Subclinical epileptiform discharges in Alzheimer's disease are associated with increased hippocampal blood flow

Christian Sandøe Musaeus*, Troels Wesenberg Kjaer, Ulrich Lindberg, Mark B Vestergaard, Henrik Bo, Daniel Zvi Press, Birgitte Bo Andersen, Peter Høgh, Preben Kidmose, Martin Christian Hemmsen, Mike Lind Rank, Steen Gregers Hasselbalch, Gunhild Waldemar, Kristian Steen Frederiksen

*Corresponding author for this work


BACKGROUND: In epilepsy, the ictal phase leads to cerebral hyperperfusion while hypoperfusion is present in the interictal phases. Patients with Alzheimer's disease (AD) have an increased prevalence of epileptiform discharges and a study using intracranial electrodes have shown that these are very frequent in the hippocampus. However, it is not known whether there is an association between hippocampal hyperexcitability and regional cerebral blood flow (rCBF). The objective of the study was to investigate the association between rCBF in hippocampus and epileptiform discharges as measured with ear-EEG in patients with Alzheimer's disease. Our hypothesis was that increased spike frequency may be associated with increased rCBF in hippocampus.

METHODS: A total of 24 patients with AD, and 15 HC were included in the analysis. Using linear regression, we investigated the association between rCBF as measured with arterial spin-labelling MRI (ASL-MRI) in the hippocampus and the number of spikes/sharp waves per 24 h as assessed by ear-EEG.

RESULTS: No significant difference in hippocampal rCBF was found between AD and HC (p-value = 0.367). A significant linear association between spike frequency and normalized rCBF in the hippocampus was found for patients with AD (estimate: 0.109, t-value = 4.03, p-value < 0.001). Changes in areas that typically show group differences (temporal-parietal cortex) were found in patients with AD, compared to HC.

CONCLUSIONS: Increased spike frequency was accompanied by a hemodynamic response of increased blood flow in the hippocampus in patients with AD. This phenomenon has also been shown in patients with epilepsy and supports the hypothesis of hyperexcitability in patients with AD. The lack of a significant difference in hippocampal rCBF may be due to an increased frequency of epileptiform discharges in patients with AD.

TRIAL REGISTRATION: The study is registered at (NCT04436341).

Original languageEnglish
Article number80
JournalAlzheimer's research & therapy
Issue number1
Pages (from-to)80
Publication statusPublished - 12 Apr 2024


  • Humans
  • Alzheimer Disease/complications
  • Hippocampus/diagnostic imaging
  • Temporal Lobe
  • Cerebrovascular Circulation
  • Epilepsy/diagnostic imaging


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