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Biomedical subjects

Paul Maruff

Publications and source records attributed to Paul Maruff.

At least 37 records · Page 2Linked to original sources

The nature and severity of cognitive impairment associated with adjuvant chemotherapy in women with breast cancer: a meta-analysis of the current literature.

OBJECTIVE: Several studies have identified that adjuvant chemotherapy for breast cancer is associated with cognitive impairment; however, the magnitude of this impairment is unclear. This study assessed the severity and nature of cognitive impairment associated with adjuvant chemotherapy by conducting a meta-analysis of the published literature to date. METHOD: Six studies (five cross-sectional and one prospective) meeting the inclusion criteria provided a total of 208 breast cancer patients who had undergone adjuvant chemotherapy, 122 control participants and 122 effect sizes (Cohen's d) falling into six cognitive domains. First, the mean of all the effect sizes within each cognitive domain was calculated (separately for cross-sectional and prospective studies); second, a mean effect size was calculated for all of the effect sizes in each cross-sectional study; and third, regression analyses were conducted to determine any relationships between effect size for each study and four different variables. RESULTS: For the cross-sectional studies, each of the cognitive domains assessed (besides attention) showed small to moderate effect sizes (-0.18 to -0.51). The effect sizes for each study were small to moderate (-0.07 to -0.50) and regression analysis detected a significant negative logarithmic relationship (R2 = .63) between study effect size and the time since last receiving chemotherapy. For the prospective study, effect sizes ranged from small to large (0.11-1.09) and indicated improvements in cognitive function from the beginning of chemotherapy treatment to 3 weeks and even 1 year following treatment. CONCLUSION: This meta-analysis suggests that cognitive impairment occurs reliably in women who have undergone adjuvant chemotherapy for breast cancer but that the magnitude of this impairment depends on the type of design that was used (i.e., cross-sectional or prospective). Thus, more prospective studies are required before definite conclusions about the effects of adjuvant chemotherapy on cognition can be made.

Analysis of Variance↗

A manual and automated MRI study of anterior cingulate and orbito-frontal cortices, and caudate nucleus in obsessive-compulsive disorder: comparison with healthy controls and patients with schizophrenia.

Functional imaging and neuropsychological data suggest that interconnected brain structures including the orbito-frontal cortex (OFC), anterior cingulate cortex (ACC) and caudate nucleus (CN) are involved in the pathophysiology of obsessive-compulsive disorder (OCD), but structural imaging studies investigating these regions have yielded inconclusive results. This may be due to inconsistencies in the identification of anatomical boundaries and methodologies utilised (i.e. automated vs. manual tracing). This magnetic resonance imaging study used manual tracing to measure volumes of selected brain regions (OFC, ACC and CN) in OCD patients and compared them with samples of healthy (HC) and psychiatric (schizophrenia; SCZ) controls (n=18 in each group). Concurrently, automated voxel-based analysis was also used to detect subtle differences in cerebral grey and white matter. For the OCD vs. HC comparison, there were no significant volumetric differences detected using the manual or the automated method (although the latter revealed a deficit in the subcortical white matter of the right temporal region). A direct comparison of the two patient groups showed no significant differences using the manual method. However, a moderate effect size was detected for OFC grey matter (reduced in SCZ), which was supported by findings of reduced OFC volume in the automated analysis. Automated analyses also showed reduced volumes in the dorsal (white matter) and ventral ACC (grey and white matter), as well as the left posterior cingulate (grey and white matter) in SCZ. The findings suggest that in contrast to findings in SCZ, there are very few (if any) gross structural anomalies in OCD.

Adult↗

A method for determining the magnitude of change across different cognitive functions in clinical trials: the effects of acute administration of two different doses alprazolam.

While there is no doubt that benzodiazepine administration leads to transient cognitive impairment in healthy adults, the nature and magnitude of such impairment has not been well described. The cognitive effects of a single dose of alprazolam 0.5 and 1 mg were therefore assessed in 36 healthy adults on measures of psychomotor function, visual attention, working memory, planning and learning in a double-blind parallel-groups study. Measures of these different cognitive functions were selected on the basis of their brevity and because they yielded distributions of performance data that were without skew, floor or ceiling effects of range restriction (i.e. normal distributions). With data satisfying the assumptions for parametric analysis, measures of effect size could be computed in addition to significance testing, thus allowing for direct and meaningful comparison between the different performance measures used. Alprazolam 0.5 mg reduced only the speed of attentional performance although the magnitude of this reduction was large (d = 0.8). At 1.0 mg, impairments in psychomotor function, equivalent to that seen for attentional function at the lower dose, were observed. In addition, moderate (d approx = 0.5) impairments in working memory, and learning also became obvious. When considered together, these results suggest that low-dose alprazolam primarily alters visual attentional function. At the higher dose psychomotor functions also become impaired, and it is likely that the combination of these led to the observed moderate impairments in higher level executive and memory processes. The current study also illustrates a method for directly comparing the magnitude of change in cognitive function between measures with different performance metrics.

Adult↗

Neurological and cognitive recovery following abstinence from petrol sniffing.

Anecdotal observations suggest that neurological impairments associated with petrol (gasoline) sniffing resolve with abstinence, although these effects have not been proven empirically. Severe exposure to leaded petrol may induce a lead encephalopathy that extends beyond any acute intoxication and requires emergency hospital treatment. Previously, in chronic petrol sniffers, we showed neurological, saccadic, and cognitive abnormalities that were more severe in petrol sniffers with a history of hospitalization for lead encephalopathy, and that correlated with blood lead levels and the length of time of sniffing petrol. Ex-petrol sniffers showed a qualitatively similar but quantitatively less severe pattern of impairment. Petrol sniffing was stopped completely in one of the study communities by modifying social, occupational, and recreational opportunities. After 2 years, we obtained biochemical and neurobehavioral (neurological, saccade, and cognitive) data from all available participants of the earlier study including 10 nonsniffers and 29 chronic petrol sniffers, with six of these individuals previously receiving hospital treatment for lead encephalopathy. Here, we report that blood lead was reduced and that neurobehavioral impairments improved, and in many cases normalized completely. The most severe petrol-related neurobehavioral impairment was observed among individuals who had longer histories of abuse and higher blood lead levels, and among petrol sniffers with a history of lead encephalopathy. Those with the greatest extent of neurobehavioral impairment showed the greatest degree of improvement with abstinence, but were less likely to recover completely. This is the first direct evidence that neurological and cognitive impairment from chronic petrol sniffing ameliorates with abstinence and may recover completely.

Adolescent↗

Repeated assessment of cognition in children and the measurement of performance change.

There is limited understanding of the problems associated with repeated neuropsychological assessment in children, including the statistics used to guide decisions about cognitive change. This study investigated the utility of a computerized assessment battery that was specifically designed for the repeated assessment of cognitive function in children. Eighty-seven participants aged 8 to 12 years completed the battery four times within a 2-hour testing session. The results support the application of this assessment battery for measuring cognitive change in children. A novel method for calculating measurement error is employed, and its use in the detection of cognitive change in individual children is discussed. An estimate of the measurement error within each of the tests is provided, and recommendations are made regarding the application of this assessment battery for measuring cognitive change in children.

Analysis of Variance↗

Adverse mental health effects of cannabis use in two indigenous communities in Arnhem Land, Northern Territory, Australia: exploratory study.

OBJECTIVE: We investigated adverse mental health effects and their associations with levels of cannabis use among indigenous Australian cannabis users in remote communities in the Northern Territory. METHOD: Local indigenous health workers and key informants assisted in developing 28 criteria describing mental health symptoms. Five symptom clusters were identified using cluster analysis of data compiled from interviews with 103 cannabis users. Agreement was assessed (method comparison approach, kappa-statistic) with a clinician's classification of the 28 criteria into five groups labelled: 'anxiety', 'dependency', 'mood', 'vegetative' and 'psychosis'. Participants were described as showing 'anxiety', 'dependency' etc., if they reported half or more of the symptoms comprising the cluster. Associations between participants' self-reported cannabis use and each symptom cluster were assessed (logistic regression adjusting for age, sex, other substance use). RESULTS: Agreement between two classifications of 28 criteria into five groups was 'moderate' (64%, kappa = 0.55, p < 0.001). When five clusters were combined into three, 'anxiety-dependency', 'mood-vegetative' and 'psychosis', agreement rose to 71% (kappa = 0.56, p < 0.001). 'Anxiety-dependency' was positively associated with number of 'cones' usually smoked per week and this remained significant when adjusted for confounders (p = 0.020) and tended to remain significant in those who had never sniffed petrol (p = 0.052). Users of more than five cones per week were more likely to display 'anxiety-dependency' symptoms than those who used one cone per week (OR = 15.8, 1.8-141.2, p = 0.013). A crude association between the 'mood-vegetative' symptom cluster and number of cones usually smoked per week (p = 0.014) also remained statistically significant when adjusted for confounders (p = 0.012) but was modified by interactions with petrol sniffing (p = 0.116) and alcohol use (p = 0.276). There were no associations between cannabis use and 'psychosis'. CONCLUSIONS: Risks for 'anxiety-dependency' symptoms in cannabis users increased as their level of use increased. Other plausible mental health effects of cannabis in this population of comparatively new users were probably masked by alcohol use and a history of petrol sniffing.

Adolescent↗

Fatigue-related impairment in the speed, accuracy and variability of psychomotor performance: comparison with blood alcohol levels.

Cognitive performance is impaired by fatigue arising from sustained wakefulness and alcohol. Three recent papers directly compared the effects of increasing fatigue and blood alcohol concentration (%BAC) to provide a framework for understanding fatigue-related cognitive impairment. While the expression of fatigue-related cognitive impairments in terms of %BAC equivalents is sound, the methodology in each study was flawed in that the statistics used to compare the effects of %BAC and fatigue on cognition did not account for variation between or within each condition. The point estimates of the difference between a baseline and any level of fatigue or %BAC provided no indication of the size of difference that could reasonably be expected by chance. Importantly, all studies showed that variation increased as cognitive performance declined because of both increasing fatigue and %BAC. The current study compared the effect of increasing levels of %BAC and fatigue on the simple reaction task from the CogState test battery on 40 healthy adults using statistical methods that account for intra-individual and within-group variability in performance. After 24 h of sustained wakefulness and with 0.08%BAC, individuals showed maximal cognitive impairment; however, the magnitude of impairment found for fatigue was equivalent only to that observed for 0.05%BAC. Re-analysis of the data using percentage change scores indicated that the magnitude of fatigue-related cognitive impairment was much greater than that detected for 0.08%BAC. This suggests that previous studies that have not accounted for variability in the performance data have overestimated the effect of fatigue on cognitive performance.

Adolescent↗

Attention, motor control and motor imagery in schizophrenia: implications for the role of the parietal cortex.

Many recent models of schizophrenia have attempted to explain the so-called first-rank symptoms in terms of a breakdown in the self-monitoring of thoughts and behaviours. These models have focused on the most common symptom of schizophrenia auditory hallucinations-suggesting that they may represent disordered self-monitoring of internal speech. As such, much attention has been given to the role of the temporal and frontal cortices in the clinical presentation of patients with schizophrenia. In this review, we examine the role of the posterior parietal cortex (PPC) in schizophrenia within the context of recent models of self-monitoring deficits in these patients. Attentional dysfunctions and certain impairments of motor control and motor imagery all point towards the involvement of the parietal cortex in the disorder. In particular, we suggest that patients experiencing passivity phenomena (e.g., delusions of control) may have particular impairments of parietal function related to poor utilisation of forward models of intended actions. We also present a novel hypothesis that suggests differential impairments of the left and right parietal cortices in schizophrenia may help explain many of the first-rank symptoms of the disorder.

Attention↗

Neurological and cognitive impairment associated with leaded gasoline encephalopathy.

BACKGROUND: A toxic encephalopathy (or 'lead encephalopathy') may arise from leaded gasoline abuse that is characterised by tremor, hallucinations, nystagmus, ataxia, seizures and death. This syndrome requires emergency and intensive hospital treatment. METHODS: We compared neurological and cognitive function between chronic gasoline abusers with (n=15) and without (n=15) a history of leaded gasoline encephalopathy, and with controls who had never abused gasoline (n=15). RESULTS: Both groups of chronic gasoline abusers had abused gasoline for the same length of time and compared to controls, showed equivalently elevated blood lead levels and cognitive abnormalities in the areas of visuo-spatial attention, recognition memory and paired associate learning. However, where gasoline abusers with no history of leaded gasoline encephalopathy showed only mild movement abnormalities, gasoline abusers with a history of leaded gasoline encephalopathy showed severe neurological impairment that manifest as higher rates of gait ataxia, abnormal rapid finger tapping, finger to nose movements, dysdiadochokinesia and heel to knee movements, increased deep tendon reflexes and presence of a palmomental reflex. CONCLUSIONS: While neurological and cognitive functions are disrupted by chronic gasoline abuse, leaded gasoline encephalopathy is associated with additional and long-lasting damage to cortical and cerebellar functions.

Administration, Inhalation↗

Antiretroviral therapy in HIV infection: are neurologically active drugs important?

BACKGROUND: The effect on neuropsychological function of antiretroviral drugs that are able to penetrate into the brain in effective concentration (neuroactive drugs) remains unclear. OBJECTIVE: To investigate whether highly active antiretroviral therapy (HAART) containing neuroactive drugs is associated with better neuropsychological performance in patients with human immunodeficiency virus disease. DESIGN: Cross-sectional survey. SETTING: Tertiary referral hospital outpatient clinics. PATIENTS: The study population consisted of 97 individuals positive for human immunodeficiency virus (stage C3, 1993 Centers for Disease Control and Prevention classification) whose condition had been stable on their current HAART regimen for a mean +/- SD of 18.5 +/- 16.5 months and who were aged 48.14 +/- 9.38 years. The patient groups were analyzed according to whether their regimen contained 3 or more neuroactive drugs (neuroHAART group; n = 41) or not (HAART group; n = 56). Thirty seronegative men matched for age and education were recruited as controls. MAIN OUTCOME MEASURE: Neuropsychological performance on 7 cognitive domains. RESULTS: The neuroHAART and HAART groups did not differ from one another on neuropsychological performance, but both patient groups were impaired compared with controls. Impaired patients in each treatment group were compared, and the neuroHAART group showed significantly better memory performance, unrelated to plasma viral load, than the HAART group. CONCLUSION: No direct benefit of neuroactive HAART therapy was found in patients with advanced human immunodeficiency virus infection. However, in neuropsychologically impaired patients, there was a benefit in memory function. This suggests that a threshold of neuropsychological impairment is required for the benefit of neuroactive HAART.

Adult↗

Development of a statistical approach to classifying treatment response in individual children with ADHD.

The use of cognitive tests as measures of treatment response in individual children with ADHD has not been adequately evaluated or commonly applied by clinicians. This is most likely due to a lack of suitable assessment tasks as well as clinicians' limited awareness of the appropriate statistical techniques for analysing cognitive change in individuals. This study investigated the application of statistical decision rules to the cognitive and behavioural measures of individual children with ADHD in order to classify a significant, positive response to medication. The previously reported data of 14 children with ADHD (combined type; ADHD-CT) were re-analysed to investigate changes in function following a low- and high-dose of stimulant medication (2.5 mg and 7.5 mg dexamphetamine, respectively). The performances of 14 age-, gender- and IQ-matched controls was also analysed to provide an estimate of the false-positive classification rate. Overall, the decision rule yielded a high sensitivity and high specificity to treatment response. In the high-dose condition, 71% of children with ADHD demonstrated improvements in both cognitive and behavioural function. This study demonstrates an evidence-based approach to evaluating concurrent cognitive and behavioural improvement in individual children with ADHD following treatment with stimulant medication.

Attention Deficit Disorder with Hyperactivity↗

Statistical and conceptual issues in defining post-operative cognitive dysfunction.

The occurrence of post-operative cognitive dysfunction is a distressing complication following surgery. In an effort to gain a more complete understanding of patients' cognitive recovery following surgical procedures common neuropsychological assessment tools have been adopted in a repeated measures design. It is widely regarded that this represents the most comprehensive method of determining cognitive status in this population but it has resulted in a number of statistical and conceptual difficulties in attempting to infer significant change. The current paper outlines these core difficulties and provides some potential methods to overcome these.

Cognition Disorders↗

Emerging patterns of cannabis and other substance use in Aboriginal communities in Arnhem Land, Northern Territory: a study of two communities.

A recent rise in cannabis use in Indigenous communities in northern Australia may have compounded existing patterns of other substance use. This paper describes these patterns in Arnhem Land in the 'Top End' of the Northern Territory (NT). Economic impacts of the cannabis trade are also described. In a descriptive cross-sectional study, random samples included 336 people (169 males, 167 females) aged 13 - 36 years. Consensus classification of lifetime and current use of cannabis, alcohol, tobacco, kava, inhalants (petrol) and other drugs was derived based on health workers' proxy assessments. A sample (n = 180, aged 13 - 36) was recruited opportunistically for interview. Lifetime cannabis users among those interviewed (n = 131, 81 males, 50 females) described their current cannabis use, usual quantities purchased and consumed, frequency and duration of cannabis use and other substance use. In the random samples, 69% (63 - 75%) of males and 26% (20 - 31%) of females were lifetime cannabis users (OR = 7.4, 4.5 - 12.1, p < 0.001). The proportion of males currently using cannabis was 67% (60 - 73%) while the proportion of females currently using cannabis was 22% (16 - 27%) (OR = 7.9, 4.8 - 13.1, p < 0.001). Current cannabis users were more likely than non-users to be also using alcohol (OR = 10.4, 4.7 - 23.3, p < 0.001), tobacco (OR = 19.0, 7.9 - 45.8, p < 0.001) and to have sniffed petrol (OR = 9.1, 4.6 - 18.0, p < 0.001) but were less likely to be using kava (OR = 0.4, 0.2 - 0.9, p < 0.001). Among those interviewed, higher tobacco consumption in current users and greater alcohol use in lifetime users was associated with increased cannabis use. Action is required to reduce cannabis use, especially in combination with other substances.

Adolescent↗

Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a combined study of two cohorts.

The objective of this study was to assess the prevalence and pattern of neuropsychological impairment in cohorts of human immunodeficiency virus (HIV)-infected individuals across pre- and post-HAART (highly active antiretroviral therapy) eras. Two cohorts of HIV-infected individuals attending tertiary referral hospital outpatient clinics were studied. The cohorts represented two eras of antiretroviral medication: monotherapy (n = 51) and HAART (n = 90). Each was compared in nine neuropsychological domains in regard to the prevalence as well as pattern of neuropsychological impairment. Because the authors intended to characterize the prevalence and pattern of neuropsychological deficits in nondemented advanced HIV-infected individuals, patients with a current diagnosis of acquired immunodeficiency syndrome (AIDS) dementia complex were not included. The prevalence of impairment was not significantly different across pre-HAART and HAART eras using a standard criterion to define impairment: -2 SD in two neuropsychological measures (41.1%/38.8%). Prevalence of deficits was not significantly reduced in patients with undetectable plasma viral load. The pattern of neuropsychological impairment was different across pre-HAART and HAART eras, with an improvement in attention, verbal fluency, visuoconstruction deficits, but a deterioration in learning efficiency and complex attention. This change remained even in patients with an undetectable plasma viral load, although the severity was partially diminished. Neuropsychological deficits remain common in the HAART era, essentially uninfluenced by HAART. The finding that some neuropsychological functions are improving while other are deteriorating indicates that these deficits do not reflect "burnt out" damage but rather that there is an active intracerebral process occurring, the nature of which is still to be determined.

AIDS Dementia Complex↗

Abnormalities of motor imagery associated with somatic passivity phenomena in schizophrenia.

Some patients with schizophrenia report that their limbs are under the control of an alien force (motor passivity). This is hypothesised to be due to the dysfunction of an internal self-monitoring system that normally permits distinctions between internally generated and external influences on intentional behaviour. Motor imagery is the mental simulation of specific motor actions and it is based upon the internal representation of intended but unexecuted motor actions. Therefore, the generation of motor imagery should be impaired in schizophrenia characterised by passivity phenomena. The generation of motor imagery was compared using the visually guided pointing task (VGPT) and the Florida praxis imagery questionnaire (FPIQ) between patients with schizophrenia characterised by high levels of passivity symptoms (passivity) and patients without passivity symptoms (no-passivity). In both the passivity and no-passivity groups, the speed of real motor sequences on the VGPT was constrained by the distance of the movement and the width of the target in accordance with Fitts' law. For the no-passivity group, the same relationship was found for imagined movements. However, in the passivity group, imagined movements were not constrained by Fitts' law. The effect of a 2-kg load to the limb performing real or imagined movements on the VGPT was identical in both groups. The duration of imagined movements was slowed although the duration of real movements was unaffected. The FPIQ showed that the passivity group had difficulty answering questions that required them to imagine kinaesthetic aspects of performing simple gestures. These results suggest that passivity phenomena in schizophrenia are associated with a specific inability to represent the timing of motor actions internally. This is consistent with the hypothesis that patients with passivity phenomena have difficulty with maintaining an internal representation of intentional behaviour.

Adult↗

Cortical activation associated with the experience of auditory hallucinations and perception of human speech in schizophrenia: a PET correlation study.

A [H(2)(15)O] PET correlation analysis technique was employed to correlate brain activations associated with self-reports of auditory hallucinations in hallucinating patients (n=8) and perception of transient, random human speech in non-hallucinating (n=7) patients and normal control subjects (n=8). Perception of externally generated human speech amongst the non-hallucinating and normal control participants was associated with a consistent pattern of extensive bilateral auditory cortex activation (Brodmann areas 40/41/42/22). Hallucinating participants demonstrated a network of cortical activations including bilateral auditory cortex, left limbic regions, right medial frontal and right prefrontal regions. The observed pattern of activation is consistent with models of auditory hallucinations as mis-remembered episodic memories of speech.

Adult↗