Self-reported confusion is related to global and regional ß-amyloid: data from the Women's healthy ageing project.

Disease-modifying treatments for Alzheimer's disease (AD) may require implementation during early stages of ß-amyloid accumulation, well before patients have objective cognitive decline. In this study we aimed to assess the clinical value of subjective cognitive impairment (SCI) by examining the cross-sectional relationship between ß-amyloid load and SCI. Cerebral ß-amyloid and SCI was assessed in a cohort of 112 cognitively normal subjects. Subjective cognition was evaluated using specific questions on memory and cognition and the MAC-Q. Participants had cerebral ß-amyloid load measured with 18F-Florbetaben Positron Emission Tomography (PET). No associations were found between measures of subjective memory impairment and cerebral ß-amyloid. However, by self-reported confusion was predictive of a higher global ß-amyloid burden (p = 0.002), after controlling for confounders. Regional analysis revealed significant associations of confusion with ß-amyloid in the prefrontal region (p = 0.004), posterior cingulate and precuneus cortices (p = 0.004) and the lateral temporal lobes (p = 0.001) after controlling for confounders. An in vivo biomarker for AD pathology was associated with SCI by self-reported confusion on cross-sectional analysis. Whilst there has been a large body of research on SMC, our results indicate more research is needed to explore symptoms of confusion.

The Women's Healthy Ageing Project: fertile ground for investigation of healthy participants 'at risk' for dementia.

Alzheimer's disease neuropathology (amyloid, tauopathies) and brain atrophy are present decades prior to manifestation of clinical symptoms. With the failure of treatment trials it is becoming clearer that the window for prevention and therapeutic intervention is before significant neuronal loss and clinical deterioration of cognition has occurred. Early identification of those at risk of disease and optimizing their management to prevent disease in later life are crucial to delaying disease onset and improving people's quality of life. The Women's Healthy Aging Project (WHAP) is a longitudinal study of over 400 Australian-born women, epidemiologically randomly sampled in 1990. The WHAP aims to identify modifiable mid-life risk factors for the development of late-life cognitive decline, improve the understanding of the pathogenesis of dementia, and target early disease identification utilizing clinical, biomarker and health risk profiles. These aims are fortified by the ability to leverage the considerable database on health, lifestyle and socio-demographics collected prospectively from 1990 to date. This is the first study with a comprehensive neuropsychological battery, over a decade of cognitive follow-up, with all participants being offered amyloid imaging from 2012, and prospective longitudinal data including clinical and physical measures and bio-bank samples from over 20 years prior.

A web-based normative data tool for assessing cognitive performance in healthy older Australians.

A decline in cognition greater than expected with ageing and accompanied by subjective cognitive concerns or functional changes may be indicative of a dementing disorder. The capacity to correctly identify cognitive decline relies on comparisons with normative data from a suitably matched healthy reference group with relatively homogeneous demographic features. Formal assessment of cognition is usually performed by specialist neuropsychologists trained in administration and interpretation of psychometric tests. With a scarcity of normative data from large cohorts of older adults, Australian neuropsychologists commonly use representative data from small international studies. Data from 727 healthy older Australians participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing have been used to create a normative dataset. A web-based calculator was developed to simplify the time-consuming process of comparing cognitive performance scores with these representative data.

Advances in structural and molecular neuroimaging in Alzheimer's disease.

Longer life expectancies lead to increases in the prevalence of age-associated illnesses. The number of Australians with dementia is predicted to rise, from 234,000 in 2009 to over 1 million by 2050, as a result of the increased prevalence of Alzheimer's disease (AD), the leading cause of dementia in the elderly. Early diagnosis of AD will become more important as disease-modifying therapies emerge within the next decade. Advances in molecular neuroimaging with amyloid-ß-specific radioligands for positron emission tomography, aided by magnetic resonance imaging techniques, allow detection of AD years before symptoms of dementia develop. Longitudinal prospective studies, such as the Australian Imaging Biomarkers and Lifestyle (AIBL) study of ageing, will determine the sensitivity and specificity of these analysis techniques for diagnosing AD and predicting cognitive decline.

Update on pharmacogenetics in epilepsy: a brief review.

Recent developments in the pharmacogenetics of antiepileptic drugs provide new prospects for predicting the efficacy of treatment and potential side-effects. Epilepsy is a common, serious, and treatable neurological disorder, yet current treatment is limited by high rates of adverse drug reactions and lack of complete seizure control in a significant proportion of patients. The disorder is especially suitable for pharmacogenetic investigation because treatment response can be quantified and side-effects can be assessed with validated measures. Additionally, there is substantial knowledge of the pharmacodynamics and kinetics of antiepileptic drugs, and some candidate genes implicated in the disorder have been identified. However, recent studies of the association of particular genes and their genetic variants with seizure control and adverse drug reactions have not provided unifying conclusions. This article reviews the published work and summarises the state of research in this area. Future directions for research and the application of this technology to the clinical practice of individualising treatment for epilepsy are discussed.

Acute stroke thrombolysis with intravenous tissue plasminogen activator in an Australian tertiary hospital.

OBJECTIVE: To report initial experience with the use of intravenous tissue plasminogen activator (tPA) to treat acute ischaemic stroke at an Australian tertiary-care hospital. DESIGN: Retrospective audit of computerised hospital stroke database. PARTICIPANTS AND SETTING: All patients with acute ischaemic stroke treated with intravenous tPA between April 1999 and July 2002 at the Royal Melbourne Hospital, VIC. MAIN OUTCOME MEASURES: Times from stroke onset to arrival at the emergency department (ED) and treatment; rates of symptomatic intracerebral haemorrhage (ICH); clinical outcome at three months; and violations of treatment protocol. RESULTS: Of 932 patients admitted with ischaemic stroke, 30 were treated with intravenous tPA. Median time from stroke onset to tPA treatment was 2 h 48 min, and median door-to-needle time was 1 h 49 min. Door-to-needle time improved in the last 12 months of the audit, with four of 15 patients achieving the recommended 60 min. Eleven patients (37%) had excellent clinical outcomes at three-month follow-up (modified Rankin score, 0-1), and 15 (50%) were functionally independent (score, 0-2). Mortality rate was 10%, similar to that of all ischaemic stroke patients during the audit period. Two patients (7%) had symptomatic ICH. Treatment deviated from protocol in seven patients (23%), five of whom received tPA over three hours after stroke onset. CONCLUSION: Rates of favourable outcomes and symptomatic ICH at our hospital were similar to those achieved in international phase III and IV trials in specialised centres.