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Background: The identification of people at risk of cognitive impairment is essential for improving recruitment in secondary prevention trials of Alzheimer's disease. We aimed to test and qualify a biomarker risk assignment algorithm (BRAA) to identify participants at risk of developing mild cognitive impairment due to Alzheimer's disease within 5 years, and to evaluate the safety and efficacy of low-dose pioglitazone to delay onset of mild cognitive impairment in these at-risk participants. Methods: In this phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group study, we enrolled cognitively healthy, community living participants aged 65–83 years from 57 academic affiliated and private research clinics in Australia, Germany, Switzerland, the UK, and the USA. By use of the BRAA, participants were grouped as high risk or low risk. Participants at high risk were randomly assigned 1:1 to receive oral pioglitazone (0·8 mg/day sustained release) or placebo, and all low-risk participants received placebo. Study investigators, site staff, sponsor personnel, and study participants were masked to genotype, risk assignment, and treatment assignment. The planned study duration was the time to accumulate 202 events of mild cognitive impairment due to Alzheimer's disease in White participants who were at high risk (the population on whom the genetic analyses that informed the BRAA development was done). Primary endpoints were time-to-event comparisons between participants at high risk and low risk given placebo (for the BRAA objective), and between participants at high risk given pioglitazone or placebo (for the efficacy objective). The primary analysis included all participants who were randomly assigned, received at least one dose of study drug, and had at least one valid post-baseline visit, with significance set at p=0·01. The safety analysis included all participants who were randomly assigned and received at least one dose of study medication. An efficacy futility analysis was planned for when approximately 33% of the anticipated events occurred in the high-risk, White, non-Hispanic or Latino group. This trial is registered with ClinicalTrials.gov, NCT01931566. Findings: Between Aug 28, 2013, and Dec 21, 2015, we enrolled 3494 participants (3061 at high risk and 433 at low risk). Of those participants, 1545 were randomly assigned to pioglitazone and 1516 to placebo. 1104 participants discontinued treatment (464 assigned to the pioglitazone group, 501 in the placebo high risk group, and 139 in the placebo low risk group). 3399 participants had at least one dose of study drug or placebo and at least one post-baseline follow-up visit, and were included in the efficacy analysis. 3465 participants were included in the safety analysis (1531 assigned to the pioglitazone group, 1507 in the placebo high risk group, and 427 in the placebo low risk group). In the full analysis set, 46 (3·3%) of 1406 participants at high risk given placebo had mild cognitive impairment due to Alzheimer's disease, versus four (1·0%) of 402 participants at low risk given placebo (hazard ratio 3·26, 99% CI 0·85–12·45; p=0·023). 39 (2·7%) of 1430 participants at high risk given pioglitazone had mild cognitive impairment, versus 46 (3·3%) of 1406 participants at high risk given placebo (hazard ratio 0·80, 99% CI 0·45–1·40; p=0·307). In the safety analysis set, seven (0·5%) of 1531 participants at high risk given pioglitazone died versus 21 (1·4%) of 1507 participants at high risk given placebo. There were no other notable differences in adverse events between groups. The study was terminated in January, 2018, after failing to meet the non-futility threshold. Interpretation: Pioglitazone did not delay the onset of mild cognitive impairment. The biomarker algorithm demonstrated a 3 times enrichment of events in the high risk placebo group compared with the low risk placebo group, but did not reach the pre-specified significance threshold. Because we did not complete the study as planned, findings can only be considered exploratory. The conduct of this study could prove useful to future clinical development strategies for Alzheimer's disease prevention studies. Funding: Takeda and Zinfandel.

Since the 2016 release of the Australian Guide to the Diagnosis of Fetal Alcohol Spectrum Disorder (FASD), considerable progress has been made in the identification and diagnosis of the disorder. As part of a larger process to review and update the Guide, the aim of this study was to identify review priorities from a broad range of stakeholders involved in the assessment and diagnosis of FASD. Sixty-two stakeholders, including healthcare practitioners, researchers, other specialists, individuals with cultural expertise, lived experience and consumer representatives completed an online survey asking them to describe up to five priorities for the review of the Australian Guide to the Diagnosis of FASD. A total of 267 priorities were described. Content analysis of responses revealed priority areas relating to diagnostic criteria (n = 82, 30.7%), guideline content (n = 91, 34.1%), guideline dissemination (n = 15, 5.6%) and guideline implementation (n = 63, 23.6%). Other considerations included prevention and screening of FASD (n = 16, 6%). Engaging stakeholders in setting priorities will ensure the revised Australian Guide can be as relevant and meaningful as possible for the primary end-users and that it meets the needs of individuals with lived experience who will be most affected by the diagnosis.

Fetal alcohol spectrum disorder (FASD) is a significant public health issue in Australia that is poorly diagnosed, chronic and costly. FASD is a diffuse acquired brain injury secondary to prenatal alcohol exposure. The prevalence rate of FASD among the general population in Australia is currently unknown; however, an Australian study in a selected high-risk population reported some of the highest rates of FASD in the world. A common misconception among clinicians is that a child must have 'the face' of FASD to have the disorder. This is incorrect. The three sentinel facial features only occur in the minority of individuals with FASD. FASD should be considered as a 'whole body' disorder as increased susceptibility to chronic health problems suggests suboptimal in utero environments places the individual at risk of later disease. Clinicians are reluctant to consider FASD as a possible diagnosis because of the concern of inducing stigma; however, this concern is neither supported by the evidence nor patient stories. The Australian Guide to the Diagnosis of FASD is now available to assist health professionals in providing timely and accurate diagnoses, which can lead to improved outcomes via evidence-based intervention and is an important first step in future prevention.

1.1 The problem, condition or issue Prenatal alcohol exposure (PAE) is associated with profound and lifelong disability. The umbrella term fetal alcohol spectrum disorder (FASD) describes a spectrum of impairments resulting from the deleterious effects of PAE (Chudley et al., 2005). Historically, the spectrum comprised four disorders: fetal alcohol syndrome (FAS), Partial FAS (pFAS), alcohol‐related neurodevelopmental disorder (ARND), and alcohol‐related birth defects (ARBD; Lange, Rovet, Rehm, & Popova, 2017). All four disorders shared PAE as their etiological base and all but ARBDs were associated with neurological deficits (ARBD comprizing physical defects). More recently, the Australian Guidelines to the diagnosis of FASD have been published (Bower & Elliot, 2016). While the core aspects of the condition remain unchanged, the Australian guidelines comprise two diagnostic categories for FASD: (a) FASD with three sentinel facial features or (b) FASD with less than three sentinel facial features.

Fetal alcohol spectrum disorder (FASD) is a significant public health issue in Australia that is poorly diagnosed, chronic and costly. FASD is a diffuse acquired brain injury secondary to prenatal alcohol exposure. The prevalence rate of FASD among the general population in Australia is currently unknown; however, an Australian study in a selected high-risk population reported some of the highest rates of FASD in the world. A common misconception among clinicians is that a child must have 'the face' of FASD to have the disorder. This is incorrect. The three sentinel facial features only occur in the minority of individuals with FASD. FASD should be considered as a 'whole body' disorder as increased susceptibility to chronic health problems suggests suboptimal in utero environments places the individual at risk of later disease. Clinicians are reluctant to consider FASD as a possible diagnosis because of the concern of inducing stigma; however, this concern is neither supported by the evidence nor patient stories. The Australian Guide to the Diagnosis of FASD is now available to assist health professionals in providing timely and accurate diagnoses, which can lead to improved outcomes via evidence-based intervention and is an important first step in future prevention.

In 2003, the College of Clinical Neuropsychologists decided to hold a pre-conference meeting (prior to the APS conference), rather than our usual conference. Nevertheless, the standard of papers remains at the level of excellence that has become associated with the CCN conferences. This year a wide range of topics are covered, in many areas of interest to clinical neuropsychologists. This meeting has seen a high level of participation from students from Perth, whilst many members from other states have still contributed. The CCN has maintained its policy of encouraging participation from students, and the range of excellent submissions gained from students will ensure that this policy will continue. The CCN, once again, looks forward to a varied and stimulating meeting.