Jonathan Schott is Professor of Neurology at the Dementia Research Centre, UCL Institute of Neurology, and Honorary Consultant Neurologist at Queen Square. His clinical practice and research centre on the dementias, with particular interests in how clinical and cognitive data, imaging and fluid biomarkers, and genetics can be used and combined to improve differential diagnosis and identify pre-symptomatic dementia. He co-leads the mental ageing programme of the MRC British 1946 birth cohort. He has published >350 papers on dementia and ageing, and co-edited the award winning Oxford Textbook of Cognitive Neurology and Dementia. He is Senior Fellow of the Higher Education Academy, Fellow of the European Academy of Neurology, Fellow of the American Academy of Neurology, and an MRC Investigator. He is is Chair Emeritus of the ISTAART advisory council and serves as Chief Medical Officer for Alzheimer’s Research UK, Europe’s largest dementia.

Abstract

Neuroimaging allows for the in vivo identification of a range of pathologies relevant to late life cognitive impairment, and a means of tracking progression over time. When applied to preclinical populations this provides a means of identifying individuals at risk of developing late life cognitive impairment and examining risk factors for developing specific pathologies and cognitive decline. Insight 46 is a longitudinal neuroimaging study embedded within the world’s oldest continuously running birth cohort – the MRC National Survey of Health and Development 1946 British birth cohort, initially comprising 5362 individuals all born in mainland Britain in one week in 1946. Between 2015-2018, i.e. at age ~69-72yrs, n=502 individuals were recruited for comprehensive clinical and biomarker assessment including multi-modal MRI and Florbetapir amyloid PET; n=440 were seen for a second visit between 2018-2021; and we have currently seen ~n=150 (our of a planned n=350) of these for a third visit including MK6240 tau PET; and a further n=300 individuals not previously seen, for Florbetaben amyloid PET. In this talk I will discuss some of the key findings of the study thus far, exploring the extent, causes and consequences of b-amyloid deposition, cerebrovascular disease and microstructural changes, as well as presenting preliminary findings relating to rates of b-amyloid accumulation, tau PET, and image-derived metrics of brain age.

Keywords: Multi-modal MRI, Amyloid PET, Tau PET, Life course epidemiology, Brain age