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; Wiberg Larsson; Daniel Zvi Press; Birgitte Bo Andersen; Peter Høgh; Preben Kidmose; Martin Christian Hemmsen; Mike Lind Rank; Steen Gregers Hasselbalch; Gunhild Waldemar; Kristian Steen Frederiksen

doi:10.1186/s13195-024-01432-9

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

Alzheimers Res Ther. 2024 Apr 12;16(1):80. doi: 10.1186/s13195-024-01432-9.

Authors

Christian Sandøe Musaeus¹, Troels Wesenberg Kjaer², Ulrich Lindberg³, Mark B Vestergaard³, Henrik Bo², Wiberg Larsson³, Daniel Zvi Press⁴, Birgitte Bo Andersen², Peter Høgh^{5

6}, Preben Kidmose⁷, Martin Christian Hemmsen⁸, Mike Lind Rank⁸, Steen Gregers Hasselbalch^{2

6}, Gunhild Waldemar^{2

6}, Kristian Steen Frederiksen^{2

6}

Affiliations

¹ Danish Dementia Research Centre (DDRC), Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Inge Lehmanns vej 8, Copenhagen, 2100, Denmark. Christian.sandoee.musaeus@regionh.dk.
² Danish Dementia Research Centre (DDRC), Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Inge Lehmanns vej 8, Copenhagen, 2100, Denmark.
³ Functional Imaging Unit, Department of Clinical Physiology and Nuclear Medicine, University of Copenhagen, Valdemar Hansens Vej 13, Glostrup, 2600, Denmark.
⁴ Berenson-Allen Center for Non-invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA.
⁵ Regional Dementia Research Centre, Department of Neurology, Zealand University Hospital, Vestermarksvej 11, Roskilde, 4000, Denmark.
⁶ Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, Copenhagen, 2200, Denmark.
⁷ Department of Electrical and Computer Engineering, Aarhus University, Finlandsgade 22, Aarhus N, 8200, Denmark.
⁸ T&W Engineering, Borupvang 2, Lillerød, 3450, Denmark.

Abstract

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 clinicaltrials.gov (NCT04436341).

Keywords: Alzheimer’s disease; EEG; Epileptiform discharges; Hyperperfusion; Spike frequency.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Associated data

ClinicalTrials.gov/NCT04436341