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Intracranial pressure parameters in idiopathic normal pressure hydrocephalus patients with or without improvement of cognitive function after shunt treatment.

BACKGROUND/AIMS: Previous research has shown improvements in the clinical triad (gait, incontinence and cognitive dysfunction) after shunt surgery in idiopathic normal pressure hydrocephalus (iNPH) patients with intracranial pulse pressure amplitudes >4-5 mm Hg, the pulse amplitudes being <4 mm Hg in the nonresponders. However, it is unknown whether similar differences exist regarding change in cognitive functioning after shunt surgery. The aim of this study was to compare preoperative intracranial pressure (ICP) parameters between iNPH that either improved or not improved in cognitive function after shunt treatment. METHODS: Neuropsychological testing was performed before and after surgery in 27 consecutive iNPH patients treated with ventriculoperitoneal shunts. The ICP recordings were performed as part of routine preoperative assessment, stored as raw data files, and analyzed retrospectively. The mean ICP as well as single ICP wave amplitudes were computed and analyzed in consecutive 6-second time windows. RESULTS: Significant improvement in neuropsychological tests, defined as a 4-point improvement in Folstein Mini-Mental State Examination or improvement by one standard deviation in 50% of subtests of Dementia Rating Scale, was found in 12 patients (44%; shunt responders). In these patients, mean ICP was similar though the mean ICP wave amplitude was significantly higher than in the shunt nonresponders. CONCLUSIONS: While preoperative mean ICP was similar, the mean ICP wave amplitudes were considerably higher in iNPH patients with significant change in cognitive function following shunt surgery.

Aged↗

Diagnosis and management of memory loss and cognitive disorders among elderly persons.

Memory loss and other cognitive dysfunctions, although common in elderly persons, are not universal features of old age. Instead they herald the presence of various neuropsychiatric diseases, which are first recognized as syndromes. The two most common neuropsychiatric syndromes, dementia and delirium, produce global changes in cognition and other capacities. They are differentiated by the patient's level of consciousness, which is impaired in delirium but intact in dementia. Delirium is generally reversible and often indicates serious physical illness. Although dementia is occasionally reversible, the mainstays of its management and treatment are palliative. Comorbid psychiatric symptoms are common in patients with both delirium or dementia, and their recognition and treatment constitute an important task for the geropsychiatrist. The differential diagnosis of primary dementing illness and other psychiatric illnesses such as depression is complex, because symptoms of the two kinds of disorders often coexist and common pathogenetic mechanisms may underlie both syndromes.

Aged↗

Cognitive status and quality of life after treatment for primary CNS lymphoma.

OBJECTIVE: To evaluate the cognitive status and quality of life (QOL) in a cohort of 19 consecutive patients treated in a prospective European Organization for Research and Treatment of Cancer study (20962) for primary CNS lymphoma (PCNSL). All patients were in complete remission after combined modality treatment with IV and intrathecal high-dose methotrexate (MTX)-based chemotherapy followed by whole brain radiotherapy (WBRT). METHODS: An extensive neuropsychological assessment, including QOL measures, was conducted in 19 patients with PCNSL. The results were compared with matched control subjects with systemic hematologic malignancies treated with systemic chemotherapy or non-CNS radiotherapy. In addition, a neuroradiologic evaluation was carried out in 18 patients with PCNSL. RESULTS: Cognitive impairment was found in 12 patients with PCNSL (63%) despite a complete tumor response. Four patients (21%) showed severe cognitive deficits, and the percentage of impaired test indices correlated with age. In comparison, only two control subjects (11%) showed cognitive dysfunction (p = 0.002). Forty-two percent of the patients with PCNSL, in contrast to 81% of the control subjects, resumed work. White matter abnormalities were observed in 14 patients with PCNSL, and 14 had cortical atrophy. Cortical atrophy correlated with cognitive functioning, age, and Karnofsky performance score. Group differences in cognitive status and QOL could not be explained by anxiety, depression, or fatigue. CONCLUSIONS: Combined modality treatment for primary CNS lymphoma is associated with cognitive impairment even in patients aged <60 years.

Adult↗

Homocysteine and cognition--a historical perspective.

The discovery of a relationship between homocysteine and cognition stems from clinical observations of an association between vitamin B12 and folate deficiency and cognitive dysfunction. This retrospective details the history of vitamin B12 and folic acid and the conceptual evolution of their association with dementia. The hematological and neuropsychiatric manifestations of these deficiencies are discussed, together with the nature of their relationship with dementia, generalized cognitive decline and discrete neuropsychological function. An evaluation of the potential of reversing "homocysteine-associated" and/or "vitamin-associated" cognitive decline raises questions as to whether current interventions can unequivocally determine if homocysteine independently impacts on cognitive function. Alternative approaches specifically designed to address this issue are discussed.

Alzheimer Disease↗

Spontaneous subarachnoid hemorrhage. Prognostic factors for social readjustment.

Sixty-seven patients surviving spontaneous subarachnoid haemorrhage (SAH) have been followed up for 2-12 years (mean: 7 years) in order to determine prognostic factors concerning the long-term disability in familial and social functioning. A correlation was found between the severity of the neurological deficit at the time of admission and the degree of familial and social disability at the end of the observation period. In addition, the Barthel-Index on discharge was shown to be of prognostic value for readjustment for social--but not for familial--functioning. Other clinical variables in the acute stage, however, including source of bleeding, sex, age, interval between SAH and admission, level of consciousness, cognitive functions, as well as initial Hunt and Hess grading and Glasgow Coma Scale scoring, did not influence the long-term social prognosis. Furthermore, residual neurological signs, cognitive dysfunctions, and the Glasgow Outcome score on discharge were not related to the extent of social handicap in the long-term outcome. At the end of the observation period, significant correlations were found between the presence of persisting neurological and cognitive deficits but also disability in ADL functions and occupational capacity and the decline in familial and social functioning.

Adolescent↗

Dementia rating scale performance: a comparison of vascular and Alzheimer's dementia.

Differences in the pattern of neuropsychological dysfunction associated with Alzheimer's disease (AD) and vascular dementia (VaD) were examined using the Dementia Rating Scale (DRS). We examined three groups of patients: (1) Patients with AD; (2) patients with single stroke (CVA); and (3) patients with multiple cerebral infarctions (MI). Comparisons of cognitive dysfunction were conducted on patients that met the DRS criteria for dementia. Dementia groups were similar in age, education, and severity of dementia. Comparisons of the AD and two VaD groups across the specific DRS-scales (Attention, Conceptualization, Construction, Initiation/Perseveration, and Memory) indicated that patients with AD were more impaired on the DRS-Memory while the patients with VaD were more impaired on the DRS-Construction. Additionally, patients with VaD related to MI scored lower on the DRS-Initiation/Perseveration as compared to patients with AD, and patients with AD scored lower on the DRS-Conceptualization as compared to patients with VaD related to CVA. These results are indicative of qualitative differences in the pattern of cognitive deficits associated with the two types of dementia.

Aged↗

Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma.

BACKGROUND: A number of patients who have undergone adjuvant (CMF) chemotherapy for operative primary breast carcinoma have reported impaired cognitive function, sometimes even years after completion of therapy. The possible role of cytostatic treatment as a causative factor has scarcely been investigated. The objective of the current study was to examine the late effects on neuropsychologic functioning of CMF adjuvant chemotherapy given to patients with breast carcinoma. METHODS: Thirty-nine breast carcinoma patients who had been treated with adjuvant CMF (6 courses) followed (n = 20) by 3 years of tamoxifen 20 mg daily or not (n = 19) were examined with neuropsychologic tests and interviews. The control group consisted of 34 age-matched axillary lymph node negative breast carcinoma patients who received the same surgical and radiation therapy but no systemic adjuvant treatment. The CMF patients were examined a median of 1.9 years after the sixth CMF course, and the controls a median of 2.4 years after surgery of the primary tumor. RESULTS: Patients treated with CMF reported significantly more problems with concentration (31% vs. 6%, P = 0.007) and with memory (21% vs. 3%, P = 0.022) than the control patients. No relation was found between reported complaints and results on the neuropsychologic tests. Impairment in cognitive function was found in 28% of the patients treated with chemotherapy compared with 12% of the patients in the control group (odds ratio 6.4 [95% confidence interval 1.5-27.6] P = 0.013). Hormonal therapy had no influence on patients' self-reports of symptoms or cognitive function. Cognitive impairment following chemotherapy was noticed in a broad domain of functioning, including attention, mental flexibility, speed of information processing, visual memory, and motor function. CONCLUSIONS: Breast carcinoma patients treated with adjuvant CMF chemotherapy have a significantly higher risk of late cognitive impairment than breast carcinoma patients not treated with chemotherapy (OR 6.4). This cognitive impairment is unaffected by anxiety, depression, fatigue, and time since treatment, and not related to the self-reported complaints of cognitive dysfunction.

Adult↗

Deficient cumulative learning: an animal model of retarded cognitive development.

Biological insults that produce profound mental retardation (MR) in humans have generally been found to produce little cognitive dysfunction in animal models. Based on the fact that impaired transfer of learning is one of the hallmark characteristics of mentally retarded humans, we proposed that this discrepancy may largely reflect the common use of a single learning task as the critical cognitive index rather than an assessment of cumulative learning. Consistent with this hypothesis, rats exposed to prenatal hyperphenylalaninemia (a model of maternal PKU) evidenced significant impairment when tested on a series of 10 problems designed to allow for positive transfer of learning. This same treatment, however, did not alter learning rate of the individual tasks that comprised this series when presented singly to experimentally naive animals. Deficient transfer of learning contributed significantly to the impairment observed in the maternal PKU group. These results support the hypothesis that the assessment of cumulative learning is an important component of animal models of impaired cognitive development.

Acoustic Stimulation↗

Benzimidazole derivatives. Part 5: design and synthesis of new benzimidazole-arylpiperazine derivatives acting as mixed 5-HT1A/5-HT3 ligands.

A series of new mixed benzimidazole-arylpiperazine derivatives were designed by incorporating in general structure III the pharmacophoric elements of 5-HT(1A) and 5-HT(3) receptors. Compounds 1-11 were synthesized and evaluated for binding affinity at both serotoninergic receptors, all of them exhibiting high 5-HT(3)R affinity (K(i)=10-62nM), and derivatives with an o-alkoxy group in the arylpiperazine ring showing nanomolar affinity for the 5-HT(1A)R (K(i)=18-150nM). Additionally, all the synthesized compounds were selective over alpha(1)-adrenergic and dopamine D(2) receptors (K(i)>1000-10,000nM). Compound 3 was selected for further pharmacological characterization due to its interesting binding profile as mixed 5-HT(1A)/5-HT(3) ligand with high affinity for both receptors (5-HT(1A): K(i)=18.0nM, 5-HT(3): K(i)=27.2nM). In vitro and in vivo findings suggest that this compound acts as a partial agonist at 5-HT(1A)Rs and as a 5-HT(3)R antagonist. This novel mixed 5-HT(1A)/5-HT(3) ligand was also effective in preventing the cognitive deficits induced by muscarinic receptor blockade in a passive avoidance learning test, suggesting a potential interest in the treatment of cognitive dysfunction.

Animals↗

Neuropsychological functioning in opiate-dependent subjects receiving and following methadone maintenance treatment.

OBJECTIVE: An accumulating body of research suggests that former heroin abusers in methadone maintenance therapy (MMT) exhibit deficits in cognitive function. Whether these deficits are present in former methadone maintained patients following discontinuation of MMT is unknown. This study tests the hypothesis that former heroin users who have detoxified from methadone maintenance therapy and are drug-free have less pronounced cognitive impairment than patients continuing long-term MMT. METHOD: A series of neuropsychological tests were administered to three groups of subjects: 29 former heroin addicts receiving methadone maintenance treatment, 27 former heroin addicts withdrawn from all opiates, and 29 healthy controls without a history of drug dependence. Testing included Wechsler Adult Intelligence Scale-Revised Vocabulary Test, the Stroop Color-Word Test, the Controlled Oral Word Association Test, the Benton Visual Retention Test, and a Substance Use Inventory. FINDINGS: Both methadone-maintained and abstinent subject groups performed worse than controls on tasks that measured verbal function, visual-spatial analysis and memory, and resistance to distractibility. Abstinent subjects performed worse than their methadone maintained counterparts on tests measuring visual memory and construct formation. Cognitive impairment did not correlate with any index of drug use. CONCLUSIONS: We confirmed previous findings of neuropsychological impairment in long-term MMT recipients. Both patients receiving MMT and former heroin users in prolonged abstinence exhibited a similar degree of cognitive impairment. Cognitive dysfunction in patients receiving methadone maintenance may not resolve following methadone detoxification.

Adult↗

GABAB receptor antagonist SGS742 improves spatial memory and reduces protein binding to the cAMP response element (CRE) in the hippocampus.

Memory storage in the brain requires protein synthesis initiated through signaling pathways that control transcription. Such mechanisms are under active investigation for therapies in disorders involving cognitive dysfunction. Long-term memory can be improved by inhibiting activation or reducing expression of transcription factors such as ATF4/CREB2 and some C/EBP family members which appear to serve as memory suppressors. Here, we provide evidence that GABAB receptor antagonists may enhance cognition, at least in part, by this mechanism. We tested a GABAB receptor antagonist, SGS742 (CGP36742), on hippocampal-dependent memory and hippocampal nuclear CRE-binding activity in rats. As a result, acute in vivo administration of SGS742 both improved memory and reduced total hippocampal CRE-binding activity of which a large proportion in the basal state could be immunoneutralized with CREB2 antibodies. Consistent with its activity on information storage mechanisms, acute SGS742 effectively improved long-term memory in retrograde protocols, in which drug was given at times when memory formation can be interrupted by blocking new protein production. In conclusion, GABAB antagonists may provide a pharmacological therapy for cognitive impairment, sharing mechanistic features with genetic approaches to reduce CREB2 activity and to augment long-term memory.

Animals↗

Huperzine A improves cognitive deficits caused by chronic cerebral hypoperfusion in rats.

The effects of (-)-huperzine A, a promising therapeutic agent for Alzheimer's disease, on learning behavior and on alterations of the cholinergic system, the oxygen free radicals and energy metabolites induced by permanent bilateral ligation of the common carotid arteries were investigated in rats. Daily oral administration of huperzine A produced a significant improvement of the deficit in the learning of the water maze task, beginning 28 days after ischemia, correlating to about 33-40% inhibition of acetylcholinesterase activity in cortex and hippocampus. Huperzine A significantly restored the decrease in choline acetyltransferase activity in hippocampus and significantly reduced the increases in superoxide dismutase, lipid peroxide, lactate and glucose to their normal levels. The present findings demonstrate that the improvement by huperzine A of the cognitive dysfunction in the late phase in chronically hypoperfused rats is due to its effects, not only on the cholinergic system, but also on the oxygen free radical system and energy metabolism. Our results strongly suggest that huperzine A has therapeutic potential for the treatment of dementia caused by cholinergic dysfunction and/or decrease of cerebral blood flow.

Acetylcholinesterase↗

The prevalence of depression in relation to cerebral atrophy and cognitive performance in 70- and 74-year-old women in Gothenburg. The Women's Health Study.

BACKGROUND: Hospital-based studies report that depression in the elderly is associated with brain atrophy. This notion could not be confirmed in a population study on 85-year-olds. We aimed to assess depression in relation to brain atrophy and cognition in 70- and 74-year-old women. METHODS; A representative sample of 70- and 74-year-old women (N = 501) was examined with a psychiatric examination including the Mini-Mental State Examination (MMSE), measuring global cognitive function, and computerized tomography (CT) of the brain (N = 268). Depression was diagnosed according to DSM-III-R. Previous depression was diagnosed by history and by information from previous examinations in this 24-year longitudinal study. RESULTS: The prevalence of depression was 11.6%, including 8.4% with major depression (MDD). Among those who were currently mentally healthy, 43.0% had a history of previous depression. Women with current MDD had lower scores on the MMSE than the mentally healthy women. This association was only found in women with a lower level of education. Current depressives, previous depressives and mentally healthy women without a history of depression did not differ on CT with regard to brain atrophy or white matter lesions. The association between MDD and lower cognitive performance was independent of the association of cognitive performance with structural brain changes on CT. CONCLUSIONS: Brain atrophy on CT is not associated with depression in the general population, despite the fact that individuals with depression have a worse cognitive performance. The finding that cognitive performance was not decreased in individuals with previous depression suggests that cognitive dysfunction is a state phenomenon in depression.

Aged↗

Prevalence of human immunodeficiency virus-associated cognitive impairment in a group of Hispanic women at risk for neurological impairment.

Human immunodeficiency virus (HIV)-associated cognitive impairment, a significant cause of morbidity, affects up to 30% of HIV-infected people. Its prevalence doubled as patients began to live longer after the introduction of highly active retroviral therapy. Women are now one of the fastest growing groups with acquired immunodeficiency syndrome (AIDS) in the United States and Puerto Rico, but relatively little is known about the prevalence and characteristics of cognitive dysfunction in HIV-infected women. In this study the authors investigated its prevalence in a group of HIV-1-seropositive Hispanic women in Puerto Rico. Forty-nine women with a nadir CD4 cell count of < or = 500 cells/mm3 were enrolled. Cognitive impairment was defined according to the American Academy of Neurology criteria for HIV dementia as modified to identify an "asymptomatic cognitively impaired" group. Observed prevalence was compared with prevalence in other populations in United States, Europe, and Australia. Differences in clinical markers and neuropsychological test performance among the cohort stratified by cognitive impairment were tested. Cognitive impairment was observed in 77.6% (38/49) of cases; asymptomatic cognitive impairment in 32.7% (16/49); minor cognitive motor disorders in 16.3% (8/49); and HIV-associated dementia (HAD) in 28.6% (14/49). Cognitive impairment did not correlate with age, CD4 cell count, viral load, or treatment modality. The cross-sectional prevalence of HIV-associated cognitive impairment was 77.6% (28.6% for HAD). These findings should enhance awareness of the prevalence of HIV-associated cognitive impairment, both clinically apparent and "asymptomatic," in Hispanic women and lead to improvements in areas such as education and compliance and to reevaluation of treatment interventions.

Adult↗

The incidence of cognitive decline after (not) undergoing coronary artery bypass grafting: the impact of a controlled definition.

BACKGROUND: After coronary artery bypass grafting (CABG), 20-30% of patients are reported to suffer from cognitive decline. Studies reporting these high incidences, however, have not included an appropriate control group. METHODS: We repeatedly administered a series of neuropsychological tests to 112 healthy middle-aged volunteers not undergoing surgery, and applied two widely used definitions of cognitive decline to their test results. In addition, we re-analysed the neuropsychological test data of 281 CABG patients with a definition of cognitive decline that takes into account the natural variability of test performance that was found in the volunteers. RESULTS: Three months after their first assessment, 14-28% of the volunteers suffered from cognitive decline according to the definitions of cognitive decline after CABG. Using the controlled definition of cognitive decline that takes the natural variability in test performance into account, we found that only 7.7% of the CABG patients suffered from cognitive decline at 3 months after their operation. CONCLUSION: These data suggest that the incidence of cognitive dysfunction after CABG has previously been greatly overestimated.

Aged↗

Role of cognitive function in assessing informed consent for endoscopy.

BACKGROUND: Patient understanding of the consent process is often suboptimal and the reasons for this are poorly understood. In particular the role of cognitive function in assessing the level of understanding of consent has not been evaluated. AIMS: This study aims to assess the level of patient understanding of the informed consent process and the role of cognitive function in those with low levels of understanding. METHODS: The study was prospective, interviewing patients immediately after they had given consent but before undergoing their procedure. Understanding of the reason for the procedure, the risks attendant upon it, details of the procedure itself and post procedure care was scored with the total representing overall level of understanding. A mini mental state examination (MMSE) was then performed with the score recorded. RESULTS: 100 patients were interviewed. A low level of understanding was shown in 36%. Ninety two patients had a MMSE score greater than 24. All patients with a high level of understanding had MMSE scores greater then 24 compared with 78% of those with a low level of understanding. All patients (n = 8) who displayed a MMSE score less than 24 had a low level of understanding. Men displayed poorer levels of understanding than women. A subnormal MMSE only identified 22% of those with low levels of understanding. CONCLUSIONS: Understanding of the consent process is suboptimal. Adequate cognitive function does not predict a high level of understanding of the informed consent process while cognitive impairment precludes it. It is evident, however that factors other than cognitive dysfunction are at play when attempting to explain low levels of understanding.

Adult↗

Epileptic seizures and event-related potentials (P300) in childhood partial epilepsies.

To clarify the relationship between cognitive function and clinical seizures, auditory event-related potentials (P300) were examined in 72 patients (185 trials) with partial epilepsy. Twenty-six patients (67 trials) had idiopathic partial epilepsies (IPE), and 46 (118 trials) symptomatic or cryptogenic partial epilepsies (SPE). In this study, to rule out the effects of epileptogenesis and other factors, we only examined patients with partial epilepsies undergoing carbamazepine (CBZ) monotherapy at doses of less than 16 mg/kg/day. The results were: 1) the mean age-corrected P300 latency in the patients with SPE (394 +/- 38 msec) was significantly prolonged compared with that in the patients with IPE (378 +/- 28). 2) The prolongation of the P300 latency had no relationship to the seizure frequency, seizure type or seizure duration. 3) In both epileptic groups, there was no significant correlation between the seizure-free period and the age-corrected P300 latency. Our results suggest that the effect of clinical seizures on the cognitive function may be relatively little, and that the cognitive dysfunction in partial epilepsies may mainly originate from epileptogenesis or other factors.

Adolescent↗

Cognitive correlates of diffuse cerebral atrophy determined by computed tomography.

The relationship between severity of diffuse cerebral atrophy determined by computed tomography (CT) and severity of cognitive impairment was examined in 55 men, 50 to 77 years old. Partial correlations, controlling for the effects of age and education, indicated that increased cerebral atrophy was associated with decline in orientation, recent memory, and general level of intellectual functioning. Correlations between degree of atrophy and decline in immediate and remote memory were not significant. Despite significant associations between cerebral atrophy and some aspects of intellectual functioning, considerable variance in performance on cognitive tasks was not explained by cerebral atrophy. Therefore, the degree of diffuse cortical and central atrophy observed on CT scan did not closely predict the degree of cognitive dysfunction, nor did the observation of cerebral atrophy necessarily indicate the presence of dementia.

Aged↗