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PubMed1998

The cerebellar cognitive affective syndrome.

Anatomical, physiological and functional neuroimaging studies suggest that the cerebellum participates in the organization of higher order function, but there are very few descriptions of clinically relevant cases that address this possibility. We performed neurological examinations, bedside mental state tests, neuropsychological studies and anatomical neuroimaging on 20 patients with diseases confined to the cerebellum, and evaluated the nature and severity of the changes in neurological and mental function. Behavioural changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis, and in some cases they were the most noticeable aspects of the presentation. These changes were characterized by: impairment of executive functions such as planning, set-shifting, verbal fluency, abstract reasoning and working memory; difficulties with spatial cognition including visual-spatial organization and memory; personality change with blunting of affect or disinhibited and inappropriate behaviour; and language deficits including agrammatism and dysprosodia. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. We have called this newly defined clinical entity the 'cerebellar cognitive affective syndrome'. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits that link prefrontal, posterior parietal, superior temporal and limbic cortices with the cerebellum.

Adult↗

PubMed2002

A developmental approach to understanding Fragile X syndrome in females.

The psychological phenotype of females with fragile X syndrome (FraX) is discussed, focusing primarily on empirical findings over the past decade and on studies of probands with the full mutation (FM). A developmental approach is used to help characterize specific patterns of cognitive, neuropsychological, social, emotional, and behavioral functioning across the lifespan of females with FraX. Approximately half of females with the syndrome present with cognitive abilities that fall in the borderline to mentally retarded range, and the remaining females with average intellectual functioning may experience relative deficits in math achievement and problems with attention and executive functioning. Reports of socio-emotional functioning are somewhat inconsistent, due in part, perhaps, to methodological differences in study design. To date, much of what we understand about the psychological phenotype of FraX is based on cross-sectional studies of girls and women with the disorder. Symptoms associated with shyness, and social anxiety and avoidance have been reported in some school-age, adolescent, and adult females with FraX. Only recently have efforts begun to identify the developmental trajectory of FraX in infants and toddlers. There is a void of information specific to these developmental periods. Identifying key deficits in cognitive and socio-emotional functioning has important implications for early detection and intervention for girls with FraX. Directions for future research are discussed.

Adolescent↗

PubMed2005

[Functional imaging of neurocognitive dysfunction in attention deficit hyperactivity disorder].

Attention Deficit Hyperactivity Disorder (ADHD) is a neurobiological disorder of early childhood onset. Defining symptoms are chronic impairments of attention, impulse control and motor hyperactivity that frequently persist until adulthood. Miscellaneous causes of the disorder have been discussed. Accumulating evidence from imaging- and molecular genetic studies strengthened the theory of ADHS being a predominantly inherited disorder of neurobiological origin. In the last 15 years, non-invasive brain imaging methods were successfully implemented in pediatric research. Functional magnetic resonance imaging studies gave major insight into the neurobiological correlates of executive malfunction, inhibitory deficits and psychomotoric soft signs. These findings are in good accordance with brain morphometric data indicating a significant volumetric decrease of major components of striato-thalamo-cortical feedback loops, primarily influencing prefrontal executive functioning (e.g. basal ganglia). Empirical evidence points to a broad array of associated behavioral disturbances like deficient visuomotor abilities and oculomotor dysfunctions. This paper reviews the current empirical evidence derived from prior imaging studies. Special emphasis is given to the relevance of oculomotor dysfunctions in clinical and research settings, as well as their assessment in the MR environment.

Attention Deficit and Disruptive Behavior Disorder↗

PubMed2006

The impact of neuropsychological deficits on functional stroke outcomes.

This review examines the available literature on neuropsychological outcomes of stroke and the literature on the ability of specific areas of neuropsychological deficit to predict functional stroke outcome. The literature reviewed indicates that post-stroke deficits in executive function, memory, language, and speed of processing are common, with those identified as having progressive 'post-stroke dementia' presenting with a similar, though more impaired profile, with increased impairments particularly noted in the area of memory. It is clear that some aspects of neuropsychological functioning (e.g., presence of neglect, aphasia, anosognosia; and verbal memory and attention deficits) show promise as a means of predicting post-stroke functional outcomes. Examining the available literature, it becomes evident that there is a need for long-term, large scale (i.e., population based) follow-up studies, evaluating likely long-term neuropsychological outcomes of stroke and their prognostic utility.

Brain Damage, Chronic↗

PubMed2004

Cigarette smoking in a student sample: neurocognitive and clinical correlates.

Why do adolescents begin to smoke in the face of profound health risks and aggressive antismoking campaigns? The present study tested predictions based on two theoretical models of tobacco use in young adults: (1) the self-medication model; and (2) the orbitofrontal/disinhibition model. Investigators speculated that a significant number of smokers were self-medicating since nicotine possesses mood-elevating and hedonic properties. The self-medication model predicts that smokers will demonstrate increased rates of psychopathology relative to nonsmokers. Similarly, researchers have suggested that individuals with attention-deficit/hyperactivity disorder (ADHD) employ nicotine to enhance cognitive function. The ADHD/self-medication model predicts that smokers will perform poorly on tests of executive function and report a greater number of ADHD symptoms. A considerable body of research indicates that tobacco use is associated with several related personality traits including extraversion, impulsivity, risk taking, sensation seeking, novelty seeking, and antisocial personality features. Antisocial behavior and related personality traits as well as tobacco use may reflect, in part, a failure to effectively employ reward and punishment cues to guide behavior. This failure may reflect orbitofrontal dysfunction. The orbitofrontal/disinhibition model predicts that smokers will perform poorly on neurocognitive tasks considered sensitive to orbitofrontal dysfunction and will obtain significantly higher scores on measures of behavioral disinhibition and antisocial personality relative to nonsmokers. To test these predictions, we administered a battery of neuropsychological tests, clinical scales, and personality questionnaires to university student smokers and nonsmokers. Results did not support the self-medication model or the ADHD/self-medication model; however, findings were consistent with the orbitofrontal/disinhibition model.

Adolescent↗

PubMed2005

Event-related potentials for response inhibition in Parkinson's disease.

This study investigated inhibitory function in patients with Parkinson's disease (PD) by recording event-related brain potentials (ERPs) during a Go/NoGo task. Fourteen healthy volunteers and 13 patients with PD without dementia performed a cued continuous performance test that included Go and NoGo trials. The peak latency, amplitude, and topographic distributions of the ERPs to Go and NoGo stimuli were analyzed. Cognitive function was evaluated using the Wisconsin Card Sorting Test (WCST), Kana Pick-out Test, and Verbal Fluency Test (VFT). Performances in the WCST and VFT were significantly impaired in the PD group as compared with the control group. The PD group had significantly higher rates of omission and commission errors during the ERP task. The ERP study found no differences in the latency and amplitude of the Go-P3 between the two groups. By contrast, the NoGo-P3 latency was significantly longer in the PD group than in the control group. The amplitudes of the NoGo-P3 and NoGo-N2 were also significantly smaller in the PD group than in the control group. The NoGo-P3 latency was significantly correlated with the Kana Pick-out Test and VFT scores. The NoGo-P3 amplitude was significantly correlated with the WCST and VFT scores, as well as with the number of commission errors. There were no significant correlations between the cognitive function tests and either the Go-P3 or NoGo-N2 measures. The behavioral and ERP data suggest that there is selective impairment of inhibitory function in PD and that this deficit may be related to impaired inhibitory executive function in the frontal lobe.

Aged↗

PubMedDate not supplied

The role of cognitive impairment in desire for hastened death: a study of patients with advanced AIDS.

To examine the relationship between cognitive impairment and desire for death in patients with advanced AIDS we evaluated 128 patients with advanced AIDS consecutively admitted to three long-term care facilities. Participants completed a clinical assessment that included a self-report measure of desire for hastened death in the medically ill (Schedule of Attitudes toward Hastened Death), three measures of cognitive functioning designed to screen for cognitive impairment (Dementia Rating Scale, Mini-Mental State Exam, HIV Dementia Scale), and other measures of physical and psychological functioning. Participants who were classified as cognitively impaired obtained significantly higher scores on the measure of desire for death than did patients without cognitive impairment. This modest association between cognitive impairment and desire for death remained significant even after controlling for the impact of depression on desire for death. Specific aspect of cognitive functioning such as memory and psychomotor coordination appeared to be more salient than executive functioning or abstract reasoning. Cognitive impairment appears to have a modest, but significant impact on patients' desire for hastened death. Aggressive treatment of cognitive symptoms in the terminally ill is necessary in order to disentangle the various factors that may drive end-of-life treatment decisions.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Dopamine and the regulation of cognition and attention.

Dopamine (DA) acts as a key neurotransmitter in the brain. Numerous studies have shown its regulatory role for motor and limbic functions. However, in the early stages of Parkinson's disease (PD), alterations of executive functions also suggest a role for DA in regulating cognitive functions. Some other diseases, which can also involve DA dysfunction, such as schizophrenia or attention deficit hyperactivity disorder (ADHD) in children, as shown from the ameliorative action of dopaminergic antagonists and agonists, respectively, also show alteration of cognitive functions. Experimental studies showed that selective lesions of the dopaminergic neurons in rats or primates can actually provide cognitive deficits, especially when the mesocorticolimbic component of the dopaminergic systems is altered. Data from the experiments also showed significant alteration in attentional processes, thus raising the question of direct involvement of DA in regulating attention. Since the dopaminergic influence is mainly exerted over the frontal lobe and basal ganglia, it has been suggested that cognitive deficits express alteration in these subcortical brain structures closely linked to cortical areas, more than simple deficit in dopaminergic transmission. This point is still a matter of debate but, undoubtedly, DA acts as a powerful regulator of different aspects of cognitive brain functions. In this respect, normalizing DA transmission will contribute to improve the cognitive deficits not only related to neurologic or psychiatric diseases, but also in normal aging. Ontogenic and phylogenetic analysis of dopaminergic systems can provide evidences for a role of DA in the development of cognitive general capacities. DA can have a trophic action during maturation, which may influence the later cortical specification, particularly of pre-frontal cortical areas. Moreover, the characteristic extension of the dopaminergic cortical innervation in the rostro-caudal direction during the last stages of evolution in mammals can also be related to the appearance of progressively more developed cognitive capacities. Such an extension of cortical DA innervation could be related to increased processing of cortical information through basal ganglia, either during the course of evolution or development. DA has thus to be considered as a key neuroregulator which contributes to behavioral adaptation and to anticipatory processes necessary for preparing voluntary action consequent upon intention. All together, it can be suggested that a correlation exists between DA innervation and expression of cognitive capacities. Altering the dopaminergic transmission could, therefore, contribute to cognitive impairment.

Adult↗

PubMed2002

Male rats exposed to cocaine in utero demonstrate elevated expression of Fos in the prefrontal cortex in response to environment.

Prenatal cocaine exposure has been associated with disruption in attention and short-term memory in exposed children and in animal models. The biochemical change or changes responsible for these cognitive deficits are not known. An intriguing possibility, however, is that cocaine exposure during development disrupts the morphology or function of the frontal cortex, a region thought to contribute to cognitive and executive functions. In this report, we examined the effects of intravenous prenatal cocaine exposure on the expression of the immediate-early gene, c-fos, in the adolescent offspring to determine potential sites of disruption. The expression of Fos protein was similar in unhandled rats prenatally treated with saline or cocaine. Prenatal cocaine exposed rats that were handled, but not footshocked, however, demonstrated a dramatic selective increase in Fos expression in the ventral and medial prefrontal cortex. A footshock-induced increase in Fos expression in the prefrontal cortex was noted in prenatal saline, but not prenatal cocaine rats. Interestingly, no differences were noted in baseline or footshock-induced increased Fos expression in nuclei of the amygdala in prenatal cocaine and prenatal saline rats, indicating some aspect of the central response to stress appear unchanged. The unusual activation of the neurons of the medial and ventral prefrontal cortex may be a consequence of in utero cocaine exposure that contributes to the reported deficit in cognition.

Animals↗

PubMed2006

Differential expression of synaptic proteins in the frontal and temporal cortex of elderly subjects with mild cognitive impairment.

Alterations in synaptic protein stoichiometry may contribute to neocortical synaptic dysfunction in Alzheimer disease (AD). Whether perturbations in synaptic protein expression occur during the earliest stages of cognitive decline remain unclear. We examined protein levels of synaptophysin (SYP), synaptotagmin (SYT), and drebrin (DRB) in 5 neocortical regions (anterior cingulate, superior frontal, superior temporal, inferior parietal, and visual) of people clinically diagnosed with no cognitive impairment (NCI), mild cognitive impairment (MCI), mild/moderate AD, or severe AD. Normalized SYP levels were decreased approximately 35% in the superior temporal and inferior parietal cortex in severe AD compared with NCI. SYT levels were unchanged across clinical diagnosis in the cortical regions. Levels of DRB, a dendritic spine plasticity marker, were reduced approximately 40% to 60% in all cortical regions in AD compared with NCI. DRB protein was also reduced approximately 35% in the superior temporal cortex of MCI subjects, and DRB and SYP levels in the superior temporal cortex correlated with Mini-Mental State Examination and Braak scores. In contrast, DRB levels in the superior frontal cortex increased approximately 30% in MCI subjects. The differential changes in DRB expression in the frontal and temporal cortex in MCI suggest a disparity of dendritic plasticity within these regions that may contribute to the early impairment of temporal cortical functions subserving memory and language compared with the relative preservation of frontal cortical executive function during the initial stages of cognitive decline.

Aged↗

PubMed2006

Neurocognition as a stable endophenotype in bipolar disorder and schizophrenia.

Linkage and association studies have paid increasing attention to neurocognition as a putative endophenotype. However, there exists little documentation of its trait stability in schizophrenia or bipolar disorder. Our aim was to determine the longitudinal stability of neurocognitive performance in bipolar versus schizophrenia probands. We administered a neurocognitive battery at two time points, approximately 5 years apart, in 16 schizophrenia and 16 bipolar disorder age-matched subjects. There were no significant changes over time on variables including education, estimated IQ, depression, psychosis, global functioning, or medication status. Schizophrenia subjects showed significant deterioration in one measure of executive functioning but no significant changes in seven of eight other domains. Bipolar patients showed stability over time in attentional measures but greater variability in other domains. These preliminary findings suggest that neurocognitive domains appear longitudinally stable across broad domains in schizophrenia. In contrast, stable functioning may be more limited to attentional domains in bipolar disorder.

Adult↗

PubMed2026

Social support and cognitive function in postmenopausal women.

OBJECTIVE: An active social lifestyle may protect against cognitive decline in older adults, but few studies have examined specific social support dimensions in relation to specific cognitive domains. This study examines associations between social support dimensions and cognitive function in older women. METHODS: The Early versus Late Intervention Trial with Estradiol (ELITE) was a randomized, double-blinded, placebo-controlled trial of oral 17β-estradiol versus placebo in postmenopausal women, designed primarily to evaluate the timing hypothesis on atherosclerosis progression and cognitive decline; the present analysis is a secondary, hypothesis-generating examination of the psychosocial substudy data (2009-2012). A total of 448 women completed psychosocial assessments every 6 months. Cognitive function was assessed at baseline, 2.5, and 5 years using composite scores for executive function, verbal memory, visual memory, and global cognition derived from 14 standardized tests. Perceived social support was assessed using the Medical Outcomes Study-Social Support Survey (MOS-SSS; 0-100 scale). Paired cognitive-psychosocial assessments were analyzed using linear mixed-effects models adjusted for age, marital status, blood pressure medication, BMI, education, income, race, and randomized treatment (hormone therapy or placebo). RESULTS: A total of 298 women (mean age 60.3 y) provided 322 paired visits. Positive associations were observed between instrumental social support and visual memory (β(SE)=0.0044(0.0022), 95% CI: -0.00002 to 0.0088, P=0.051) and between positive social interaction and global cognition (β(SE)=0.0092(0.0046), 95% CI: 0.0001-0.0182, P=0.047). In age-stratified analyses, the positive social interaction-global cognition association was significant among women <65 years (P=0.042) but not women ≥65 years (P=0.34). No association survived false discovery rate (FDR) correction for multiple comparisons. CONCLUSIONS: In this sample of healthy middle- to older-aged women, no association between specific dimensions of social support and cognitive domains was statistically significant after correction for multiple comparisons. These hypothesis-generating findings suggest any association is modest at best and warrant confirmation in studies designed specifically for this question.

Cognitive function↗

PubMed2006

Random number generation during sleep deprivation: effects of caffeine on response maintenance and stereotypy.

Neurophysiological and functional imaging studies have demonstrated that frontal regions of the brain are particularly responsive to homeostatic sleep pressure. Previous neuropsychological studies indicate that sleep deprivation causes impairments in prefrontal cortical function. Random number generation (RNG) is thought to provide a sensitive index of executive functions that rely on the prefrontal cortex. The present study tested the hypothesis that sleep deprivation would impair RNG and that caffeine would mitigate this impairment. Healthy young men (n = 21) participated in two 40-h sleep deprivations 1 week apart. During each sleep deprivation period subjects received either caffeine or placebo according to a randomized, double-blind cross-over design, and they completed an oral RNG task at 3-h intervals. Comparison of test sessions at analogous times of day revealed that sleep deprivation was associated with significant drops in the number of responses, a threefold increase in the percentage of rule violations, 59% greater response redundancy and a 20% increase in stereotypy of adjacent response pairs. Sleep deprivation did not consistently alter counting tendency. Caffeine ameliorated the decrease in the number of responses but did not mitigate other deficits in RNG that arose during sleep deprivation. These findings are consistent with prior reports of diminished vigilance and increased perseveration during extended wakefulness. They support the conclusion that caffeine preserves simple aspects of cognitive performance during sleep deprivation, whereas caffeine may not prevent detrimental effects of sleep deprivation on some complex cognitive functions.

Adult↗

PubMed2006

Cognitive function of older patients receiving adjuvant chemotherapy for breast cancer: a pilot prospective longitudinal study.

OBJECTIVES: To report on the longitudinal cognitive functioning of older women receiving adjuvant chemotherapy for breast cancer. DESIGN: Neuropsychological and functional status testing were performed before chemotherapy and 6 months after chemotherapy. SETTING: Cancer center. PARTICIPANTS: Thirty-one patients aged 65 and older with Stage I to III breast cancer. Of the 31 patients enrolled, three refused post-testing, and 28 were evaluable. MEASUREMENTS: The following domains of cognitive function were examined: attention; verbal memory; visual memory; and verbal, spatial, psychomotor, and executive functions. RESULTS: Participants had a mean age of 71 (range 65-84): 39% Stage I, 50% Stage II, and 11% Stage III. The number of scores 2 standard deviations (SDs) below the norm were calculated for each patient before and 6 months after chemotherapy; 14 (50%) had no change, 11 (39%) worsened, and three (11%) improved (P=.05). Seven patients (25%) experienced a decline in cognitive function, defined as a 1-SD decline from pre- to post-testing in two or more neuropsychological domains. Exploratory analyses revealed no significant difference between functional status, comorbidity, and depression scale scores and change in overall quality-of-life scores before and after chemotherapy. CONCLUSION: In this cohort of older women receiving adjuvant chemotherapy, a subset experienced a decline in cognitive function from before chemotherapy to 6 months after chemotherapy. Further prospective study is needed to confirm these observations and to identify the subgroup at special risk.

Age Factors↗

PubMed2006

Heterogeneity in executive impairment in patients with very mild Alzheimer's disease.

BACKGROUND/AIMS: The presence of executive impairment in mild Alzheimer's disease (AD) has primarily been demonstrated by means of group comparison. Whether executive dysfunction is a common feature of mild AD or only present in a subgroup of patients remains unclear. The aim of this study was to describe the frequency of impairment on a set of internationally well-known executive tests in patients with very mild AD. METHODS: Thirty-six patients with very mild AD (MMSE scores above 23) and 32 healthy control subjects were administered a battery of 7 executive tests: Trail Making part B, Stroop Interference Test, modified Wisconsin Card Sorting Test (WCST), category- and letter-based verbal fluency, a design fluency task and the Similarities subtest from WAIS. Impairment was defined as a score of 2 SD or more below control means. RESULTS: Executive impairment on at least 1 measure was seen in 76% of the patients, and 50% were impaired on 2 or more tests. Trail Making B and Stroop Interference Test were impaired in more than 40%, whereas only few patients were impaired on Similarities, WCST and design fluency. A wide variation of executive test profiles was seen among the patients. CONCLUSION: Executive impairments are common in early AD and not just a feature characteristic of a subgroup of patients. Complex attentional skills are more frequently affected than other executive functions. There is, however, considerable heterogeneity among AD patients in the pattern of executive dysfunction.

Aged↗

PubMed1998

Reduplicative paramnesia: longitudinal neurobehavioral and neuroimaging analysis.

Reduplicative paramnesia (RP) is a delusion in which the patient perceives familiar places, objects, or events to have been duplicated. The current case describes the development of RP in an 81-year-old male following a large right frontal lobe infarction. As the patient had been hospitalized previously with hemorrhagic contusions, neurologic, neuropsychological, and neuroimaging data were obtained both prior to and following RP onset. Psychophysiologic data were obtained following the development of the delusion. Both premorbidly and at follow-up, neuropsychological functioning was characterized by significant impairments of learning and memory and frontal-executive functions. Language and visuospatial skills and motor speed were intact both before and after RP onset. The case is described within the context of preexisting theories of RP, and it is surmised that the delusion is secondary to temporal-limbic-frontal dysfunction giving rise to a distorted sense of familiarity and impaired ability to resolve the delusion via reasoning.

Accidental Falls↗

PubMedDate not supplied

[Cognitive functions of the frontal lobe].

INTRODUCTION AND DEVELOPMENT: One way to divide the different regions of the frontal lobe is according to its connections with the thalamic regions. Each of these regions, with their own particular cytoarchitecture, phylogeny and ontogeny, are also involved in distinct cognitive functions. The dorsolateral prefrontal cortex enables plans of action to be developed and executed, and working memory, which is needed for most cognitive processing, is the driving force behind what we call the executive functions. The orbital cortex and its subcortical connections make up a circuit that allows attention to be held and directed through a series of inhibitory mechanisms; this in turn prevents interference by stimuli that are irrelevant for a particular purpose. Finally, the cingulate cortex plays a part in initiating actions, in the intentionality of responses and in focusing attention. CONCLUSIONS: A deeper knowledge of the mechanisms behind the workings of the frontal lobe can explain the clinical pictures that are observed in many of the pathologies that appear during infancy, such as attention deficit hyperactivity disorder.

Animals↗

PubMed2005

Gambling task performance in traumatic brain injury: relationships to injury severity, atrophy, lesion location, and cognitive and psychosocial outcome.

OBJECTIVE: To determine the sensitivity of the Gambling Test (GT) to the neurocognitive effects of traumatic brain injury (TBI) and to examine the cognitive, neural, and psychosocial correlates of impaired GT performance in patients with TBI. BACKGROUND: The GT is sensitive to behavioral deficits in patients with prefrontal brain damage, especially in ventral regions. Patients with TBI and behavioral deficits often have focal ventral prefrontal damage as well as diffuse damage. Analysis of the correlates of the GT in this population has implications for interpretation of the GT in other groups. METHOD: Seventy-one TBI patients were administered the GT, neuropsychological tests, and psychosocial outcome questionnaires. Patients also had high-resolution structural magnetic resonance imaging analyzed for both lesion location and tissue compartment volumes. RESULTS: The GT was sensitive to TBI in general, but not to TBI severity or quantified chronic phase atrophy. Marked impairment was observed in (but not limited to) patients with large frontal lesions. There were modest correlations between the GT and tests of working memory and executive functioning as well as between self- and other-rated real-life memory, executive, and emotional problems. CONCLUSIONS: The GT can be a useful adjunct to assessment of patients with TBI. Interpretation of GT performance in patients with complex neuropsychological deficits such as TBI should consider the influence of domain-general resources in addition to specific ventral prefrontal function.

Adult↗