Biomedical subjects

Howard Chertkow

Publications and source records attributed to Howard Chertkow.

15 recordsLinked to original sources

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

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.

Journal Article↗

PubMed2003

Semantic category differences in cross-form priming.

Findings of category-specific impairments have suggested that human semantic memory may be organized around a living/nonliving dichotomy. In order to assess implicit memory performance for living and nonliving concepts, one group of neurologically intact individuals participated in a cross-form conceptual priming paradigm. In Block 1, pictures primed words while in Block 2 words were used to prime pictures. Across all phases of the experiment, subjects decided whether items represented something which was living or nonliving, and response times were recorded. Results revealed greater priming for living concepts across both blocks. Greater priming for living concepts may have occurred because of increased or prolonged conceptual activation of these concepts. Results are discussed in the context of theoretical accounts of the category-specific impairments observed in brain-damaged populations.

Adolescent↗

PubMed2002

Regional magnetization transfer ratio changes in mild cognitive impairment.

Reduction in temporal lobe volume is consistently found in dementia of Alzheimer's type (DAT). However, due to the lack of a consistent association between brain volume and cognitive decline in mild cognitive impairment (MCI), volumetric measures are not a reliable predictor for the progression of the disease. In our study, we hypothesized that changes in the magnetization transfer ratio (MTR) may reflect underlying brain pathology in the absence of quantifiable volumetric changes. Such a measure may be used as a predictor for abnormal cognitive decline in elderly subjects. The study was carried out on 15 normal elderly controls, 11 subjects with DAT, and 12 subjects with MCI. We used MTRs with magnetic resonance imaging (MRI) to detect tissue changes in the four lobes of each hemisphere, and compared that to the volumetric changes in the same regions. Our results indicate that the MTR of both temporal lobes is significantly reduced in subjects with MCI in the absence of significant volumetric changes. In comparison, DAT subjects have significantly reduced temporal lobe volumes and MTR. We conclude that changes in MTR have the potential to mark the progression of MCI to DAT, before volumetric changes are detected on conventional MRI scans.

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PubMed2002

Magnetization transfer ratio in mild cognitive impairment and dementia of Alzheimer's type.

Almost half of the elderly subjects that are diagnosed with mild cognitive impairment (MCI) go on to develop dementia of Alzheimer's type (DAT) over a 5-year follow-up. MCI and DAT subjects show regional decreases in the volume of brain structures, which correlate with the cognitive decline among these groups. Volumetric changes are found more consistently in the DAT group than in the MCI group. Since not all MCI subjects demonstrate volumetric decline, we propose that the underlying changes in the structural integrity of the brain, measured using magnetization transfer ratio (MTR), may be used as an additional predictor for abnormal cognitive decline in the elderly. Magnetic resonance (MR) images were obtained in 15 DAT, MCI, and elderly control subjects. Using automatic tissue classification, the brain region of each MR volume was segmented into gray matter and white matter. Mean and standard error of the mean MTR measured within the gray matter was found to be significantly lower in the MCI (30.77 +/-0.29; P = 0.037) and the DAT (29.37 +/-0.41; P = 0.000) group compared to the control group (32.11 +/-0.20). The MTR of white matter was significantly lower only in the DAT group. The gray matter volume was significantly lower (P = 0.000) in the DAT (387.29 +/-26.04 cm(3)) group compared to controls (532.93 +/-20.53 cm(3)) and MCI (464.64 +/-16.93 cm(3)). No significant differences were found in the white matter volume between the three groups. We conclude that changes in MTR are measurable even in the absence of detectable volumetric changes in gray and white matter in the MCI group. Furthermore, MTR changes may present a novel MRI measure for the early diagnosis of dementia of Alzheimer's type.

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PubMed2002

Semantic memory.

Our concepts about objects, states, and events are stored in a cognitive structure termed semantic memory. There are several types of neurologic disorders that may cause impairments of semantic memory. Clinical evaluations of these impairments are complex, because semantic memory is linked to other cognitive systems that, when damaged, may produce related syndromes or difficulties. In an attempt to gain further understanding of these breakdown patterns, we review data from both neuropsychologic and brain activity research that have been concerned with how object concepts are represented and localized in the brain. Although these data have spawned varying and controversial views regarding the content and organization of semantic knowledge, converging evidence suggests that semantic memory is mainly localized in the posterior region of the left temporal lobe, and that particular categories of knowledge may be represented in different but overlapping regions within this area.

Functional Laterality↗

PubMed2002

Increased variability accompanies frontal lobe damage in dementia.

Performance variability on neuropsychological measures is not a unitary phenomenon, and different measures (consistency, dispersion, diversity) evaluate separate elements of variability. It has been suggested that increased variability may be a specific attribute of frontal lobe pathology. This hypothesis was tested in 2 matched groups of demented subjects, 8 with dementia of the Alzheimer type (DAT), 5 with frontal lobe dementia (FLD), compared with 10 elderly normal controls (ENC). A Stroop test and Reaction Time measures were administered weekly for 5 weeks to all subjects. Both measures contained three subtests varying in degree of complexity. The results from the Stroop task indicated that the FLD group showed significantly greater variability on measures of consistency (fluctuations over time) and diversity (between participant variability) regardless of the complexity of the subtest. For the Reaction Time subtests, measures of consistency and diversity showed significantly greater variability in FLD, but were affected in a different pattern. Greater variability in terms of consistency of performance was manifested only in the more attentionally demanding of the Reaction Time subtests (Choice Reaction Time, CRT). On the measure of diversity, variable performance was found to be greater on the Simple Reaction Time (SRT) subtest than on the more effortful CRT. Dispersion (within participant variability) was only assessed on the reaction time subtests. The results indicate no significant evidence for an increase in dispersion for the FLD patients. The hypothesis that variability will be increased in frontal lobe dementia is thus confirmed, and the independence of the three forms of variability measurement is demonstrated in dementia subjects.

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PubMed2002

A case study of pure word deafness: modularity in auditory processing?

AL, a woman with an acquired disturbance of auditory processing beginning in the second decade, was originally diagnosed as having pure word deafness. Recent analysis with a wide range of stimuli suggests that her comprehension deficit also extends to a subset of musical and non-verbal environmental sounds. The perceptual demands of the different auditory stimuli appear to account for part of the apparent material specificity. Additionally, over the years, the presumed temporal lobe cortical pathology has been supplemented by a mild to moderate, peripheral low-frequency hearing loss and evidence of dysfunction in lower level auditory processing pathways. The current peripheral dysfunction closely resembles cases recently labeled as auditory neuropathy. The diagnosis of pure word deafness should not be based on a limited set of auditory stimuli; additionally, a careful assessment using modern audiological techniques should be performed to evaluate peripheral auditory functions.

Achievement↗

PubMed2002

Mild cognitive impairment.

Mild cognitive impairment is an emerging term that encompasses the clinical state between elderly normal cognition and dementia. Controversy surrounds its characterization, implementation, and definition. Mild cognitive impairment is now the focus of natural history studies, biomarker studies, along with Alzheimer's disease prevention studies. The mild cognitive impairment stage may be the optimum stage at which to intervene with preventive therapies. Depending on the cohort source and definition, between 19 and 50% of mild cognitive impairment individuals progress to dementia (usually Alzheimer's disease) over 3 years. Despite controversy, progress has been achieved in defining risk factors for progression from mild cognitive impairment to dementia. New treatments to prevent development of Alzheimer's disease are targeting mild cognitive impairment as a treatment group and neurologists will increasingly be called upon to make this diagnosis.

Brain Diseases↗

PubMedDate not supplied

Word-reading thresholds in Alzheimer disease and mild memory loss: a pilot study.

PURPOSE: To determine whether subjects with early Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI) would demonstrate significant abnormalities on tests of word reading threshold (WRT), spatial contrast sensitivity (SCS), and color discrimination (CD). METHODS: Prospective cohort study of 13 AD subjects, 13 subjects with Mild Cognitive Impairment (MCI), and 12 healthy elderly normal controls (ENC). CD was determined using the Farnsworth D-15 method. SCS was tested using a Vistech photographic chart. For WRT determination, pattern-masked words were presented successively at increasing target durations. The threshold was determined as the target duration at which 50% of the words were read. RESULTS: The mean number of errors in Color Discrimination and Spatial Contrast Sensitivity did not differ significantly among the three groups. WRT was significantly longer in the AD group (122.6 +/- 70.8 ms) in comparison with ENC group (53.8 +/- 15.9 ms) (p < 0.001). A WRT threshold limit of 85 msec correctly classified 11/12 ENC subjects and 10/13 AD subjects. Four of the 13 MCI subjects also exceeded this threshold and all four progressed to AD within 2 year follow-up. CONCLUSION: Word Reading Threshold determination discriminates mild AD subjects from ENC, and correlates with severity of cognitive impairment. It may have diagnostic and prognostic utility in early AD and MCI subjects.

Aged↗

PubMedDate not supplied

Visual retinocortical function in dementia of the Alzheimer type.

BACKGROUND: Some histological investigations have reported anomalies in the primary visual pathways of individuals with dementia of the Alzheimer type (DAT), while others have suggested that these visual structures are spared by the disease process. OBJECTIVES: This study was conducted to address this issue of substantial controversy. We determined in vivo whether DAT alters the functioning of the primary visual pathways by evaluating pattern-reversal electroretinograms (ERGs) and cortical visual evoked potentials (VEPs). METHODS: Twenty-seven individuals with mild to moderate DAT and 27 age- and sex-matched control subjects were included in the investigation. ERG and VEP recordings were obtained from all participants with the use of a clinical electrodiagnostic system. Stimulus conditions were biased towards a preferential response from the magnocellular and parvocellular subdivisions of the visual system. RESULTS: Amplitude and latency of the ERG were not affected by DAT. The VEP amplitude was not attenuated in DAT individuals, but there was a delay in the latency of the VEPs arising from both magnocellular and parvocellular streams of visual processing. CONCLUSION: Our results indicate that while the inner retina appears to be spared by the disease process, the visual function is altered upstream in the retinocortical visual pathways of individuals with DAT.

Aged↗

PubMedDate not supplied

Behavioral and electrical brain measures of semantic priming in patients with Alzheimer's disease: implications for access failure versus deterioration hypotheses.

This study investigated the nature of anomia and semantic memory deficits in patients with Alzheimer's disease (DAT). We measured reaction time (RT) and the N400 event-related brain potential (ERP) in a word-picture semantic priming paradigm for DAT patients and elderly controls. For patients, pictures were classified as a function of the individual's naming ability to determine whether naming deficits reflected a failure to access a picture's name or reflected a deterioration of its semantic representation. As expected, DAT patients had significantly poorer naming performance than controls. For successfully named pictures, robust RT and ERP priming effects were obtained in both groups. In DAT patients, priming for unnamed pictures was heterogeneous. The results are discussed in terms of current hypotheses of semantic memory deficits in DAT.

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