Olfaction and Alzheimer's disease

Disturbances in the sense of smell may be important both clinically and theoretically in Alzheimer's disease. Initial evidence of poor olfactory recognition performance in Alzheimer's and parkinsonian dementias was followed by two reports which corroborated olfactory dysfunction in Alzheimer's disease. The neuroanatomical and neurochemical bases for this disturbance are discussed. Despite an abundance of preclinical and clinical data linking olfaction with acetylcholine, a preliminary study failed to show any effect of scopolamine on olfactory thresholds. Two of the olfaction-Alzheimer's studies found significantly better performance in other demented groups (alcoholics and patients with vascular dementia), suggesting possible utility in the differential diagnostic workup. The effect of aging per se on olfactory performance cannot be assessed without rigorous control for cognitive dysfunction in sampled populations.     

Olfaction and apathy in Parkinson's disease

BackgroundOlfactory deficits are frequent among patients with idiopathic Parkinson's disease (PD). Additionally, apathy (as quantified by the Apathy Evaluation Scale), is more prevalent in PD patients compared to the general population. Olfactory impairment and apathy are associated with dysfunction in overlapping brain regions. Neuroimaging studies indicate that the anterior cingulate gyrus and medial orbitofrontal cortex are hypoactive in apathetic patients and are also involved in secondary olfactory processing. However, no study until this point has been published investigating whether there is any association between olfactory dysfunction and apathy in PD patients.MethodsIn our study seventy consecutive patients with PD took the Brief Smell Identification Test (B-SIT), completed the Apathy Evaluation Scale (AES) and were administered the Folstein Mini-Mental Status exam (MMSE).ResultsApathetic PD patients performed poorly on the B-SIT compared with non-apathetic PD patients and olfactory impairment correlated with apathy. The simultaneous disruption of olfaction and emotion in Parkinson's could be the result of disease pathology in brain regions involved in both olfactory and emotional processing and reinforces the idea that this link between olfaction and emotions may have clinical consequences.     

Olfaction in Parkinson's disease

It has become increasingly apparent that Parkinson's disease (PD) can no longer be considered purely a motor disease, as numerous sensory alterations accompany this disorder either before or early in its clinical progression. Most notable among such disturbances are decrements in smell function. Such anomalies have been documented in approximately 90% of patients with early-stage sporadic PD and appear to progress little, if at all, with the development of the more classic PD-related motor symptoms. In this paper, I briefly review the nature of the olfactory dysfunction observed in PD and current theories as to its pathological basis.     

Olfaction and social drive in schizophrenia

BACKGROUND: The neurobiology of social dysfunction in schizophrenia is unknown, but smell identification deficits (SIDs) exist in schizophrenia, and olfaction is related to social affiliation in other mammals. The SIDs have been linked with negative symptoms and the deficit syndrome, but any specificity of SIDs for social dysfunction is unstudied. Low intelligence might explain this relationship, if it is associated with both negative symptoms and SIDs. We examined whether SIDs in schizophrenia were related broadly to negative symptoms, as are a number of other neuropsychological measures, or whether they might show a more specific relationship with social drive. METHODS: Smell Identification Test scores, Wechsler Adult Intelligence Scale-Revised IQ, symptomatology assessed with the Positive and Negative Syndrome Scale, and the deficit syndrome were determined in 70 patients with DSM-IV schizophrenia. RESULTS: The SIDs were related to negative symptoms and the deficit syndrome, but the association of SIDs with diminished social drive explained both relationships. Smell identification was also related to Wechsler Adult Intelligence Scale-Revised IQ, but intelligence was independent of the relationship of SID and social drive. The worse Smell Identification Test scores in male patients were attributable to a greater preponderance of men with the deficit syndrome. CONCLUSIONS: These analyses demonstrated independent relationships of Smell Identification Test scores to social drive and intelligence that together accounted for almost 50% of the variance in Smell Identification Test scores. There may be common neural substrates for the low social drive and SIDs in schizophrenia.     

Olfaction and taste processing in autism.

BACKGROUND: Autism is often associated with sensory symptoms, but few studies have examined chemosensory functions in this population. We examined olfactory and taste functioning in individuals with autism to characterize chemosensory processing and test competing hypotheses about underlying brainstem versus cortical abnormalities. METHODS: Twenty-one participants (10-18 years) with autism were compared with 27 well-matched control participants with typical development. Taste identification was tested via sucrose, NaCl, citric acid, and quinine solutions applied to standard locations on the anterior tongue. Taste detection thresholds were established in the same regions with electrogustometry, and olfactory identification was evaluated with "Sniffin' Sticks." RESULTS: Participants with autism were significantly less accurate than control participants in identifying sour tastes and marginally less accurate for bitter tastes, but they were not different in identifying sweet and salty stimuli. Taste detection thresholds via electrogustometry were equivalent. Olfactory identification was significantly worse among participants with autism. CONCLUSIONS: True differences exist in taste and olfactory identification in autism. Impairment in taste identification with normal detection thresholds suggests cortical, rather than brainstem dysfunction. Further research is needed to determine the neurologic bases of olfactory and taste impairments, as well as the relationship of chemosensory dysfunction to other characteristics of autism.     

Olfaction in neurodegenerative disorder.

There has been an increase of interest in olfactory dysfunction since it was realised that anosmia was a common feature of idiopathic Parkinson's disease (PD) and Alzheimer-type dementia (AD). It is an intriguing possibility that the first sign of a disorder hitherto regarded as one of movement or cognition may be that of disturbed smell sense. In this review of PD, parkinsonian syndromes, essential tremor, AD, motor neurone disease (MND) and Huntington's chorea (HC) the following observations are made: 1). olfactory dysfunction is frequent and often severe in PD and AD; 2). normal smell identification in PD is rare and should prompt review of diagnosis unless the patient is female with tremor-dominant disease; 3). anosmia in suspected progressive supranuclear palsy and corticobasal degeneration is atypical and should likewise provoke diagnostic review; 4). hyposmia is an early feature of PD and AD and may precede motor and cognitive signs respectively; 5). subjects with anosmia and one ApoE-4 allele have an approximate 5-fold increased risk of later AD; 6). impaired smell sense is seen in some patients at 50% risk of parkinsonism; 7). smell testing in HC and MND where abnormality may be found, is not likely to be of clinical value; and 8). biopsy of olfactory nasal neurons shows non-specific changes in PD and AD and at present will not aid diagnosis.     

Olfaction in Parkinson's disease and related disorders

Olfactory dysfunction is an early 'pre-clinical' sign of Parkinson's disease (PD). The present review is a comprehensive and up-to-date assessment of such dysfunction in PD and related disorders. The olfactory bulb is implicated in the dysfunction, since only those syndromes with olfactory bulb pathology exhibit significant smell loss. The role of dopamine in the production of olfactory system pathology is enigmatic, as overexpression of dopaminergic cells within the bulb's glomerular layer is a common feature of PD and most animal models of PD. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with the most smell loss. When compromised, these systems, which regulate microglial activity, can influence the induction of localized brain inflammation, oxidative damage, and cytosolic disruption of cellular processes. In monogenetic forms of PD, olfactory dysfunction is rarely observed in asymptomatic gene carriers, but is present in many of those that exhibit the motor phenotype. This suggests that such gene-related influences on olfaction, when present, take time to develop and depend upon additional factors, such as those from aging, other genes, formation of α-synuclein- and tau-related pathology, or lowered thresholds to oxidative stress from toxic insults. The limited data available suggest that the physiological determinants of the early changes in PD-related olfactory function are likely multifactorial and may include the same determinants as those responsible for a number of other non-motor symptoms of PD, such as dysautonomia and sleep disturbances.     

Olfaction in child and adolescent anorexia nervosa

Previous studies indicate disturbed olfactory functions in anorexia nervosa with presumable relationship to the clinical symptom of food aversion and weight loss. However, these studies are in part limited due to inadequately matched control samples, insufficient exclusion criteria, complex interactions of the olfactory and trigeminal system, and the lack of regard to co-morbidity and medication. Thus, we investigated olfactory function in 26 female adolescent patients with anorexia nervosa and 23 healthy controls matched for age, gender, handedness, and intelligence. No significant group differences were identified. Controlling for co-morbid disorders, psychopharmacological treatment, and depressivity revealed superior olfactory identification performance in the "pure" anorexia nervosa group (n = 15) in contrast to the controls. Superior identification may be mediated by increased attentional processes towards food stimuli in patients with anorexia nervosa. Effects of co-morbidity and medication highlight the role of neurobiological factors in the etiology of anorexia nervosa. Furthermore, as other neuropsychiatric disorders such as Parkinson's disease or attention deficit hyperactivity disorder show distinct olfactory function patterns, olfaction may be suitable as phenotypic marker with potential relevance for (differential) diagnosis in neuropsychiatric disorders.     

Olfaction and cognition in schizophrenia: sex matters

Cognitive and olfactory deficits occur in schizophrenia, but little is known whether sex modifies these deficits. We examined the relationship between olfaction and cognition in 55 schizophrenia patients and 32 healthy controls. Patients and controls demonstrated significant differences performing cognitive tasks. In patients, sex modified all relationships of odor identification to cognition. Female patients showed significantly stronger trends than male patients correlating better smell identification with higher scores on intelligence, memory, and attention, whereas their correlations of odor identification with executive functioning contradicted those of male patients. Odor acuity significantly correlated with several cognitive measures, especially in male patients, in whom better acuity was generally associated with better cognition. Female patients again differed significantly from males; odor acuity correlations with cognitive measures were weaker, or contradicted, those of male patients. These findings indicate significant sex differences in olfactory processing in schizophrenia. Combining the sexes in research analyses may obscure important differences.     

Olfaction During Pregnancy and Postpartum Period

Chemosensory Perception - Studies of the effect of pregnancy on olfactory function are contradictory—some report reduced function, others hypersensitivity, and still others no change at all....     

Olfaction and peripheral olfactory connections in methimazole-treated rats.

Methimazole has been reported to produce extensive degenerative changes in olfactory epithelium and a severe deficit in odor detection [Genter BM, Owens DM, Carlone HB, Crofton KM. Fundam. Appl. Toxicol. 1996;29:71-77; Genter BM, Owens DM, Deamer NJ, Blake BL, Wesley DS, Levi PE. Toxicol. Pathol. 1995;23:477-486.]. To examine this further, rats were tested on olfactory detection and discrimination problems before and after intraperitoneal injection of 300 mg/kg methimazole. In the first 2 days after treatment, experimental rats had nasal congestion and a modest decrement on odor detection and odor mixture discrimination tasks. They performed almost as well as control rats on the third post injection day. In a separate group of rats, anterograde transport of horseradish peroxidase from olfactory epithelium to the bulb was examined 1, 2, 3, and 5 days after administration of methimazole. The treatment produced a modest but progressive disruption of bulbar input: 2 days after administration only approximately 10% of bulbar glomeruli had reduced levels of reaction product while 30-40% of glomeruli had little or no reaction product in 3-5 day survival rats. These results indicate that methimazole is not a particularly effective olfactotoxin and does not produce anosmia or even a severe hyposmia.