Electrophysiological study of working memory in mild cognitive impairment patients.
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Analysis of Variance↗
Biomedical subjects
H Chertkow
Publications and source records attributed to H Chertkow.
The semantic category effect increases with worsening anomia in Alzheimer's type dementia.
A large number of patients (n=72) with probable Alzheimer's type dementia (DAT) and mild cognitive impairment (MCI) carried out a picture naming task which comprised stimuli from biological and nonbiological categories. The results were stratified into five ranges of overall naming ability. Every group except those with scores within the range of elderly normal individuals demonstrated better nonbiological naming than biological naming, an effect which increased with worsening impairment. In general, patients diagnosed with other dementia (n=15) did not fit well within the pattern of the DAT/MCI participants, except those known to have a significant semantic impairment. A category effect favoring nonbiological items appears to be robust and produce a predictable pattern across progressive levels of impairment in AD.
Aged↗
Dissociable brain regions process object meaning and object structure during picture naming.
Although imaging studies have indicated that the fusiform gyrus is important in tasks of picture naming, whether this region encodes an object's structure or its meaning is not clear. We used positron emission tomography to examine cerebral blood flow (CBF) changes in response to a picture naming task that varied on two dimensions: familiarity (or difficulty: hard vs easy) and category (tools vs animals). Results show that although familiarity effects are present in the frontal and left lateral posterior temporal cortex, they are absent from the fusiform gyrus. This provides strong evidence that the processing carried out in the fusiform gyrus relates to an object's structure, not to its meaning, and that the left posterior middle temporal gyrus instantiates in part the semantic network that represents the object's meaning.
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The impact of semantic impairment on word stem completion in Alzheimer's disease.
Both the extent of semantic memory impairment and the level of processing attained during encoding might constitute critical factors in determining the amount of word-stem completion (WSC) priming encountered in Alzheimer's disease (AD) subjects. We investigated the impact of varying encoding level in AD and elderly normal subjects, using a set of stimuli ranked as "intact" or "degraded" in terms of each subject's semantic knowledge on probe questions. For both shallow and deep encoding conditions, overall priming in the two subject groups was equivalent. However, for the deep encoding condition, consisting of a semantic judgment task performed on each target word, the priming effect noted in AD subjects was significantly smaller for semantically degraded items than for semantically intact items. Results indicate that the degree of semantic impairment represents one important variable affecting the amount of WSC priming which results when deep encoding procedures are used at study.
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Assessment of suspected dementia.
At the Second Canadian Consensus Conference on Dementia (CCCD) (February, 1998), a group of neurologists, geriatricians, and psychiatrists met to consider guidelines for evaluation of dementia in Canada. This review paper formed a background paper for their discussion of dementia diagnosis. These experts from across the country concluded that diagnosis of suspected dementia cases continued to rest on skilled clinical assessment. Mental status exam, preferably in some quantifiable form, has become an essential part of the assessment. Selected laboratory tests are advisable in all cases (CBC, TSH, electrolytes, calcium, and glucose), but the CCCD continued to advise that CT scanning was mandatory only in selected cases where clinical findings pointed to another possibility besides Alzheimer's disease. The growing list of other diagnostic measures with potential usefulness in diagnosis of Alzheimer's disease or dementia in general was reviewed, but the evidence was judged as insufficient to support routine use of these tests by physicians. As new treatments for Alzheimer's disease become available, neurologists face new diagnostic challenges--differentiating Mild Cognitive Impairment, Frontotemporal dementias and Mixed dementias, and Lewy Body Dementia. Guidelines to aid in differential diagnosis are presented.
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Recommendations of the Canadian Consensus Conference on Dementia--dissemination, implementation, and evaluation of impact.
BACKGROUND: Subsequent to the development of consensus statements on a clinical topic, it is vital to establish a plan for dissemination, implementation and evaluation of impact. Consensus statements can be used for both guiding continuing medical education (CME) and producing clinical practice guidelines (CPGs). Insufficient attention to dissemination can lead to a failure to change physician behaviour and improve patient outcomes. METHODS: A plan to disseminate the conclusions of the Canadian Consensus Conference on Dementia (CCCD) was developed. This plan was based on a literature review of CME and CPGs. A Medline search was performed on the dissemination and evaluation of the 1989 Canadian Consensus Conference on the Assessment of Dementia (CCCAD) and other published guides for physicians on dementia care. CCCD dissemination that has occurred to date (June, 2000) was reviewed in this paper. RESULTS: Lectures and unsolicited printed material are weak forms of CME. Small-group interactive CME that provides practice opportunities appears to be the most effective way to change physician behaviour. The ability of CPGs to change physician behaviour is uncertain. It appears that inadequate attention has been placed on CPG dissemination and implementation. The CCCAD had a modest impact on clinical practice in Canada. While dissemination of the conclusions of the CCCD has taken place, evaluation of the impact of the CCCD has yet to be done. Local initiatives utilizing the conclusions of the CCCD are on-going. CONCLUSIONS: Further work is needed on how to optimize the impact of consensus statements and CPGs. While dissemination of the CCCD has occurred, it is currently unknown whether it has led to any change in physician practices.
Canada↗
An evaluation of the retinal nerve fiber layer thickness by scanning laser polarimetry in individuals with dementia of the Alzheimer type.
PURPOSE: To determine, using scanning laser polarimetry, whether or not the retinal nerve fiber layer (RNFL) is altered in dementia of the Alzheimer type (DAT). METHODS: Thirty individuals with mild to moderate DAT and 30 healthy age-matched controls participated in the study. Fundus images were acquired with a Nerve Fiber Analyzer. RNFL thickness measurements were obtained under an ellipse located 1.75 disc diameter from the optic nerve head (ONH) center. RESULTS: No differences in RNFL thickness were observed between DAT and healthy subjects. The regional distribution of RNFL thickness was similar between the two test groups, with the RNFL being thickest in the superior and inferior retinal segments relative to the nasal and temporal regions. CONCLUSIONS: Our data indicate that the RNFL is not altered in DAT, at least in the earlier stages of the disease.
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The spectrum of category effects in object and action knowledge in dementia of the Alzheimer's type.
The validity and origin of category effects in the anomia demonstrated by individuals with dementia of the Alzheimer's type (DAT) remains controversial. Twenty DAT subjects were tested with picture naming and semantic association judgment tests. Picture and word stimuli were drawn from biological, nonbiological, and actions-verbs categories, all of equal difficulty and previously normed on elderly controls. DAT subjects made significantly more naming and semantic judgment errors in the biological category than in the nonbiological category. They were relatively more accurate in naming and making judgments for actions-verbs when presented as words or as 5-s animations. When line drawings of actions were shown for naming, performance deteriorated significantly. Converging results from these 2 tasks provide strong evidence for a semantic memory impairment preferentially affecting biological items to a greater extent than nonbiological items or action verbs in DAT.
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Evaluation of heme oxygenase-1 as a systemic biological marker of sporadic AD.
BACKGROUND: Heme oxygenase-1 (HO-1) is a 32-kDa stress protein that catalyzes the degradation of heme to biliverdin. HO-1 immunoreactivity is greatly increased in neurons and astrocytes of the hippocampus and cerebral cortex of individuals with AD and colocalizes to senile plaques and neurofibrillary tangles. METHODS: We investigated whether systemic HO-1 regulation is also deranged in AD patients and whether blood HO-1 measurements provide a peripheral biomarker of the disease. Plasma HO-1 protein levels were measured by competitive ELISA and lymphocyte HO-1 mRNA levels were determined by Northern analysis in patients with early probable sporadic AD, normal elderly controls (NEC), normal younger controls, individuals with age-associated cognitive decline (AACD) not meeting AD criteria, and patients with non-Alzheimer dementia, nondementing neurologic illness, and chronic medical disorders. CSF HO-1 protein concentrations were also determined by ELISA in pathologically confirmed AD and control cases. RESULTS: Mean plasma HO-1 protein concentrations were significantly lower in AD patients (0.85 +/- 0.14 microg/mL) compared with NEC (1.77 +/- 0.34 microg/mL; p < 0.05) and control patients. The AACD group exhibited plasma HO-1 concentrations (1.06 +/- 0.33 microg/mL) intermediate between, but not different from, those of the AD patients and NEC. Lymphocyte HO-1 mRNA levels were lower in the AD cohort relative to NEC (p < 0.001) and individuals with AACD, non-Alzheimer dementia, nondementing neurologic illness, and chronic medical conditions. Lymphocyte HO-1 mRNA levels were also lower in the AACD group relative to NEC (p < 0.05). In comparison with all groups excluding AACD, the sensitivity and specificity of lymphocyte HO-1 mRNA measurement for diagnosis of early sporadic AD are 88% and 75%. Mean CSF HO-1 protein concentrations were lower (p < 0.01) in AD cases (19.07 ng/mL) relative to control values (32.48 ng/mL). CONCLUSIONS: Plasma and CSF HO-1 protein and lymphocyte HO-1 mRNA levels are decreased in subjects with sporadic AD. Quantitative assay for lymphocyte HO-1 mRNA expression may serve as a useful biologic marker in early sporadic AD.
Adult↗
Word priming without awareness: A new approach to circumvent explicit memory contamination.
A major methodological limitation arising in the experimental study of implicit memory is that tasks that are characterized as implicit memory tests can be seriously contaminated by the use of covert explicit memory strategies. Given the evidence indicating that brief presentation of words (below the awareness threshold of subjects) can produce semantic priming, we wondered whether rapid visual presentation of primed words might provide an avenue to produce word priming without explicit memory contamination. Normal subjects were tested for word priming on a speeded category membership decision task. Explicit or implicit encoding procedures were used in four different experiments. Results demonstrated that brief presentation of words can indeed offer a means of producing word priming in absence of explicit recognition or recall of the primed words presented during the study phase. They also showed that such priming is equivalent in degree to the priming measured when using either a conventional implicit memory design or an explicit encoding procedure prior to the study of the primes.
Adolescent↗
Object identification deficits in dementia of the Alzheimer type: combined effects of semantic and visual proximity.
Identification deficits in dementia of the Alzheimer Type (DAT) often target specific classes of objects, sparing others. Using line drawings to uncover the etiology of such category-specific deficits may be untenable because the underlying shape primitives used to differentiate one line drawing from another are unspecified, and object form is yoked to object meaning. We used computer generated stimuli with empirically specifiable properties in a paradigm that decoupled form and meaning. In Experiment 1 visually similar or distinct blobs were paired with semantically close or disparate labels, and participants attempted to learn these pairings. By having the same blobs stand for semantically close and disparate objects and looking at shape-label confusion rates for each type of set, form and meaning were independently assessed. Overall, visual similarity of shapes and semantic similarity of labels each exacerbated object confusions. For controls, the effects were small but significant. For DAT patients more substantial visual and semantic proximity effects were obtained. Experiment 2 demonstrated that even small changes in semantic proximity could effect significant changes in DAT task performance. Labeling 3 blobs with "lion," "tiger," and "leopard" significantly elevated DAT confusion rates compared to exactly the same blobs labeled with "lion," "tiger," and "zebra." In conclusion both visual similarity and semantic proximity contributed to the identification errors of DAT patients.
Aged↗
Dementia assessment and CAT scans in primary care.
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Aged↗
The neural substrate of picture naming.
A PET study of 10 normal males was carried out using the bolus H215O intravenous injection technique to examine the effects of picture naming and semantic judgment on blood flow. In a series of conditions, subjects (1) passively viewed flashing plus signs, (2) noted the occurrence of abstract patterns, (3) named animal pictures, or (4) carried out a semantic judgment on animal pictures. Anticipatory scans were carried out after the subjects were presented with the instructions but before they began the cognitive task, as they were passively viewing plus signs. Our results serve to clarify a number of current controversies regarding the neural substrate of picture naming. The results indicate that the fusiform gyrus is unlikely to be the region where low-level perceptual processing such as shape analysis is undertaken. In fact, our evidence suggests that activation of the fusiform gyrus is most likely related to visual perceptual semantic processing. In addition, the inferior/middle frontal lobe activity observed while performing the picture naming and semantic judgment tasks does not appear to be due to the effects of anticipation or preparation. Furthermore, there appears to be a set of regions (a semantic network) that becomes activated regardless of whether the subjects perform a picture naming or semantic judgment task. Finally, picture naming of animals did not activate either parietal regions or anterior inferior left temporal regions, regardless of what subtraction baseline was used.
Adult↗
Lack of prognostic significance of SPECT abnormalities in non-demented elderly subjects with memory loss.
OBJECTIVE: To determine if hypoperfusion abnormalities on single photon emission computed tomography (SPECT) are associated with poorer cognitive function at baseline or increased risk of decline in cognitive function and progression to dementia in memory-impaired but non-demented elderly subjects meeting the criteria for aging associated cognitive decline (AACD). DESIGN: Cross sectional study of 36 AACD subjects comparing hexamethyl propylene-amine oxime (HMPAO) SPECT results rated by visual inspection with base line cognitive functioning. Prospective study of these AACD subjects with clinical and neuropsychological follow-up over 35 months. SETTING: The memory clinic and nuclear medicine unit of a university teaching hospital. SUBJECTS: Thirty-six subjects meeting the criteria for AACD recruited from patients seen on a physician referral basis. MAIN OUTCOME MEASURES: 1) Baseline cognitive function as measured by the Mini Mental State Examination (MMSE), Boston naming, Logical Memory I subtest of the WAIS-R, and verbal fluency, correlated with SPECT status. 2) Decline in cognitive function as measured by clinical exam and the MMSE, with progression to dementia on follow-up being correlated with SPECT status at baseline. RESULTS: 18 of the 36 subjects progressed to dementia (probable Alzheimer's Disease) over follow-up. No correlation was found between the presence or absence of SPECT abnormality and MMSE or other cognitive measures. There was no correlation between the presence or absence of SPECT abnormality at initial examination, and cognitive decline according to the MMSE, or with the occurrence of clinical dementia on follow-up. CONCLUSIONS: We conclude that SPECT abnormalities assessed by visual inspection do not correlate with severity of impairment in AACD individuals, and are not useful in predicting progression to dementia in AACD subjects.
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Prevalence of potentially reversible dementias and actual reversibility in a memory clinic cohort.
BACKGROUND: Although clinics for the evaluation of cognitive dysfunction have typically emphasized the detection and treatment of the reversible causes of dementia, it remains unclear whether the treatment of such causes results in reversal of the dementia. Therefore, the appropriate work-up for dementia is in dispute. METHODS: A chart review was performed with records from an urban tertiary care referral-based memory clinic. The records for 196 patients with dementia or suspected dementia, seen between October 1991 and December 1993, were examined to determine the prevalence of potentially reversible dementias and whether the cognitive dysfunction improved or resolved after treatment. Data abstracted from the medical charts included demographic information, medication use, presence of depression, and results of neuropsychological tests, blood work and neuroimaging. The clinical diagnosis, the response to treatment, if applicable, and the outcome (mean follow-up period 16 months) were analysed. The recommendations of the 1989 Canadian Consensus Conference on the Assessment of Dementia (CCCAD) on the use of CT were retrospectively applied in each case. RESULTS: Of the 196 patients, 45 (23.0%) had a potentially reversible condition identified by history, physical examination, blood testing or CT; in only 7 (3.6% of the total) did treatment result in improvement or resolution of the dementia. These 7 patients had higher results for the Mini-Mental State examination (mean result 26) and exhibited only mild cognitive deficits. Potentially reversible lesions were found in the CT scans of 6 (3.1%) patients: 4 had normal-pressure hydrocephalus and 2 had a brain tumour. If the CCCAD recommendations had been followed, CT would have been performed in 76 (38.8%) of the patients, and 1 of the 6 patients with a lesion would have been missed. INTERPRETATION: Both potential and actual reversibility of dementia was low in these memory clinic patients. The patients whose condition improved with intervention had early and milder cognitive deficits, which suggests that thorough evaluation of early memory loss is warranted.
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A role for the hippocampal formation in implicit memory: a 3-D PET study.
The apparent preservation of word priming effects in amnesia has been interpreted as supporting the view that implicit memory depends on brain systems that are independent of mesial temporal lobe structures which are in part responsible for explicit memory disorders. Nevertheless, a number of studies have demonstrated word priming deficits in amnesic patients relatively to normal subjects, suggesting that such structures may also be involved in implicit memory. To determine whether one such structure, the hippocampal formation, is a component of the brain system subserving word priming, a 3-D PET study was carried out in 13 normal individuals. Encoding was carried out using the brief multiple presentation technique, a procedure that allows one to effectively circumvent contamination of implicit memory tasks by explicit memory strategies. Results revealed that word priming was indeed associated with an activation of the right hippocampal formation. This finding of an hippocampal involvement in word priming calls into question the notion of absolute dissociability between the brain systems underlying performance on various explicit and implicit memory tasks.
Adolescent↗
Revision of dementia guidelines.
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Dementia↗