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PubMed2002

[Dopaminergic modulation of cerebral activity and cognitive functions].

Alterations in dopaminergic system are known to lie in the basis of such diseases as Parkinson's disease, Huntington's disease, Attention Deficit/Hyperactivity Disorder, Tourette syndrome, schizophrenia and drug abuse. This induced broad investigations of dopaminergic system in nearly all the areas of neuroscience. New insights into the pathogenesis of neuropsychiatric diseases have emerged. Research in the field of dopaminergic neurotransmission and memory was awarded Nobel prize in the year 2000. New avenues for the development of more selective drugs have been opened. In their daily practice clinicians are often prescribing medications acting on presynaptic or postsynaptic sites of dopaminergic units. Thus the aim of this review was to renew some knowledge on the architecture of dopaminergic system and also to glance through some of the studies implying its modulating effect on cognitive functions.

Attention Deficit Disorder with Hyperactivity↗

PubMed1989

Recombinant human erythropoietin: impact on brain and cognitive function, exercise tolerance, sexual potency, and quality of life.

The clinical manifestations of uremia are only incompletely reversed by chronic hemodialysis. Signs and symptoms can include abnormalities in electrophysiologic indices, clinical mental status, and neuropsychological test performance, as well as decreases in exercise tolerance, sexual potency, and general quality of life. Though retention of uremic toxins is responsible for many of these symptom complexes, some may be caused, or substantially aggravated, by the anemia that almost invariably accompanies chronic renal failure. Treatment with recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) increases hematocrit values and thus reduces the anemia, in turn improving brain and cognitive function, exercise tolerance, sexual potency, and quality of life.

Anemia↗

PubMed1994

The effects of 4-aminopyridine on cognitive function in patients with multiple sclerosis: a pilot study.

4-Aminopyridine (4-AP) has a favorable effect on the disability of certain patients with MS. We investigated the effect of 4-AP on neuropsychological performance in 20 MS patients using a randomized, double-blind, placebo-controlled, crossover design. Although there was a trend for improved performance with 4-AP for two of the tests, we could not demonstrate significant effects of 4-AP on cognitive function.

4-Aminopyridine↗

PubMed1982

Anaesthesia and cognitive functioning. Mental function in postoperative day patients at the time of their release.

Day care patients at Law Hospital, who had received either a general or a local anaesthetic in conjunction with minor surgery, were assessed by five tests of mental function before surgery and before discharge from hospital some hours after surgery. These patients did not perform differently from control patients, who were subjected to the same two testing sessions, without intervening surgery or anaesthesia. It was concluded that the day cases were quite capable of normal cognitive functioning at the time of their discharge and that the procedures followed by the hospital for the discharge of day cases are generally adequate.

Adult↗

PubMed2006

Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function.

BACKGROUND: Low doses of psychostimulants, such as methylphenidate (MPH), are widely used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Surprisingly little is known about the neural mechanisms that underlie the behavioral/cognitive actions of these drugs. The prefrontal cortex (PFC) is implicated in ADHD. Moreover, dopamine (DA) and norepinephrine (NE) are important modulators of PFC-dependent cognition. To date, the actions of low-dose psychostimulants on PFC DA and NE neurotransmission are unknown. METHODS: In vivo microdialysis was used to compare the effects of low-dose MPH on NE and DA efflux within the PFC and select subcortical fields in male rats. Doses used (oral, 2.0 mg/kg; intraperitoneal, .25-1.0 mg/kg) were first determined to produce clinically relevant plasma concentrations and to facilitate both PFC-dependent attention and working memory. RESULTS: At low doses that improve PFC-dependent cognitive function and that are devoid of locomotor-activating effects, MPH substantially increases NE and DA efflux within the PFC. In contrast, outside the PFC these doses of MPH have minimal impact on NE and DA efflux. CONCLUSIONS: The current observations suggest that the therapeutic actions of low-dose psychostimulants involve the preferential activation of catecholamine neurotransmission within the PFC.

Adrenergic Uptake Inhibitors↗

PubMed1996

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↗

PubMed2005

Middle-aged children of persons with Alzheimer's disease: APOE genotypes and cognitive function in the Wisconsin Registry for Alzheimer's Prevention.

Adult children of persons with Alzheimer's disease are at increased risk of developing Alzheimer's disease because of hereditary, environmental, and health risk factors shared with affected parents. The Wisconsin Registry for Alzheimer's Prevention (WRAP) has completed baseline assessments on 452 middle-aged persons (mean = 53 years) who have at least 1 parent with AD. Forty-five percent had 1 or more apolipoprotein (APOE) epsilon4 alleles. There were few significant differences between epsilon4 carriers and noncarriers in demographics, health, and lifestyle measures or in neuropsychological performance. The high percentage of WRAP participants who are carriers of APOE epsilon4 underscores their increased risk for developing Alzheimer's disease, but the absence of differences related to APOE status and high mean scores on cognitive tests suggests that the APOE epsilon4 gene has yet to have a clinical impact on cognitive functioning. The WRAP cohort may be a valuable group to follow prospectively to characterize the nature of cognitive change in relation to risk factors and to identify underlying preclinical neurobiological changes.

Alzheimer Disease↗

PubMed1987

Comparison of the effects of atropine and glycopyrrolate on cognitive function following general anaesthesia.

Tests of orientation, concentration and short-term visual memory were used to assess 72 patients 1 day before, and 2 days after, elective major surgery. Patients were premedicated with papaveretum and either atropine or glycopyrrolate, before receiving a standard general anaesthetic. Those who had received atropine showed significant postoperative short-term memory deficit (P less than 0.01), but no change in orientation or concentration. Those who had been given glycopyrrolate showed no significant cognitive changes after surgery. As glycopyrrolate does not cross the blood-brain barrier freely, these findings support the involvement of central cholinergic mechanisms in the deterioration of cognitive function in the postoperative period.

Adult↗

PubMed1996

The coherent frequency in the electroencephalogram as an objective measure of cognitive function during propofol sedation.

Ten volunteers were studied during six stages of propofol sedation, namely awake (no propofol), light sedation (small dose of propofol), deep sedation (large dose), deep sedation with stimulation of the ulnar nerve, then light sedation again (small dose), and awake (recovery). Light and deep sedation were defined in terms of performance on a test of cognitive function: the within-list recognition (WLR) test. At each stage, the steady-state auditory evoked potential was measured at different stimulating frequencies to derive the frequency needed to achieve the maximal coherence index. This frequency is called the "maximum coherent frequency". WLR performance correlated with infusion dose (r = -0.71), plasma propofol concentration (r = -0.75), and maximum coherent frequency (r = 0.75). When the correlations were examined for the propofol sedation stages only, there remained a strong correlation between WLR performance and maximum coherent frequency (r = 0.47, P < 0.005), but no significant correlations between infusion dose and WLR (r = -0.11) or infusion dose and plasma concentration (r = 0.13). These data suggest that maximum coherent frequency provides a better measure of depth of sedation than does the dose of propofol alone.

Anesthesia Recovery Period↗

PubMed2006

Cognitive function during early abstinence from opioid dependence: a comparison to age, gender, and verbal intelligence matched controls.

BACKGROUND: Individuals with opioid dependence have cognitive deficits during abuse period in attention, working memory, episodic memory, and executive function. After protracted abstinence consistent cognitive deficit has been found only in executive function. However, few studies have explored cognitive function during first weeks of abstinence. The purpose of this study was to study cognitive function of individuals with opioid dependence during early abstinence. It was hypothesized that cognitive deficits are pronounced immediately after peak withdrawal symptoms have passed and then partially recover. METHODS: Fifteen patients with opioid dependence and fifteen controls matched for, age, gender, and verbal intelligence were tested with a cognitive test battery When patients performed worse than controls correlations between cognitive performance and days of withdrawal, duration of opioid abuse, duration of any substance abuse, or opioid withdrawal symptom inventory score (Short Opiate Withdrawal Scale) were analyzed. RESULTS: Early abstinent opioid dependent patients performed statistically significantly worse than controls in tests measuring complex working memory, executive function, and fluid intelligence. Their complex working memory and fluid intelligence performances correlated statistically significantly with days of withdrawal. CONCLUSION: The results indicate a rather general neurocognitive deficit in higher order cognition. It is suggested that cognitive deficit during early abstinence from opioid dependence is related to withdrawal induced neural dysregulation in the prefrontal cortex and is partly transient.

Adult↗

PubMed2005

Health related quality of life, cognitive function, and depression in diabetic patients with foot ulcer or amputation. A preliminary study.

BACKGROUND: Diabetic foot ulcers, foot infection, Charcot foot arthropathy, and lower extremity amputation have a severe negative effect on the health-related quality of life in individuals with diabetes. The purpose of this study was to determine if there is a relationship between these negative effects and cognitive impairment or clinical depression. METHODS: Sixty adults with diabetes completed the Short Form 36 (SF-36) Health Survey questionnaire, two screening examinations for cognitive function (Mini Mental Exam and Clock-Drawing Test), and a screening examination for depression (Zung Self-Rating Depression Scale). The two focus groups were composed of 20 subjects each who were undergoing treatment for (1) diabetic foot ulcers or active Charcot foot arthropathy or (2) lower extremity amputation. Twenty diabetic individuals without foot-related morbidity but with evidence of peripheral neuropathy as measured by insensitivity to the Semmes-Weinstein 5.07 (10 gm) monofilament comprised the control group. RESULTS: The SF-36 Health Survey score was significantly impaired in both the diabetic foot ulcer and Charcot arthropathy group (p <0.001) and amputee (p <0.000) group. There was no evidence of cognitive impairment or depression in either group. The negative impact on health-related quality of life was similar in both focus groups (p <0.314). CONCLUSION: The results of this preliminary study suggest that the negative impact on health-related quality of life in diabetic patients with foot ulcers or Charcot foot arthropathy may be as severe as in similar patients with lower extremity amputation. The negative effect did not seem to cause cognitive impairment or clinical depression in either focus group.

Adult↗

PubMed1994

Effects of vigabatrin on partial seizures and cognitive function.

Forty five patients with refractory partial seizures were studied in a prospective, randomised, placebo controlled, add on, parallel group, double blind trial of the new antiepileptic drug vigabatrin (1.5 g twice daily) followed by open treatment. Seizure frequency was monitored throughout an eight week baseline, 20 weeks double blind, and up to 18 months of open vigabatrin treatment. Cognitive function, including measures of memory and concentration, mood, and behaviour were assessed at baseline and again during the 20th week of treatment. Vigabatrin was associated with a significant reduction in a measure of motor speed and overall score on a design learning test in the first 20 weeks of treatment. In comparison with the baseline period, vigabatrin treatment was associated with a significant reduction in median complex partial seizure frequency four to 12 and 12 to 20 weeks after commencing vigabatrin (-66% and -69% in the vigabatrin group, +50% and +25% in the placebo group). Ten of 20 patients on vigabatrin and four of 23 on placebo showed a > 50% reduction in complex partial seizure frequency in the last eight weeks of double blind treatment. At least 60% of responders had maintained the response to vigabatrin when assessed during the open phase of the trial at 44 weeks. Two patients discontinued vigabatrin because of depression, which resolved on drug withdrawal.

Adolescent↗

PubMedDate not supplied

Prevalence of disorders of executive cognitive functioning among the elderly: findings from the San Luis Valley Health and Aging Study.

The San Luis Valley Health and Aging Study is a population-based epidemiologic study of chronic illness and disability among Hispanic and non-Hispanic white persons over the age of 60 in two counties in rural southern Colorado, USA. Between 1993 and 1995, we examined the prevalence of impaired executive cognitive functioning in a sample of 1,313 individuals living both in the community and in nursing homes. Overall, 1 person in 3 was found to have at least mild impairment, while 1 in 6 had moderate to severe deficits. Increasing levels of executive functioning impairment were associated with lower education, advancing age, and Hispanic ethnicity. After controlling for education and acculturation, the differences by ethnic group were no longer significant.

Aged↗

PubMed2002

Factors affecting cognitive functioning in a sample of human immunodeficiency virus-positive injection drug users.

Injection drug users represent a major vector of human immunodeficiency virus (HIV) infection in the nation's inner cities, and are an important population for harm reduction treatment interventions to target. However, there has been relatively little research examining the specific contribution of the multiple factors contributing to cognitive functioning among injection drug users that may affect engagement in, and response to, addiction and HIV-related interventions. The current study examined the independent contributions to neuropsychological (NP) test performance of premorbid educational attainment, medical and psychiatric history, long- and short-term drug use, assessed by laboratory, observation, and self-report measures, and HIV disease, assessed by plasma HIV-1 RNA viral load and CD4+ count, in a sample of 90 HIV-positive injection drug users dually addicted to heroin and cocaine. Fully 88% of the sample showed evidence of impairment (>1 standard deviation below the population mean) on an NP test battery selected to assess processes associated with successful engagement in the treatment of substance abuse and HIV, such as learning and memory of verbal information, capacity to solve new problems and deal with more than one stimulus at a time, visual-motor coordination, and visual tracking and cognitive flexibility. In addition to drug use, independent predictors of NP test performance were HIV viral load, educational attainment, and premorbid medical and psychiatric problems. Findings underscore the multiplicity of factors that contribute to cognitive impairment in HIV-positive drug-abusing individuals in addition to drug use. Clinical implications are discussed.

Adult↗

PubMedDate not supplied

[Medical engineering computer technologies of testing cognitive functions in children].

Studies of higher mental functions in children are shown to present great difficulties in many parameters. Analysis has provided a number of requirements for medical devices and complexes and principles of their construction. Based on these data, the authors have developed and put computer test systems into practice, their advantages being shown. The studies of cognitive functions in children by using computer test systems are dealt with.

Adolescent↗

PubMedDate not supplied

Longitudinal changes in cognitive function and regional cerebral function in Alzheimer's disease: a SPECT blood flow study.

In Alzheimer's disease (AD), SPECT imagining of regional cerebral blood flow (rCBF) has emphasized deficits in the posterior association cortex. Previous studies have shown an association between these deficits and cognitive performance, both on overall cognitive tests and more specific tests such as praxis and language. Frontal deficits have been reported in more severe patients. This has led to the conclusion that the deficit in AD, at least with functional neuroimaging, starts in the posterior association cortex, and later in the disease process "spreads" to involve the frontal cortex. This study set out to measure, in a group of AD patients, the change over time of cognitive performance and the pattern of functional deficit measured by neuroimaging. Change in function was measured using 99TCm-HMPAO and SPECT and change in cognitive function using the CAMCOG. Two time points were used, 0 and 2 years. Twenty-four patients satisfying the DSM-III R criteria for probable AD were studied, nine of whom were subsequently diagnosed as having AD at post-mortem. The most striking finding was the effect that decreases in frontal lobe function had on cognitive function. A similar study by the same group, using the same techniques and many of the same patients but at only one time point, showed a correlation between cognitive function and rCBF in the parietal and posterior temporal lobes. This suggests that as AD patients deteriorate from unaffected to mild or moderately affected, the posterior association cortex exerts the greatest effect on cognitive deficit. In this longitudinal study, we found, using a MANOVA, that there were significant decreases over time for all the cortical regions studied, but that no region decreased significantly more than any other. In addition we found a correlation between change in frontal rCBF and change in cognitive function (both overall cognitive function and the CAMCOG sub tests of language and praxis). These data suggest, in contrast to the previous study, that as the disease progresses from mild or moderate to moderate or severe, the frontal cortex exerts the greatest effect on cognitive decline. These data support the concept of the deficit in functional imaging spreading from posterior to anterior as the disease progresses. However, both the initial pattern of deficit and the change over time were very heterogeneous when examined qualitatively. A posterior to anterior spread is the predominant pattern for the group as a whole, but individual patients, and possibly groups of patients, may well show alternative patterns.

Aged↗

PubMed1989

Cognitive functioning in lead workers.

In a cross sectional study of occupational exposure to inorganic lead 91 men performed a series of microcomputer based tasks assessing sensor motor reaction time, memory, attention, verbal reasoning, and spatial processing. Performance on the tasks was studied in relation to three ranges of blood lead concentration (low, less than 20 micrograms/dl; medium, 21-40 micrograms/dl; and high, 41-80 micrograms/dl) and exposure response correlations for blood lead concentration, zinc protoporphyrin (ZPP) (range 7-210 micrograms/dl), and urinary aminolaevulinic acid (ALA) (range 0.5-22.0 mg/l). The results show that the high group were impaired on most of the tasks used and, in general, the magnitude of the impairment correlated better with blood lead concentration than ZPP or urinary ALA. An examination of the patterns of task impairment indicated a general slowing of sensory motor reaction time which was relatively independent of the nature of the cognitive functions being tested. There was some evidence, however, suggesting mild impairment of attention, verbal memory, and linguistic processing. In general, workers with high blood lead concentrations showed clear impairment of sensory motor functions in the absence of correspondingly strong evidence for impaired processing and memory functions. It is argued that a general slowness in responding may underlie many previous reports of widespread cognitive impairment in lead workers.

Adult↗

PubMed2006

Differential CSF butyrylcholinesterase levels in Alzheimer's disease patients with the ApoE epsilon4 allele, in relation to cognitive function and cerebral glucose metabolism.

Butyrylcholinesterase (BuChE) is increased in the cerebral cortex of Alzheimer's disease (AD) patients, particularly those carrying epsilon4 allele of the apolipoprotein E gene (ApoE) and certain BuChE variants that predict increased AD risk and poor response to anticholinesterase therapy. We measured BuChE activity and protein level in CSF of eighty mild AD patients in relation to age, gender, ApoE epsilon4 genotype, cognition and cerebral glucose metabolism (CMRglc). BuChE activity was 23% higher in men than women (p<0.03) and 40-60% higher in ApoE epsilon4 negative patients than in those carrying one or two epsilon4 alleles (p<0.0004). CSF BuChE level correlated with cortical CMRglc. Patients with high to moderate CSF BuChE showed better cognitive function scores than others. We hypothesize that CSF BuChE varies inversely with BuChE in cortical amyloid plaques. Thus, low BuChE in a patient's CSF may predict extensive incorporation in neuritic plaques, increased neurotoxicity and greater central neurodegeneration.

Acetylcholine↗