Background: Traumatic brain injury (TBI) is a leading cause of disability in Australia. Evidence shows that multidisciplinary rehabilitation and support in the six months following TBI is important for successful independent living and social re-integration. Despite this, access to services and supports during this period is often limited by environmental, socio-economic, geographic and cultural factors. Australian studies on outcomes after brain injury have reported primarily on non-Indigenous people. This study will investigate key sentinel events during the transition from hospital to home after a TBI in the first longitudinal study with Indigenous Australians.

Method: Indigenous Australians admitted to one of three major trauma hospitals in northern Australia with a TBI, and their care givers, will be recruited. Clinical and brain injury risk factor information, along with measures of cognitive function, transition events, mental health and community re-integration will be collected at three time points prior to hospital discharge, and at three and six months post-discharge. Qualitative interviews will also be conducted. Data will be analysed using regression methods for the quantitative component, and situational analysis for the qualitative component. Annual rates of brain injury will be calculated for patients admitted to tertiary hospital facilities in the study region with a diagnosis of TBI.

Discussion: Understanding the experience and events which shape the transition period is critical to determining the services and supports that may enhance transition outcomes, and ensure that such services are culturally appropriate and endorsed by Indigenous families and communities.

FFQ are commonly used to examine the association between diet and disease. They are the most practical method for usual dietary data collection as they are relatively inexpensive and easy to administer. In Australia, the Cancer Council of Victoria FFQ (CCVFFQ) version 2 and the online Commonwealth Scientific and Industrial Research Organisation FFQ (CSIROFFQ) are used. The aim of our study was to establish the level of agreement between nutrient intakes captured using the online CSIROFFQ and the paper-based CCVFFQ. The CCVFFQ and the online CSIROFFQ were completed by 136 healthy participants. FFQ responses were analysed to give g per d intake of a range of nutrients. Agreement between twenty-six nutrient intakes common to both FFQ was measured by a variety of methods. Nutrient intake levels that were significantly correlated between the two FFQ were carbohydrates, total fat, Na and MUFA. When assessing ranking of nutrients into quintiles, on average, 56 % of the participants (for all nutrients) were classified into the same or adjacent quintiles in both FFQ, with the highest percentage agreement for sugar. On average, 21 % of participants were grossly misclassified by three or four quintiles, with the highest percentage misclassification for fibre and Fe. Quintile agreement was similar to that reported by other studies, and we concluded that both FFQ are suitable tools for dividing participants’ nutrient intake levels into high- and low-consumption groups. Use of either FFQ was not appropriate for obtaining accurate estimates of absolute nutrient intakes.

Although beta-amyloid, anxiety and depression have been linked cross-sectionally to reduced memory function in healthy older adults without dementia, prospective data evaluating these associations are lacking. Using data from an observational cohort study of 178 healthy older adults without dementia followed for 3 years, we found that anxiety symptoms significantly moderated the relationship between beta-amyloid level and decline in verbal (Cohen's d = 0.65) and episodic (Cohen's d = 0.38) memory. Anxiety symptoms were additionally linked to greater decline in executive function, irrespective of beta-amyloid and other risk factors. These findings suggest that interventions to mitigate anxiety symptoms may help delay memory decline in otherwise healthy older adults with elevated beta-amyloid.

Episodic memory deficits are a core feature of neurodegenerative disorders. Muscarinic M1 receptors play a critical role in modulating learning and memory and are highly expressed in the hippocampus. We examined the effect of GSK1034702, a potent M1 receptor allosteric agonist, on cognitive function, and in particular episodic memory, in healthy smokers using the nicotine abstinence model of cognitive dysfunction. The study utilized a randomized, double-blind, placebo-controlled, cross-over design in which 20 male nicotine abstained smokers were tested following single doses of placebo, 4 and 8 mg GSK1034702. Compared to the baseline (nicotine on-state), nicotine abstinence showed statistical significance in reducing immediate (p=0.019) and delayed (p=0.02) recall. GSK1034702 (8 mg) significantly attenuated (i.e. improved) immediate recall (p=0.014) but not delayed recall. None of the other cognitive domains was modulated by either nicotine abstinence or GSK1034702. These findings suggest that stimulating M1 receptor mediated neurotransmission in humans with GSK1034702 improves memory encoding potentially by modulating hippocampal function. Hence, selective M1 receptor allosteric agonists may have therapeutic benefits in disorders of impaired learning including Alzheimer's disease.

Background: Ideally putative disease-modifying therapies for Alzheimer's disease (AD) should be tested in patients who have minimal morbidity. Current barriers to such trials in early disease include the lack of disease-specific early biomarkers, insensitivity of quantitative cognitive outcome measures, and expensive trial designs requiring large sample sizes and long duration. This paper describes principles and progress towards a novel trial design that overcomes these problems, utilizing wide-scale cognitive performance screening to define pre-trial cognitive decline trajectories which can serve as trial outcome measures to assess AD disease-modifying efficacy.

Methods: Theoretical principles important for the detection of intra-individual cognitive decline and a practical example are described.

Results: Serial evaluations of community-based volunteers demonstrate how a screening tool method to detect subtle cognitive decline can predict in vivo amyloid pathology as a trigger for etiological evaluation. Trajectories of decline appear consistent over at least two years, suggesting they could be used as a trial inclusion criterion and ameliorable outcome measure together with other AD biomarkers. Informative trial durations could be 6–12 months, or extend to incorporate staggered random withdrawal or start designs, with as few as 20 individuals per treatment arm.

Conclusions: This trial methodology offers significant advantages over current AD trial designs, including treatment at earlier stages of disease, shorter trial duration, obviation of informed consent difficulties, smaller sample sizes, reduced cost and – given adequate screening programs – sufficient subjects for multiple simultaneous trials. Importantly, it allows the rapid evaluation of putative treatments that may only be efficacious in pre-dementia states.

The present study aimed to investigate the development of attention skills through middle childhood and to document developmental trajectories associated with tasks of increasing attentional demands. The sample comprised 57 children (aged 5–12 years) who were divided, according to age, into three groups. Performance differences between the groups were compared on two measures, each including four subtests of increasing complexity and tapping both speed and accuracy: CogState, a computerised measure, and The Contingency Naming Test, a paper-and-pencil test. We predicted that there would be: (1) improvements in performance with increasing age, (2) deceases in performance with increasing task complexity and (3) parallel increments in performance on computer-based and paper-and-pencil measures. The results indicated that there were rapid improvements in performance on both computer-based and paper-and-pencil measures between the ages of 5 and 8 years indicated by changes in both response speed and response accuracy. In contrast, more moderate improvements were identified between the ages of 9 to 12 years and occurred mainly in the domain of speed.

The growing need for lumbar puncture in order to obtain cerebrospinal fluid (CSF) for the diagnosis Alzheimer's disease is becoming increasingly apparent (Herskovits and Growdon, 2010). The concept of a CSF sampling unit specializing in lumbar puncture would seem the most plausible solution. Physicians and interns are not necessarily skilled in the procedure and neurologists perform lumbar puncture rarely.

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging aimed to recruit 1000 individuals aged over 60 to assist with prospective research into Alzheimer's disease (AD). This paper describes the recruitment of the cohort and gives information about the study methodology, baseline demography, diagnoses, medical comorbidities, medication use, and cognitive function of the participants.

Methods: Volunteers underwent a screening interview, had comprehensive cognitive testing, gave 80 ml of blood, and completed health and lifestyle questionnaires. One quarter of the sample also underwent amyloid PET brain imaging with Pittsburgh compound B (PiB PET) and MRI brain imaging, and a subgroup of 10% had ActiGraph activity monitoring and body composition scanning.

Results: A total of 1166 volunteers were recruited, 54 of whom were excluded from further study due to comorbid disorders which could affect cognition or because of withdrawal of consent. Participants with AD (211) had neuropsychological profiles which were consistent with AD, and were more impaired than participants with mild cognitive impairment (133) or healthy controls (768), who performed within expected norms for age on neuropsychological testing. PiB PET scans were performed on 287 participants, 100 had DEXA scans and 91 participated in ActiGraph monitoring.

Conclusion: The participants comprising the AIBL cohort represent a group of highly motivated and well-characterized individuals who represent a unique resource for the study of AD. They will be reassessed at 18-month intervals in order to determine the predictive utility of various biomarkers, cognitive parameters and lifestyle factors as indicators of AD, and as predictors of future cognitive decline.

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 verbal 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). (JINS, 2006, 12, 368–382.)

Performance on many cognitive and neuropsychological tests may be improved by prior exposure to testing stimuli and procedures. These beneficial practice effects can have a significant impact on test performance when conventional neuropsychological tests are administered at test–retest intervals of weeks, months or years. Many recent investigations have sought to determine changes in cognitive function over periods of minutes or hours (e.g., before and after anesthesia) using computerized tests. However, the effects of practice at such brief test–retest intervals has not been reported. The current study sought to determine the magnitude of practice effects in a group of 113 individuals assessed with an automated cognitive test battery on 4 occasions in 1 day. Practice effects were evident both between and within assessments, and also within individual tests. However, these effects occurred mostly between the 1st and 2nd administration of the test battery, with smaller, nonsignificant improvements observed between the 2nd, 3rd, and 4th administrations. On the basis of these results, methodological and statistical strategies that may aid in the differentiation of practice effects from drug-induced cognitive changes are proposed. (JINS, 2003, 9, 419–428.)

Background: In the 1990s, heavy kava use in Aboriginal communities was linked to reports of unusual neurological events which were often described as ‘fits’ or ‘seizures’. Kava use has also been associated with extra-pyramidal movements. We now raise the possibility that kava toxicity and kava withdrawal may be associated with grand mal seizures. This paper describes some of ’these “seizure” episodes’ in kava drinkers. Nine communities and associated homelands in the eastern Arnhem Land (Miwatj) region (Northern Territory, NT) including 7001 Aboriginal people of whom 4217 were over 15 years. Twenty-one kava users experienced 32 “seizure” episodes for which the date of occurrence and other data was recorded in notes in community health clinic files dating from the 1980s up to 1999 in a sample of the Miwatj population. Kava, alcohol, tobacco, cannabis use and petrol sniffing, year in which “seizure” occurred, notes of kava toxicity or withdrawal. Kava toxicity effects were suspected in 15 and withdrawal effects in six of 32 “seizure” episodes. In seven episodes impaired consciousness and abnormal movements were adequately documented to suggest grand mal seizures. The maximum number of “seizures” experienced was three and three individuals experienced this number between 1990 and 1999. One was a heavy kava user. Six other individuals experienced two “seizures” each and five of these were heavy users. Sixteen individuals experienced 19 “seizures” during 1994-1997 when kava supply may have reached its peak. Fifteen of the 21 individuals experiencing “seizures” were heavy users described locally as dja[aw'marama. The clinical data and the coincidence of peak supply with records of “seizures” suggest kava toxicity and withdrawal seizures may both occur with heavy kava use. Further systematic analysis is warranted to confirm this and to assess kava's effects with respect to possible confounders such as alcohol.