A prospective cohort study of prodromal Alzheimer’s disease: Prospective Imaging Study of Ageing: Genes, Brain and Behaviour (PISA)

Michelle K Lupton,Jinglei Lv,Kerrie Mcaloney,Osvaldo P Almeida,Nancy A Pachana,Stephen Rose,Léonie Borne,Parnesh Raniga,Amelia Ceslis,Qing Zhang,Natalie Garden,Saurabh Sonkusare,Mahnoosh Kholghi,Olivier Salvado,Jessica Adsett,Ying Xia,Amir Fazlollahi,Nicholas G Martin,Michael Breakspear,Jürgen Fripp ,Mohanraj Karunanithi ,Robert Adam ,Scott D Gordon ,Gerard Byrne ,Philip Mosley ,Gail Robinson ,Christine Guo

doi:10.1016/j.nicl.2020.102527

Abstract

This prospective cohort study, “Prospective Imaging Study of Ageing: Genes, Brain and Behaviour” (PISA) seeks to characterise the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer’s disease (AD). In particular, we are recruiting midlife and older Australians with high and low genetic risk of dementia to discover biological markers of early neuropathology, identify modifiable risk factors, and establish the very earliest phenotypic and neuronal signs of disease onset. PISA utilises genetic prediction to recruit and enrich a prospective cohort and follow them longitudinally. Online surveys and cognitive testing are used to characterise an Australia-wide sample currently totalling over 3800 participants. Participants from a defined at-risk cohort and positive controls (clinical cohort of patients with mild cognitive impairment or early AD) are invited for onsite visits for detailed functional, structural and molecular neuroimaging, lifestyle monitoring, detailed neurocognitive testing, plus blood sample donation. This paper describes recruitment of the PISA cohort, study methodology and baseline demographics.

Highlights

The neurodegenerative process underlying dementia due to Alz heimer’s disease (AD) spans several decades (Morris, 2005)
The primary outcome of the PISA study is to establish a longitudinal cohort of healthy midlife-elderly individuals at high genetic risk of de mentia
This will be a unique international resource – only enabled by the recent breakthroughs in genetic analysis – and will yield new pos sibilities for basic and translational research. This protocol and cohort are of broad significance for other investigations – clinical trials in dementia prevention

Summary

Introduction

The neurodegenerative process underlying dementia due to Alz heimer’s disease (AD) spans several decades (Morris, 2005). Though the symptomatic burden of dementia typically occurs late in life, it is pre ceded by a long preclinical phase, characterized by the pernicious accumulation of neuropathology in the brain (Chiti and Dobson, 2006; Villemagne et al, 2013) This preclinical process is believed to commence decades prior to the establishment of functional decline and macroscopic brain atrophy (Dubois et al, 2016). It is possible that earlier intervention with disease-modifying therapy may increase the chance of halting or averting neurodegenerative processes, and the ensuing burden upon the individual and society This thera peutic window can only be identified with large-scale studies of those individuals at future risk of AD, but who currently lack substantial incipient neuropathology. The focus, of much ongoing de mentia research is to elucidate early pathological changes, and to identify markers capable of predicting disease progression

Methods

Results

Conclusion