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PubMed2002

Chronically Impaired Frontal Lobe Function from Subclinical Epileptiform Discharges.

Subclinical epileptiform discharges (SEDs) are a common occurrence on electroencephalograms (EEGs). Their potential for acutely disrupting cognitive functions has been well documented, but detailed studies of cognitive performance by patients with chronic exposure to disruptive SEDs have been lacking and scant data have been available to guide treatment decisions or to assist in predicting recovery. We identified a patient with frequent frontotemporally (FT) predominant SEDs and monitored cognitive performance over time with periodic neuropsychological testing and EEGs. Over a 16-year period, Full Scale IQ rose 23 points and Verbal IQ rose 30 as SEDs were suppressed. Severity of impairment, reflected by the marked increase in cognitive performance over time, was not predicted by his appearance and performance on routine tests of cognitive functions in the clinic. Quantitating total SED duration per EEG provided an objective marker to track severity over time. The cumulative effects of chronic exposure to disruptive SEDs may create a sustained "cognitive burden" or encephalopathic state that persists even in the absence of ongoing discharges.

Journal Article↗

PubMed1998

Slower and more variable reaction times in schizophrenia: what do they signify?

Extensive research has demonstrated that schizophrenic subjects are slower than normal comparison subjects on a range of reaction-time tasks. Some investigators have also observed that schizophrenic patients exhibit larger intraindividual variability in reaction times when performing these tasks than do normal comparison subjects. This study, using a lexical decision choice reaction time (CRT) task, explored the relation of mean CRT and it intra-individual variability (CRT-SD) to psychiatric symptoms and to performance on executive-motor tasks in 26 medication-free schizophrenic out-patients and 17 normal comparison subjects. Schizophrenic subjects had both significantly slower and more variable CRTs which were unrelated to general intellectual abilities (IQ). Among schizophrenic subjects, both CRT and CRT-SD were significantly related to severity of psychotic symptoms, failure to maintain cognitive set, and poorer motor coordination and global functioning. After controlling for mean CRT, CRT-SD showed unique covariation with clinical symptoms (positive, disorganized and tension/hostility). Conversely, mean CRT showed unique covariation with the failure to maintain cognitive set and with stereotypic mannerisms, independent of CRT-SD. These results suggest that slower CRT and increased intra-individual variability in CRT, while not fully independent of one another, may reflect separate aspects of symptomatic and cognitive dysfunction in schizophrenia.

Adult↗

PubMed1998

Neuropsychological consequences of extreme weight loss and dietary restriction in patients with anorexia nervosa.

This study examined the effects of weight loss and nutritional status on the cognitive performance of patients with anorexia nervosa. The intellectual, memory, attentional, verbal fluency and visuospatial abilities of 34 females with anorexia were compared to that of 31 normal weight-for-height females. Group differences in anxiety and depression were found but neither variable was related to the cognitive performance of patients with anorexia. Moreover, nutritional status and weight loss bore little relationship to the cognitive scores of the patient group. Overall, patients with anorexia were found to be deficient in their ability to recall meaningful prose and visuospatial information. The failure to find many cognitive deficits in this sample may reflect the fact that few patients with anorexia exhibited frank nutritional deficiencies.

Adult↗

PubMed1999

Neuropsychological performance and cognitive olfactory event-related brain potentials in young and elderly adults.

The P3 event-related brain potential (ERP) reflects neuroelectric activity related to the speed of cognitive processing and allocation of attentional resources. The objective of the present study was to assess the relationship between the P3 and Slow Wave components of the olfactory event-related potential (OERP) with neuropsychological performance in young (n = 16) and elderly (n = 16) adults. OERPs were recorded monopolarly from midline electrode sites while subjects estimated the odor magnitude of each stimulus, eliciting highly reproducible P3s. Results showed that the late cognitive components (P3 amplitude, P3 latency and Slow Wave area) decline with age and that this decreased neuronal efficiency is associated with reductions in the neuropsychological performance indexed by the Trail Making Test and the California Verbal Learning Test.

Adult↗

PubMed2006

Education, cognitive test scores, and black-white differences in dementia risk.

OBJECTIVES: To compare dementia risks of elderly black and white subjects and to determine whether differences in education and cognitive test scores contribute to the inconsistency in reported differences between these groups. DESIGN: Longitudinal, 6-year follow-up. PARTICIPANTS: Two thousand seven hundred eighty-six older black and white subjects in the Cardiovascular Health Study. MEASUREMENTS: Age, education (>10 years vs < or =10 years), Modified Mini-Mental State Examination score (3MS, < or =85 vs >85). Potential confounders were sex, depression, apolipoprotein E4 genotype, vascular disease, and baseline magnetic resonance imaging changes. RESULTS: White subjects with low education and black subjects with high education had twice the risk of dementia of white subjects with high education (95% confidence interval (CI)=1.5-2.4 and 95% CI=1.4-2.7); black subjects with low education had five times the risk of dementia (95% CI=3.4-7.7). Likewise, for subjects with low 3MSE scores, black subjects had 6.7 times the risk of dementia (95% CI=4.7-9.7) and white subjects had 2.7 times the risk of dementia (95% CI=2.2-3.5) as white subjects with high 3MSE scores. Finally, in Cox models, there was no significant black-white difference in dementia risk after adjustment for all confounders and baseline 3MSE. CONCLUSION: Black race was associated with greater dementia risk even after adjustment for education and other potential confounders. This black-white difference in dementia risk was markedly attenuated after adjustment for baseline cognitive screening scores. The apparent race effect may reflect gaps in the quality of education or differences in the trajectory of impaired cognitive function experienced by the two groups. Future investigations might take these findings into consideration for the design of studies evaluating black-white differences in dementia risk.

Aged↗

PubMed2006

Dynamic sculpting of brain functional connectivity and mental rotation aptitude.

Changes in long-range synchronization are considered a key mechanism for the integration and segregation of cortical regions mediating cognitive processes. Such synchronization or functional connectivity is reflected in human electroencephalographic (EEG) coherence and in steady-state visually evoked potential (SSVEP) coherence. In this chapter, the relationship between cognitive proficiency in the mental rotation task (MRT) and functional connectivity reflected in SSVEP event-related partial coherence is described. The capacity to estimate changing levels of functional connectivity with a relatively high temporal resolution makes it possible to examine the relationship between functional connectivity at various points in time and aptitude. In the current study, the relationships between functional connectivity and two mental rotation aptitude measures, mental rotation speed and mental rotation accuracy, are described. We observed that functional connectivity was correlated with proficiency and that this correlation was both positive and negative for various regions and points in time. It is suggested that cognitive aptitude is related to the brain's capacity to enhance functional connectivity or communication between cortical regions that are relevant to the cognitive demands while attenuating irrelevant communication. This capacity is termed functional connectivity sculpting, and it is proposed that functional connectivity sculpting may constitute an important functional component of the neural substrate of learning and aptitude.

Brain↗

PubMed2002

The concept of vascular cognitive impairment.

Vascular dementia (VaD) is increasingly recognised to reflect an outmoded concept in that it identifies cases too late for preventive therapy to have an opportunity to prevent the development of dementia and uses a cognitive paradigm inappropriately based on Alzheimer's disease. A replacement is urgently required and a new concept, that of vascular cognitive impairment (VCI), has been proposed to meet this need. It is imperative that criteria for VCI are developed on the basis of knowledge and data rather than supposition and assumption, as was the case for VaD. This review details the state of knowledge that we have now reached concerning the fundamental points of severity and cognitive paradigm and also covers a number of other imaging-related essential points embracing atrophy, leukoaraiosis, infarct volume and infarct location. Finally, the increasingly important concept of mixed dementia (co-existent Alzheimer's disease and VCI) is discussed.

Aged↗

PubMed2005

Cost of Alzheimer's disease in a developing country setting.

PURPOSE: To evaluate the economic impact of AD in Denizli, Turkey. DESIGN AND METHODS: This observational study was conducted with 42 AD patients and their primary caregivers. During the initial interview, demographic data and medical histories were collected with questionnaires. For an observational period of 15 days, data on time spent for patient care were collected using standard forms. Calculations on direct cost (e.g. per day medication, outpatient physician visits during the last 3 months), indirect cost (e.g. time spent for care by caregiver for daily living (ADL) and instrumental activity of daily living (IADL)) were made by summing up and taking averages of the appropriate items. ANOVA, and linear regressions were the methods for comparisons. RESULTS: The primary caregivers of the patients mainly were their children and/or spouses. The maximum mean time spent (h/week) was 21.0 (17.5) for severely damaged cognition. The average annual cost per case was between $1,766 [95% Confidence Intervals (CI); 1.300-2.231] and $4,930 (95% CI; 3.3714-6.147). The amount of caregiver cost was the most significant item in the overall cost and it showed an increase with the declining cognitive function of patients. Daily medication cost reflected the same pattern. In contrast, cost of outpatient physician was the lowest among the patients with the worst cognition. CONCLUSIONS: These results suggest that recently AD has become a significant cost for developing countries. This pilot study gives an idea of the cost of AD in developing countries where determining the actual cost can be difficult.

Aged↗

PubMed2000

Exploring the cognitive basis of right-hemisphere pragmatic language disorders.

Despite considerable interest in the linguistic dimensions of right-hemisphere (RH) pragmatic language disorders, the cognitive bases for these are rarely examined. This study investigated two alternative explanations. First, RH pragmatic language disorders may reflect failure of the RH to synthesise incoming and preexisting information, verbal and visuospatial. In this case language and visuospatial performance should covary. Alternatively such disorders may reflect damage to executive control of all cognitive processing secondary to frontal system failure. In this case language and executive function would be associated. Further, in the former case, subjects should be insensitive to the plausibility of information, whereas in the latter they would be fixated by the literal meaning of information and therefore highly sensitive to plausibility. Eighteen patients with RH damage were compared to 20 matched controls on a range of language and neuropsychological tasks. Pragmatic performance was generally correlated to RH (visuospatial) function, not to executive function. Nonetheless RH patients were found to have problems ignoring plausibility. Thus the specific RH hypothesis described needs to be reconsidered.

Adult↗

PubMed1997

Frontotemporal dementia versus vascular dementia: differential features on mental status examination.

OBJECTIVE: After Alzheimer's disease, vascular dementia (VaD) and frontotemporal dementia (FTD) are among the most common dementing illnesses. FTD may have a neuropsychological profile similar to that of VaD, and patients with these dementias may be difficult to distinguish on clinical examination. The purpose of this study was to elucidate distinct cognitive profiles of a large group of FTD and VaD patients on a brief, clinical mental status examination. DESIGN: A comparison of 39 FTD patients and 39 VaD patients on a brief, clinical mental status examination. SETTING: A Dementia Research Center and affiliated, university hospitals. METHODS: The FTD patients were diagnosed by noncognitive clinical and neuroimaging criteria, and the VaD patients met NINDS-AIREN criteria for vascular dementia. The two dementia groups were comparable on three dementia assessment scales. MEASUREMENTS: The mental status measures included the neuropsychological battery from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), plus supplementation from the Neurobehavioral Cognitive Status Examination (NCSE) for cognitive areas not assessed by the CERAD). RESULTS: The FTD and VaD groups differed significantly on the mental status examination measures. FTD patients performed significantly better than the VaD patients on digit span and constructions, despite comparable performance by both groups on calculations. Although not statistically significant, the FTD group performed worse than the VaD group on verbal fluency and abstractions. These differences were not explained by group differences in age and education. CONCLUSION: These results suggest that cognitive differences between FTD and VaD groups reflect greater frontal pathology in contrast to relative sparing of posterior cortex and subcortical white matter in FTD. These cognitive differences as measured by a mental status examination may help distinguish between these two dementia syndromes.

Aged↗

PubMed2000

REM mentation in narcoleptics and normals: an empirical test of two neurocognitive theories.

This study tested the two main neurocognitive models of dreaming by using cognitive data elicited from REM sleep in normals and narcoleptics. The two models were the "activation-only" view which holds that, in the context of sleep, overall activation of the brain is sufficient for consciousness to proceed in the manner of dreaming (e.g., Antrobus, 1991; Foulkes, 1993; Vogel, 1978); and the Activation, Input source, Modulation (AIM model), which predicts that not only brain activation level but also neurochemical modulatory systems exert widespread effects upon dreaming (Hobson & McCarley, 1977; Hobson, Pace-Schott, & Stickgold, 2000). Mental activity was studied in nocturnal REM in 15 narcoleptics and 9 normal healthy persons and in REM at the onset of daytime naps and nighttime sleep (SOREM) in narcoleptics. The study was performed in the subjects' homes, using instrumental awakenings and ambulatory polysomnographic techniques, and focused upon visual vividness, mentation report length, improbable and discontinuous bizarre features, and reflective consciousness. Within each subject group, most cognitive variables tended to fluctuate in line with expected variations in circadian activation level. When comparing the cognitive variables between the two groups, reflective consciousness was clearly highest in narcoleptics, whereas improbabilities and discontinuities were lower, with mentation report length and visual vividness differing less between the groups. These findings are consistent with the AIM model of sleep mentation, but not with the activation-only model.

Adolescent↗

PubMed2006

Ziprasidone-induced cognitive enhancement in schizophrenia: specificity or pseudospecificity?

OBJECTIVE: Ziprasidone may improve cognition in schizophrenia; however, this could be related to clinical symptom improvement, reflecting "pseudospecificity". We tested the hypothesis that ziprasidone improves cognition in the absence of clinical improvement. METHODS: We conducted a 12-week, open-label study of ziprasidone in 10 schizophrenia patients who met non-response criteria (<20% reduction in BPRS scores over 12 weeks). We conducted comprehensive cognitive testing and assessed change from baseline to end of study. RESULTS: We detected significant improvement on three measures of episodic memory (p<0.01) in these clinically non-responsive patients. Trend-level improvements were noted on tests involving processing speed and executive function. CONCLUSIONS: These data suggest that ziprasidone has cognitive benefits unrelated to an influence on other disease parameters.

Adolescent↗

PubMed2001

Demographic, health, cognitive, and sensory variables as predictors of mortality in very old adults.

Cognitive and sensorimotor predictors of mortality were examined in the Australian Longitudinal Study of Ageing, controlling for demographic and health variables. A stratified random sample of 1,947 males and females aged 70 and older were interviewed, and 1,500 were assessed on measures of health, memory. verbal ability, processing speed, vision, hearing, and grip strength in 1992 and 1994. Analyses of incident rate ratios for mortality over 4- and 6-year periods were conducted using Cox hierarchical regression analyses. Results showed that poor performance on nearly all cognitive variables was associated with mortality, but many of these effects were explained by measures of self-rated health and disease. Significant decline in hearing and cognitive performance also predicted mortality as did incomplete data at Wave 1. Results suggest that poor cognitive performance and cognitive decline in very old adults reflect both biological aging and disease processes.

Aged↗

PubMed2003

Early brain injury in children: development and reorganization of cognitive function.

Children who sustain congenital or acquired brain injury typically experience a diffuse insult that impacts many areas of the brain. Yet research has only recently begun to examine the development of these children, who often provide excellent examples of the presence or absence of neural plasticity. Development and recovery after such injuries reflects both restoration and reorganization of cognitive functions. To understand these processes, research should focus on questions and assessment paradigms oriented toward the acquisition (rather than the recovery) of cognitive functions. Outcomes may appear similar across types of insults, even when the sources of difficulties and their neural correlates are different. Comparisons of outcomes involving intellectual functions, memory and learning, reading, and language/discourse in children who sustain congenital injury (spina bifida meningomyelocele) and acquired injury (traumatic brain injury) illustrate these principles and the value of research on diffuse brain injury in children.

Brain Injuries↗

PubMed1992

Alzheimer Disease Assessment Scale: a subtest analysis.

The Alzheimer Disease Assessment Scale (ADAS) was administered to 61 Alzheimer patients, 52 elderly controls, and 80 controls between age 7 and 54 years. The Alzheimer group was categorized into different severity levels of dementia based on MMSE scores: very mild (> or = 24), mild (> or = 20), moderate (10-19), and severe (0-9). All 11 ADAS Cognitive subtest scores for the mild, moderate, and severe dementia groups were statistically worse than the elderly control group. This was also the case for the very mild group, except for Naming, Commands, Constructional Praxis, and Ideational Praxis. In terms of magnitude of effect, memory and spontaneous language items were the earliest indicators on the ADAS, while praxis, commands, and naming items were only sensitive later in the course of the disorder. The best single indicators of progression throughout the severity continuum of dementia (i.e., from normal to severe) were the Orientation subtest, the ADAS Cognitive score, and the ADAS Total score. The ADAS Noncognitive subtests generally did not show the progression with increasing dementia that was evident on the ADAS Cognitive subtest. Differences in educational level had no statistically significant effects on any of the ADAS subtest scores, and age differences were few and small in magnitude. The differential rate of decline of the various ADAS subtests appears to reflect both the changing pattern of cognitive impairments as a function of severity of DAT and also to some extent the psychometric limitations of some of the subtests.

Aged↗

PubMed2006

Using imagery in cognitive-behavioral treatment for eating disorders: tackling the restrictive mode.

A restrictive thinking style in the eating disorders, often referred to as "anorexic thinking," is often resistant to cognitive-behavioral interventions, even when apparent motivation is relatively high. It is argued that this difficulty is due in part to the ingrained nature of such thinking patterns, regardless of diagnosis. Those patterns reflect the ego-syntonic element of the eating disorders, and manifest as difficulty for the patient in identifying and challenging negative automatic thoughts and maladaptive core beliefs. There is a need to develop cognitive techniques that allow the individual to identify maladaptive cognitions as reflecting their restrictive schema mode, rather than being the only way of thinking and seeing the world. This study describes the use of imagery to enable patients to distinguish the restrictive thoughts from other cognitive perspectives. The restrictive "mode" is presented as part of the individual's personality structure (drawing on cognitive-behavioral models of personality), rather than being an external entity. This technique is designed to facilitate conventional cognitive-behavioral therapy, freeing the patient to challenge her cognitions and to engage in behavioral experiments. We present case material to illustrate this technique and its use in conjunction with other cognitive-behavioral techniques. Future directions and potential limitations are also discussed.

Adult↗

PubMed2005

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex affects divided attention immediately after cessation of stimulation.

Transcranial magnetic stimulation has evolved into a powerful neuroscientific tool allowing to interfere transiently with specific brain functions. In addition, repetitive TMS (rTMS) has long-term effects (e.g. on mood), probably mediated by neurochemical alterations. While long-term safety of rTMS with regard to cognitive functioning is well established from trials exploring its therapeutic efficacy, little is known on whether rTMS can induce changes in cognitive functioning in a time window ranging from minutes to hours, a time in which neurochemical effects correlated with stimulation have been demonstrated. This study examined effects of rTMS on three measures of executive function in healthy subjects who received one single rTMS session (40 trains of 2 s duration 20 Hz stimuli) at the left dorsolateral prefrontal cortex (DLPFC). Compared to a sham condition one week apart, divided attention performance was significantly impaired about 30-60 min after rTMS, while Stroop-interference and performance in the Wisconsin Card Sorting Test was unaffected after rTMS. Repetitive TMS of the left DLPFC, at stimulation parameters used in therapeutic studies, does not lead to a clinically relevant impairment of executive function after stimulation. However, the significant effect on divided attention suggests that cognitive effects of rTMS are not limited to the of acute stimulation, and may possibly reflect known neurochemical alterations induced by rTMS. Sensitive cognitive measures may be useful to trace those short-term effects of rTMS non-invasively in humans.

Adult↗

PubMed2005

Involvement of sensorimotor, limbic, and associative basal ganglia domains in L-3,4-dihydroxyphenylalanine-induced dyskinesia.

Dyskinesia represents a debilitating complication of L-3,4-dihydroxyphenylalanine (L-dopa) therapy for Parkinson's disease. Such motor manifestations are attributed to pathological activity in the motor parts of basal ganglia. However, because consistent funneling of information takes place between the sensorimotor, limbic, and associative basal ganglia domains, we hypothesized that nonmotor domains play a role in these manifestations. Here we report the changes in 2-deoxyglucose (2-DG) accumulation in the sensorimotor, limbic, and associative domains of basal ganglia and thalamic nuclei of four groups of nonhuman primates: normal, parkinsonian, parkinsonian chronically treated with L-dopa without exhibiting dyskinesia, and parkinsonian chronically treated with L-dopa and exhibiting overt dyskinesia. Although nondyskinetic animals display a rather normalized metabolic activity, dyskinetic animals are distinguished by significant changes in 2-DG accumulation in limbic- and associative-related structures and not simply in sensorimotor-related ones, suggesting that dyskinesia is linked to a pathological processing of limbic and cognitive information. We propose that these metabolic changes reflect the underlying neural mechanisms of not simply motor dyskinesias but also affective, motivational, and cognitive disorders associated with long-term exposure to L-dopa.

Animals↗