A PERSPECTIVE IMAGING STUDY OF AGEING (PISA): GENETIC RISK PREDICTION FOR STUDYING AN AT-RISK POPULATION FOR ALZHEIMER’S DISEASE

Abstract

While the burden of dementia occurs late in life, neuropathology accumulates for decades prior to onset of dementia. It is imperative to develop methods to identify those at the very early stage of dementia. This is the aim of the Prospective Imaging Study of Aging: Genes, Brain and Behaviour (PISA) study, which seeks to (1) Identify healthy middle-aged adults at high risk of dementia; (2) Discover biological and imaging markers of early neuropathology; (3) Identify modifiable risk factors; (4) Establishing a cohort of preclinical patients for future clinical trial. The main study is a longitudinal cohort study on at risk younger adults (40–70 yrs) with no clinical symptom. This is achieved by levering our extensive in-house cohorts, comprising ∼16,000 individuals in the target age range with available GWAS data. A genetically enriched cohort was selected to study the preclinical Alzheimer's disease (AD), based on APOE genotype and polygenic risk scores (PRS). The main study began early 2016. We have verified the predictin accuracy of PRS score on data from ADNI, AddNeuroMed, Sydney MAS, OATS (presented in another abstract at AAIC). We developed an in-house online questionnaire to collect longitudinal data on cognition and lifestyle from the total cohort, and an onsite, multidisciplinary test battery to collect high-quality data from a subset of the cohort. As part of this onsite battery, we have developed and tested a comprehensive suite of imaging sequences on MRI and PET, including high resolution T1, T2, QSM, fMRI, ASL, and amyloid-PET (Florbetaben). A novel naturalistic fMRI paradigm is designed to study perception, attention and episodic memory. Furthermore, smart sensing devices are given to participants to collect continuous data on lifestyle factors, such as physical activities and sleep.