AIBL is a study of over 1,100 people assessed over a long period of time ( > 4.5 years) to determine which biomarkers, cognitive characteristics, and health and lifestyle factors determine subsequent development of symptomatic Alzheimer’s Disease (AD).
The baseline inception cohort consisted of:
- 211 individuals with AD as defined by NINCDS-ADRDA (McKhann et al, 1984);
- 133 individuals with Mild Cognitive Impairment (MCI) – a clinical syndrome characterized by reduced cognitive performance (often involving memory), which represents a high risk state for the development of frank AD (Petersen et al.,1999; Winblad et al., 2004);
- 768 healthy individuals without cognitive impairment. This group included volunteers with at least one copy of the ApoE ε4 allele, volunteers without a copy of the ApoE ε4 allele and 396 volunteers who expressed subjective concern about their memory function. Memory complaints were elicited by the response to the question, “do you have difficulties with your memory?”.
Why is AIBL important?
Wiith Australia’s ageing population, the number of people suffering from dementia is expected to rise from 245,400 (1.1% of population) in 2009 to 1.13 million (3.2% of projected population) by 2050 (Access Economics Aug 2009). It is one of the fastest growing sources of major disease burden, overtaking coronary heart disease in total wellbeing cost by 2023 (Access Economics Aug 2009) and will become the third greatest source of health and residential aged care spending within about 2 decades. These costs alone will be around 1% GDP (Access Economics Aug 2009). By the 2060s, spending on dementia is set to outstrip that of any other health condition and is projected to be $83 billion (in 2006-07 dollars); around 11% of the entire and residential aged care sector spending (Access Economics Aug 2009).
Alzheimer’s Disease accounts for 50%-75% of dementia cases; delaying its onset by five years could nearly halve the cost of dementia to our society (Access Economics 2005), saving $8.9 billion per year in 2032 and $41.4 billion by 2062.
What will AIBL achieve?
- determine a set of diagnostic markers, biomarkers and psychometrics that can be used to objectively monitor disease progression;
- the early Detection of Alzheimer’s disease;
- develop hypotheses about diet and lifestyle factors that might delay the onset of the disease, providing preventative guidelines; and
- enable the design of studies that may lead to clinically proven preventative strategies for Alzheimer’s.
How will it achieve this?
AIBL is organised into the following research streams:
|Biomarkers||Blood samples have been taken from each participant for testing ranging from clinical pathology screening to novel biomarker examinations, to differentiate between those with and without AD.|
|Clinical & Cognitive||A comprehensive neuropsychological assessment has been carried out and includes cognitive and mood tests, assessment of vital signs, collection of medical history (personal and family) and medication information, and questionnaires about lifestyle factors.|
|Lifestyle||The lifestyle research stream is examining diet and exercise through questionnaires, monitoring and DEXA scans in a subset of participants.|
|Neuroimaging||Participants undergo scans using the structural neuroimaging with Magnetic Resonance Imaging (MRI) and beta amyloid imaging with Pittsburgh Compound B (PiB) Positron Emission tomography (PET) methods.|
What has been achieved so far?
- Established Australian Cognitive Norms – U.S. Standards were previously used.
- Reinforced the close association between aβ amyloid protein and Alzheimer’s disease in humans, confirming the pioneering work of Prof. Colin Masters.
- Shown that aβ plaque formation occurs before brain atrophy and parallels the prevalence of Alzheimer’s disease 15 years later, bringing forward the detection of Alzheimer’s disease potentially by at least 18 months.
- Identified a biomarker panel which can differentiate between healthy people and those with cognitive decline (subject of provisional patent).
- Identified biomarkers levels which can be used to assess cognitive decline before the development of dementia.
- Increased age and lower free testosterone levels in men can impact plasma aβ42:40 levels and hence hormonal levels should be considered in prediction of AD in the very early stages of the disease.
- Increased aβ burden in healthy females is related to poor episodal memory and likely to represent preclinical AD. Further investigation is required in males.
- Iron levels are higher in the brain tissue of MCI and AD patients, and that AD patients are more likely to be anaemic or have lower blood haemoglobin levels which are not explained by dietary deficiency.
- AD patients have elevated plasma homocysteine levels and decreased red cell folate levels.
- Use of PiB PET imaging can potentially identify those at very high risk of developing Alzheimer’s Disease and can be used to select cohorts for trials of Alzheimer’s Disease preventative drugs or non-drug lifestyle interventions.
- Three compartment analysis quantification technique is effective for correction of partial volume effects (known to challenge accurate quantification of PET scans) in scan results.
- MILXview medical image and analysis software, developed by CSIRO, allows for more reproducible longitudinal analysis and brain atrophy estimation, but will require further validation.
Lifestyle / Prevention
Elderly people participating in higher levels of physical activity are more likely to experience enhanced cognitive performance.
In healthy older adults, anticholinergic drugs have a modest effect on the psychomotor speed and executive function, but no effects on other areas of cognition.
AIBL on the international stage
The AIBL study now has many works published in internationally recognised journals (see the Publications page). AIBL has generated support from pharmaceutical companies, the U.S. Alzheimer’s Association and various private U.S. philanthropic groups and receives several requests per month from potential academic collaborators, both national and international, wishing to use data and blood samples for their research.