Several studies suggest that blood-brain barrier integrity is impaired in Alzheimer’s dementia. In this project it is hypothesized that dynamic contrast enhanced magnetic resonance imaging can be used to demonstrate this phenomenon, comparing Alzheimer’s dementia, Lewy body dementia and control individuals. The relationship of blood-brain barrier permeability to systemic inflammatory status as measured by urinary neopterin-to-creatinine ratio and blood cytokine assays is being investigated. Patients are being followed up to determine whether a baseline MRI assessment of blood-brain barrier integrity is predictive of future cognitive decline. The Academic Clinical Fellow working on the project may come from Psychiatry or Neurology backgrounds.
Clinical Academic Training
An exciting opportunity has arisen for an ambitious academic clinical fellow to work at the interface of cardiothoracic surgery with medical physics and neuroscience for identification of novel aspects of the function of the cerebral vessels that could be used as early biomarkers for dementia.
Atypical parkinsonian syndromes are rare complex neurodegenerative diseases such as progressive supranuclear palsy. Patients rapidly deteriorate, accruing multiple disabilities including walking, swallowing, visual and cognitive dysfunction. Patients quickly become dependent and die typically within 6 years of disease onset.
Unfortunately there is no curative or disease modifying treatment and management is supportive. It is not known how best to care for patients with these class of diseases. In particular, would it be more useful to have a multidisciplinary clinic, with therapists, allied health professionals and a coordinator present at the appointment, or a straight forward appointment with a single clinician with separate referrals to other agencies as needed. We are therefore assessing examples of both types of services with longitudinal quantitative and qualitative assessments. This will be used to determine benefits for quality of life and health economics. Results will be used to inform national guidelines and best management practice going forwards.
An association exists between intracranial pulsing and cognitive decline. This is seen in blood and CSF flow. Increased arterial stiffness is a possible mechanism; measures of pressure pulsing would help to confirm this. While flow measurements can be made relatively easily, intracranial pressure measurements are challenging. We have developed a novel approach measuring pulsations of the tympanic membrane and shown this to be associated with the MOCA cognitive assessment test in healthy subjects. There would be good support for a clinical academic trainee to explore these measurements of CSF dynamics in cognitively impaired patients.
Alzheimer’s disease (AD), Lewy Body Dementia (DLB) and Parkinson’s Disease (PD) have complex aetiology and pathogenesis and predicting the rate of clinical progression remains challenging. In Southampton, we showed that systemic inflammation increases the risk for earlier onset and/or progression of AD. In this project we will perform an in-depth analysis of serum and CSF samples to link pathways of inflammation to clinical progression. We will also measure amyloid, tau and alpha-synuclein and use state-of-the-art biophysical technology to link inflammation to specific conformers Collectively, this work may lead to novel composite biomarker to allow better diagnosis and allow better prediction of cognitive decline.