Odor identification, consistency of label use, olfactory threshold and their relationships to odor memory over the human lifespan.

The purpose of this study was to investigate olfactory threshold, odor identification, consistency of label use and their relationships to odor memory in the context of semantic/episodic memory across the human lifespan. A total of 137 subjects aged 4-90 years were tested with several olfactory test procedures. We found that olfactory sensitivity was well developed in children despite the finding that their odor naming and odor memory were inferior to that of adults. In the elderly population, olfactory functions gradually declined, with odor memory and odor identification demonstrating the most significant decline. Semantic encoding was differentially related to odor memory over the human age span. Whereas consistency of label use was the main predictor for odor memory in children and young adults, olfactory identification ability was the main predictor in the elderly study group. We also calculated response bias for the separate age groups and found no differences between children, young adults and elderly. However, with age false alarm rates increased. We conclude that children possess equal olfactory sensitivity compared with adults; however, due to limitations in linguistic capabilities and familiarity to odorants, odor memory and odor identification performance was limited. Additionally, our data indicate major alterations of olfactory processing in advanced age with substantial losses in odor memory and odor identification performance.     

Semantic Factors in Episodic Recognition of Common Odors in Early and Late Adulthood: a Review

Information on long-term memory for common odors is discussed.Olfactory parameters (i. e. familiarity, recognition, identification)and their relationship to current memory theory are highlighted.Emphasis is focused on the impact of semantic memory on episodicodor recognition. In contrast to previous research suggestingthat verbal/semantic factors play a negligible role in olfactorymemory, the present review indicates that episodic odor informationis mediated by factors that can be subsumed under the rubricof semantic memory. Specific odor knowledge, such as perceivedfamiliarity and identifiability, is strongly and positivelyrelated to episodic odor memory performance. Age-related impairmentsin various olfactory and cognitive parameters and the potentialdetrimental effects in episodic odor memory are discussed. Finally,the issue of whether olfactory memory should be conceptualizedas an independent process, or whether it shares characteristicswith memory for verbal and visual information, is addressed.Chem. Senses 22: 623–633, 1997.     

Differentiating the Cognitive Profile of Schizophrenia from That of Alzheimer Disease and Depression in Late Life

Background

To compare the cognitive profile of older patients with schizophrenia to those with other neuropsychiatric disorders assessed in a hospital-based memory clinic.

Methods

Demographic, clinical, and cognitive data of all patients referred to the memory clinic at the Centre for Addiction and Mental Health between April 1, 2006 and August 15, 2008 were reviewed. We then identified four groups of older patients with: (1) late-life schizophrenia (LLS) and no dementia or depression (DEP); (2) Alzheimer''s disease (AD); (3) DEP and no dementia or LLS; (4) normal cognition (NC) and no DEP or LLS.

Results

The four groups did not differ in demographic data except that patients with AD were about 12 years older than those with LLS. However, they differed on cognitive tests even after controlling for age. Patients with LLS were impaired on most cognitive tests in comparison with patients with NC but not on recalling newly learned verbal information at a short delay. They experienced equivalent performance on learning new verbal information in comparison with patients with AD, but better performance on all other tests of memory, including the ability to recall newly learned verbal information. Finally, they were more impaired than patients with DEP in overall memory.

Conclusions

Patients with LLS have a different cognitive profile than patients with AD or DEP. Particularly, memory impairment in LLS seems to be more pronounced in learning than recall. These findings suggest that cognitive and psychosocial interventions designed to compensate for learning deficits may be beneficial in LLS.     

Higher Olfactory Threshold and Decreased Odor Identification Ability in HIV-infected Persons

In order to evaluate whether the olfactory system is involvedin HIV infection, two patient groups defined along a decreasein cellular immunity and a healthy control group were testedfor olfactory threshold, odor identification and odor memory.Chem. Senses 20: 325–328, 1995.     

Olfactory Discrimination Ability for Aliphatic Esters in Squirrel Monkeys and Humans

Using a behavioral paradigm designed to simulate olfactory-guidedforaging, the ability of five squirrel monkeys to distinguishiso-amyl acetate from n-and iso-forms of other acetic esters(ethyl acetate to decyl acetate) and from other esters carryingthe iso-amyl group (iso-amyl propionate to iso-amyl capronate)was investigated. We found (i) that all five animals were clearlyable to discriminate between all odor pairs tested; (ii) a significantnegative correlation between discrimination performance andstructural similarity of odorants in terms of differences incarbon chain length of both the aliphatic alcohol group andthe aliphatic acid group of the esters; and (iii) that iso-and n-amyl acetate were perceived as qualitatively similar despitedifferent steric conformation. Using a triple-forced choiceprocedure, 20 human subjects were tested on the same tasks inparallel and showed a very similar pattern of discriminationperformance compared with the squirrel monkeys. Thus, the resultsof this study provide evidence of well-developed olfactory discriminationability in squirrel monkeys for aliphatic esters and supportthe assumption that human and non-human primates may share commonprinciples of odor quality perception. Chem. Senses 22: 457–465,1997.     

Olfactory deficits in cystic fibrosis: distribution and severity

Patients (n = 20) with cystic fibrosis (CF) exhibited olfactoryimpairment relative to a group of unaffected controls (n = 15).Detection thresholds for the floral odorant phenylethylmethylethylcarbinol(PEMEC) were significantly elevated and performance on the Universityof Pennsylvania Smell Identification Test (UPSIT) was significantlydepressed. Three patients displayed thresholds markedly higherthan those of any other participants. These patients were alsothe only participants to perform at a chance level on the multiple-choiceitems of the odor identification test, UPSIT. The average deficitof the patients on the threshold and identification tasks inthe present study reinforces an earlier challenge to the reportedhypersensitivity of CF patients to chemosensory stimuli. Inaddition, this study suggests that some CF patients displayan olfactory deficit that is general and complete.     

Numerical Simulation of Environmental Modulation of Chemical Signal Structure and Odor Dispersal in the Open Ocean

Hydrodynamic models were used to simulate the dispersal of amodel fish pheromone at three characteristic depth regimes (mixedlayer, and 300 and 1000 m) of broad extent in the open oceanat the scale of individual organisms. The models were calibratedto experimental studies of dye dispersal at these depths andthe goldfish pheromone system was used as the model odorant.There are profound differences in the time course and geometryof dispersing odor fields with depth. Below the thermoclineodor fields spread primarily as horizontal patches with dispersalrates about five times slower at 1000 m as compared to 300 m.In the mixed layer, odors disperse rapidly in all directionsand the maximum radial distance of spread of a physiologicallyactive odor patch is less than half of the deep water value.Increases in the threshold sensitivity of olfactory receptorscan greatly increase effective odor field size. Chemical signalsimpact the encounter dynamics among oceanic organisms by affectingthe distance at which the target (emitting) individual is perceived.Perception distances due to olfactory cues can be significantlygreater than for other senses in pelagic oceanic environments.Environment specific modulation of odor fields then affectsthe signal properties and therefore utility of chemoreceptionthat, in turn, bear on encounter probabilities and transferfunctions in oceanic ecosystems. Chem. Senses 21: 121–134,1996.     

'Sniffin' Sticks': Olfactory Performance Assessed by the Combined Testing of Odour Identification, Odor Discrimination and Olfactory Threshold

‘Sniffin’ Sticks' is a new test of nasal chemosensoryperformance based on pen-like odor dispensing devices. It comprisesthree tests of olfactory function, namely tests for odor threshold(n-butanol, testing by means of a single staircase), odor discrimination(15 pairs of odorants, triple forced choice) and odor identification(16 common odorants, multiple forced choice from four verbalitems per test odorant). After extensive preliminary investigationsthe tests were applied to a group of 104 healthy volunteers(52 female, 52 male, mean age 49.5 years, range 18–84years) in order to establish test-retest reliability and tocompare them with an established measure of olfactory performance(the Connecticut Chemosensory Clinical Research Center Test,CCCRC). Performance decreased with increasing age of the subjects(     

Odor recognition memory as a function of odor-naming performance

A series of experiments sought to clarify the relationship between odor naming and memory by manipulating odor label availability during a dual naming-memory task. Experiment 1 demonstrated that recognition memory and odor naming were both better when the naming task provided participants with odor label alternatives. Consistent and correct odor naming was associated with nearly perfect memory, whereas inconsistent or incorrect naming was associated with very weak memory if any at all. Experiment 2 showed that the availability of odor labels was effective at improving memory only if labels were available at both memory encoding and retrieval, suggesting that the labels were aiding memory by improving the identification of the odors. Odor naming was manipulated in Experiment 3 by varying the number of available labels from 4 to 16 during each odor-naming trial. As found in the previous experiments, naming and memory were strongly related in each of the labeling conditions. Experiment 4 showed that corrective naming feedback produced better memory performance but only when the feedback led to correct odor naming. It was concluded that perceptual processes related to matching olfactory input to acquired, multidimensional representations of odors play a critical role in both odor naming and episodic memory.     

Analysis of Medication Off-odors Using an Electronic Nose

Packaging materials have been implicated as a source for off-odorsin pharmaceutical products. A new instrumentation method employingan array of conducting polymer gas sensors was used to identifythe offending packaging components in the canister of a pharmaceuticalinhalant. A case study is described in which tainted inhalersas well as elastomeric components of the canisters were ‘sniffed’by the electronic nose. The electronic nose was able to differentiatebetween tainted and untainted canisters. Signal processing algorithmsperformed on the raw data from the sensors suggested that specificelastomeric components were responsible for the off-odor. Afurther experiment suggested that the propellant (Freon) extractedthe odor from the elastomeric components as the medication wasexpelled from the canister. These data indicate that the electronicnose is a potential tool to solve odor problems in which humanodor assessment is not feasible due to excess exposure to themedically active ingredient. Chem. Senses 22: 119–128,1997.     

Olfactory Training in Patients with Parkinson's Disease

Objective

Decrease of olfactory function in Parkinson''s disease (PD) is a well-investigated fact. Studies indicate that pharmacological treatment of PD fails to restore olfactory function in PD patients. The aim of this investigation was whether patients with PD would benefit from “training” with odors in terms of an improvement of their general olfactory function. It has been hypothesized that olfactory training should produce both an improved sensitivity towards the odors used in the training process and an overall increase of olfactory function.

Methods

We recruited 70 subjects with PD and olfactory loss into this single-center, prospective, controlled non-blinded study. Thirty-five patients were assigned to the olfactory training group and 35 subjects to the control group (no training). Olfactory training was performed over a period of 12 weeks while patients exposed themselves twice daily to four odors (phenyl ethyl alcohol: rose, eucalyptol: eucalyptus, citronellal: lemon, and eugenol: cloves). Olfactory testing was performed before and after training using the “Sniffin'' Sticks” (thresholds for phenyl ethyl alcohol, tests for odor discrimination, and odor identification) in addition to threshold tests for the odors used in the training process.

Results

Compared to baseline, trained PD patients experienced a significant increase in their olfactory function, which was observed for the Sniffin'' Sticks test score and for thresholds for the odors used in the training process. Olfactory function was unchanged in PD patients who did not perform olfactory training.

Conclusion

The present results indicate that olfactory training may increase olfactory sensitivity in PD patients.     

Memory Concerns,Memory Performance and Risk of Dementia in Patients with Mild Cognitive Impairment

Background

Concerns about worsening memory (“memory concerns”; MC) and impairment in memory performance are both predictors of Alzheimer''s dementia (AD). The relationship of both in dementia prediction at the pre-dementia disease stage, however, is not well explored. Refined understanding of the contribution of both MC and memory performance in dementia prediction is crucial for defining at-risk populations. We examined the risk of incident AD by MC and memory performance in patients with mild cognitive impairment (MCI).

Methods

We analyzed data of 417 MCI patients from a longitudinal multicenter observational study. Patients were classified based on presence (n = 305) vs. absence (n = 112) of MC. Risk of incident AD was estimated with Cox Proportional-Hazards regression models.

Results

Risk of incident AD was increased by MC (HR = 2.55, 95%CI: 1.33–4.89), lower memory performance (HR = 0.63, 95%CI: 0.56–0.71) and ApoE4-genotype (HR = 1.89, 95%CI: 1.18–3.02). An interaction effect between MC and memory performance was observed. The predictive power of MC was greatest for patients with very mild memory impairment and decreased with increasing memory impairment.

Conclusions

Our data suggest that the power of MC as a predictor of future dementia at the MCI stage varies with the patients'' level of cognitive impairment. While MC are predictive at early stage MCI, their predictive value at more advanced stages of MCI is reduced. This suggests that loss of insight related to AD may occur at the late stage of MCI.     

Central Processing of Odor Concentration is a Temporal Phenomenon as Revealed by Chemosensory Event-Related Potentials (CSERP)

Chemosensory event-related potentials (CSERP) can be used toexamine central nervous odor processing. An important questionfor understanding odor perception is how different concentrationsare processed. In the present study two odors were chosen whichactivate either the olfactory (linalool) or the trigeminal (menthol)system. Both odors were presented to 11 subjects in four differentconcentrations. Four subjects had to attend actively to theodors while the others perceived the odors under passive attention.The results showed that increased concentrations of the olfactorystimulus resulted in shorter latencies of the N1 component butdid not affect the amplitudes of the CSERP. However, the amplitudesof the stimulus dependent, exogenous components (N1, P2) increasedwith higher concentrations of the trigeminal stimulus. The amplitudeof the late positive complex, which reflects endogenous processes,was usually larger when the odorous stimuli had to be attendedto actively. It is concluded that olfactory intensity codingresults in a qualitatively different but not in a stronger neuronalresponse of the human brain. Chem. Senses 22: 9–26, 1997.     

SNPs Associated with Cerebrospinal Fluid Phospho-Tau Levels Influence Rate of Decline in Alzheimer's Disease

Alzheimer''s Disease (AD) is a complex and multifactorial disease. While large genome-wide association studies have had some success in identifying novel genetic risk factors for AD, case-control studies are less likely to uncover genetic factors that influence progression of disease. An alternative approach to identifying genetic risk for AD is the use of quantitative traits or endophenotypes. The use of endophenotypes has proven to be an effective strategy, implicating genetic risk factors in several diseases, including anemia, osteoporosis and heart disease. In this study we identify a genetic factor associated with the rate of decline in AD patients and present a methodology for identification of other such factors. We have used an established biomarker for AD, cerebrospinal fluid (CSF) tau phosphorylated at threonine 181 (ptau₁₈₁) levels as an endophenotype for AD, identifying a SNP, rs1868402, in the gene encoding the regulatory sub-unit of protein phosphatase B, associated with CSF ptau₁₈₁ levels in two independent CSF series . We show no association of rs1868402 with risk for AD or age at onset, but detected a very significant association with rate of progression of disease that is consistent in two independent series . Our analyses suggest that genetic variants associated with CSF ptau₁₈₁ levels may have a greater impact on rate of progression, while genetic variants such as APOE4, that are associated with CSF Aβ₄₂ levels influence risk and onset but not the rate of progression. Our results also suggest that drugs that inhibit or decrease tau phosphorylation may slow cognitive decline in individuals with very mild dementia or delay the appearance of memory problems in elderly individuals with low CSF Aβ₄₂ levels. Finally, we believe genome-wide association studies of CSF tau/ptau₁₈₁ levels should identify novel genetic variants which will likely influence rate of progression of AD.     

Influence of Stimulus Duration on a Regional Measure of NaCl Taste Sensitivity

The present study demonstrates that perithreshold temporal integrationoccurs in the human taste system across stimulus durations rangingfrom 200 to 1500 ms in a manner analogous to that seen in othermajor sensory systems. Thus, the notion that gustation is comparativelyinsensitive to temporal stimulus parameters at threshold levelsis disproved. Chem. Senses 22: 171–175, 1997.     

Disease association tests by inferring ancestral haplotypes using a hidden markov model

Motivation: Most genome-wide association studies rely on singlenucleotide polymorphism (SNP) analyses to identify causal loci.The increased stringency required for genome-wide analyses (withper-SNP significance threshold typically 10^–7) meansthat many real signals will be missed. Thus it is still highlyrelevant to develop methods with improved power at low typeI error. Haplotype-based methods provide a promising approach;however, they suffer from statistical problems such as abundanceof rare haplotypes and ambiguity in defining haplotype blockboundaries. Results: We have developed an ancestral haplotype clustering(AncesHC) association method which addresses many of these problems.It can be applied to biallelic or multiallelic markers typedin haploid, diploid or multiploid organisms, and also handlesmissing genotypes. Our model is free from the assumption ofa rigid block structure but recognizes a block-like structureif it exists in the data. We employ a Hidden Markov Model (HMM)to cluster the haplotypes into groups of predicted common ancestralorigin. We then test each cluster for association with diseaseby comparing the numbers of cases and controls with 0, 1 and2 chromosomes in the cluster. We demonstrate the power of thisapproach by simulation of case-control status under a rangeof disease models for 1500 outcrossed mice originating fromeight inbred lines. Our results suggest that AncesHC has substantiallymore power than single-SNP analyses to detect disease association,and is also more powerful than the cladistic haplotype clusteringmethod CLADHC. Availability: The software can be downloaded from http://www.imperial.ac.uk/medicine/people/l.coin Contact: I.coin{at}imperial.ac.uk Supplementary Information: Supplementary data are availableat Bioinformatics online. Associate Editor: Martin Bishop