Investigating Shunt-Responsiveness in Idiopathic Normal Pressure Hydrocephalus Using White Matter Tractography and Degenerative Biomarker Profiles

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Idiopathic Normal Pressure Hydrocephalus (iNPH) is a disease in which patients develop dementia and problems with walking and bladder control due to hydrocephalus, where pressure increases in the normal fluid filled brain structures (ventricles) result in them getting larger and compressing critical brain structures. It is a common and severely disabling illness which affects between up to 3.7% of over 65 year-olds. Unlike typical dementias iNPH is treatable. Patients with these symptoms who are found to have features of iNPH on brain scans can have "cerebrospinal fluid (CSF) shunting", a process where brain fluid is surgically distracted to an area of lower pressure such as the abdominal cavity. Without treatment patients with iNPH progress to an immobile, demented and incontinent state. For unknown reasons, some patients with the correct features of iNPH on their brain scans do not respond to CSF shunting. There are "predictive tests" which can help inform who will improve with surgery. These tests carry risks as they involve assessing for improvement of symptoms after draining a large volume of CSF from the lower spine or accessing the spinal cavity with a needle and measuring the CSF pressure dynamics. Unfortunately, there is no known treatment for those individuals who do not respond to CSF-shunting and they must be supported with their progressive dementia, the cause of which is never really explained. Diffusion Tensor Imaging is a research Magnetic Resonance Imaging (MRI) scanning technique that can show very detailed white matter pathways in the brain which cannot be seen on conventional MRI brain scans. In this study we intend to perform white matter tractography using DTI in patients being investigated for iNPH and compare the scans from thirty iNPH patients and compare those whorespond to CSF shunting ("shunt-responsive") and those who do not ("shunt-unresponsiveness"). This will help us understand why some patients respond to CSF shunting and will also help us to develop non-invasive tests for these patients in the future. As white matter tractogrphy is influenced by neurodegenerative disease it will be important to account for co-existing neurodegeneration. We also hypothesise that patients with imaging features of iNPH who do not respond to predictive testing may have another cause for their symptoms such as neurodegenerative dementia (e.g. Parkinson's disease or Alzheimer's disease). In this study we also intend to test for a wide-range of dementias using blood tests, CSF tests, advanced brain imaging (amyloid-PET scanning) to develop "degenerative biomarker profiles" on the study patients. If we find evidence of neurodegenerative dementias in patients who do not respond to predictive testing, we will then be able to start work on providing a clear path of investigation and treatment for these unfortunate individuals.