The consequences of, and relationship between, amyloid deposition, grey matter microstructural change and atrophy in the MRC NSHD 1946 birth cohort (360G-Wellcome-200109_Z_15_Z)

The development of disease modifying therapies to delay the clinical onset of Alzheimer’s disease (AD) is of the highest public health importance. Robust biomarkers of the long pre-symptomatic period between the first appearance of the histopathological hallmarks of AD and the onset of clinical symptoms will be crucial for recruitment and monitoring in drug trials and clinical practice. I will analyse the multi modal MRI and amyloid PET imaging data of 500 individuals from the MRC National Survey for Health and Development (NSHD; the British 1946 birth cohort) to address the following key objectives: 1. Investigate whether amyloid deposition leads to microstructural grey matter change utilising diffusion based MRI and a new and novel multi-shell acquisition technique (NODDI).2. Investigate the extent and pattern of grey matter atrophy associated with amyloid deposition and compare sensitivity of diffusion based/NODDI metrics with measures of grey matter atrophy.3. Evaluate the sensitivity of tests of cognition, audition and olfaction in assessing early impairment of cortical function and the relationship with the the neuroimaging data.4. Investigate the relationship between neuroimaging metrics and cognitive trajectory throughout life.