CSIRO second round funding for the Australian imaging, biomarkers and lifestyle (AIBL2) study on ageing
AIBL is a multicentre, multidisciplinary study of Alzheimer’s Disease (AD) and ageing, funded by the CSIROs national flagship initiative, and encompasses research centres in both Western Australia and Victoria. The AIBL study is aimed at improving awareness of the causes of AD and understanding its diagnosis, in order to develop preventative strategies. Launched in November 2006, it is a prospective, longitudinal study of ageing comprising three groups of patients: those with Alzheimer’s Disease (AD), Mild Cognitive Impairment (MCI) and healthy volunteers respectively. The first phase, completed in March 2010, was a 3-year longitudinal study of 1000 individuals. Phase two of the study continues for a further 3 years, and includes 3 additional follow-up assessments of phase one participants, along with an additional 500 newly recruited participants. It also includes the implementation and evaluation of a lifestyle–based intervention program for the prevention of AD.
All participants undergo a comprehensive examination at 18-month intervals comprising neuropsychological and clinical assessments, and an evaluation of health and lifestyle factors. The lifestyle evaluation includes completion of questionnaires on diet and exercise patterns by all participants at 18-month intervals. A fasting blood sample (80 ml) is also taken from each participant for biomarker analysis.
During phase one, PiB-PET and MRI neuro-imaging is carried out on 250 participants. During phase two, all participants are offered brain imaging and asked to undergo lumbar puncture for cerebrospinal fluid (CSF) collection. At baseline, a sub-group of participants is also assessed by acti-graph accelerometer for an objective measure of activity levels and Dual Energy X-Ray Absorptiometry (DEXA), in order to assess body composition. Furthermore, all participants complete questionnaires related to their personality and subjective memory difficulties, while participant informants are asked to complete 3 questionnaires relating to changes in the participant’s behaviour, personality and ability to perform daily activities.
It is hoped that the comprehensive and longitudinal nature of the AIBL study will help researchers to develop a set of diagnostic biomarkers and psychometrics that will objectively monitor disease progression and generate hypotheses about diet and lifestyle, to delay the onset of AD.
Although Autosomal Dominant AD (ADAD) represents less than 1% of all cases of Alzheimer’s Disease, it is an attractive model to study because the known biochemical consequences of the inherent genetic mutations are believed to underlie the pathological basis of the disorder. The opportunity to determine the sequence of imaging and biomarker changes in pre-symptomatic gene carriers destined to develop ADF may reveal critical information about the pathological cascade that culminates in symptomatic disease. Because clinical and pathological phenotypes of dominantly inherited AD appear similar to those of the far more common late-onset “sporadic” AD, the nature and sequence of brain changes in early-onset AD may also be relevant for late-onset AD. However, there are few individuals with ADAD and they are dispersed worldwide, hence the requirement for DIAN as a systematic way to evaluate this population and use the data to develop a global patient registry.
DIAN looks at dominantly inherited AD in individuals for whom the diagnosis is certain (mutation carriers), in comparison with their non-carrier siblings who serve as a naturally occurring control group. All DIAN study participants are assessed longitudinally using comprehensive clinical, cognitive, genetic, neuro-imaging, and biomarker protocols; all data is collected in a consistent manner and entered into a central repository.
All study participants are assessed at baseline. Thereafter, the interval between baseline and follow-up assessments ranges from 12 to 36 months, and is determined by the age of the individual in relation to the affected parent’s age at onset. In order to remain active within the DIAN cohort, all study participants are required to complete clinical and cognitive assessments, and provide a blood sample at specific points in time. Participation in the MRI, FDG-PET, PiB-PET neuro-imaging and CSF studies is strongly encouraged at each assessment, but not mandatory.
This study involves three Western Australian research centres (Edith Cowan University, Hollywood Private Hospital and the McCusker Foundation for Alzheimer’s Disease Research) and is contingent upon the work of principal investigator, Professor Ralph Martins. The study is aimed at identifying factors that influence memory changes, and in individuals with memory loss, the characteristics associated with dementia of the Alzheimer’s type to enable identification of individuals at a higher-than-average risk of developing dementia.