Brain Iron Toxicity and Neurodegeneration – A 7T MRI study

  • Research type

    Research Study

  • Full title

    Brain Iron Toxicity and Neurodegeneration – A 7T MRI study (BITaN)

  • IRAS ID

    276174

  • Contact name

    Akram A. Hosseini

  • Contact email

    akram.hosseini@nuh.nhs.uk

  • Sponsor organisation

    Reseach and Innovation, Nottingham University Hopsitals NHS Trust

  • Duration of Study in the UK

    2 years, 7 months, 0 days

  • Research summary

    Alzheimer's disease is a devastating condition that initially causes a gradual decline in memory, thinking and reasoning skills, resulting in disruption of daily life and the onset of dementia. The early diagnosis of Alzheimer's disease is possible by identification of traces of Amyloid protein, either in the brain or from the fluid around the brain, called cerebrospinal fluid. However, so far, treatments based on reducing Amyloid have not been shown to be effective in treating Alzheimer's disease. Excessive iron has been found to contribute to the deposition of Amyloid, thus promoting the development of Alzheimer's disease and therefore, iron-targeted treatments have become an important new direction in Alzheimer's disease.

    Magnetic resonance imaging (MRI) is a relatively cheap, widely used medical imaging technique, and it can be repeated safely to monitor changes in the brain with time. Ultra-High Field MRI uses a very strong magnetic field to produce very high-resolution images that can depict brain shrinkage of less than a millimeter. It can also be used to produce novel images that are very sensitive to the amount of iron in the brain.

    This research will build on strong local expertise in neuroimaging and the availability of powerful and modern MRI scanners at the Sir Peter Mansfield Imaging Centre at the University of Nottingham.

    We aim to use Ultra-High Field MRI at 7 Tesla (7T) to study the way that changes in brain iron with time relate to brain shrinkage in the brains of patients with Alzheimer's disease. We will invite people from our Memory Clinics, who have mild Alzheimer's disease and evidence of abnormal amyloid/tau protein in their cerebrospinal fluid to take part in this study.
    Once the participants have consented to join the trial, they will undergo an Ultra-High Field MRI scan, have a small blood sample taken and undergo a series of memory and thinking tests. If samples of their cerebrospinal fluid have already been stored, we will test this sample rather than asking people to undergo a further lumbar puncture. After 12 months, we will ask the participants to come back into the research clinic and to repeat the series of tests. We will recruit healthy volunteers
    of the same age. With permission, anonymous data and MRI images will be added to a Europe-wide database to enable other researchers to use these data.

    We plan to use the results of this 3-year study to:
    - Improve our understanding of the trajectory of iron accumulation in the brain and its relation to memory and thinking (cognition), amyloid markers in the cerebrospinal fluid, and the presence of a gene that increases the risk of developing Alzheimer's (called Apolipoprotein E).
    - Identify specific features on brain scans that may improve the diagnosis of early Alzheimer's disease.
    - To use the above features to monitor minor changes in the brain and possibly predict the speed of progression of Alzheimer's disease to help people manage their condition.
    - Potentially form the basis for future studies into the role of iron in early Alzheimer's disease including new treatment targets and a faster way of monitoring drug trials.
    - Form a resource for future research.

  • REC name

    East Midlands - Nottingham 2 Research Ethics Committee

  • REC reference

    20/EM/0023

  • Date of REC Opinion

    4 Feb 2020

  • REC opinion

    Favourable Opinion