Reliability and validity of the Delis-Kaplan Executive Function System: an update.
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Cognition Disorders↗
Biomedical subjects
Joel H Kramer
Publications and source records attributed to Joel H Kramer.
Hippocampal volume and retention in Alzheimer's disease.
This study tested the hypothesis that the hippocampus has a relatively specific role in retaining information over delays. Thirty-seven subjects with probable Alzheimer's disease were evaluated with a verbal memory task and structural MRI. Cortical gray matter but not hippocampal volume predicted immediate free recall. In contrast, hippocampal volume was the best predictor of how well information was retained over a delay, even after controlling for levels of immediate recall. Results suggest that the role of the hippocampus is relatively specific to the consolidation of new memories.
Aged↗
The role of perceptual bias in complex figure recall.
Several studies have demonstrated that constructional and organizational abilities affect how well visual stimuli are remembered. The purpose of the present study was to determine whether perceptual bias, independent of constructional ability, influenced visual memory performance. Participants were 118 normal adults who were administered the Rey-Osterrieth Complex Figure (ROCF) and a similarity judgement task requiring then to decide which of two hierarchically constructed comparison figures most resemble a standard figure. The initial steps of a multiple regression analysis indicated that delayed recall of the ROCF was directly related to copy accuracy, inversely related to age, and better in males than females. In the final step of the regression model, performance on the similarity judgement task also predicted ROCF recall, with a more global perceptual bias predicting better recall. Results indicate that even when copy accuracy and demographic variables are accounted for, components of visual perception influence how well visual stimuli are encoded and recalled. Findings are consistent with research correlating global processing and spatial ability, and suggest that in addition to copy ability and organization, visuoperceptual bias must be considered as a moderator variable when interpreting performance as a visual memory test.
Adult↗
Forgetting in dementia with and without subcortical lacunes.
Alzheimer's disease (AD) and subcortical ischemic vascular disease (SIVD) are common causes of dementia, often co-occur, and can present quite similarly, making differential diagnosis clinically challenging. This study tested the hypothesis that patients with SIVD retain information better than AD patients. Participants were 35 dementia patients with subcortical lacunes (SIVD group), 27 dementia patients without lacunar infarction (AD group), and 56 normal controls. Results indicated that despite comparable levels of initial acquisition, AD patients showed more rapid forgetting. Further analysis indicated that memory patterns within the SIVD group were heterogeneous, with some participants exhibiting rapid forgetting and some exhibiting good retention. SIVD participants with good retention showed a trend for greater executive impairments relative to SIVD participants with rapid forgetting and AD participants. Results suggest that rapid forgetting in SIVD may imply concomitant AD, whereas the dementia in patients with good retention may be purely vascular in origin. Three SIVD patients with rapid forgetting followed to autopsy all had AD pathology, further supporting the link between memory patterns and AD.
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Clinical and neuropsychological features in autopsy-defined vascular dementia.
Studies reporting that ischemic vascular dementia (IVD), compared to Alzheimer's disease (AD), is associated with relatively greater impairment of executive function and relatively preserved episodic memory raise the question of whether there is a distinctive neuropsychological profile of impairment associated with IVD and whether this might be useful in clinical diagnosis. However, prior reports are almost all based on clinically diagnosed cases, raising obvious issues of possible circularity and leaving unanswered questions of validity. Here we report on clinical and neuropsychological findings in 18 prospectively studied cases that had substantial pathology-defined cerebrovascular disease (CVD) at autopsy. Nine cases had minimal AD pathology, while the remainder had moderate or severe degrees of AD pathology. Cognitive status at last evaluation ranged from mild cognitive impairment to moderate dementia. Clinical features were quite variable; only 40% of cases with high CVD levels had elevated Hachinski Ischemia Scale scores and neither abrupt onset nor stepwise progression was found in most high CVD cases, even when AD changes were essentially absent. The presence of dementia was predictably related to the level of neurofibrillary pathology, but was not related to the severity of CVD. Neuropsychologists expert in the evaluation of dementia used a priori criteria to diagnose neuropsychological protocols (blind to all other data) from cases with pathology-informed diagnoses of AD, IVD, and mixed dementia. Sensitivity and specificity were both high for AD, sensitivity for detecting pure IVD was poor, and values were intermediate for detecting IVD irrespective of AD levels. A illustrative case example is included. We conclude that the profile of cognitive impairment in IVD is highly variable, but that in clinical settings neuropsychological readings may contribute to the differential diagnosis of dementia.
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Recognition of emotion in the frontal and temporal variants of frontotemporal dementia.
Recent studies have suggested that the frontal and temporal variants of frontotemporal dementia (fvFTD and tvFTD) are both associated with impairments in emotional processing. However, the degree and type of emotional processing deficits in the two syndromes have not been previously compared. We used the Florida Affect Battery to examine recognition of facial expressions of emotion in fvFTD and tvFTD patients who have no evidence of visual perceptual difficulties for faces. In general, both groups were impaired at recognizing emotions compared with age-matched controls. In tvFTD, this deficit was limited to emotions with a negative valence (sadness, anger, fear), while fvFTD patients showed impairment for positive valence (happiness) as well. These results suggest that damage to frontal lobe regions in FTD may lead to more profound impairment in recognition of emotion than when damage is more limited to the temporal lobe.
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Right and left medial orbitofrontal volumes show an opposite relationship to agreeableness in FTD.
Recent investigations of the neuroanatomy of complex social behaviors suggest that the underlying brain circuits involve multiple cortical and subcortical structures. The neuroanatomic origins of agreeableness have not yet been clearly elucidated. However, frontotemporal dementia (FTD) patients can evidence dramatic alterations in agreeableness arising from frontal and temporal lobe damage. Based on previous research, we hypothesized that agreeableness would be negatively correlated with left medial orbitofrontal cortex size and positively correlated with right amygdala volume. First-degree relatives of 27 FTD patients (diagnosed according to the Lund-Manchester criteria) were asked to fill out the NEO-Five Factor Inventory to assess the patients' current level of agreeableness, a construct comprised of the facets trust, straightforwardness, altruism, compliance, modesty, and tender-mindedness. These patients underwent T(1)-weighted MRI imaging, and gray matter volumes for right and left orbitofrontal lobes and amygdalas were derived via segmentation and region of interest tracing, normalizing for total intracranial volume. Regression analysis revealed that 38% of the variance in the NEO agreeableness score was predicted by a model in which right orbitofrontal volume (beta = 0.731) was positively correlated with agreeableness, and left orbitofrontal lobe volume (beta = -0.638) was negatively correlated with agreeableness (p < 0.01). Contrary to our hypothesis, amygdala volume did not significantly predict agreeableness. This finding partly replicates a previous study that used a different measure of social functioning, the Interpersonal Adjective Scale, to delineate a left frontal-right amygdala circuit for agreeableness. These data support the hypothesis that regulation of agreeableness arises from a balanced, mutually inhibitory circuit involving both hemispheres.
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Double dissociation of social functioning in frontotemporal dementia.
BACKGROUND: Efforts to characterize changes in social functioning in frontotemporal dementia (FTD) have failed to elicit clear dissociation between frontal and temporal variants of the disease based on behavioral measures. METHODS: This study obtained premorbid and current first-degree relative ratings using an established measure of interpersonal functioning, the Interpersonal Adjectives Scales, to measure personality change in 16 patients with frontal variant (FLV) and 13 with temporal variant (TLV) FTD, and in a control group of 16 patients with AD. RESULTS: All three groups showed significant change over time in multiple domains, including increased introversion (FG) and submissiveness (HI). However, patients with both FTD subtypes evidenced significantly greater increases in overall interpersonal pathology vector length [VL] than did patients with AD, who remained within the normal range on all scores. Patients with FLV showed a 2 SD increase in submissiveness (HI), but their cold-heartedness (DE) change scores were not significantly different from those of patients with AD. Conversely, the TLV cold-heartedness (DE) score increased 2 SD compared to minimal change for the AD and FLV groups, yet change in submissiveness (HI) did not differentiate between AD and TLV groups. CONCLUSIONS: The Interpersonal Adjectives Scales differentiated both FTD groups from patients with AD on the basis of both degree and direction of personality change. Also, the two subtypes of FTD showed distinctly different patterns of change in social functioning: patients with temporal variant shifted toward severe interpersonal coldness with mild loss of dominance, whereas patients with frontal variant showed the opposite pattern.
Alzheimer Disease↗
Challenging the clinical utility of the 14-3-3 protein for the diagnosis of sporadic Creutzfeldt-Jakob disease.
BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and fatal neurodegenerative disorder for which there is no noninvasive and disease-specific test for premortem diagnosis. Previous studies have suggested that, in the proper clinical context, the 14-3-3 protein in cerebrospinal fluid is a reliable marker for sporadic CJD. OBJECTIVE: To assess the sensitivity of the cerebrospinal fluid 14-3-3 protein test among patients with definite sporadic CJD. DESIGN AND SETTING: We reviewed cases of sporadic CJD referred to our institution that were ultimately proved by pathological examination and on which cerebrospinal fluid 14-3-3 testing had been performed. PARTICIPANTS: Patients with CJD referred to our institution for clinical and/or pathological evaluation (biopsy- or autopsy-confirmed diagnosis) from January 1, 1998, through July 15, 2002, and on whom 14-3-3 testing had been performed. Thirty-two such patients with definite sporadic CJD were identified. Main Outcome Measure The 14-3-3 test results, from various laboratories, in these 32 patients. RESULTS: Seventeen of the 32 patients had a positive result for the 14-3-3 test, yielding a sensitivity of only 53%. A positive 14-3-3 result was significantly correlated with a shorter time between disease onset and the lumbar puncture for the 14-3-3 test. CONCLUSIONS: Testing for the 14-3-3 protein is only modestly sensitive to sporadic CJD, and we caution against ruling out a diagnosis of the disease on the basis of a negative 14-3-3 result.
14-3-3 Proteins↗
Age and gender interactions on verbal memory performance.
Age and gender effects on verbal episodic memory are well established. However, the possibility of interactions between age and gender has been raised by studies linking estrogen and verbal memory performance, and by research suggesting gender differences in age-related cortical atrophy. We evaluated whether age by gender interactions in verbal memory were present. Subjects within three years of the median age of menopause were excluded from a large cohort of normal subjects, resulting in a younger sample (16-47 years) of 288 men and 285 women, and an older sample (55-89 years) of 201 men and 245 women. All subjects were administered the CVLT-2, a multiple-trial list-learning task. Verbal memory was negatively correlated with age for younger men, older men, and older women, but not for younger women. Multivariate analyses indicated age by gender interactions on memory for the younger group but not the older group. Results indicate that verbal memory declines with age for younger men but not younger women, whereas both older men and older women show age-related declines. These findings are consistent with hypotheses linking estrogen and verbal memory performance, and with imaging data suggesting that age-related hippocampal atrophy is found in younger men but not younger women. The role of estrogen on cognition in normal aging warrants further study.
Adolescent↗
Psychometrically matched measures of global cognition, memory, and executive function for assessment of cognitive decline in older persons.
Item response theory methods were used to derive psychometrically sophisticated measures of global cognition, memory, and executive function. Goals were that these measures (a) could be derived from commonly used neuropsychological tests, (b) would have linear measurement properties, and (c) would be psychometrically matched. Scale development was based on a sample of 400 older individuals with cognitive function ranging from normal to demented. Scales were reasonably matched with linear measurement over an ability range relevant to many important clinical applications. Cognitively normal, mild impairment, and dementia participant groups differed on baseline measures and rate of decline. Association of measures with quantitative structural magnetic resonance imaging variables followed expected patterns. This approach to scale development may have applications for other neuropsychological assessment problems.
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Distinctive neuropsychological patterns in frontotemporal dementia, semantic dementia, and Alzheimer disease.
OBJECTIVE: To assess the ability of a brief neuropsychological bedside screening battery to discriminate between Alzheimer disease, frontotemporal dementia, and semantic dementia. METHODS: Subjects were 21 patients with frontotemporal dementia, 14 patients with semantic dementia, and 30 patients with Alzheimer disease comparable in terms of Mini Mental Status Examination score, age, and education. Frontotemporal dementia and semantic dementia diagnoses were made clinically using the consensus criteria of Neary et al. 1 Subjects were administered a brief neuropsychological screening assessing episodic memory, working memory, executive function, naming, spatial ability, abstract reasoning, and calculations. RESULTS: Both the Alzheimer disease and semantic dementia groups were significantly impaired relative to the frontotemporal dementia group on verbal memory, whereas only the Alzheimer disease group was impaired on visual memory. Frontotemporal dementia patients performed significantly worse on backward digit span and made significantly more executive errors than Alzheimer disease and semantic dementia patients. Semantic dementia patients were more impaired than Alzheimer disease and frontotemporal dementia patients on confrontation naming. Discriminant function analyses identified the 5 most discriminating variables that correctly classified 89.2% of cases. CONCLUSIONS: Frontotemporal dementia, semantic dementia, and Alzheimer disease are associated with distinct neuropsychological profiles that classify these dementia syndromes with considerable success. The neuropsychological profiles highlight the distinctiveness between the 3 syndromes, are consistent with the known loci of neuropathology in these conditions, and can potentially serve as an adjunct to the current clinical criteria.
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Very early-onset familial Alzheimer's disease: a novel presenilin 1 mutation.
BACKGROUND: Early-onset familial Alzheimer's disease (EOFAD) is linked to mutations in three autosomal dominant genes: PS1, PS2 and APP. The clinical presentation and age of onset of mutations is variable. OBJECTIVES: The aim of this report is to describe a novel PS1 mutation believed to be causal for a very early onset of AD. METHODS: This is a case history using information from medical records, relative interviews and genetic testing results to describe the pre-clinical prodrome and clinical course of a patient with EOFAD. RESULTS: A previously undescribed G206V mutation in PS1 was found in the proband. CONCLUSION: The G206V mutation in PS1 is probably causal of a case of EOFAD with significant premorbid features.
Adult↗
Emotion comprehension in the temporal variant of frontotemporal dementia.
Frontotemporal dementia (FTD) is a neurodegenerative disease characterized by behavioural disorders that suggest abnormalities of emotional processing. Patients with the temporal variant of FTD (tvFTD) are particularly at risk for developing deficits in emotional processing secondary to atrophy in the amygdala, anterior temporal cortex (ATC) and orbital frontal cortex (OFC), structures that are components of the brain's emotional processing systems. In addition, previous studies have suggested that predominantly right, as opposed to left temporal atrophy is more likely to be associated with behavioural and emotional impairments in tvFTD. However, emotional processing has never been assessed directly in this group. We examined one aspect of emotional processing, namely the comprehension of facial expressions of emotion (emotional comprehension) in nine individuals with tvFTD, and correlated performance on this measure with atrophy (as measured from T(1)-weighted MRI scans by region of interest analysis) in the amygdala, ATC and OFC. Compared with age-matched controls, the tvFTD group was impaired in emotional comprehension, with more severe impairment for emotions with negative valence, including sadness, anger and fear, than for happiness. Emotional comprehension was correlated with atrophy in the right amygdala and the right OFC, and not with atrophy in other structures. When individual profiles of amygdala atrophy were examined across patients and compared with control values, right amygdala atrophy was always accompanied by left amygdala atrophy, whereas patients with volume loss in the left amygdala could have normal or decreased right amygdala volumes. Thus, emotional comprehension appeared to be most impaired when bilateral amygdala atrophy was present, and was not associated with the degree of left amygdala atrophy. Our data indicate that tvFTD is associated with impairments in emotional processing that may underlie some behavioural problems in this disorder, and that the emergence of such deficits depends on the specific pattern of anatomical injury. These results have implications both for the clinical presentation in tvFTD patients and for the study of the neuroanatomical basis of emotion.
Aged↗
Cognitive functioning in children with sickle cell disease: a meta-analysis.
OBJECTIVE: To establish whether sickle cell disease (SCD) affects cognitive functioning in children with no evidence of cerebral infarction. METHODS: We conducted a meta-analysis of studies of cognition in SCD to determine the size of any statistical difference between children with SCD and controls. Methodological factors were evaluated according to the size and frequency of group differences. RESULTS: There were small but reliable decrements in cognitive functioning on IQ measures (4.3-point difference overall). The most methodologically rigorous studies showed a highly similar pattern. Sampling issues associated with the effect size for IQ were identified. Measures of specific abilities appear more sensitive than IQ scores to cognitive decrements in SCD. CONCLUSIONS: SCD is associated with cognitive effects even in the absence of cerebral infarction. The causes of this cognitive decrement may include direct effects of SCD on brain function or indirect effects of chronic illness.
Adolescent↗
Oxygen reverses deficits of cognitive function and memory and increased heart rate induced by acute severe isovolemic anemia.
BACKGROUND: Erythrocytes are transfused to improve oxygen delivery and prevent or treat inadequate oxygenation of tissues. Acute isovolemic anemia subtly slows human data processing and degrades memory, increases heart rate, and decreases self-assessed energy level. Erythrocyte transfusion is efficacious in reversing these effects of acute anemia. We tested the hypothesis that increasing arterial oxygen pressure (Pao2) to 350 mmHg or greater would supply sufficient oxygen to be equivalent to augmenting hemoglobin concentration by 2-3 g/dl and thus reverse the effects of acute anemia. METHODS: Thirty-one healthy volunteers, aged 28 +/- 4 yr (mean +/- SD), were tested with verbal memory and standard, computerized neuropsychologic tests before and twice after acute isovolemic reduction of their hemoglobin concentration to 5.7 +/- 0.3 g/dl. Two sets of tests were performed in randomized order at the lower hemoglobin concentration: with the volunteer breathing room air or oxygen. The subject and those administering the tests and recording the results were unaware which gas was administered. As an additional control for duration of the experiment, 10 of these volunteers also completed the same tests on a separate day, without alteration of hemoglobin concentration, at times of the day similar to those on the experimental day. Heart rate, mean arterial blood pressure, and self-assessed sense of energy were recorded at the time of each test. RESULTS: Reaction time for digit-symbol substitution test increased, delayed memory was degraded, mean arterial pressure and energy level decreased, and heart rate increased at a hemoglobin concentration of 5.7 g/dl (all P < 0.05). Increasing Pao2 to 406 +/- 47 mmHg reversed the digit-symbol substitution test result and the delayed memory changes to values not different from those at the baseline hemoglobin concentration of 12.7 +/- 1.0 g/dl, and decreased heart rate (P < 0.05). However, mean arterial pressure and energy level changes were not altered with increased Pao2 during acute anemia. CONCLUSION: The authors confirmed that acute isovolemic anemia subtly slows human reaction time, degrades memory, increases heart rate, and decreases energy level. The findings of this study support the hypothesis that increasing Pao2 to 350 mmHg or greater by breathing oxygen reverses all of these effects of acute anemia except for decreased energy.
Acute Disease↗
Anthocyanosides of Vaccinium myrtillus (bilberry) for night vision--a systematic review of placebo-controlled trials.
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Anthocyanins↗
Effects of Alzheimer disease on fronto-parietal brain N-acetyl aspartate and myo-inositol using magnetic resonance spectroscopic imaging.
Previous magnetic resonance (MR) spectroscopy studies of Alzheimer disease (AD) reporting reduced N-acetyl aspartate (NAA) and increased myo-Inositol (mI) used single voxel techniques, which have limited ability to assess the regional distribution of the metabolite abnormalities. The objective of this study was to determine the regional distribution of NAA and mI alterations in AD by using MR spectroscopic imaging. Fourteen patients with AD and 22 cognitively normal elderly were studied using structural MR imaging and MR spectroscopic imaging. Changes of NAA, mI, and various metabolite ratios were measured in frontal and parietal lobe gray matter (GM) and white matter. This study found: (1) when compared with cognitively normal subjects, AD patients had increased mI and mI/creatine (Cr) ratios primarily in parietal lobe GM, whereas frontal lobe GM and white matter were spared; (2) in the same region where mI was increased, AD patients had also decreased NAA and NAA/Cr ratios, replicating previous findings; (3) however, increased mI or mI/Cr ratios did not correlate with decreased NAA or NAA/Cr ratios; and (4) using mI/Cr and NAA/Cr together improved sensitivity and specificity to AD from control as compared with NAA/Cr alone. In conclusion, decreased NAA and increased mI in AD are primarily localized in parietal lobe GM regions. However, the NAA and mI changes are not correlated with each other, suggesting that they represent different processes that might help staging of AD.
Aged↗