OZR Back-up mandate: Subclinical epileptiform activity and melatonin disruptions in the Alzheimer's disease continuum.

Alzheimer's disease (AD) is the most common cause of dementia and characterised by amyloid beta (Aβ) plaques and tangles consisting of hyperphosphorylated tau. Epilepsy is a known comorbidity of AD. Early soluble and fibrillar forms of Aβ already induce neuronal hyperexcitability and epileptiform activity in rodent models, which in turn aggravate disease progression. I will investigate the prevalence of (subclinical) epileptiform activity in an early stage of the human disease (mild cognitive impairment (MCI)) and evaluate its effects on conversion rate to dementia. Melatonin disruptions have been described in cerebrospinal fluid (CSF) of AD patients. I will validate the use of plasma melatonin as alternative for CSF melatonin in AD. I will compare melatonin levels in these biological fluids between dementia, MCI due to AD and healthy controls to evaluate disruptions in an early disease stage. Melatonin had positive effects on cognition in an overall MCI population, which is why I will correlate melatonin levels with changes in cognition in a longitudinal way, specifically in MCI due to AD. Finally, we hypothesize that low melatonin levels will correlate with more epileptiform activity in the AD continuum. Melatonin has indeed anticonvulsive effects in animal models. Since epileptiform activity might lead to disease progression, attenuation of the epileptic phenomena is a possible explanation for melatonin's positive effects on cognition in MCI patients.