Fifteen Years of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study: Progress and Observations from 2,359 Older Adults Spanning the Spectrum from Cognitive Normality to Alzheimer’s Disease

Abstract

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer’s disease dementia (AD)) as an ‘Inception cohort’ who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an ‘Enrichment cohort’ (as of 10 April 2019). Objective: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. Methods: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. Results: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aβ-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. Conclusion: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims.

Plasma p-tau181/Aβ1-42ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ1-42and future cognitive decline

“…The p-tau181/Aβ 1-42 ratio has long been considered to have the best statistical power of the CSF markers for representing AD, as it incorporates both hallmarks of the AD disease pathway and represents a later stage of the disease pathway. Indeed this ratio in CSF has helped identify late stage changes in synaptic and neuronal degradation markers and inflammatory markers associated with AD [37], as well as show high concordance with Aβ-PET [15-17, 20]. Here analyses of the plasma markers at a second time point in this study showed increased performance of all markers, including the p-tau181/Aβ 1-42 ratio, at predicting amyloid status at Assessment 2, which may reflect further accumulation of positive biomarker signals compared to a static baseline in the amyloid negative cohort.…”

“…The Australian Imaging, Biomarkers and Lifestyle (AIBL) study is a prospective longitudinal cohort of adults over the age of 60 designed to understand the natural history of AD, with recruitment and testing procedures described in detail [20]. Participants undergo 18 monthly neuropsychological and clinical assessment and blood donation, with AIBL clinical classification confirmed by an expert clinical panel consisting of a neurologist, geriatrician, and neuropsychologist; all blinded to biomarker status.…”

No Influence of Age-Related Hearing Loss on Brain Amyloid-β

“…Participants in this study were older adults (aged 50 years and over) enrolled in the Australian Imaging Biomarkers and Lifestyle (AIBL) Study, a prospective longitudinal cohort study of aging and AD [ 12 ]. Individuals from this cohort who did not have a mild cognitive impairment or dementia diagnosis underwent positron emission tomography (PET) imaging, had an objective audiometric assessment of their hearing within 5 years of their scans, had cognitive assessment within 2 years of their PET scan, and had no diagnosed mild cognitive impairment or dementia were selected ( n = 143).…”

Rates of regional tau accumulation in ageing and across the Alzheimer's disease continuum: An AIBL 18F-MK6240 PET study

“…Participants were deemed to be cognitively unimpaired (CU) if their performance on neuropsychology assessments was within 1.5 standard deviations of published normative data for their age group. A diagnosis of mild cognitive impairment (MCI) or Alzheimer’s disease dementia (AD) was assigned in accordance with international consensus criteria, as previously described (16). This study has been approved by the institutional review boards of all participating institutions, and all participants signed an informed consent form.…”