The Cholinergic ResponsE in Early lewy body Disease (CREED) study

Degeneration of cholinergic nuclei and associated cortical cholinergic loss are central features of Lewy body dementia (LBD). Cholinergic loss is evident in established LBD but also occurs in early or prodromal states and contributes significantly to the manifestation of cognitive and neuropsychiatric symptoms within these conditions.

However there are no specific, easy to use, biomarkers of cholinergic function that can: 1) provide a metric of disease severity 2) predict response to cholinergic treatment and/or 3) act as a clinical outcome surrogate for the development of novel cholinergic therapeutics.

Our proposal aims to develop a validated, low cost, simple to acquire, non-invasive biomarker based on a specific encephalography (EEG) spatio-temporal feature motif which is strongly associated with cholinergic function and which is fit for purpose in this patient group.

We hypothesize that: 1) our EEG cholinergic index will be reduced in early and prodromal LBD and will demonstrate normalisation after treatment with a cholinesterase inhibitor and 2) the baseline index and longitudinal change in the index in patients with early/prodromal LBD treated with a cholinesterase inhibitor will correlate with improvements in cognition and other clinical symptoms and thus demonstrate its validity as a predictive biomarker of response and clinical outcome surrogate.