Biomarking the Alzheimer landscape : could melatonin be the key to detect subclinical epileptiform activity?
In this thesis subclinical epileptiform activity (SEA) and melatonin disruptions in Alzheimer’s disease (AD) were evaluated, as both might serve either as biomarker or as potential new treatment target/treatable phenomena in AD. Although melatonin seems to have multiple anti-AD properties, we showed evidence for disruptions in cerebrospinal fluid (CSF) and blood night-time melatonin levels in AD patients as compared to age-matched controls in a systematic review. Next, we found no significant differences in daytime serum or CSF melatonin levels between patients with dementia due to AD, mild cognitive impairment due to AD and healthy controls, nor could we find an association between daytime melatonin levels and cognition or cognitive decline in AD in a retrospective study. We however did find a good correlation between CSF and serum melatonin levels in AD, suggesting valid use of blood melatonin levels to study melatonin disruptions in AD. In a prospective study, we found the prevalence of SEA to be significantly increased in AD participants who never experienced a seizure before, as compared to healthy controls, with the prevalence increasing through the different disease stages. We concluded that different neurophysiological techniques (LTM-EEG, hd-EEG, MEG) to detect SEA in AD remain complementary. When looking at hd-EEG, there does seem to be an added value of using an inferior temporal chain of electrodes in detecting epileptiform activity in AD. Adding this inferior temporal chain to the standard LTM-EEG caps/nets could therefore be a potential way forward, concluding two examinations into one. AD patients with SEA scored worse on neuropsychological visuospatial and attention tests, and showed increased volumes in left frontal, (left) temporal and (left and right) entorhinal regions on brain MRI. This should be kept in mind because the identification of AD patients with SEA might become increasingly important, as neuronal hyperactivity and SEA might lead to disease progression in AD. Whereas blood and saliva melatonin do not seem to be a good biomarker for disease stage in AD, they might have potential to become an interesting biomarker for SEA in AD. We found increased melatonin levels at 04:00 in plasma and at 01:00 in saliva in AD participants with SEA as compared to those without. Whether the melatonin surge in AD participants with SEA is rather a cause or consequence of this SEA, merits further investigation.
Brussel : Vrije Universiteit Brussel & Universiteit Antwerpen , 2024
xiv, 158 p.
Supervisor: Engelborghs, Sebastiaan [Supervisor]
Supervisor: Smolders, Ilse [Supervisor]
Supervisor: Nagels, Guy [Supervisor]
Supervisor: Versijpt, Jan [Supervisor]
Supervisor: Seynaeve, Laura [Supervisor]
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The publisher created published version Available from 26.03.2026
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Creation 22.03.2024
Last edited 28.03.2024
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