Appropriate availability of trace elements (TE) such as iron, selenium, zinc and copper is vital for healthy brain structure and function. Dysregulation of these elements has been linked to age related cognitive decline, and dementia (Shcherbatykh and Carpenter, 2007).
By employing the new, powerful MRI methodology of Quantitative Susceptibility Mapping (QSM) (Acosta-Cabronero et al., 2016) to estimate the concentration of TE in-vivo and the unique life-course cognitive, socio-economic and health data available in the Aberdeen Children of the Nineteen Fifties (ACONF) Birth Cohort, this project aims to elucidate the trace elements that modify brain ageing and identify those responsible for providing resilience or vulnerability to dementia.
The student will investigate the link between TE nutritional status, MRI detected brain TE content and brain ageing in the ACONF. This birth cohort, comprising healthy individuals from NE Scotland, are part of a longitudinal investigation of age related health by University of Aberdeen researchers (www.abdn.ac.uk/birth-cohorts). They are a uniquely valuable research cohort due to the remarkably rich life-course data available, including birth data (Aberdeen Maternity and Neonatal Database) and childhood intelligence and demographic data collected as part of the Aberdeen Child Development study. Recently, a subset (n=251) of this cohort was recruited into a project that aims to stratify resilience and depression longitudinally (STRADL), where subjects underwent extensive cognitive, emotional and health phenotyping.
The consequences of brain TE levels on cognitive function will be examined. Cognitive test data are available for multiple domains, including the digit symbol test of processing speed and delayed recall tests of short term memory. These tests examine cognitive domains sensitive to ageing and the early signs of dementia.
The TE nutrient status within the cohort will be assessed through the measurement of relevant biomarkers within existing STRADL plasma/blood samples. These data will be analysed with brain imaging derived TE concentrations together with life-course cognitive function in order to determine if the TE status of an individual may influence brain function throughout the life-course.
The successful candidate will be trained in state of the art MRI image acquisition and processing techniques, including methods for quantifying in vivo brain structure and function, and the in vivo quantification of TE concentrations in brain tissue. To accurately assess the in vivo status of the TE of interest, they will be trained in the direct measurement of tissue and plasma TE concentrations by inductively coupled plasma mass spectrometry (ICP-MS) and microwave digestion. In addition where appropriate, biomarkers of TE status will be measured using in vitro methods such as ELISAs, Western blots and functional enzyme assays.
This multidisciplinary approach will give unique insight into the direct and indirect influence of nutritional TE status on brain structure and function, and the resultant consequences for cognitive ability, cognitive reserve and dementia risk.
Shcherbatykh I, Carpenter DO. The role of metals in the etiology of Alzheimer's disease. J Alzheimers Dis. 2007 May;11(2):191-205.
Acosta-Cabronero, J., Betts, M.J., Cardenas-Blanco, A., Yang, S., Nestor, P.J. In vivo MRI mapping of brain iron deposition across the adult lifespan (2016) Journal of Neuroscience, 36 (2), pp. 364-374.