactory-related brain structures was determined in 15 patients and 15 controls using MRI. RESULTS: One hundred seventy-nine patients (66.8%) had anosmia, 55 (20.5%) had microsmia, and 34 (12.7%) had normosmia. Frontal impacts produced less dysfunction than back or side impacts. Of the 66 retested patients, 24 (36%) improved slightly, 30 (45%) had no change, and 12 (18%) worsened; only 3 patients, none of whom initially had anosmia, regained normal olfactory function. Trauma severity was related to olfactory test scores in patients with microsmia. Parosmia prevalence decreased from 41.1% to 15.4% over an 8-year posttrauma period. Olfactory bulb and tract volumes of male, but not female, patients with HT were greatly reduced relative to volumes of controls. CONCLUSIONS: Patients complaining of HT-related olfactory dysfunction typically have anosmia and rarely regain normal olfactory ability, parosmia prevalence decreases over time in such patients, and damage to olfaction-related brain structures can be observed in most such patients using an appropriate MRI protocol.


Asunto(s)
Traumatismos Craneocerebrales/complicaciones , Vías Olfatorias/patología , Trastornos de la Sensación/etiología , Olfato/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Traumatismos Craneocerebrales/fisiopatología , Traumatismos Craneocerebrales/psicología , Depresión/complicaciones , Depresión/psicología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Trastornos del Olfato/etiología , Prevalencia , Trastornos de la Sensación/diagnóstico , Trastornos de la Sensación/epidemiología , Caracteres Sexuales , Factores de Tiempo , Índices de Gravedad del Trauma
18.
Neurology ; 38(8): 1237-44, 1988 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-3399075

RESUMEN

To explore the nature of the olfactory dysfunction associated with Parkinson's disease (PD), 81 PD patients who scored well on a cognitive screening test were administered the 40-odorant University of Pennsylvania Smell Identification Test; 38 were additionally given a forced-choice phenylethyl alcohol odor detection threshold test. Clinical ratings of 11 neurologic symptoms (three bilateral) were obtained at the time of testing, and odor identification was retested in 24 patients at intervals ranging from 5 to 39 months. Relative to matched controls, the PD patients exhibited consistent and marked decrements on both types of olfactory tests (ps less than 0.0001). The odor identification deficit was not restricted to any subset of odorants and did not evidence longitudinal change. A factor analysis of the intercorrelations among the variables yielded six easily interpretable factors: general motor, oral motor, olfactory function, cognitive function, tremor, and gender. Olfactory test scores were independent of all other measures, including disease stage and duration. Seventy-two percent of the PD patients were unaware of a smell disorder before testing; those who were aware had significantly lower test scores. A statistical comparison of PD patients' olfactory test scores to those obtained from Alzheimer's disease patients found the olfactory disorders of these diseases to be indistinguishable. The data support the hypothesis that the olfactory deficit of PD is a general and stable one which likely occurs early in the disease process.


Asunto(s)
Enfermedad de Parkinson/fisiopatología , Olfato , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
19.
Neurology ; 53(4): 880-2, 1999 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-10489062

RESUMEN

Scores on the University of Pennsylvania Smell Identification Test (UPSIT), as well as the numbers of MRI-determined plaques within the inferior frontal and temporal lobes, were obtained on three or four separate occasions in each of five MS patients over an 18- to 20-month period. A close association was observed, longitudinally, between the remission and exacerbation of plaque numbers and UPSIT scores, with more plaques reflecting lower UPSIT scores. These observations further support the hypothesis that olfactory loss in MS is associated with fluctuations in plaque numbers in central olfactory brain regions.


Asunto(s)
Esclerosis Múltiple/patología , Esclerosis Múltiple/fisiopatología , Bulbo Olfatorio/patología , Bulbo Olfatorio/fisiopatología , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad
20.
Neurology ; 41(5 Suppl 2): 77-80; discussion 80-1, 1991 May.
Artículo en Inglés | MEDLINE | ID: mdl-2041598

RESUMEN

Olfactory dysfunction is among the first signs of Alzheimer's disease (AD), idiopathic Parkinson's disease (PD), and the parkinsonism-dementia complex (PDC) of Guam. We have recently demonstrated that the odor identification and detection deficits of patients with PD are equivalent to those of patients with mild AD when subtle differences in cognitive function are statistically controlled for by analysis of covariance. In contrast, patients with progressive supranuclear palsy (PSP) and patients with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism evidence olfactory function much more similar to that of normal controls. In the present study, we administered the University of Pennsylvania Smell Identification Test and the Picture Identification Test to 24 patients with early signs of the PDC of Guam and statistically compared their test scores to those of 24 early-stage AD and 24 early-stage PD patients of similar age and gender from the United States mainland. Although the PDC group evidenced slightly more difficulty in identifying pictures than did the other 2 groups, the odor identification deficit associated with this disorder was of the same magnitude as that observed in AD and PD, suggesting that olfactory testing cannot be used to distinguish among these 3 diseases and that the olfactory dysfunction of these disorders may reflect a common neurologic substrate.


Asunto(s)
Enfermedad de Alzheimer/complicaciones , Demencia/complicaciones , Enfermedades del Sistema Nervioso/complicaciones , Enfermedad de Parkinson/complicaciones , Olfato , Adulto , Anciano , Análisis de Varianza , Femenino , Guam , Humanos , Masculino , Enfermedades del Sistema Nervioso/fisiopatología , Pruebas Neuropsicológicas , Reconocimiento Visual de Modelos
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