Neuropathology of Cognitive Fluctuation in Dementia with Lewy Bodies

Cognitive fluctuations (CF) are defined as spontaneous variations in cognition, especially in aspects of alertness and attention, and occur in about 90% of people with dementia with Lewy bodies (DLB), the second commonest degenerative cause of dementia. In certain individuals, CF are often so marked in early stages of the disease that cognition and behaviour can rapidly shift from severely impaired to normal or near-normal. This suggests that DLB patients experiencing CF retain sufficiently intact neuronal networks to support normal memory, thinking and behaviour and thus may be amenable to novel drug treatment strategies. Key brain areas involved in CF in DLB have been identified in neuroimaging studies (e.g. the precuneus/posterior parietal lobe, reticular formation and intralaminar thalamic nuclei). However, no evidence of gross degenerative pathology has been found in these areas using imaging technology. This suggests that ultrastructural and/or biochemical changes in such areas may underlie the pathogenesis of CF in DLB.
This PhD project will thus test the hypothesis that ultrastructural and/or biochemical changes in key brain areas result in CF in DLB, by comparing cellular and neurochemical changes in donated post-mortem brain tissue taken from DLB, age-matched disease-control group Alzheimer’s disease (AD) and control subjects.

The student will therefore carry out the following procedures:

1. Identify specific changes in neurochemistry of the precuneus, reticular formation and intrathalamic nuclei in post-mortem tissue taken from DLB patients, compared with that of AD and normal healthy individuals, using immunohistochemistry and autoradiography, with an emphasis on cholinergic, glutamatergic and monoaminergic systems.

2. Assess cholinergic, glutamatergic and monoaminergic neurone populations and associated degenerative pathology in the above brain areas in post-mortem tissue taken from DLB patients, against age-matched AD and normal healthy individuals, using quantitative morphometry.

Person Specification and Eligibility Criteria

- First Class / Upper Second honours science degree (awarded or expected)
- EU Resident
- Self-motivated
- Good interpersonal skills

How to Apply

Applications must be made using the online application form http://www.ncl.ac.uk/postgraduate/apply/.

Only mandatory fields need to be completed. However, you will need to include the following information:
• insert the programme code 4850F in the programme of study section
• select ‘Master of Research/Doctor of Philosophy (Medical Sciences) - Neuroscience’ as the programme of study
• insert the studentship code IN080 in the studentship/partnership reference field
• attach a covering letter and CV. The covering letter must state the title of the studentship, quote the studentship reference code IN080 and state how your interests and experience relate to the project
• attach degree transcripts and certificates and, if English is not your first language, a copy of your English language qualifications.