Olfactory Identification Tasks Research Articles

29 Smoking as a Risk Factor: Altered Brain Activity in Areas Associated with Preclinical Alzheimer's Disease

Objective:Those at genetic risk for Alzheimer's Disease (AD) because of the ApoE ε4 allele show differences in activation during olfactory information processing and memory in areas such as MTL structures, entorhinal cortex, posterior cingulate, precuneus, and inferior parietal lobule, suggesting preclinical AD neuropathology and olfactory impairment as a biomarker for predicting later AD onset (Murphy, 2019). The effects of smoking on AD have varied, with early studies suggesting either no effect or protective effects, and recent studies suggesting smoking as a risk factor for AD but with the need for further investigation in preclinical stages. Therefore, this study focused on olfaction and smoking as risk factors for preclinical AD neuropathology by studying differences in fMRI BOLD signal changes in smokers and nonsmokers during olfactory tasks.Participants and Methods:Archival data from 25 non-demented older adults recruited from the UCSD Alzheimer's Disease Research Center who completed an Assessment Scale-Cognitive Subscale (ADAS-Cog) and functional MRI scans at 3T, acquired during performance of an odor identification task. Odor Identification (OI) measured correct (hits) or incorrect (misses) identification of odors presented by an olfactometer to deliver the odor stimuli in short, controlled durations during fMRI scanning.Results:fMRI data were preprocessed using fMRIprep, smoothed at 4mm, scaled, and first level analyses were conducted using 3dDeconvolve in AFNI with time points corresponding to hits and misses as regressors. Differences between smokers and nonsmokers revealed smokers show a larger difference in BOLD signal change from hits minus misses at five significant clusters (p = 0.01 with the minimum cluster size [voxels] at 42). Peak areas of significant clusters included the right precuneus, right calcarine gyrus, left inferior parietal lobule, left superior parietal lobule, and left middle occipital gyrus. Analyses suggested a greater difference in activity between hits and misses in smokers compared to nonsmokers, with more activity during hits.Conclusions:Differences in activation between smokers and nonsmokers during an olfactory identification task, with greater activity in smokers during hits, suggests greater effort to correctly identify an odor. These findings of hyperactivation in areas (such as the precuneus and inferior parietal lobule) are similar to findings of hyperactivation during odor memory observed in studies of ε4 carriers during preclinical stages. Results provide further insight into smoking as a risk factor for AD. Moreover, results suggest the risk of smoking could potentially be reflected in altered activity in olfactory information processing networks in preclinical stages of AD. The study highlights the need for research to further understand the role smoking plays in the development of AD and the use of olfaction as a biomarker to aid in disease detection, prevention, and stage-associated treatments.

Olfactory Function and Markers of Brain Pathology in Non-Demented Individuals with Autosomal Dominant Alzheimer's Disease.

Olfactory dysfunction is one of the earliest signs of Alzheimer's disease (AD), highlighting its potential use as a biomarker for early detection. It has also been linked to progression from mild cognitive impairment (MCI) to dementia. To study olfactory function and its associations with markers of AD brain pathology in non-demented mutation carriers of an autosomal dominant AD (ADAD) mutation and non-carrier family members. We analyzed cross-sectional data from 16 non-demented carriers of the Presenilin1 E280A ADAD mutation (mean age [SD]: 40.1 [5.3], and 19 non-carrier family members (mean age [SD]: 36.0 [5.5]) from Colombia, who completed olfactory and cognitive testing and underwent amyloid and tau positron emission tomography (PET) imaging. Worse olfactory identification performance was associated with greater age in mutation carriers (r = -0.52 p = 0.037). In carriers, worse olfactory identification performance was related to worse MMSE scores (r = 0.55, p = 0.024) and CERAD delayed recall (r = 0.63, p = 0.007) and greater cortical amyloid-β (r = -0.53, p = 0.042) and tau pathology burden (entorhinal: r = -0.59, p = 0.016; inferior temporal: r = -0.52, p = 0.038). Worse performance on olfactory identification tasks was associated with greater age, a proxy for disease progression in this genetically vulnerable ADAD cohort. In addition, this is the first study to report olfactory dysfunction in ADAD mutation carriers with diagnosis of MCI and its correlation with abnormal accumulation of tau pathology in the entorhinal region. Taken together, our findings suggest that olfactory dysfunction has promise as an early marker of brain pathology and future risk for dementia.

Odorant‐induced brain activation as a function of normal aging and Alzheimer’s disease

AbstractBackgroundOlfactory dysfunction consistently occurs in patients with Alzheimer’s disease (AD), beyond the mild and gradual decline in olfactory ability found in normal aging. This dysfunction begins early in the disease course, typically before clinical diagnosis, and progresses with disease severity. While odor identification and detection deficits clearly differentiate AD from controls, there remains uncertainty as to whether these are determined by olfactory threshold. The primary purpose of the current fMRI study was to examine the neural correlates of olfactory processing in healthy young and old adults and compare them with AD patients.MethodHealth young adults (n=10), healthy old adults (n=10), and AD patients (n=12) participated in psychophysical olfactory testing and an fMRI odorant detection paradigm. We analyzed the interplay between age and disease‐related psychophysical olfactory declines and odorant‐induced brain activation. This tested whether odor threshold deficits reflect disease progression and explain group differences in detection, identification and brain activity.ResultAD patients had decreased odor detection task‐related signal in all regions of the primary olfactory cortex, with activity in the entorhinal cortex best differentiating the groups. Within the secondary olfactory regions, AD patients showed decreased activity in orbitofrontal cortex compared to healthy age matched individuals. Moderated‐mediation analyses on neuro‐psychophysical relationships found that increased brain activation in the entorhinal cortex moderated the negative effect of disease‐related threshold decline on olfactory detection.ConclusionEven in the face of declining olfactory thresholds, older adults compensated for this effect with increased brain activation in a primary olfactory brain region. This was the case for odor detection but not odor identification. fMRI activation induced by an olfactory identification task may eventually be useful in improving early detection of AD and may, eventually, facilitate early treatment interventions in subjects at risk for AD.

Fimbria-Fornix Volume Is Associated With Spatial Memory and Olfactory Identification in Humans.

White matter pathways that surround the hippocampus comprise its afferent and efferent connections, and are therefore crucial in mediating the function of the hippocampus. We recently demonstrated a role for the hippocampus in both spatial memory and olfactory identification in humans. In the current study, we focused our attention on the fimbria-fornix white matter bundle and investigated its relationship with spatial memory and olfactory identification. We administered a virtual navigation task and an olfactory identification task to 55 young healthy adults and measured the volume of the fimbria-fornix. We found that the volume of the right fimbria-fornix and its subdivisions is correlated with both navigational learning and olfactory identification in those who use hippocampus-based spatial memory strategies, and not in those who use caudate nucleus-based navigation strategies. These results are consistent with our recent finding that spatial memory and olfaction rely on similar neural networks and structures.

Individuals at risk for Alzheimer's disease show differential patterns of ERP brain activation during odor identification.

BackgroundStudies suggest that older adults at risk of developing Alzheimer’s disease may show olfactory processing deficits before other signs of dementia appear.MethodsWe studied 60 healthy non-demented individuals, half of whom were positive for the genetic risk factor the Apolipoprotein E ɛ4 allele, in three different age groups. Event-related potentials to visual and olfactory identification tasks were recorded and analyzed for latency and amplitude differences, and plotted via topographical maps.ResultsVarying patterns of brain activation were observed over the post-stimulus epoch for ɛ4- versus ɛ4+ individuals on topographical maps. Individuals with the ɛ4 allele demonstrated different ERP peak latencies during identification of olfactory but not visual stimuli. High correct ApoE classification rates were obtained utilizing the olfactory ERP.ConclusionsOlfactory ERPs demonstrate functional decline in individuals at risk for Alzheimer’s disease at much earlier ages than previously observed, suggesting the potential for pre-clinical detection of AD at very early stages.

Olfactory Deficits and Amyloid-β Burden in Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Aging: A PiB PET Study

Olfactory deficits and increased amyloid-β (Aβ) burden are observed in people with amnestic mild cognitive impairment (aMCI); both factors may be predictive of Alzheimer's disease (AD). We explored whether olfactory identification is related to in vivo measures of Aβ burden using Pittsburgh Compound B (PiB) PET. Nineteen control, 24 aMCI, and 20 AD participants completed an olfactory identification task and underwent PiB PET scanning. Control participants performed better on olfactory identification and showed lower PiB binding than aMCI patients. There was a significant correlation between both factors when pooling all groups together but not when considering each group separately. In addition, the olfactory identification score did not differ between aMCI participants who were PiB-positive and those who were PiB-negative. We conclude that AD-related olfactory identification deficits are not directly related to Aβ burden.

An Expectation-Based Approach to Explaining the Crossmodal Influence of Color on Orthonasal Odor Identification: The Influence of Expertise

In a previous series of experiments, the present authors demonstrated that when people are asked to identify the flavors of various drinks on the basis of orthonasal olfactory cues, their judgments are sometimes influenced by the colors of the drinks. Here, we explored the role that expertise plays in mediating color–flavor interactions. Non-experts and flavor experts took part in an odor identification task in which they smelled a number of drinks whose flavors were incongruent with what their colors would suggest. When a particular color, identified by participants as being one that generated a strong flavor expectation, was added to these drinks (as compared to when no such color was added), a significantly greater proportion of both non-expert and flavor expert participants’ identification responses were consistent with this expectation. No significant difference in response behavior was found between these two groups of participants. Using a novel experimental approach that controlled for individual differences, the results of the present study add to the literature showing that flavor experts are not only susceptible to color-induced olfactory biases but perform no differently than non-experts in olfactory identification tasks.

Can I Smell Gas (or Is It Lilac)? Olfactory Semantic Deficits in Mild Cognitive Impairment and Alzheimer’s Disease

Olfactory decline represents one of the earliest signs of Alzheimer’s disease (AD), and deficits in olfactory identification have now been identified in persons with amnestic mild cognitive impairment (aMCI). Whether the olfactory identification deficit in AD reflects underlying degraded semantic knowledge or lower-order olfactory deficits is uncertain. To address this question, we focused on the kinds of errors committed when participants were given a unirhinal olfactory identification task at baseline and after 1 year. The aim was to assess whether more errors were committed when the target smell is either semantically related or unrelated to the distracters. Fourteen AD, 13 aMCI, and 10 control participants were tested using a modified version of the University of Pennsylvania Smell Identification Test. Examination of error types showed that the control group predominantly selected distracters which were related to the target; in contrast, distracters that were unrelated to the target odor were selected as frequently as related odors by the AD and aMCI groups, for both nostrils. This pattern was maintained 1 year later, and previously designated aMCI patients who then met criteria for AD were more inclined to choose the unrelated distracters than were aMCI patients who did not meet AD criteria. Olfactory identification deficits in AD and aMCI plausibly reflect deterioration in ability to access olfactory-mediated semantic knowledge. This pattern of errors may help distinguish the olfactory identification deficits observed in AD from olfactory identification deficits observed in other conditions not associated with semantic loss.

Use of the Brief Smell Identification Test for olfactory deficit in a Norwegian population with Alzheimer's disease

Several studies have shown that Alzheimer's disease (AD) is associated with hyposmia. Olfactory identification may be a cheap and simple additional test in the assessment of early cognitive changes. The sense of smell is influenced by factors such as experience and culture and the aim of the present study was to assess the validity of the Brief Smell Identification Test (B-SIT) in distinguishing patients with AD from healthy gender and age-matched controls in a Norwegian population. The study included 39 patients with a diagnosis of probable AD, and 52 gender and age-matched controls. Olfactory function was assessed with B-SIT, and a non-standardized olfactory identification task (freshly ground coffee). The difference in olfactory performance between patients and controls was highly significant, both for the whole AD patient group and the subgroup of patients with MMSE >or= 24. Receiver operating curve (ROC) analyses indicated that B-SIT distinguished patients from controls with high sensitivity and specificity. All the odours in B-SIT with the exception of turpentine showed highly significant differences between patients and controls. AD-associated memory impairment did not seem to affect the answers given for B-SIT in this population. For patients with AD, the Brief Smell Identification Test (B-SIT) appears to be well-suited for detecting a deficit in olfactory identification in a Norwegian population.

Brain activation during odor perception in males and females.

Several studies indicate that women outperform men in olfactory identification tasks. The psychophysical data are more divergent when it comes to gender differences at levels of odor processing which are cognitively less demanding. We therefore compared cerebral activation with H2(15)O PET in 12 females and 11 males during birhinal passive smelling of odors and odorless air. The odorous compounds (odorants) were pure olfactory, or mixed olfactory and weakly trigeminal. Using odorless air as the baseline condition, activations were found bilaterally in the amygdala, piriform and insular cortices in both sexes, irrespective of the odor. No gender difference was detected in the pattern of cerebral activation (random effect analysis SPM99, corrected p < 0.05) or in the subjective perception of odors. Males and females seem to use similar cerebral circuits during the passive perception of odors. The reported female superiority in assessing olfactory information including odor identification is probably an effect of a difference at a cognitive, rather than perceptive level of olfactory processing.

Cannabis use is associated with schizotypy and attentional disinhibition

While most neurochemical research into the pathogenesis of schizophrenia (SZ) has focused on the dopaminergic, glutamatergic, and serotonergic systems, the exact nature and cause of this disorder have proven intractable. Given the recent discovery and elucidation of the endogenous cannabinioid system, a re-examination of the cannabis-induced exacerbation hypothesis of SZ is warranted. The purpose of the present study was to assess whether current cannabis users exhibit personality correlates and neurocognitive deficits similar to those observed in SZ patients. 15 current cannabis users, 15 drug-free controls, and 10 past cannabis users were assessed on tasks which assess attentional inhibition, spatial working memory, olfactory identification, and schizotypal personality. Current cannabis users demonstrated deficits in attentional inhibition, decreased reaction time, and significantly higher scores on the schizotypal personality questionnaire (SPQ) compared with the non-using and past cannabis using groups. No group differences were found on the working memory or olfactory identification tasks. These results suggest that cannabis use can mimic attentional deficits seen in acute schizophrenia and is associated with schizotypal personality, thus setting the stage for a possible cannabinoid model of SZ.

Impairment of olfactory identification in obsessive-compulsive disorder.

Olfactory identification ability has been associated with processing in the orbitofrontal cortex (OFC), an area that has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). Although olfactory sensitivity is normal in patients with OCD, no study has investigated olfactory identification in this disorder. A group of 20 subjects with OCD and 23 age- and education-matched controls performed a standardized test of olfactory identification. They also performed computerized tests of spatial memory span, spatial working memory and spatial recognition memory that have been shown previously to be sensitive to cognitive deficits in patients with OCD. Performance on the olfactory identification task, spatial recognition task and spatial span task was significantly worse in the OCD group than controls. While impairment in spatial cognition is consistent with previous studies of OCD, its significance for brain-behaviour models of OCD is unclear. However, the finding of abnormal olfactory identification in patients with OCD is consistent with the hypothesis that there is a disruption to processing at the level of the OFC in the disorder.

Olfactory identification deficit in relation to schizotypy

Past studies have shown that schizophrenic men tend to be impaired on the olfactory identification task. We examined individual differences in the olfactory function in relation to schizotypy. Healthy individuals who might carry latent liability for schizophrenia participated in olfactory identification and acuity tasks. Psychometrically ascertained schizotypic men showed deficits on the olfactory identification task but not on the olfactory acuity task. The olfactory identification function partly depended on the menstrual cycle in women. But further systematic research is needed to clarify the possible role of estrogen.