Odor Identification and Self-reported Olfactory Functioning in Patients with Subtypes of Mild Cognitive Impairment

Olfactory dysfunction is a very early symptom of Alzheimer's disease (AD), and olfactory dysfunction has also been found in mild cognitive impairment (MCI). The goal of the present study was to compare odor identification ability and self-reported olfactory functioning in patients with different types of MCI. We included 104 elderly participants classified into two groups: patients with mild cognitive impairment (MCI) and elderly controls (EC). Based on their performance in neuropsychological testing the study population was divided into four groups of participants based on cognitive features: amnestic MCI single domain (11), amnestic MCI multiple domain (19), non-amnestic MCI single domain (21) and non-amnestic MCI multiple domain (13), respectively. The MCI patients were compared to 40 elderly controls (EC) controls with no cognitive deficit. Comparison for odor identification revealed a significant difference between amnestic MCI multiple domain patients and the EC group. No other group comparison was significant. Statistical analyses for self-reported olfactory functioning revealed no significant group differences between any subgroup of MCI patients and the control group. Correlational analyses indicated that odor identification ability was related to cognition whereas no relationship was found for self-reported olfactory functioning. The present study showed that amnestic MCI patients with additional deficits in other cognitive domains have a specific odor identification impairment. Together with cognitive testing, olfactory testing may more accurately help predict whether or not a patient with MCI will convert to AD in the near future.     

Odor identification in mild cognitive impairment subtypes

The current study examined odor identification using the Brief Smell Identification Test (BSIT) in mild cognitive impairment (MCI) subtypes (17 "amnestic MCI", 46 "amnestic-plus MCI", and 25 "MCI other"). Performance in participants with MCI was compared to that of participants with Alzheimer's disease (AD, n=44) and healthy elderly (n=21). MCI participants performed worse than controls, but better than those with AD. MCI subtypes did not differ. The magnitude of difference between MCI participants and controls was modest, raising some question of the clinical utility of the BSIT in early detection of MCI and early differential diagnosis.     

Olfactory identification and incidence of mild cognitive impairment in older age

CONTEXT: Mild cognitive impairment (MCI) is often a precursor to Alzheimer disease, but knowledge about factors that predict its development is limited. OBJECTIVE: To test the hypothesis that impaired odor identification is related to increased risk of incident MCI. DESIGN: Longitudinal cohort study. SETTING: Academic research. PARTICIPANTS: Subjects were 589 community-dwelling older persons without cognitive impairment at study baseline, at which time odor identification was assessed using the 12-item Brief Smell Identification Test (mean +/- SD score, 9.3 +/- 1.9). MAIN OUTCOME MEASURES: Incidence of MCI and rate of decline in cognitive function. RESULTS: During annual observation of up to 5 years, 177 subjects developed MCI. In a proportional hazards model adjusted for age, sex, and education, odor identification score predicted development of MCI (relative risk, 1.15; 95% confidence interval, 1.07-1.23), with risk increased by 50% in persons with below-average (score of 8 [25th percentile]) compared with above-average (score of 11 [75th percentile]) odor identification scores. Results were not substantially changed in subsequent analyses that controlled for level of cognitive function or disability, presence of stroke, or smoking status at baseline or that required MCI to persist for at least 1 year. Impaired odor identification was also associated with a lower level of global cognition at baseline and with more rapid decline in episodic memory, semantic memory, and perceptual speed. CONCLUSION: Among older persons without manifest cognitive impairment, difficulty in identifying odors predicts subsequent development of MCI.     

Olfactory identification and apolipoprotein E epsilon 4 allele in mild cognitive impairment

To investigate olfactory identification and apolipoprotein E ε4 allele in patients with mild cognitive impairment (MCI), we used Cross-Cultural Smell Identification Test (CC-SIT) from University of Pennsylvania to assess olfactory identification performance and polymerase chain reaction (PCR) to detect apolipoprotein E ε4 (ApoE ε4) allele in 28 patients with MCI and the 30 age-matched control subjects in present study. The Mann-Whitney U test demonstrated that the MCI group performed significantly worse on CC-SIT than the normal aging group (P<0.01). For MCI patients olfaction scores correlated positively with CAMCOG-C (r=0.61, P<0.01), but not with age, gender or years of education. In normal subjects, the CC-SIT score showed no significant associations with age, gender, years of education, or CAMCOG-C. As the least common allele in Chinese, ε4 was found in 13.3% of controls and in 35.8% of MCI in this study. ApoE ε4 was significantly higher in MCI group than normal group (χ²=4.65, P<0.01). There was a significant effect of allele status on odor identification: subjects with ε4 allele were not able to identify as many odors as the subjects without ε4 allele (P<0.01). These results suggested that the decreased olfactory identification in MCI may be a marker for the early diagnosis of Alzheimer’s disease, and ApoE genotype may be part of the basis of olfactory identification decline.     

Olfactory identification and apolipoprotein E 4 allele in mild cognitive impairment

To investigate olfactory identification and apolipoprotein E epsilon 4 allele in patients with mild cognitive impairment (MCI), we used Cross-Cultural Smell Identification Test (CC-SIT) from University of Pennsylvania to assess olfactory identification performance and polymerase chain reaction (PCR) to detect apolipoprotein E epsilon 4 (ApoE epsilon 4) allele in 28 patients with MCI and the 30 age-matched control subjects in present study. The Mann-Whitney U test demonstrated that the MCI group performed significantly worse on CC-SIT than the normal aging group (P<0.01). For MCI patients olfaction scores correlated positively with CAMCOG-C (r=0.61, P<0.01), but not with age, gender or years of education. In normal subjects, the CC-SIT score showed no significant associations with age, gender, years of education, or CAMCOG-C. As the least common allele in Chinese, epsilon 4 was found in 13.3% of controls and in 35.8% of MCI in this study. ApoE epsilon 4 was significantly higher in MCI group than normal group (chi(2)=4.65, P<0.01). There was a significant effect of allele status on odor identification: subjects with epsilon 4 allele were not able to identify as many odors as the subjects without epsilon 4 allele (P<0.01). These results suggested that the decreased olfactory identification in MCI may be a marker for the early diagnosis of Alzheimer's disease, and ApoE genotype may be part of the basis of olfactory identification decline.     

Complex discourse production in mild cognitive impairment: Detecting subtle changes

Background: Mild cognitive impairment (MCI) is characterised by memory impairment that is greater than would be expected for an individual's age and educational background. Differentiating MCI from normal cognition in ageing is a compelling social, clinical, and scientific concern. Of those with MCI, 50% progress to Alzheimer's dementia within 5 years, while many individuals remain stable or return to normal functioning. Importantly, early identification of MCI has important implications for speech‐language pathology intervention.

Aims: The purpose of this study was to investigate whether performance on a complex elicited discourse production task differentiated individuals with MCI from those with normal cognition. The variables of interest were discourse length, complexity, and quality.

Methods & Procedures: Eight individuals with MCI and eight age‐ and gender‐matched controls were tested with the Mini‐Mental State Exam (MMSE), Logical Memory Subtest (LMS) of the Weschsler Memory Scale, and the Boston Naming Test (BNT). For the experimental task, each participant provided a complex, elicited discourse sample that was unconstrained in terms of discourse genre, in response to verbal instructions.

Outcomes & Results: The MMSE and LMS scores differentiated the groups in the expected direction, with the control group outperforming the MCI group. The groups performed comparably on the BNT. Performance on the experimental discourse production task distinguished the groups on measures of length and quality, but not in syntactic complexity.

Conclusions: These findings suggest that performance on a complex elicited discourse production task uncovers subtle differences in the abilities of individuals with MCI, such that measures of length and quality differentiated them from individuals with normal cognition.     

Olfaction and apathy in Alzheimer's disease,mild cognitive impairment,and healthy older adults

Objectives: Apathy is a prevalent neuropsychiatric manifestation in individuals with Alzheimer's disease (AD) that is associated with decreased social functioning and increased caregiver burden. Olfactory deficits are also commonly observed in AD, and prior work has indicated a link between increased apathy and olfactory dysfunction in individuals with Parkinson's disease. Here, we examined odor identification performance in patients with probable AD (n = 172), individuals with mild cognitive impairment (MCI; n = 112), and neurologically and psychiatrically healthy older adults (n = 132) and its relation to apathy, depression, and overall psychopathology. Method: Participants were administered the Sniffin’ Sticks odor identification test and measures assessing severity of apathy, depression, and overall neuropsychiatric symptomatology. Results: Consistent with previous research, AD and MCI patients were significantly worse at identifying odors than healthy older adults. Additionally, a sex by diagnosis interaction was observed. AD patients had significantly higher levels of apathy relative to MCI and control participants. Of note, across the entire sample odor identification deficits were correlated with level of apathy at the level of p < 0.01, but not with depression or neuropsychiatric symptom severity, when controlling for Mini-Mental State Examination (MMSE) score. Conclusion: Collectively, these data suggest that olfactory disturbance and apathy in AD may result from the progression of disease pathology in shared neural substrates.     

A comparative study of odor identification and odor discrimination deficits in Parkinson's disease

The aim of this study was to compare the characteristics of odor discrimination and odor identification deficits in a large population of patients with Parkinson's disease (PD) and to determine which of these olfactory tests best distinguishes between patients with PD and control subjects. Olfactory performance was assessed in 404 patients with PD and 150 controls, using the odor identification and discrimination parts of the Sniffin' Sticks battery. Mean identification and discrimination scores in patients with PD were significantly lower than in controls. Linear regression analysis using a 95% confidence interval revealed that, relative to the performance of controls, 65.0% of patients with PD had an impairment in odor identification, whereas 42.1% of patients were impaired on the odor discrimination task. ROC curves revealed a higher sensitivity and specificity for odor identification than for odor discrimination in separating patients from controls. In patients with PD, odor discrimination performance decreased with increasing disease duration, whereas odor identification was not correlated with disease stage or duration. In PD, odor identification is more frequently impaired than odor discrimination and allows a better discrimination between patients and controls. Although an odor identification deficit is generally believed to be independent of disease progression, the impairment in odor discrimination appears to increase with disease duration. © 2008 Movement Disorder Society     

Loss of awareness of hyposmia is associated with mild cognitive impairment in Parkinson's disease

BackgroundHyposmia is a common non-motor symptom in Parkinson's disease (PD). However, patients with PD are sometimes unaware of their olfactory dysfunction, resulting in an under-diagnosis of this symptom. To determine whether the loss of awareness of hyposmia results from cognitive impairment in patients with PD, we investigated the relationship between the degree of hyposmia self-awareness and the cognitive status of non-demented PD patients.MethodsThirty-one non-demented patients with PD and 20 healthy controls (HC) were assessed via a self-reported olfactory questionnaire and an odor identification test. PD patients were sub-classified as having mild cognitive impairment (PD-MCI) or as cognitively normal (PD-CN) (according to the current PD-MCI criteria). We compared the degree of hyposmia self-awareness between the PD-MCI and PD-CN groups.ResultsThe PD-MCI group scored the lowest on the odor identification test among all groups, whereas PD-MCI patients tended to rate their olfactory function higher on the self-reported olfactory questionnaire than PD-CN patients. Differences in the scores of subjective and objective olfactory measures between the PD-MCI and PD-CN groups were significant (p = 0.0069).ConclusionsThe loss of awareness of hyposmia is closely associated with mild cognitive impairment (MCI) in PD patients.     

Clinical features of MCI: motor changes

Mild cognitive impairment (MCI) is a classification reserved for nondemented elderly individuals at increased risk for future decline to dementia, compared to those with normal cognition. Cognitive tests, particularly those assessing verbal recall, have been found to be useful in the identification of elderly people with MCI. We argue that a variety of motor/psychomotor evaluations are also sensitive to MCI. Motor assessments described as complex correctly categorize normal versus MCI elderly with comparable accuracies to those obtained by cognitive tests. Unlike performance on verbally based cognitive measures, motor-test scores appear to be relatively independent of educational attainment, indicating that the use of certain motor tests may be particularly valuable in the identification of MCI among elderly with widely varying educational backgrounds.     

Olfactory evaluation in Mild Cognitive Impairment: correlation with neurocognitive performance and endothelial function

Mild Cognitive Impairment (MCI) is an intermediate condition between normal aging and dementia, associated with an increased risk of progression into the latter within months or years. Olfactory impairment, a well‐known biomarker for neurodegeneration, might be present in the condition early, possibly representing a signal for future pathological onset. Our study aimed at evaluating olfactory function in MCI and healthy controls in relation to neurocognitive performance and endothelial function. A total of 85 individuals with MCI and 41 healthy controls, matched for age and gender, were recruited. Olfactory function was assessed by Sniffin’ Sticks Extended Test (Burghart, Medizintechnik, GmbH, Wedel, Germany). A comprehensive neurocognitive assessment was performed. Endothelial function was assessed by flow‐mediated dilation (FMD) of the brachial artery by ultrasound. MCI individuals showed an impaired olfactory function compared to controls. The overall olfactory score is able to predict MCI with a good sensitivity and specificity (70.3 and 77.4% respectively). In MCI, olfactory identification score is correlated with a number of neurocognitive abilities, including overall cognitive status, dementia rating, immediate and delayed memory, visuospatial ability and verbal fluency. FMD was reduced in MCI (2.90 ± 2.15 vs. 3.66 ± 1.96%, P = 0.016) and was positively associated with olfactory identification score (ρ_s=0.219, P = 0.025). The association remained significant after controlling for age, gender, and smoking. In conclusion, olfactory evaluation is able to discriminate between MCI and healthy individuals. Systemic vascular dysfunction might be involved, at least indirectly, in olfactory dysfunction in MCI.     

Olfactory screening test in mild cognitive impairment

Abstract 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.     

Olfactory identification and discrimination in obsessive-compulsive disorder

Background: Neuroimaging and neuropsychological data from patients with an obsessive‐compulsive disorder (OCD) indicate the dysfunction of the orbitofrontal cortex (OFC). Olfactory processing has been associated with OFC function, although results from OCD studies regarding this sensory modality have been inconclusive. No previous study has analyzed both odor discrimination and identification capacity in OCD patients using “Sniffin' Sticks” tests. The aim of our study was to assess odor threshold, identification, discrimination, and nonverbal memory in OCD patients, in order to determine whether these functions were affected. Methods: Olfactory function was measured in 29 OCD patients and 29 healthy volunteers (HV) using the “Sniffin' Sticks” test and their nonverbal memory was scored with the Rey–Osterrieth Complex Figure Test. Results: OCD patients showed significant impairment in their odor performance and in their execution of the nonverbal memory task compared to HV. No statistical associations were found between the deficits in the two areas. The severity of depressive and obsessive‐compulsive symptoms did correlate with olfactory identification. Conclusion: Our findings support the hypothesis that olfactory and memory dysfunctions in OCD reflect different neurobiological alterations of the disorder, and point to the modulation effect of depressive and obsessive‐compulsive symptoms on odor performance. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.     

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.     

Left hippocampal volume loss in Alzheimer's disease is reflected in performance on odor identification: a structural MRI study.

The very high sensitivity and specificity of odor identification tasks in discriminating between Alzheimer's patients and normals suggests that they reflect the presence of underlying neuropathology. Significant neuropathological changes are seen in areas critical to processing olfactory information, even in the early stages of Alzheimer's disease (AD). The current study was designed to investigate whether performance on olfactory tasks (odor threshold and odor identification) was related to volumetric MRI measures of mesial temporal areas central to olfactory information processing and important in the neuropathology of AD. Participants were 8 male and 5 female patients with probable AD, and 10 male and 12 female normal age-matched controls, diagnosed at the UCSD Alzheimer's Disease Research Center. The study investigated correlations between volumetric measures of hippocampus, the parahippocampal gyrus and the amygdala, and the psychophysical measures of olfactory function. Robust relationships were observed between mesial temporal lobe volumes and olfactory functional measures. The finding of a strong relationship between left hippocampal volume and performance on the odor identification task (r = .85) is compatible with a left-hemisphere superiority for verbally mediated olfactory tasks. The findings suggest a neural substrate for the breakdown in functional performance on verbally mediated odor identification tasks in Alzheimer's disease and suggest the utility of quantitative MRI measures and psychophysical performance in the assessment of AD. These results support the potential clinical utility of inclusion of odor identification tests in diagnostic batteries for detecting AD.     

Validation of a Short Telephone Test (T3MS) for the Diagnosis of Cognitive Impairment

The identification of cognitive impairment in general practice requires short but accurate tests. For epidemiologic surveys and genetic family studies cognitive tests are desirable which can be administered over the telephone. We assessed the ability of a telephone version of the Modified Mini Mental State Examination (T3MS) to identify mild cognitive impairment (MCI) and mild dementia in Alzheimer's disease (AD) and compared it with the diagnostic accuracy of the conventional Mini Mental State Examination (MMSE). The study refers to 34 patients of the outpatient clinic for cognitive disorders of the technical university of Munich of whom 18 had MCI and 16 had mild dementia in AD, respectively. The study also included 14 cognitively unimpaired age-matched probands. The T3MS and MMST were validated against an expert diagnosis base on a comprehensive diagnostic workup. Statistical analysis was performed using the receiver-operator-characteristics (ROC) method. The T3MS outperformed the MMST in the distinction between MCI patients and cognitively unimpaired individuals. In the separation between cognitively unimpaired probands and patients with mild AD the T3MS achieved a sensitivity and specificity of 100 %. The T3MS is a short and practical but accurate telephone test for the identification of mild dementia in AD for use in epidemiological surveys and genetic family studies. The interview achieves higher diagnostic precision than the MMSE and contributes to a valid assessment of cognitive performance. For the identification of mild cognitive impairment, however, the T3MS was less appropriate.     

Inspection time in non-demented older adults with mild cognitive impairment

The aim of this study was to examine inspection time (IT) performance in older adults with mild cognitive impairment (MCI), who are at higher risk of developing further cognitive decline or dementia. IT is described as an index of speed of informational intake. IT correlates with measures of fluid intelligence and is possibly a marker for the integrity of the cholinergic system of the brain. IT may therefore be useful in aiding the diagnosis of early-stage progressive cognitive impairment. The current study compares IT in 28 people with MCI to 28 age, gender and education-matched controls. The computer-based, visual IT task required participants to discriminate between two visual stimuli that were presented for brief periods. Participants' IT performance was compared to their performance on cognitive and memory tasks. Group comparison showed that participants with MCI performed significantly worse on IT than controls and was not affected by years of education. In combination with other clinical, neuropsychological and biological tests, IT may be a useful assessment tool for improving the identification of older adults at risk for clinically relevant cognitive decline.     

Subtle memory decline over 12 months in mild cognitive impairment

OBJECTIVE: Screening of normal older persons for progressive memory decline is a worthwhile strategy in the pursuit of the earliest possible stages of pre-clinical Alzheimer's disease (AD) or mild cognitive impairment (MCI). Reliable tests are needed to both detect MCI and measure the natural history of decline over months rather than years. We aimed to detect memory decline over 1 year in a group of older individuals with well-characterised amnestic MCI. METHODS: The continuous learning task (CLT) from the CogState test battery was administered 8 times in 12 months to 15 individuals with MCI and 35 controls matched for age, education, IQ and gender. All subjects were recruited from an ongoing aging study. The rate of change in CLT performance over the year was compared between groups and also compared to that detected with a word list learning task and a computerised paired associate learning task. RESULTS: At baseline, memory performance in the amnestic MCI group was significantly worse than controls on all memory tests. However, at 12 months the magnitude of the difference between the groups had increased significantly on the CLT due to decline in memory accuracy in the MCI group. No decline over 12 months was detectable on the routine memory tests. CONCLUSIONS: Subtle memory decline is detectable in amnestic MCI using reliable and sensitive tests of memory. Such measures may assist in the early identification of AD and also in trials of putative disease-modifying therapies to be conducted over as little as 12 months.     

Taste in mild cognitive impairment and Alzheimer’s disease

In this prospective study we investigated the quantitative and qualitative taste function of patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). 29 healthy, elderly subjects, 29 MCI and 30 AD patients were tested using a validated taste test, the “taste strips”. Additionally, odor identification, odor discrimination, odor threshold, the mini-mental state examination (MMSE) and Apo E epsilon 4 status were examined. Regarding taste, there was a significant reduction of total taste scores and also the score for individual tastes on either side of the tongue between controls and MCI/AD patients. There was no significant difference in the taste scores between MCI and AD patients. A taste test may be a useful procedure for differentiating between healthy subjects and patients with MCI/AD in a clinical context. For diagnosing MCI versus AD, further tests such as smell test, MMSE, Apo E epsilon 4 status, FDG-PET and MRI appear to be useful.     

阿尔茨海默病嗅觉障碍的研究

目的 :研究阿尔茨海默病 (AD)患者嗅觉障碍。方法 :配对的AD患者和正常老年人各 3 0例 ,分别行简易智能状态检查(MMSE)、日常生活活动量表 (ADL)、图片识别试验、气味感知阈值、图片介导的气味识别试验及气味再认记忆试验检查。结果 :AD组的气味感知、气味识别和气味再认记忆功能较正常对照组差 (P <0 0 1) ;相关分析显示 ,AD组患者的嗅觉障碍与MMSE总分密切相关 (P <0 0 5 ) ;结论 :AD患者的嗅觉功能全面受损 ,嗅觉障碍是疾病的早期症状 ,是认知障碍的简单反映