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Biomedical subjects

Paul Maruff

Publications and source records attributed to Paul Maruff.

At least 19 recordsLinked to original sources
PubMed2006

Valproic acid is associated with cognitive decline in HIV-infected individuals: a clinical observational study.

BACKGROUND: Valproic acid (VPA) is often used to control pain in HIV-related neuropathy. However, the effect of VPA on cognitive functions in advanced HIV-infected individuals is largely unknown. A recent study would suggest that it may have a neuroprotective effect, the doses used were low and the observation period short. METHODS: We used a well studied HIV-infected cohort assessed for a median of 15 (range 6-27 months) to determine whether individuals who were receiving VPA showed any cognitive benefits. Multiple regression procedures allowed us to control for the effects of HAART and HIV disease status as well as numbers of visits and variation in VPA intake over-time. RESULTS: We found a negative effect of VPA (mean dose of 850 mg/d for 18 months on average; range 6-27 months) on cognitive performance in eight advanced HIV-infected individuals compared to 32 advanced HIV-infected individuals on no VPA who had comparable neuropsychological performance at baseline. Control for plasma HIV viral load provided similar results. CONCLUSION: Our results suggest that further studies of VPA in advanced HIV-infection should cautiously include high doses over prolonged periods of at least 18 months in order to more accurately determine whether the posited neuroprotective benefit of VPA still occurs or whether it is replaced by toxicity.

Cognition↗
PubMed2006

Evaluating brain activity in obsessive-compulsive disorder: preliminary insights from a multivariate analysis.

Obsessive-compulsive disorder (OCD) has been linked to a dysfunction of brain corticostriatal networks, although functional imaging studies of OCD rarely apply network-sensitive analysis methods. In this study, we compared a univariate and a multivariate analysis of PET data in OCD patients and healthy subjects; the latter approach was considered more suitable for characterizing functional networks of brain activity. Although both methods suggested there was abnormal corticostriatal activity in OCD patients, the nature, extent and magnitude of this activity was clearly enhanced by the multivariate approach. Implications for the analysis of such studies are discussed.

Adult↗
PubMed2006

The influence of different error estimates in the detection of post-operative cognitive dysfunction using reliable change indices with correction for practice effects.

The reliable change index (RCI) expresses change relative to its associated error, and is useful in the identification of post-operative cognitive dysfunction (POCD). This paper examines four common RCIs that each account for error in different ways. Three rules incorporate a constant correction for practice effects and are contrasted with the standard RCI that had no correction for practice. These rules are applied to 160 patients undergoing coronary artery bypass graft (CABG) surgery who completed neuropsychological assessments preoperatively and 1 week post-operatively using error and reliability data from a comparable healthy non-surgical control group. The rules all identify POCD in a similar proportion of patients, but the use of the within subject standard deviation, expressing the effects of random error, as an error estimate is a theoretically appropriate denominator when a constant error correction, removing the effects of systematic error, is deducted from the numerator in a RCI.

Aged↗
PubMed2006

Variable benefit in neuropsychological function in HIV-infected HAART-treated patients.

The authors examined cognitive performance change in 101 individuals with advanced HIV infection on highly active antiretroviral therapy (HAART), using standard neuropsychological testing in three visits, over a 27-month-period. Cognitive performance stabilized in a majority of HIV+ participants over time. A neuroactive HAART regimen was associated with neuropsychological improvement. Decline occurred in a minority with lower nadir CD4. The current CD4 count and plasma viral load were not associated with cognitive change.

AIDS Dementia Complex↗
PubMed2006

The effects of growth hormone (GH) deficiency and GH replacement on cognitive performance in adults: a meta-analysis of the current literature.

OBJECTIVE: There is growing evidence in the neuropsychological literature that growth hormone (GH) deficiency is associated with cognitive impairment. There is also evidence that this impairment may be ameliorated with GH replacement therapy. The current study assessed the nature and severity of cognitive impairment associated with growth hormone deficiency, as well as effect of GH replacement on cognitive function by conducting a meta-analysis of the published literature to date. METHOD: Thirteen studies met the inclusion criteria and these included: five cross-sectional studies investigating GH deficiency; and, eight (eight prospective, two of which also included cross-sectional comparisons) investigating GH replacement. Effect sizes (Cohen's d) falling into six cognitive domains were computed (separately for GH deficiency and GH replacement). RESULTS: For GH deficiency, each of the cognitive domains assessed (besides language) showed moderate to large impairments when compared to matched controls (Effect sizes -0.46 to -1.46). For GH replacement, even though treated patients still performed moderately to largely below that of controls, when compared to their own baselines (as in prospective analyses), moderate improvements were found in cognitive performance, particularly attention and memory. CONCLUSION: This meta-analysis clearly demonstrates the link between GH and cognitive performance, where poor performance can be ameliorated with GH treatment.

Adolescent↗
PubMed2006

A statistical approach for classifying change in cognitive function in individuals following pharmacologic challenge: an example with alprazolam.

INTRODUCTION: The effects of any drug treatment on cognitive function are typically studied in groups of subjects. Observations made about the behavior of the drug, in the study sample, are then generalized to the population from which the sample was drawn. However, the magnitude and pharmacodynamic qualities of the response to many central nervous system-active drugs are known to vary in the population. Therefore, it is useful to consider statistical models for the detection of cognitive change in response to a drug treatment in individual subjects. MATERIALS AND METHODS: In this report, we first outline the statistical assumptions and requirements for the reliable estimation of clinically relevant individual change in cognition. We then used the sedative benzodiazepine, alprazolam, as a pharmacologic challenge in healthy volunteer subjects to test our statistical model, using a parallel groups placebo-controlled study design. After treatment, the nature and severity of alprazolam-induced cognitive change was determined for each individual. RESULTS: Our proposed method and analysis showed an excellent sensitivity and specificity for alprazolam-related cognitive deterioration in individuals. DISCUSSION AND CONCLUSIONS: These findings, although preliminary, suggest that statistically reliable decisions about the effects of sedative drugs on cognition can be made for individuals.

Adult↗
PubMed2006

Assessing cognitive function in cancer patients.

GOALS OF WORK: Some patients with cancer suffer cognitive impairment after chemotherapy. A brief, sensitive instrument is required to screen patients for cognitive impairment. In this study, we compare three possible screening instruments. MATERIALS AND METHODS: Cancer patients (n=31) who had received adjuvant chemotherapy within 2 years underwent cognitive evaluation on three occasions. Fluent English speakers (n=20) completed the High Sensitivity Cognitive Screen (HSCS), the computer-based Headminder and CogHealth, and the Functional Assessment of Cancer Therapy-cognitive function (FACT-COG) questionnaire. Patients not fluent in English (NESB) (n=11) performed CogHealth and Headminder. RESULTS: The patients were aged 31-65 years, and 94% were women with breast cancer. At baseline, 6 of 20 (30%) had moderate-severe cognitive impairment on HSCS, 17 of 31 (55%) had scores greater than one standard deviation (SD) below the mean for normative data in one to two of three domains on Headminder, and on CogHealth, 8 of 31 (26%) were greater than one SD below the mean in at least two of six domains. A large practice effect was seen for the HSCS, with moderate-severe cognitive impairment decreasing from 30 to 5% between the first and second assessment. On FACT-COG, 9 of 19 patients (47%) rated their cognition as greater than one SD below that of a pre-chemotherapy breast cancer control group, with impact on quality of life greater than one SD below for 10 of 19 (53%) patients. No correlation was seen between objective cognitive testing and the FACT-COG. CONCLUSIONS: CogHealth and Headminder were suitable for NESB patients. The HSCS is not recommended for longitudinal studies with short intervals between testing due to practice effect. There is poor correlation between the patients' perception of their cognitive impairment and the objective tests.

Adult↗
PubMed2006

Cognitive function in growth hormone deficiency and growth hormone replacement.

There is converging evidence from neuropsychological studies that growth hormone (GH) is associated with cognitive function. The aim of the current study was to review the existing neuropsychological literature for studies in which cognitive assessment had been conducted in patients with GH deficiency (GHD), and where change in cognitive function had been assessed following treatment with GH. Studies that have investigated relationships between GH and cognitive function and those that have developed methodological and statistical approaches that could be useful in future GH studies were identified. In this review, GH levels were found to be associated with cognitive function. Untreated individuals with GHD showed reliable impairment in memory and attentional functions when compared with matched controls. Appropriately designed prospective studies also indicated that cognitive function improved with GH treatment. It was concluded that individuals with GHD do show cognitive impairment and that this is ameliorated to some extent by GH treatment. It is now important to establish the clinical importance of these findings, and further work is required to understand better the nature, magnitude and meaning of GH-related cognitive impairments and improvements.

Cognition↗
PubMed2006

Cognitive testing in early phase clinical trials: outcome according to adverse event profile in a Phase I study.

BACKGROUND: It has been proposed that objective cognitive testing provides additional information to that collected via adverse event (AE) recordings. However, in clinical trials of compounds with potentially negative effects on cognition, the results of cognitive testing may overlap with AE recordings. AIMS: To examine cognitive function in subjects who do and do not report sedation-related AEs in a Phase I clinical trial. METHODS: Five computerized cognitive tasks were administered to 28 healthy male volunteers enrolled in a simulated Phase I study using midazolam to induce sedation-related AEs and cognitive dysfunction. For each subject, the magnitude of cognitive change between pre-dose and 1 hr post-dose assessments was calculated. Group and individual level cognitive outcome was compared between subjects who did and did not report sedation-related AEs following administration of 1.75 and 5.25 mg midazolam. RESULTS: At both doses of midazolam, cognitive dysfunction was observed in both subject groups (i.e., those who did and did not report AEs). Analysis of individual outcomes identified consistent cognitive dysfunction among subjects who reported sedation-related AEs. Further, in the 5.25 mg condition a subset of individuals (66.7%) who did not report sedation-related AEs nevertheless displayed substantial cognitive dysfunction. CONCLUSIONS: Following administration of oral midazolam, there is a dissociation between sedation-related AE recordings and performance on computerized cognitive tests of motor function, attention, strategy use and problem solving, learning and delayed recall. Inclusion of computerized cognitive tests in early phase trials may allow identification of subtle cognitive change, beyond that which is possible by self-report and clinical observation.

Adolescent↗
PubMed2006

Detection of postoperative cognitive decline after coronary artery bypass graft surgery is affected by the number of neuropsychological tests in the assessment battery.

BACKGROUND: The assessment of postoperative cognitive dysfunction after coronary artery bypass graft surgery is made with the repeated administration of cognitive tests. This classification is vulnerable to error, and it has been suggested that increasing the number of tests in a battery while maintaining constant inclusion criteria for postoperative cognitive dysfunction increases the rate of false positive classification of deterioration. The current study tested this by applying a constant rule for cognitive dysfunction using combinations of two to seven cognitive tests. METHODS: Two hundred and four coronary artery bypass graft patients (surgical) and 90 healthy nonsurgical controls aged 55 years or older completed a battery of cognitive tests at baseline (preoperative) and 1 week later (postoperative). In both groups, postoperative cognitive dysfunction was classified using all unique combinations of two to seven cognitive tests when performance deteriorated on two or more tests by at least the value of the baseline standard deviation. RESULTS: The average incidence of cognitive dysfunction progressively increased in both groups as the number of cognitive tests increased from two (surgical: 13.3%; control: 3.1%) to seven tests (surgical: 49.4%; control: 41.1%). CONCLUSIONS: Increasing the number of tests used to classify postoperative cognitive dysfunction appears to increase the sensitivity to change in the coronary artery bypass graft group. However, accompanying false positive classifications suggest that this improved sensitivity reflected increased error. Future rules for postoperative cognitive dysfunction need to account for this error and include a control group.

Aged↗
PubMed2006

Cognitive effects of immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder.

A growing body of literature has examined the cognitive effects of immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). However, a clear understanding of the types and magnitude of such effects are difficult to discern from such a large and varied collection of published reports. This review evaluated a total of 40 relevant placebo-controlled studies published since Rapport and Kelly's [1993. Psychostimulant effects on learning and cognitive function. In: Matson, J.L. (Ed.), Handbook of Hyperactivity in Children. Allyn & Bacon, Boston, pp. 97-136] original review of cognitive effects of methylphenidate in children with ADHD. Of these published studies, 63.5% identified some improvement in cognitive function following methylphenidate treatment. Methylphenidate improved performance on saccadic eye movement, planning/cognitive flexibility, attention/vigilance, and inhibitory control tasks in 83.3%, 71.4%, 70.6%, and 69.7% of studies, respectively. A total 58.3% and 50% of studies that evaluated the effect of methylphenidate on tasks of memory and working memory/divided attention, respectively, noted improvement. Variability of findings across studies may be explained by differential effects of methylphenidate on brain function, intra- and inter-individual variability in medication response, methodological limitations, and problems associated with repeated neuropsychological assessment and metric properties of commonly utilised neuropsychological instruments.

Attention Deficit Disorder with Hyperactivity↗
PubMed2006

The neuropsychological profile of symptomatic AIDS and ADC patients in the pre-HAART era: a meta-analysis.

It remains essential to document the neuropsychological profile of acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) and minor forms human immunodeficiency virus (HIV)-associated neurocognitive impairment by quantifying the magnitude of impairment across eras of treatment. Indeed, with the introduction of the highly active antiretroviral therapy (HAART), there is evidence of changes in aspects of ADC. To allow quantitative and qualitative comparisons with the HAART era studies, we developed a summary of neuropsychological performance acquired in pre-HAART era studies in advanced HIV infection and ADC. Using a meta-analytical procedure and a test nomenclature that accounts for task complexity, we found that individuals with symptomatic infection (but no AIDS) demonstrated a global mild level of cognitive impairment, except for the domains complex attention/psychomotor speed, motor coordination, and learning, which showed moderate impairment. Individuals with AIDS demonstrated a global moderate level of cognitive impairment with a predominance of deficits in attention, complex attention/psychomotor speed, learning, motor coordination, with additional deficits in verbal memory and reasoning. Individuals with ADC demonstrated the most severe cognitive disturbances in domains of learning, motor coordination, with additional deficits in veibal fluency and verbal memory. Moderate impairment was evidenced in domains of complex attention/psychomotor speed, whereas naming and visuospatial functions were relatively preserved. The profile of deficits in ADC suggests that it may not be only interpreted as a worsening form of the impairment that is seen in the AIDS and symptomatic stages of HIV disease but that there are also additional deficits suggestive of an alternate pathogenetic process(es).

AIDS Dementia Complex↗
PubMed2006

The development of sustained attention in children: the effect of age and task load.

This study explored how children's sustained attention develops and the effect of manipulating task parameters on sustained attention. The sample comprised 57 children (5-12 years) who completed CogState and Score! (Test of Everyday Attention for Children). Novel variability and traditional indices indicated rapid development from 5-6 to 8-9 years on all measures and a developmental plateau from 8-9 to 11-12, with growth evident on some measures. Findings suggest that sustained attention improves to age 10, then plateaus with only minor improvements. Further, performance was generally poorer on high load tasks compared to low load, with the same developmental pattern uncovered.

Age Factors↗
PubMed2006

Practice effects associated with the repeated assessment of cognitive function using the CogState battery at 10-minute, one week and one month test-retest intervals.

There are many situations in which cognitive tests need to be administered on more than two occasions and at very brief test-retest intervals to detect change in group performance. However, previous literature has not specifically addressed these important issues. The main aim of the current study was to examine these two factors by using a computerized cognitive battery designed specifically for the repeated assessment of cognition (i.e., CogState) in healthy young adult individuals. A further aim of the study was to examine how many times the battery needed to be completed before performance, as measured by the battery, stabilized. Forty-five adults (age range: 18-40 years) completed the battery four times at 10-minute test-retest intervals, and a fifth time at an interval of one week. The results illustrated that when brief test-retest intervals were used (i.e., 10 minutes), performance stabilized after the second assessment, as significant practice effects were generally observed between the first and the second assessments. Practice effects were also observed on some of the tasks at a one-week test-retest interval. Due to these findings, 55 adults (age range: 18-40 years) completed the battery twice at 10-minute test-retest intervals (i.e., to eliminate the initial practice effect), and a third time at an interval of one month. No practice effects were observed. The implications of the results are discussed in terms of methods that can be adopted in order to minimize practice effects when this particular cognitive battery is used.

Adolescent↗
PubMed2006

A comparison of the effect of high- and low-dose fentanyl on the incidence of postoperative cognitive dysfunction after coronary artery bypass surgery in the elderly.

BACKGROUND: Postoperative cognitive dysfunction (POCD) after coronary artery bypass graft surgery is a common complication for which, despite many clinical investigations, no definitive etiology has been found. The current use of both high- and low-dose fentanyl as anesthetic techniques allowed us to investigate the effect of fentanyl on the incidence of POCD. METHODS: Three hundred fifty patients scheduled to undergo elective coronary artery bypass graft surgery were randomized to receive either high-dose fentanyl (50 microg/kg) or low-dose fentanyl (10 mug/kg) as the basis of the anesthetic. All patients underwent neuropsychological testing before surgery and at 1 week, 3 months, and 12 months after surgery. RESULTS: One hundred sixty-eight patients in the low-dose group and 158 patients in the high-dose group were included in the final analysis. Neuropsychological testing was performed on 88%, 93%, and 92% of patients at 1 week, 3 months, and 12 months, respectively. There was no difference between group mean scores at any of the three testing times. Analysis of individual patients by the 20% rule did not detect any differences between groups. The one SD rule, which has fewer false-positive results, detected significantly more patients with POCD in the low-dose group than in the high-dose group at 1 week (23.6% vs. 13.7%; P = 0.03) but not at the other testing times. Patients with POCD spent an average of 1.2 days longer in the hospital than those without POCD (P = 0.021). CONCLUSIONS: High-dose fentanyl is not associated with a difference in the incidence of POCD at 3 or 12 months after surgery. Low-dose fentanyl leads to shorter postoperative ventilation times and may be associated with a greater incidence of POCD 1 week after surgery. Early POCD is associated with an increased duration of stay in the hospital.

Aged↗
PubMed2006

Changes in cannabis use and its consequences over 3 years in a remote indigenous population in northern Australia.

BACKGROUND: Few studies describe cannabis use in indigenous populations, and no longitudinal studies are available in Australia. We conducted 3-year follow-up interviews and assessments in Aboriginal communities in Arnhem Land (Northern Territory, NT). METHODS: A randomly selected sample (n = 161; 80 males, 81 females aged 13-36 years) was assessed in October 2001 and then reassessed in September 2004. An opportunistically recruited sample (n = 104; 53 males, 51 females aged 13-36 years) was also interviewed in 2001 and followed-up in 2004. Cannabis and other substance use were determined by combining proxy assessments by local Aboriginal health workers, medical records and data from interviews. Changes in cannabis use and symptoms of misuse were assessed using McNemar's test for paired proportions and the Wilcoxon signed rank test. Logistic regression assessed associations between clinical presentations and cannabis use at both time-points. RESULTS: Those who used cannabis at both baseline and follow-up were at greater risk than those who never used it to have suffered: auditory hallucinations; suicidal ideation; and imprisonment. In the randomly selected cohort there were fewer cannabis users at follow-up than at baseline (P = 0.003). The reduction was evident in females generally (P = 0.008) and older males (aged = 16 at baseline) (P = 0.007). In those interviewed at both baseline and follow-up we measured no statistically significant reduction in frequency and levels of use, although fewer cannabis users reported symptoms of misuse such as: fragmented thought processes; memory disruption; difficulties controlling use; and auditory and visual hallucinations. CONCLUSIONS: Modest reductions in cannabis use and its consequences in this population were demonstrated. These may be the result of enhanced supply control and broader socio-political changes.

Adolescent↗
PubMed2005

The assessment of cognitive function in advanced HIV-1 infection and AIDS dementia complex using a new computerised cognitive test battery.

The validity of a new computerised battery called CogState was determined in 60 individuals with advanced human immunodeficiency virus-1 (HIV-1) infection from which eleven were assessed as AIDS dementia complex (ADC) stage 1 or 2. Twenty-one seronegative individuals were recruited as controls. Participants were evaluated with a brief computerised examination, lasting 10-15 min, assessing reaction time, accuracy in working memory and learning. They were also assessed with a standard neuropsychological examination lasting 1h 30 min on average. The computerised assessment demonstrated a good sensitivity of 81.1% and specificity of 69.9% as well as good positive predictive value (81%) and acceptable construct validity (.45-.62). Slowed reaction time and learning deficits in the computerised battery were characteristic of ADC. This study supports the utility of a brief computerised battery in the detection of HIV-associated neurocognitive impairment that could be used for wide-scale screening.

AIDS Dementia Complex↗