Claire Murphy

Olfactory thresholds are associated with degree of dementia in Alzheimer's disease

Recent neuroanatomical studies have noted that regions of the olfactory pathways contain high levels of neuritic plaques and neurofibrillary tangles, pathological hallmarks of Alzheimers disease; and that the olfactory epithelium, the most peripheral level of the system, exhibits anatomical and biochemical changes in Alzheimers disease. The present experiments investigated thresholds for olfactory and taste stimuli in patients with Probable Alzheimers disease. Olfactory thresholds of Alzheimers patients were significantly elevated relative to controls and were significantly correlated with scores on dementia scales. Taste thresholds of Alzheimers patients were within normal limits and unrelated to scores on dementia scales. These results suggest that increased olfactory thresholds in patients with Alzheimers disease reflect the effects of the disease process and, thus, may aid in the diagnosis and in the understanding of Alzheimers disease.

Clinical study and literature review of nasal irrigation.

Objectives/Hypothesis Nasal disease, including chronic rhinosinusitis and allergic rhinitis, is a significant source of morbidity. Nasal irrigation has been used as an adjunctive treatment of sinonasal disease. However, despite an abundance of anecdotal reports, there has been little statistical evidence to support its efficacy. The objective of this study was to determine the efficacy of the use of pulsatile hypertonic saline nasal irrigation in the treatment of sinonasal disease.

Cortical Activation in Response to Pure Taste Stimuli During the Physiological States of Hunger and Satiety

This event-related functional magnetic resonance imaging (er-fMRI) study investigated BOLD signal change in response to a series of pure gustatory stimuli that varied in stimulus quality when subjects were hungry and sated with a nutritional pre-load. Group analyses showed significant differences in activation in the hunger minus satiety condition in response to sucrose, caffeine, saccharin, and citric acid within the thalamus, hippocampus, and parahippocampus. When examining the hunger and satiety conditions, activation varied as a function of stimulus, with the majority of the stimuli exhibiting significantly greater activation in the hunger state within the insula, thalamus, and substantia nigra, in contrast to decreased activation in the satiated state within the parahippocampus, hippocampus, amygdala, and anterior cingulate. Region of interest (ROI) analysis revealed two significant interactions, ROI by physiology and ROI by physiology by stimulus. In the satiety condition, the primary (inferior and superior insulae) and secondary (OFC 11 and OFC 47) taste regions exhibited significantly greater brain activation in response to all stimuli than regions involved in processing eating behavior (hypothalamus), affect (amygdala), and memory (hippocampus, parahippocampus and entorhinal cortex). These same regions demonstrated significantly greater activation within the hunger condition than the satiety condition, with the exception of the superior insula. Furthermore, the patterns of activation differed as a function taste stimulus, with greater activation in response to sucrose than to the other stimuli. These differential patterns of activation suggest that the physiological states of hunger and satiety produce divergent activation in multiple brain areas in response to different pure gustatory stimuli.

Odor identification as an early marker for Alzheimer's disease: Impact of lexical functioning and detection sensitivity

The impact of lexical functioning and detection sensitivity on the deficit of odor identification in Alzheimers disease (AD) was studied in persons diagnosed with probable and questionable AD. Tests consisted of lexical-based odor identification, lexical-based picture identification, picture-based odor identification, and odor-detection threshold. Results suggest (1) that odor identification is poorer than picture identification in probable and questionable AD, (2) that odor identification continues to be poor even when lexical demands are eliminated, (3) that odor detection does contribute to the odor-identification deficit, but does not account for it completely, and (4) that odor identification tests have a correct classification rate of 83-100%. Odor identification tests can be very useful tools in diagnosing AD and should be considered an important addition to existing diagnostic test batteries.

Nutrition and chemosensory perception in the elderly

The elderly persons perception of foods and food flavor is affected by age-associated changes in the chemical senses (taste, smell, and trigeminal sensation). Both classic and modern psychophysical techniques have been applied to achieve some understanding of these changes. Taste threshold sensitivity declines with age; however, the magnitude of the decline and the degree to which taste qualities are differentially affected remains to be understood. Suprathreshold taste intensity perception is affected by age, but there is a differential effect of taste quality. Experiments with blended foods have indicated that both olfactory and taste deficits contribute to older peoples difficulty with food identification. Experiments assessing threshold sensitivity, suprathreshold intensity, and suprathreshold identification have all demonstrated significant impairment in olfaction in old age. In fact, these effects are far greater than in the taste system. Patients with Alzheimers disease show even greater olfactory deficits than normal elderly and the effect is related to the degree of dementia. We have ruled out nasal disease in these patients as the primary causes of olfactory insensitivity, because significant impairment remains when the influence of nasal airflow and nasal cytology has been removed statistically. Both normal elderly and patients with Alzheimers disease show impairment in odor memory. Sensitivity to, familiarity with, and identifiability of the odors all play a role in odor memory performance. Flavor preference also changes over the lifespan. Older subjects, for instance, rate high concentration of sugar and salt as pleasanter than young subjects do. Multiple influences contribute to this phenomenon. Elderly persons and those of lower nutritional status have shown preferences for higher concentrations of casein hydrolysate than young persons and those of higher nutritional status, suggesting that dietary preference can be related to chemosensory cues. There are significant age-associated changes in chemosensory perception that have the potential to interact with dietary selection and nutrition in the elderly. A better understanding of these phenomena may promote health and well-being in the elderly.

Loss of olfactory function in dementing disease

Alzheimers (AD) patients show neuropathological changes in areas of the brain central to olfactory processing, suggesting the theoretical importance and potential diagnostic utility of investigating functional changes in olfaction in these patients. Persons with Downs Syndrome who live to the fourth decade develop neuropathological changes in the brain similar to those found in AD. A series of investigations have been conducted to assess olfaction function in both patients with Alzheimers disease and persons with Downs Syndrome. Functional testing included olfactory threshold, odor identification, odor similarity judgements, odor recognition memory, odor recall, odor fluency. Both Alzheimers patients and persons with Downs Syndrome showed significant impairment in olfactory function, with some measures showing more impairment than others in the early stages of the disease process. Longitudinal investigation of several of the measures indicated decreased function over time consonant with falling DRS scores. Normal controls who tested positive for the APOE4 allele showed impaired odor identification compared to those who were allele negative. Patients with Huntingtons Disease showed olfactory functional impairments, although the degree of impairment differed from the cortical dementias for some of these tasks. The sensitivity and specificity of these assessments will be discussed in relation to analogous assessments in other sensory modalities.

Very Early Changes in Olfactory Functioning Due to Alzheimer's Disease and the Role of Apolipoprotein E in Olfactiona

ABSTRACT: Alzheimers disease (AD) is a progressive neurodegenerative illness marked by memory loss and at least one other cognitive disturbance. Early diagnosis of the disease has proved difficult and has therefore been the focus of much research. Apolipoprotein E (ApoE), a protein manufactured and distributed throughout the body, has shown specificity of binding to the βA4 peptide, the primary component in the senile plaques of AD. Furthermore, the ApoE, epsilon 4 (ɛ4) allele, is overrepresented in AD. These two lines of evidence suggest that ApoE, specifically the ɛ4 allele, plays an important role in the development of AD. Further support for this hypothesis appears in neuropsychological data showing cognitive decrements in ostensibly nondemented individuals with the ɛ4 allele, compared to those without the allele. It is also well known that olfaction is compromised in AD. Thus, the purpose of this study was twofold: (1) to examine very early changes in olfactory functioning due to AD and (2) to examine the role of ApoE in olfactory functioning in people at risk for AD by virtue of early cognitive decline. Results demonstrated changes in olfactory threshold the year immediately preceding change in diagnosis from normal control to AD. Also, in individuals with mild cognitive impairment, those with the ApoE ɛ4 allele show poorer thresholds than those without the ɛ4 allele.

FMRI brain activation in response to odors is reduced in primary olfactory areas of elderly subjects

Olfactory function is affected by aging and deficits often result in decreasing quality of life, health and safety. The present study investigated the cortical substrate of olfactory deficits related to aging with functional Magnetic Resonance Imaging (fMRI), with a retronasal olfactory stimulation protocol using flavored aqueous solutions presented to the mouth. Activation was found in young subjects in the piriform/amygdalar region and in the orbitofrontal cortex and in other areas previously found activated in neuroimaging studies using odorized air, including insula and cerebellum. Activation was seen in similar areas in old subjects but the degree of activation was significantly lower in regions receiving primary olfactory projections (piriform cortex, entorhinal cortex, and amygdala). This result supports the hypothesis of dysfunction and/or degeneration in areas critical to olfactory processing as a major cause of olfactory deficits in the older population.

At the interface of sensory and motor dysfunctions and Alzheimer's disease

Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimers disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age‐related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled “Sensory and Motor Dysfunctions in Aging and AD.” The scientific sessions of the workshop focused on age‐related and neuropathologic changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the central nervous system are affected by AD pathology and that interventions targeting amelioration of sensory‐motor deficits in AD may enhance patient function as AD progresses.

Olfactory event-related potentials and aging: normative data.

Unlike the clinical usages of evoked potentials (e.g. brain stem auditory evoked potentials for the assessment of auditory function), normative data for the olfactory event-related potential (OERP) have been unavailable. The principal objective was to establish normative data across the human life span for OERPs with a given set of parameters. Participants were 140 persons from seven age groups (16-19, 20-29, 30-39, 40-49, 50-59, 60-69 and 70-79 years of age), with equal numbers of males and females, screened for nasal health and dementia. The odor stimulus was amyl acetate, presented at nasal temperature in a humidified airstream delivered by an air-dilution olfactometer at a constant flow rate, using a 60-s inter-stimulus interval. OERPs were recorded at Fz, Cz, and Pz electrode sites, amplified and averaged over trials. Amplitudes of the N1/P2 and P3 and latencies of the P2 and P3 were analyzed. Processing speed decreased at a constant rate over decades for the sensory (P2 latency) as well as cognitive (P3 latency) components. Decline in amplitude over decades was also apparent. Normative data will be useful in research on olfactory function and in clinical assessment of olfactory functional status.