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PubMed2005

Olfactory screening test in mild cognitive impairment.

Mild cognitive impairment (MCI) is a transient status between physiologic ageing and dementia. Each year more than 12% of subjects with MCI develop Alzheimer's disease. This study evaluated the presence of an olfactory deficit in amnesic MCI (aMCI) patients. Twenty-nine patients diagnosed with aMCI and a homogeneous control group of 29 subjects were enrolled in the study. Olfactory function was assessed by the Sniffin' Sticks Screening Test (SSST) and the Mini Mental State Examination, the Clinical Dementia Rating, the Geriatric Depression Scale and the Mental Deterioration Battery were used to evaluate the neurocognitive status. aMCI patients showed a significant impairment of their olfactory identification compared to controls (SSST score: 8.3+/-2.1 vs. 10.8+/-0.9; p<0.001). These results suggest that olfactory tests should be part of the diagnostic armamentarium of pre-clinical dementia. A long-term follow up might confirm the olfactory identification function as an early and reliable marker in the diagnosis of pre-clinical dementia.

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PubMed1989

Luteinizing hormone-releasing hormone (LHRH)-expressing cells do not migrate normally in an inherited hypogonadal (Kallmann) syndrome.

Kallmann syndrome inherited hypogonadotropic hypogonadism with anosmia, is associated with an X-chromosome deletion at Xp 22.3. In a Kallmann fetus, we have found an absence of luteinizing hormone-releasing hormone (LHRH)-expressing cells in the brain despite dense clusters of LHRH cells and fibers in the nose. LHRH-containing cells and neurites end in a tangle beneath the forebrain, within the dural layers of the meninges, on the dorsal surface of the cribriform plate of the ethmoid bone. Normal fetal brains, matched for age and sex, had LHRH cells and fibers, as expected, in the hypothalamus and preoptic area. Since LHRH-expressing cells recently were discovered to migrate from the olfactory placode into the brain, it appears that the hypogonadotropism of the Kallmann syndrome can be accounted for by a failure of LHRH cells to migrate into the brain.

Brain↗
PubMed2004

Expression of expanded polyglutamine protein induces behavioral changes in Drosophila (polyglutamine-induced changes in Drosophila).

Spinocerebellar ataxia type-3 or Machado-Joseph disease (SCA3/MJD) is an autosomal dominant neurodegenerative disease caused by triplet nucleotide expansion. The expansion of the polyglutamine tract near the C terminus of the MJD1 gene product, ataxin-3, above a threshold of 40 glutamine repeats causes neuronal loss and degeneration. The expanded ataxin-3 forms aggregates, and nuclear inclusions, within neurons, possibly due to the misfolding of mutant proteins. Here we report upon the behavioral test changes related to truncated and expanded forms of MJD protein (MJDtr) in Drosophila, and show that expanded MJDtr, when expressed in the nervous system, causes characteristic locomotor dysfunction and anosmia. This phenomenon has not been previously reported in humans or in transgenic Drosophila models. In addition, the in vivo expression of the antiapoptotic gene bcl-2 showed no evidence of ameliorating the deleterious effect of MJDtr-Q78s, either in the eye or in the nervous system. The study shows that such Drosophila transgenic models express olfactory dysfunction and ataxic behavior as observed in human patients.

Animals↗
PubMed2003

Olfactory function in mild cognitive impairment and Alzheimer's disease: an investigation using psychophysical and electrophysiological techniques.

OBJECTIVE: To clarify the olfactory deficit hypothesis regarding Alzheimer's disease, the authors compared olfactory function in patients with Alzheimer's disease, subjects with mild cognitive impairment, and healthy comparison subjects. METHOD: Olfactory function of 14 patients with mild Alzheimer's disease, eight subjects with mild cognitive impairment, and eight healthy age-matched comparison subjects was assessed with both psychophysical tests and olfactory event-related potentials. RESULTS: Group comparison of the psychophysical test results showed a significant main effect of diagnosis for odor detection threshold, odor discrimination, and odor identification. These results correlated only partially with those obtained from olfactory event-related potentials. Seven Alzheimer's disease patients and four with mild cognitive impairment showed no olfactory event-related potentials, suggesting hyposmia, while all comparison subjects had clearly discernible responses. Patients with Alzheimer's disease were significantly more likely to be nonresponders. In the four Alzheimer's disease patients and four subjects with mild cognitive impairment who had clear electrophysiological responses, amplitudes and latencies of the various event-related potential components were normal, i.e., similar to those of the comparison subjects, although 12 of the 14 Alzheimer's disease patients and seven of the eight mildly impaired subjects were classified as functionally anosmic with psychophysical methods. CONCLUSIONS: The electrophysiological results confirm prior findings of olfactory dysfunction in patients with Alzheimer's disease and preclinical Alzheimer's disease. Investigations of larger study groups with detailed cognitive examination and postmortem diagnosis may resolve the intriguing possibility of early diagnosis and discrimination of Alzheimer's disease subtypes through chemosensory event-related potentials in addition to existing biomarkers.

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PubMed2000

Olfactory dysfunction discriminates probable Alzheimer's dementia from major depression: a cross-validation and extension.

The present study was conducted to cross-validate and extend the hypothesis that olfactory dysfunction could discriminate between groups of patients with Alzheimer's disease and major depression. Forty patients meeting the DSM-IV criteria for either Alzheimer's disease or major depression (20 per group) underwent assessment with the Pocket Smell Test (PST), a three-item screening measure of odor identification, and the Mini-Mental State Examination (MMSE). A PST score of < or = 1 (1 or 0 correct) discriminated between the groups with a hit rate of 97.5% (sensitivity = 95%, specificity = 100%). The optimal hit rate for the MMSE (< or =24) was less effective (hit rate = 90%, sensitivity = 80%, specificity = 100%). Age, gender, and education had minimal impact on the PST for both groups. Olfactory assessment continues to add to the diagnostic utility in the differential diagnosis of Alzheimer's disease versus major depression in elderly patients.

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PubMed1988

Familial 'sleep apnea plus' syndrome: report of a family.

We describe a familial disorder consisting of sleep apnea, anosmia, colorblindness, partial complex seizures, and cognitive dysfunction. The phenotypic expression of the syndrome suggests an autosomal dominant inheritance with incomplete penetrance.

Adult↗
PubMed2004

Kallmann's syndrome and schizophrenia.

OBJECTIVE: Kallmann's Syndrome is a heritable disorder characterized by the association of hypogonadotropic hypogonadism and anosmia or hyposmia. A common pathogenesis for KS and schizophrenia had been proposed based on shared pathologies of these two disorders, although no such clinical associations have ever been reported. METHOD: We report a 35 year old man with schizophrenia and Kallmann's Syndrome. The patient presented with signs and symptoms of hypogonadism, severe hyposmia and normal endocrine functions of the anterior pituitary. Hyposmia has been attributed to the absence of the olfactory bulbs and tracts and atrophy of the olfactory gyri, but normal olfactory mucosa. The patient presented with paranoid schizophrenia with persecutory delusions, auditory hallucinations, thought disorder, depersonalization, and gradual but marked global deterioration. RESULTS: Psychiatric evaluation revealed an entirely different psychopathological and personality profile between the patient and the six other Kallmann patients studied. Cycle sequencing analysis revealed a normal sequence of all 14 exons of the KAL gene. In conclusion, based on the presented case, Kallmann's Syndrome and schizophrenia represent a rare clinical association rather than a syndrome with a common pathogenesis, which if present should be confined to the olfactory dysfunction.

Adult↗
PubMedDate not supplied

[Refsum's disease].

Refsum's disease although rare is of great interest for it may benefit at least partially from treatment. Its clinical diagnosis depends on the association of pigmented retinitis, polyneuritis and cerebellar syndrome. It is confirmed beyond doubt by the increased C.S.F. protein and phytanemia. A full family history is necessary for it is possible to detect heterozygous carriers of the defect by enzyme studies on fibroblast cultures.

Adolescent↗
PubMed1999

Disorders of smell and taste.

As with almost any aspect of medical practice, a thorough history and physical examination coupled with a good understanding of the anatomy and physiology of an organ system are the key factors in reaching a diagnosis. The information in this article is provided to assist the internist with the diagnosis of chemosensory disorders and the differentiation of malingering or other disease process as well as providing insight into the workup, prognosis, and treatment of patients with taste and smell disorders.

Diagnosis, Differential↗
PubMed1991

Short nasal respiratory cilia and impaired mucociliary function.

A 48-year-old man was examined because of anosmia. He was otherwise healthy except for mild arterial hypertension. He had stopped smoking 20 years ago. Previously he had been exposed to sulfuric acid gases for 3 years in his work. Clinical examination revealed no findings to explain his anosmia. The patient was fertile, indicating normal sperm/cilia motility. Nasal mucociliary function was examined by radioactive tracer and found to be markedly and constantly impaired. Ciliary ultrastructure in cross-sections was normal. However, in longitudinal sections the length of the cilia varied from 0.6 microns to 3.9 microns. The mean length of the cilia from the cell membrane to the tip was 2.5 +/- 0.9 microns, in contrast to normal ciliary length of 5-7 microns. These findings represent a new structural defect among the various known ciliary abnormalities.

Cilia↗
PubMedDate not supplied

Factors influencing food intake in patients with heart failure: a comparison with healthy elders.

BACKGROUND AND RESEARCH OBJECTIVE: Promoting adequate nutritional intake of patients with heart failure (HF) is an essential component of comprehensive management. This goal can be hampered by decreased appetite, as well as psychological, social, and HF-related factors that can affect food intake. Factors related to aging may also affect food intake in older patients. The purpose of this study was to compare patients with HF to healthy elders regarding the extent to which they perceived how appetite and hunger, emotional and social, and illness factors affected the amount of food they ate in the previous week. SUBJECTS AND METHODS: Sixty-seven patients with HF were recruited from 3 Midwestern HF clinics. As part of a larger study examining nutrition in HF, patients filled out the Food Eating Experiences and Diet (FEED) questionnaire, an instrument designed to assess factors affecting appetite and hunger. Patients were asked to rate their hunger and appetite on a visual analog scale. On Likert-type scales, they rated the extent to which appetite/hunger, emotional/social, and illness factors affected the amount of food intake. Sixty-eight healthy elders were recruited from 2 Midwestern senior citizen centers. As part of a study collecting a large data set for comparison with HF patients, healthy elders provided demographic and health information and filled out the FEED questionnaire. RESULTS AND CONCLUSIONS: Factors rated as affecting food intake most often by patients with HF were decreased hunger sensations, diet restrictions, fatigue, shortness of breath, nausea, anxiety, and sadness. Factors rated most often by healthy elders as affecting food intake were diminished hunger sensations, early satiety, eating alone, and decreased senses of taste and smell. Among patients with HF, many factors unique from those present due to age were reported to affect food intake.

Aged↗
PubMedDate not supplied

Olfactory tau pathology in Alzheimer disease and mild cognitive impairment.

OBJECTIVE: To examine the occurrence of tau pathology in the olfactory system in aged subjects and its relation to the severity of Alzheimer disease (AD) pathology. MATERIAL AND METHODS: 273 autopsy cases (167 female, 106 male, aged 61-102, mean 83.2+/-4.5 SD years) underwent a standard neuropathological assessment with immuno-histochemical study of tau and Abeta amyloid in the olfactory bulb and nerve, and diagnosis of AD using established consensus criteria including Braak staging of neuritic AD pathology. RESULTS: All cases of definite AD (Braak stages 5 and 6, n = 96) showed large numbers of neuropil threads and neurofibrillary tangles, with amyloid deposits in 50%, and neuritic plaques only in two cases. Braak stage 4 (n = 73) was associated with tau pathology in the olfactory system in 90.4 and amyloid deposits in 9%, Braak stage 3 (n = 56) with mainly mild to moderate olfactory tau lesions in 44.6 and Abeta deposits in 9%. Braak stage 2 (n = 22) showed olfactory tau pathology in 36.4% without amyloid deposits, whereas Braak stages 0 and 1 (n = 25) were all negative. Olfactory tau pathology showed highly significant correlation with neuritic Braak staging in the brain, while both scores showed significant but low correlation with age. CONCLUSIONS: These data confirm previous studies demonstrating considerable tau pathology in the olfactory system in all definite AD cases, in more than 2/3 of limbic AD and in more than 1/3 of elderly individuals with or without mild cognitive impairment associated with Braak stage 2. Clinical dementia correlated with both Braak and olfactory tau scores, indicating that both are associated with a high risk of cognitive decline.

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