Biomedical subjects

Howard Chertkow

Publications and source records attributed to Howard Chertkow.

At least 19 recordsLinked to original sources

PubMed2007

Olfaction in patients with mild cognitive impairment and Alzheimer's disease.

Understanding of olfactory dysfunction in Alzheimer's disease (AD) remains limited. In particular, it is not known how early in the course of the disease olfactory deficits occur, and whether they are restricted to identification or involve other aspects of olfaction. We studied olfactory (odor detection thresholds, quality discrimination, and identification) and cognitive (attention, reasoning, memory, naming and fluency) functioning in patients with AD, with mild cognitive impairment (MCI), and in normal elderly control (NEC) participants. MCI patients were impaired in olfactory sensitivity and identification, while a discrimination deficit was accounted for by abnormal thresholds. AD patients were impaired in all three domains, and were worse than the MCI group. Odor discrimination (OD) and identification performance correlated more prominently than detection thresholds with performance on neuropsychological tests. We concluded that deficits in olfactory detection thresholds and identification occur early in AD, before clinical symptoms are fully developed, and decline further over the course of the disease. High detection thresholds, together with impaired identification, may be useful as an early indicator of AD.

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PubMed2006

Spatial patterns of cortical thinning in mild cognitive impairment and Alzheimer's disease.

Cortical thickness is a more reliable measure of atrophy than volume due to the low variability in the cytoarchitectural structure of the grey matter. However, this more desirable measure of disease-related alterations is not fully evaluated in early dementia. The study presented here is the first to report the spatial patterns of cortical thickness in the pre-clinical stages of Alzheimer's disease, namely mild cognitive impairment (MCI). Cortical thickness measurements for 34 healthy elderly, 62 MCI and 42 Alzheimer's disease subjects were made using fully automated magnetic resonance imaging-based analysis techniques in order to determine the pattern of cortical thinning as a function of disease progression. The thickness of the cortex decreased significantly when the healthy elderly brains were compared to those with MCI, mainly in the medial temporal lobe region and in some regions of the frontal and the parietal cortices. With the progression of disease from MCI to Alzheimer's disease, a general thinning of the entire cortex with significant extension into the lateral temporal lobe was found. In all cases, the results were more pronounced in the left hemisphere. In conclusion, we have shown that there is a specific pattern in the thinning of the cortical ribbon which is in agreement with the previous histological reports. These novel findings support the notion of increased isocortical involvement with the progression of disease.

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PubMed2006

The nature of lexico-semantic processing deficits in mild cognitive impairment.

Lexico-semantic impairments in Alzheimer disease (AD) have been attributed to abnormalities in both intentional and automatic access to semantic memory. However, the order in which these impairments appear during the course of the disease is unclear. We sought to answer this question by documenting lexico-semantic impairments in 61 subjects with mild cognitive impairment (MCI), a pre-AD stage, and by comparing them to those of 39 AD and 60 normal elderly (NE) subjects. All subjects were tested with intentional access tasks (picture naming and semantic probes), automatic access tasks (lexical decision and priming), and executive function tasks (Stroop and Stroop-Picture naming). Results indicated that the MCI group was only impaired on tasks of intentional access relative to the AD group who was impaired on both types of tasks. Because most MCI subjects eventually develop AD, these results suggest that intentional access to semantic memory is impaired before automatic access. Further, impairments on the Stroop-Picture naming task but not on the Stroop task, suggest that lexico-semantic impairments in the MCI group may be related to inhibition deficits during semantic search. Findings are discussed in light of executive dysfunctions within the framework of semantic memory theories.

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PubMed2006

Mild cognitive impairment.

Mild cognitive impairment is a syndrome defined as cognitive decline greater than expected for an individual's age and education level but that does not interfere notably with activities of daily life. Prevalence in population-based epidemiological studies ranges from 3% to 19% in adults older than 65 years. Some people with mild cognitive impairment seem to remain stable or return to normal over time, but more than half progress to dementia within 5 years. Mild cognitive impairment can thus be regarded as a risk state for dementia, and its identification could lead to secondary prevention by controlling risk factors such as systolic hypertension. The amnestic subtype of mild cognitive impairment has a high risk of progression to Alzheimer's disease, and it could constitute a prodromal stage of this disorder. Other definitions and subtypes of mild cognitive impairment need to be studied as potential prodromes of Alzheimer's disease and other types of dementia.

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PubMed2006

Progress in clinical neurosciences: Canadian guidelines for the development of antidementia therapies: a conceptual summary.

The magnitude of the problems faced by an aging Canadian society has been clearly identified. Perhaps the single most important problem is the increasing incidence of dementia. Alzheimer's disease (AD) accounts for 50-60% of the dementias in later life within a spectrum of other contributing dementias. Regulatory approval has been given to Acetylcholinesterase inhibitors for the symptomatic treatment of mild to moderate AD, and conditional approval to memantine for the symptoms of moderate to severe AD. There has been no regulatory approval for the treatment of the degenerative dementias beyond AD. The very rapid progress in the past decade in biotechnology and in the molecular biology of the dementias is supporting a new generation of innovative treatment strategies that will more directly target the underlying disease pathogenic mechanisms. Such treatments will foreseeably include immunotherapies, anti-aggregants that may prevent misfolding and deposition of proteins, and neuroregenerative interventions. These Guidelines follow the 2nd Canadian Conference on the Development of Antidementia Therapies, held in 2004, which covered a range of design, methodological and ethical issues facing clinical researchers and regulatory authorities. They are intended to provide a common point of reference and guidance in Canada for therapeutic development of the dementias.

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PubMed2006

Cognitive estimation impairment in Alzheimer disease and mild cognitive impairment.

Intact executive functioning is believed to be required for performance on tasks requiring cognitive estimations. This study used a revised version of a cognitive estimations test (CET) to investigate whether patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) were impaired on the CET compared with normal elderly controls (NECs). Neuropsychological tests were administered to determine the relationship between CET performance and other cognitive domains. AD patients displayed impaired CET performance when compared with NECs but MCI patients did not. Negative correlations between tests of working memory (WM) and semantic memory and the CET were found in NECs and AD patients, indicating that these cognitive domains were important for CET performance. Regression analysis suggests that AD patients were unable to maintain semantic information in WM to perform the task. The authors conclude that AD patients display deficits in working memory, semantic memory, and executive function, which are required for adequate CET performance.

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PubMed2006

Memory for gist and detail information in Alzheimer's disease and mild cognitive impairment.

Two experiments examined different forms of gist and detail memory in people with Alzheimer's disease (AD) and those with amnestic mild cognitive impairment (MCI). In Experiment 1, 14 AD, 14 MCI, and 22 control participants were assessed with the Deese-Roediger-McDermott paradigm. Results indicated that false recognition of nonstudied critical lures (gist memory) was diminished in the AD compared with the MCI and control groups; the two latter cohorts performed similarly. In Experiment 2, 14 AD, 20 MCI, and 26 control participants were tested on a text memory task. Results revealed that recall of both macropropositions (gist information) and micropropositions (detail information) decreased significantly in AD and in MCI as compared with control participants. This experiment also revealed that the impairment was comparable between gist and detail memory. In summary, the results were consistent across experiments in the AD but not in the MCI participants. The discrepancy in MCI participants might be explained by differences in the degree of sensitivity of the experimental procedures and/or by the differences in the cognitive processes these procedures assessed.

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PubMed2005

Establishing visual category boundaries between objects: a PET study.

Individuals with Alzheimer's disease (AD) often have problems in recognizing common objects. This visual agnosia may stem from difficulties in establishing appropriate visual boundaries between visually similar objects. In support of this hypothesis, showed that AD subjects have difficulties in establishing visual category boundaries between continuously graded shapes. In an attempt to investigate the neural basis of these impairments, the current study required a group of neurologically healthy elderly participants to categorically classify a series of ellipses varying in width while regional blood flow changes were measured using positron emission tomography (PET). Two categorization conditions were compared in order to isolate changes in cortical activity that dissociated the categorization of shapes situated either near or far from a category boundary that divided the width continuum. The participants produced a discontinuity in the probability and speed of categorizing the shapes at some point along the continuum, suggesting that the objects were classified into distinct categories. Moreover, a comparison of the PET scans obtained while the subjects were categorizing the shapes situated near vs. far form the category boundary revealed significant differences in cortical activity in the parietal and frontal brain areas. These findings suggest that both visuo-spatial and decision making mechanisms may be involved in establishing categorical distinctions between continuously graded stimuli. It is proposed that the functional role of the parietal and frontal cortical regions in establishing visual boundaries between categories of objects may be relevant for understanding object recognition impairments in AD.

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PubMed2005

The effect of Alzheimer's disease and aging on conceptual combination.

Alzheimer's disease (AD) subjects, healthy elderly, and young adults interpreted a series of novel noun-noun expressions composed of familiar object words. Subjects interpreted each item by selecting one of three possible definitions: a definition in which the referents of each noun were associated together in a particular context (e.g., rabbit cat: a cat that is raised by rabbits); a definition based on integrating the semantic attributes from each noun into a single referent (e.g., rabbit cat: a cat that has long ears and hops); and a semantic foil. The results show that the AD subjects selected significantly fewer integrational definitions and significantly more foils than healthy elderly subjects. Healthy elderly participants were also found to select significantly more foil definitions than the young adult subjects. These findings suggest that AD individuals have difficulty in integrating semantic features when interpreting novel noun-noun expressions and that both AD and healthy elderly individuals have morphosyntactic impairments related to the identification of the modifying and head nouns of noun-noun expressions.

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PubMed2005

Focused attention deficits in patients with Alzheimer's disease and mild cognitive impairment.

Reaction time (RT) tasks take various forms, and can assess psychomotor speed, (i.e., simple reaction time task), and focused attention (i.e., choice reaction time (CRT) task). If cues are provided before stimulus presentation (i.e., cued choice reaction time (CCRT) task), then a cueing effect can also be assessed. A limited number of studies have addressed the nature of focused attention impairments in Alzheimer's disease (AD). Additionally, it is unknown whether similar impairments occur in Mild Cognitive Impairment (MCI). The current study used three RT tasks to address the nature of focused attention impairments in AD and MCI subjects. The results suggest that there were significant CRT and CCRT differences in AD subjects when compared to NECs. Furthermore, slowed RTs were also present in the MCI group, which provides evidence for impaired focussed attention and the inability to benefit from a cue in both the MCI and AD groups. The implications of the impairments related to the MCI group could potentially prove useful in early diagnosis of cognitive impairments in the elderly.

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PubMed2005

The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.

OBJECTIVES: To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. DESIGN: Validation study. SETTING: A community clinic and an academic center. PARTICIPANTS: Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). MEASUREMENTS: The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. RESULTS: Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). CONCLUSION: MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.

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PubMed2005

Towards practical cognitive assessment for detection of early dementia: a 30-minute computerized battery discriminates as well as longer testing.

Early detection of cognitive decline may lead to more effective treatment. Clinical cognitive assessment is essential for early detection, but must be brief with easily interpretable results. The present study defines and evaluates a 30-minute cognitive battery consisting of a subset of tests that comprise a longer computerized battery recently validated in detecting mild cognitive impairment (MCI). Participants were from three tertiary care memory clinics and an assisted living facility (final group: N=161) with consensus diagnoses of cognitively healthy, MCI, or mild dementia. A comprehensive NeuroTrax battery evaluated memory, executive function, visual spatial perception, verbal function, information processing speed, and motor skills. Validity of a single summary measure ('MCI Score') designed for dementia detection and built exclusively from tests of memory, executive function, and visual spatial perception was evaluated with receiver operating characteristic (ROC) analysis. Discriminant validity (area under the curve: AUC) was at least as large for the 6-parameter MCI Score as for a 20-parameter score necessitating administration of the entire battery. Further, the MCI Score had a larger AUC with reduced variance relative to its constituent parameters. AUC for distinguishing dementia was 0.886; AUC for distinguishing cognitively healthy was 0.823. Finally, the MCI Score discriminated among all three diagnostic groups (ANOVA; F[2,150]=52.54, p<0.001). Hence a reduced NeuroTrax battery (30 minutes) with MCI Score is a useful clinical tool for summarizing cognitive data relevant to early dementia detection.

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PubMed2004

Evaluation of HFE (hemochromatosis) mutations as genetic modifiers in sporadic AD and MCI.

BACKGROUND: Pathological brain iron deposition has been implicated as a source of neurotoxic reactive oxygen species in Alzheimer disease (AD). Recent reports suggest that heterozygosity for the two common hfe mutations responsible for hereditary hemochromatosis (HH) may be a risk factor for AD, possibly by accelerating brain iron accumulation. METHODS: To test this hypothesis, we genotyped 213 sporadic AD, 106 MCI, and 63 normal elderly control (NEC) individuals for the H63D and C282Y hfe mutations by polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP) analysis. We determined the relationship of these mutations to the demographic, clinical, and neuropsychological features of AD and MCI, and evaluated whether an interaction existed between hfe and apolipoprotein E (apoE) status in these patients. RESULTS: We observed no significant impact of H63D or C282Y heterozygosity on age at AD symptoms onset or diagnosis, age at onset of cognitive symptoms (AD and MCI combined), rates of MCI-to-AD conversion or specific neuropsychological deficits. No interactions between hfe zygosity and apoE status were discerned. Patients homozygous for H63D exhibited trends towards accelerated MCI-to-AD conversion rates and a subset of younger individuals (aged 55-75) exhibited earlier onset of cognitive symptoms relative to wild-type hfe and H63D heterozygotes. CONCLUSIONS: Contrary to earlier reports, the results of the present study do not implicate the common hfe mutations as genetic modifiers of sporadic AD and MCI. Trends towards accelerated cognitive dysfunction in H63D homozygotes warrant further study.

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PubMed2004

Functional and anatomical memory indices in patients with or at risk for Alzheimer's disease.

We investigated the sensitivity of the P300 event-related brain potential (ERP) recorded during a memory-demanding task to memory function in subjects with dementia of the Alzheimer's type (DAT), those with mild cognitive impairment (MCI), and normal elderly controls. We also explored the ability of neuropsychological (delayed verbal memory), neuroanatomical (MRI-based hippocampal volume), and electrophysiological (memory search P300 amplitude) memory measures to distinguish between the three subject groups using discriminant function analyses. Fourteen patients with DAT, 16 with MCI, and 15 age- and education-matched controls were tested. P300 amplitude was reduced in DAT subjects at all levels of memory load; however, it did not differ between MCI and control subjects. Delayed verbal memory performance best discriminated DAT from MCI and control subjects, while delayed verbal memory and hippocampal volume best discriminated MCI subjects from controls. These results support the utility of neuropsychological and neuroanatomical measures in diagnosing dementia and do not support the notion that P300 amplitude is sensitive to mild memory dysfunction when measured using the current task.

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PubMed2004

Selective attention impairments in Alzheimer's disease: evidence for dissociable components.

Tasks emphasizing 3 different aspects of selective attention-inhibition, visuospatial selective attention, and decision making-were administered to subjects with mild Alzheimer's disease (AD) and to healthy elderly control (HEC) subjects to determine which components of selective attention were impaired in AD subjects and whether selective attention could be dissociated into different components. The tasks were administered with easy versus hard levels of difficulty to assess proportional slowing as the key variable across tasks. The results indicated that the inhibitory and visual search tasks showed greater proportional slowing in subjects with AD than in HEC subjects, and that the task involving inhibition was significantly more affected in subjects with AD. Furthermore, there were no significant intertask correlations, and the results cannot be explained simply in terms of generalized cognitive slowing. These results provide evidence that inhibition is the most strikingly affected aspect of selective attention that is observed to be impaired in early stages of AD.

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PubMed2004

Common and constrasting areas of activation for abstract and concrete concepts: an H2 15O PET study.

Lesion studies indicate that the lateral and inferior temporal cortex is a critical area of semantic memory storage, but little is known about the cortical organization of semantics within this area. One proposition has been that dominant physical characteristics of objects (structure, motility) are determining factors. A positron emission tomography experiment using the H2(15)O bolus method was performed to test this hypothesis by contrasting activation for concrete and abstract concepts. Unlike previous studies that considered this question, the task required explicit word meaning judgments, and blocks of trials were designed to be of equal difficulty for the two word classes. The task required elderly participants to read aloud the pair of words that was closer in meaning (e.g., spade-shovel vs. spade-carpet). Subtraction analyses that compared the semantic judgment tasks with a baseline condition indicated that both abstract and concrete concepts activated the left lateral temporal cortex. A direct comparison of abstract versus concrete scans indicated differences in the lateralization of fusiform activation. We conclude that although concreteness might be a critical factor in the fusiform cortex, it is not dominant in the lateral temporal cortex. A multistudy overview suggests that tasks that focus on one concept per trial activate areas posterior to y = -40, whereas those that invoke several concepts, as in the present study, activate areas anterior to this. Increased processing complexity may proceed in a posterior-anterior direction in the lateral temporal cortex.

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PubMed2004

Validity of the Mindstreams computerized cognitive battery for mild cognitive impairment.

The NeuroTrax Mindstreams computerized cognitive assessment system was designed for widespread clinical and research use in detecting mild cognitive impairment (MCI). However, the capability of Mindstreams tests to discriminate the elderly with MCI from those who are cognitively healthy has yet to be evaluated. Moreover, the comparability between these tests and traditional neuropsychological tests in detecting MCI has not been examined. A two-center study was designed to assess the discriminant validity of tests in the Mindstreams Mild Impairment Battery. Participants were 30 individuals diagnosed with MCI, 29 with mild Alzheimer's disease (AD), and 39 healthy elderly. Testing was with the Mindstreams battery and traditional neuropsychological tests. Receiver operating characteristic (ROC) analysis was used to examine the ability of Mindstreams and traditional measures to discriminate those with MCI from cognitively healthy elderly. Between-group comparisons were made (Mann-Whitney U test) between MCI and healthy elderly and between MCI and mild AD groups. Mindstreams outcome parameters across multiple cognitive domains significantly discriminated between MCI and healthy elders with considerable effect sizes (p < 0.05). Measures of memory, executive function, visual spatial skills, and verbal fluency discriminated best, and discriminability was at least comparable to that of traditional neuropsychological tests in these domains. Mindstreams tests are effective in detecting MCI, providing a comprehensive profile of cognitive function. Further, the enhanced precision and ease of use of these computerized tests make the NeuroTrax system a valuable clinical tool in the identification of elders at high risk for dementia.

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PubMed2003

Validity of a novel computerized cognitive battery for mild cognitive impairment.

BACKGROUND: The NeuroTrax Mindstreams computerized cognitive assessment system was designed for widespread clinical and research use in detecting mild cognitive impairment (MCI). However, the capability of Mindstreams tests to discriminate elderly with MCI from those who are cognitively healthy has yet to be evaluated. Moreover, the comparability between these tests and traditional neuropsychological tests in detecting MCI has not been examined. METHODS: A 2-center study was designed to assess discriminant validity of tests in the Mindstreams Mild Impairment Battery. Participants were 30 individuals diagnosed with MCI, 29 with mild Alzheimer's disease (AD), and 39 healthy elderly. Testing was with the Mindstreams battery and traditional neuropsychological tests. Receiver operating characteristic (ROC) analysis was used to examine the ability of Mindstreams and traditional measures to discriminate those with MCI from cognitively healthy elderly. Between-group comparisons were made (Mann-Whitney U test) between MCI and healthy elderly and between MCI and mild AD groups. RESULTS: Mindstreams outcome parameters across multiple cognitive domains significantly discriminated among MCI and healthy elderly with considerable effect sizes (p < 0.05). Measures of memory, executive function, visual spatial skills, and verbal fluency discriminated best, and discriminability was at least comparable to that of traditional neuropsychological tests in these domains. CONCLUSIONS: Mindstreams tests are effective in detecting MCI, providing a comprehensive profile of cognitive function. Further, the enhanced precision and ease of use of these computerized tests make the NeuroTrax system a valuable clinical tool in the identification of elderly at high risk for dementia.

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