David Ames

Baseline data from the Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing

consequent morbidity, health expenditure and societal burden. We have already shown that detection of cognitive decline is associated with increased risk of PET-PIB amyloid accumulation, and that a computerized battery can be used in a longitudinal aging study to detect objective subtle decline. The current study used CogHealth in the community to determine whether concerned but healthy persons: (i) tolerate 3 monthly screening over a year, and (ii) show impairment or serial decline. Methods: Community volunteers ( 50 years) willing to undergo 3 monthly computerized testing over 12 months (M) were recruited by brief media announcements. A subgroup participated in focus groups after the first and last visit. Participants with impairment defined as failure to pass simple integrity checks or >1.65 standard deviations below the mean compared with population-based normative data or serial decline using linear regression will be offered further medical assessment. Participants’ doctors interest was also surveyed. Results: 301 volunteers without existing cognitive impairment were recruited from a total of 394 screened by telephone interviews. Mean age was 61.8 6 7.2 years (89M, 212F). Focus group interviews suggested high participant enthusiasm for screening. The proportion of participants who failed integrity checks or timed out at each time point was: baseline 13% (n1⁄4301); 3M 6% (n1⁄4271); 6M 3% (n1⁄4253), 9M 3% (n1⁄4258) and 12M 3% (n1⁄4263). 87% participants completed 12M testing. Overall, 20% failed one or more integrity check over the course of the study. Only 11% of participant doctors returned completed surveys. Conclusions: Concern about early AD appears high in the community with enthusiastic demand for study entry, and high motivation to complete serial screening. In contrast practitioner interest was low. Serial monitoring in the community with such brief computerized test batteries appears to be feasible and acceptable. Future work is required to evaluate the sensitivity of demonstrated impairment or serial decline to significant medical conditions, and cost-effectiveness.

Identifying protein biomarkers for early diagnosis of Alzheimer's disease

was used to validate iTRAQ data. Results: In three replicate iTRAQ experiments ten proteins were significantly deregulated in MCI and AD plasma, relative to controls. These proteins included; apolipoprotein B-100, complement C3, C4b-binding protein, afamin, vitamin D-binding protein precursor, isoform 1 of Gelsolin actin regulator, Ig mu chain C region (IGHM protein), histidine-rich glycoprotein, fibrinogen beta and gamma chains. Western-blotting confirmed that afamin was decreased in the AD group, and IGHM was increased in aMCI+amdMCI and AD. Conclusions: These findings demonstrate that expression level changes are observed to multiple proteins in MCI and AD plasma. Some of these, such as afamin and IGHM, may be candidate biomarkers for AD and preclinical conditions such as MCI.

Normative data from the AIBL study: Language, visuoconstruction, and executive functioning in a large healthy elderly cohort

Background: It has been reported that normal individuals are risk averse for decisions framed as gains, but risk seeking for decisions framed as losses. Alzheimer’s disease (AD) is known to be associated with altered decision making patterns and high-risk behaviors in many ways. In this study, we investigated the effects of highlighting rewards versus highlighting punishments in the risky decision-making of AD patients. Methods: Nine literate AD patients (Mini Mental Status Examination score 1⁄4 10w23, Clinical Dementia Rating 1⁄4 1w2) and age, education matched eleven healthy volunteers completed a computerized risky decision-making task in which mathematically equivalent dilemmas were presented in terms of opportunities to gain monetary rewards (‘‘positive frame’’) or to avoid suffering losses (‘‘negative frame’’). The proportion of risk-aversion and risk-seeking choices and each deliberation times were measured when the participants made decisions under positively versus negatively framed dilemmas. Mini International Neuropsychiatric Interview and Hamilton Rating Scale for Depression were measured for exclusion of depression or other psychiatric disorders. Results: As expected, healthy elderly participants made more risktaking choices under the negatively framed dilemma whereas more riskaverse choices under the positively framed dilemmas (p 1⁄4 0.022). On the other hand, AD patients did not care gain or loss frame (p 1⁄4 0.791). Risky choice tendency in both gain and loss tasks was increased in AD patients (F1⁄4 8.562, p1⁄4 0.009). Deliberation time in AD was not significantly different from control participants according to the economic value and frame type. (F1⁄4 0.538, p1⁄4 0.473) Conclusions: These preliminary results suggest that risky choice in AD is associated with attenuated sensitivity to emotional frames that highlight rewards or punishments, possibly reflecting altered valuations of prospective gains and losses.