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Cognitive deficits in patients with small cell lung cancer before and after chemotherapy.

We conducted a prospective study of cognitive function in patients with small cell lung cancer (SCLC). A previous study had shown SCLC patients to have deficits in memory, frontal lobe executive functioning, and motor skills before they received prophylactic cranial irradiation (PCI). This study was performed to determine whether these deficits were related to chemoradiation treatment. We evaluated two groups of patients: one newly diagnosed and untreated, the other post-chemoradiation and before PCI. Strict eligibility criteria were used to minimize any preexisting factors that might influence cognitive functioning. Results showed that patients with SCLC have cognitive deficits before receiving chemoradiation, specifically on tests of verbal memory, frontal lobe executive functions, and motor coordination. There was no difference between the treated and untreated patients on any test. Etiologic considerations currently under study include paraneoplastic phenomena.

Adolescent

Behavioural changes after closed head injury. A neuropsychological issue.

The long-term behavioural consequences of moderate to severe closed head injury (CHI) have been examined within a neuropsychological framework. It is argued that neuropsychological assessment must be considered if the behavioural sequelae of a brain injury are to be fully appreciated and assessment and rehabilitation modules appropriately formulated. Functioning of the frontal lobes is emphasised because this is the area most at risk when a head injury occurs. The meaning of 'executive functions' is examined, and the behavioural and rehabilitation implications of an impaired 'executor' are discussed. It is demonstrated that traditional individual and family-based psychotherapeutic techniques are inappropriate for people with impaired executive functions.

Behavior

Neuropsychological changes in a prospectively followed cohort of homosexual and bisexual men with and without HIV infection.

We evaluated neuropsychological test performance of 168 homosexual and bisexual men with and without human immunodeficiency virus (HIV) infection (113 HIV+ subjects and 55 HIV- controls) over 4.5 years of semiannual follow-up. Analyses of the longitudinal data were performed by applying generalized estimating equations (GEEs) to regression analyses with repeated measures. Compared with the HIV- men, the HIV+ subjects performed more poorly on memory testing. Performance on all tests tended to improve over time, but this improvement was attenuated or eliminated in the HIV+ group for tests of language and attention. Within the HIV+ subjects, improvement over time in tests of memory, executive function, language, and attention was attenuated or eliminated in patients with lower CD4 levels; more advanced HIV disease was associated with poorer memory and executive function and with attenuated or reduced learning effects for memory, motor speed, and language tests. Clinically significant neurologic findings were associated with worse memory and orientation and with attenuated or reversed learning effects for memory, language, and attention tests. There were 33 deaths in the HIV+ group. In the men who died, there was more rapid decline in executive, language, and attentional test performance. These observations remained significant after controlling for HIV disease severity. We conclude that HIV infecting the CNS results in progressive cognitive change that is closely associated with neurologic findings. In addition, our findings suggest a relation between more rapid cognitive progression and death.

Adult

Is the phonological loop responsible for intelligence-related differences in forward digit span?

Children with mild mental retardation were compared with CA-matched and verbal-age-matched children without mental retardation on a forward digit span task. Forward digit span is typically used as a measure of the phonological loop (Baddeley, 1986). We hypothesized that intelligence-related differences in forward digit span are largely due to central executive functioning rather than phonological loop functioning. Results showed that the highly significant group difference in forward digit span was reduced to nonsignificance when a measure of central executive functioning was covaried out.

Attention

Developmental impact of frontal lobe injury in middle childhood.

Executive function of frontal lobe systems, like intelligent behavior, appears to demonstrate two major features: it is adaptive and goal-directed. Disruption of executive function following injury to the frontal lobes in childhood might be predicted to impact the trajectory of normal cognitive, behavioral, and social development. Case studies of two children injured at different ages showed the primary developmental impact to involve the behavioral and social realms. While cognitive development may be suspected to also be considerably influenced, assessment of changes in cognitive abilities by traditional psychometric means was found to be problematic. Psychometric changes were found to occur over a prolonged period of time, emphasizing the importance of documenting observations and chronicling postinjury events.

Brain Injuries

On testing the face validity of planning/problem-solving tasks in a normal population.

Clinically, tests of executive functions tend to be chosen on face validity. If such tests are to be used to evaluate a clinical population, their ability to measure executive functions should be reliably demonstrated in a normal population. In order to investigate the reliability of such tests, a sample of 130 normal adults (74 women, 56 men) ages 17 to 55 years were administered 4 tests purporting to measure planning/problem-solving: the Tower of London Test, the Six Element Test, the Twenty Questions Test, and the Rey Complex Figure Test. A structural equation modeling approach provided by the LISREL 8 program was used to evaluate three models hypothesized to explain the relationship among the test variables and the latent construct of planning/problem-solving. An adequate model was unable to be estimated, thus raising questions about the meaning of the latent construct planning/problem-solving and the psychometric structure of the Tower of London Test.

Adolescent

Association between striatal reduction and poor Wisconsin card sorting test performance in patients with schizophrenia.

Several findings support the hypothesis that the striatum is implicated in executive functions and in the modulation of goal-directed behavior, and could play a key role in the pathophysiology and in the production of symptoms and signs in schizophrenia. We have studied the relationship between the objective measures of the striatal structures, as evaluated by magnetic resonance imaging (MRI), and the Wisconsin Card Sorting Test (WCST) performance in a schizophrenic sample. Thirty-five schizophrenic patients underwent MRI scans of striatal structure and neuropsychological evaluation of executive functions by WCST. Poor WCST performers had a reduction of the left caudate nucleus and putamen, and right total striatum when compared to 24 healthy controls. Significant correlation coefficients were also observed between neuropsychological indexes and left striatal measures. The findings suggest the existence of a relationship between abnormalities of striatal structure and abnormal executive-type or organizational cognitive functions.

Adult

Long-term neuropsychological outcome and loss of social autonomy after traumatic brain injury.

OBJECTIVE: To assess which social activities were still impaired 5 years after a traumatic brain injury (TBI) in adults, and which neuropsychological impairments were associated with this loss of social autonomy. DESIGN: Cross-sectional study of 79 patients selected from the follow-up cohort of an epidemiologic survey of 2,116 TBI patients. SETTING: The present study was of ambulatory patients seen at hospital or at their homes. The inception cohort was from the trauma center of a university hospital and from a general hospital that is representative of level II trauma centers in Aquitaine, France. PATIENTS: Seventy-nine patients selected from a representative sample of 407 patients who were included in the 5-year follow-up study of the initial cohort (convenience sample). MAIN OUTCOME MEASURES: Glasgow Outcome Scale (GOS) and loss of social autonomy as assessed by the European Brain Injury Society's European Head Injury Evaluation Chart; assessment of neurobehavioral impairments by means of the Neurobehavioral Rating Scale-Revised. RESULTS: Up to 16 patients suffered disability for at least one social skill because of cognitive/behavioral reasons. Seven needed full-time supervision. Performing administrative tasks and financial management, writing letters and calculating, driving, planning the week, and using public transport were the most impaired social abilities. Loss of social autonomy was mainly observed in severely injured patients. Univariate analysis showed that mental fatigability, motor slowing, memory difficulties, and disorders of executive function were associated with low scores on the GOS, unemployment, and difficulties in shopping, using public transport, and performing financial management and administrative tasks. CONCLUSION: Persistent impairments of executive functions and speed of psychomotor processing are major factors associated with loss of social autonomy and inability to return to work long after TBI in adults. Improving these impairments in concrete social situations represents a major challenge for cognitive rehabilitation.

Activities of Daily Living

The relationship between sexual abuse and mild traumatic brain injury.

It remains unclear why some individuals with mild traumatic brain injury (MTBI) complain of cognitive deficits many months after the injury. Given neuropathological changes associated with prolonged stress, such as occurs with repeated sexual abuse (SA), it seems possible that individuals who experienced SA might be predisposed to greater deficits after MTBI. Four groups of subjects were administered measures of cognitive and emotional functioning. These groups were those with MTBI (n = 10), those with a history of SA (n = 10), those with both MTBI and SA (n = 10), and normal control (NC) subjects (n = 10). Compared to the NC subjects, those with MTBI demonstrated deficits in working memory, those with SA demonstrated deficits in executive functioning, and those with both MTBI and SA demonstrated the greatest number of deficits which were in working memory, executive functioning and memory. Tests of anxiety, depression and post-traumatic stress disorder, while demonstrating significant symptoms in all clinical groups, did not correlate with the neuropsychological tests that differentiated the groups.

Adult

Executive dysfunction in Alzheimer's disease.

Executive functioning was examined in 20 patients with Alzheimer's disease (AD) and 20 normal elderly subjects. The results showed that AD patients present lower performance compared to control subjects in all executive tasks, confirming that some executive deficits may be present in the first stages of the disease. A factorial analysis suggested that these deficits can be related to two domains of the executive functions: the inhibition abilities and the capacity to co-ordinate simultaneously storage and processing of information. Moreover, the performance on these factors is correlated to different anterior and posterior cortical areas.

Aged

Olfactory identification deficiency and WCST performance in men with schizophrenia.

Several studies using the University of Pennsylvania Smell Identification Test (UPSIT), which requires forced choice olfactory identifications, have reported olfactory identification deficits in patients with schizophrenia. This report examines the possible links between olfactory identification (usually attributed to the orbitofrontal cortex) and executive functions (usually attributed to dorsolateral prefrontal cortex) in 24 male patients with schizophrenia and 21 male comparison subjects. Olfactory performance was investigated under two conditions: spontaneous identification and forced choice identification. Executive function was assessed with the Wisconsin Card Sorting Test (WCST). Compared with controls, patients with schizophrenia exhibited a higher average number of cigarettes smoked per day, lower spontaneous identification scores on olfactory performance, and a higher percentage of perseverative errors on the WCST; there was a significant relationship between the two performance measures. Simpson-Angus scores, neuroleptic drug treatment levels, and scores on the Positive and Negative Syndrome Scale were not correlated with either olfactory measure. The lack of correlation between the forced choice olfactory identification score and the WCST score is consistent with findings in previous studies that used the UPSIT. By contrast, use of a spontaneous identification condition to assess olfactory performance did produce a significant association with WCST performance.

Adult

Cognition and white matter hyperintensities in older depressed patients.

OBJECTIVE: The authors compared amounts of white matter hyperintensity in late- and early-onset depressed patients and never-depressed older subjects, compared neuropsychological function in these groups, and investigated the association between white matter hyperintensities and cognitive function in depression. METHOD: Sixty currently depressed patients whose first depression occurred after age 50 years, 35 depressed patients over age 50 whose first depression occurred before age 35, and 165 nonpsychiatrically ill subjects over age 50 underwent magnetic resonance imaging (MRI) and neuropsychological evaluation. Areas of white matter hyperintensity were measured from MRI images. RESULTS: The late-onset patients had more white matter hyperintensity than either of the other groups. Compared to the nondepressed subjects, the patients had significantly lower scores in the cognitive domains of nonverbal intelligence, nonverbal memory, constructional ability, executive ability, and information processing speed. The cognitive abnormalities were mostly confined to the late-onset patients, and the presence of a large amount of white matter hyperintensity was associated with significantly poorer executive skills. However, most of the scores were not in the significantly impaired range. CONCLUSIONS: Large amounts of white matter hyperintensity are more frequent in patients with late-onsetdepression than in elderly subjects with early-onset or no depression. Both late- and early-onset elderly depressed patients show mild decrements in some "right hemisphere" cognitive skills; the late-onset subjects also show deterioration in information processing speed and executive functions. Patients with large amounts of white matter hyperintensity have significantly poorer executive function.

Age Factors

Improvement in cognitive functions and psychiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine.

Cognitive functions and psychopathology were assessed in 36 treatment-refractory schizophrenic patients before initiation of clozapine, and at 6 weeks and 6 months, thereafter. Before treatment, cognitive impairment was found in each measure of memory, attention, and executive function as compared with 26 normal controls. After both 6 weeks and 6 months of treatment, significant improvement occurred in the Controlled Oral Word Association Test, a measure of retrieval from reference memory. Improvement was also noted at 6 months in the Category Instance Generation Test, another measure of retrieval from reference memory, and in some, but not all, tests of executive function, attention, and recall memory. Clozapine treatment also resulted in significant improvement in Brief Psychiatric Rating Scale (BPRS) Total and Positive symptom scores at both 6-week and 6-month assessment points. There was some evidence for a relationship between improvement in psychopathology and cognitive function. The improvement in cognitive function during clozapine treatment could have consequences for capacity to work and social function.

Adult

The cerebellum and cognitive function: implications for rehabilitation.

OBJECTIVE: To characterize the cognitive effects of isolated cerebellar lesions. DESIGN: Review of two inpatient cases. SETTING: The rehabilitation unit of a tertiary general hospital. PATIENTS OR OTHER PARTICIPANTS: Two patients with acute ischemic strokes who had solitary cerebellar infarcts. INTERVENTIONS: Assessment with standard neuropsychological tests. Scores were compared with patients' premorbid levels and standardized test norms. A classical conditioning eyeblink paradigm was performed. MAIN OUTCOME MEASURES: Neuropsychological measures of intellectual and executive functions, learning and memory, visual-spatial abilities, language functioning, fine motor speed, and dexterity. RESULTS: Test findings suggested lesion-associated deficits in higher aspects of cognition (visuospatial reasoning, verbal and visual memory, and intellectual and executive functions). These functions are not usually associated with the fundamentally motoric role of the cerebellum. CONCLUSIONS: (1) Lesions in the cerebellum can be associated with impairments in higher cognitive functioning. (2) Such effects may be severe enough for a diagnosis of dementia under current diagnostic criteria. (3) These rehabilitation patients may benefit from comprehensive cognitive examination to determine if cognitive effects will detract from their participation. (4) Further research is needed to localize which cerebellar areas affect which cognitive abilities.

Aged

Neuropsychological and neuroanatomical correlates of confabulation.

In the present exploratory investigation we report nine confabulatory patients of comparable age, education, and general level of intelligence in the acute epoch of recovery after rupture and clipping of ACoA aneurysms. Five of the nine cases had "spontaneous" confabulation, severe anterograde amnesia, markedly poor attentional and executive functions, and denial of illness. These patients all had multiple lesions that involved basal forebrain, ventral frontal lobe, and striatum. The other four patients manifested only "momentary" or "provoked" confabulations. These patients also had severe anterograde amnesia but showed relatively mild deficits in executive functions. These patients had lesions restricted to the basal forebrain except for one who had additional orbital frontal damage. Analysis of these two groups of confabulatory patients suggests that there is a common profile of deficits and anatomic foundation associated with confabulation; "spontaneous" confabulation appears to require extensive, simultaneous disruption of medial basal forebrain and frontal cognitive systems resulting in profound executive and memory deficits, whereas more limited lesions to the basal forebrain or orbital frontal cortex will result in "transient" or "provoked" confabulatory responses and a more restricted profile of cognitive deficits.

Adult

The alpha(2) antagonist idazoxan remediates certain attentional and executive dysfunction in patients with dementia of frontal type.

Abstract The mixed alpha(1)/alpha(2) adrenoceptor agonist clonidine has been shown by us previously to impair certain attentional and executive functions in healthy volunteers. The present investigation examines the effects of the alpha(2) adrenoceptor antagonist idazoxan (IDZ) on cognitive function in patients with dementia of frontal type (DFT). Using a placebo-controlled ABBA design, three DFT patients were given two doses of IDZ and tested on a range of computerised tests of attention, memory and executive function. Idazoxan was found to produce dose-dependent improvements in performance, particularly on tests of planning, sustained attention, verbal fluency and episodic memory. In contrast, IDZ produced deficits in performance on a test of spatial working memory. These results suggest that IDZ may be useful as a putative cognitive enhancer, particularly in patients showing a specific pattern of frontal lobe dysfunction.

Adrenergic alpha-Antagonists

Cognitive rehabilitation following anterior communicating artery aneurysm bleeding: a case report.

The present case report documents the successful rehabilitation of a severely amnesic anterior communicating artery aneurysm patient. The patient was able to return to his premorbid high-level occupation after significant improvement in executive functioning, moderate improvement in visual memory, modest improvement in immediate verbal memory, and minimal improvement in delayed verbal memory. An interdisciplinary approach to rehabilitation was utilized in conjunction with empirically based intervention strategies. The implications of improved executive functions versus memory functions for successful rehabilitation are discussed.

Adult

Can standard measures identify subclinical markers of autism?

This study compared the executive function and theory-of-mind abilities of siblings of autistic individuals to those of siblings of learning-disabled controls. Three different analyses of the dependent measures provided convergent support for a potential subclinical marker in the executive function domain. No group differences in theory-of-mind abilities were found. However, power analyses revealed that the measures employed in this study, which are typically used with autistic individuals, were not sufficiently sensitive to detect any group differences that might exist in "unaffected" family members. Suggestions for future research are provided, including the need to develop more sensitive tasks that produce larger effects and measure more elementary cognitive operations.

Adolescent