Levetiracetam Increases Hippocampal Blood Flow in Alzheimer’s Disease as Measured by Arterial Spin Labelling MRI

Article type: Research Article

Authors: Press, Daniel Zvi^{a; 1} | Musaeus, Christian Sandøe^{a; b; 1; *} | Zhao, Li^c | Breton, Jocelyn M.^{a; d} | Shafi, Mouhsin M.^a | Dai, Weiying^e | Alsop, David C.^f

Affiliations: [a] Berenson-Allen Center for Non-invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA | [b] Department of Neurology, Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark | [c] Key Laboratory for Biomedical Engineering of Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang, China | [d] Department of Psychiatry, Columbia University, New York, NY, USA | [e] Department of Computer Science, State University of New York at Binghamton, Binghamton, NY, USA | [f] Department of Radiology, Division of MRI Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA

Correspondence: [*] Correspondence to: Christian Sandøe Musaeus, Rigshospitalet, University of Copenhagen, Inge Lehmanns Vej 8, 2100 Copenhagen, Denmark. E-mail: christian.sandoee.musaeus@regionh.dk.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Patients with Alzheimer’s disease (AD) have an increased risk of developing epileptiform discharges, which is associated with a more rapid rate of progression. This suggests that suppression of epileptiform activity could have clinical benefit in patients with AD. Objective:In the current study, we tested whether acute, intravenous administration of levetiracetam led to changes in brain perfusion as measured with arterial spin labeling MRI (ASL-MRI) in AD. Methods:We conducted a double-blind, within-subject crossover design study in which participants with mild AD (n = 9) received placebo, 2.5 mg/kg, and 7.5 mg/kg of LEV intravenously in a random order in three sessions. Afterwards, the participants underwent ASL-MRI. Results:Analysis of relative cerebral blood flow (rCBF) between 2.5 mg of levetiracetam and placebo showed significant decreases in a cluster that included the posterior cingulate cortex, the precuneus, and the posterior part of the cingulate gyrus, while increased cerebral blood flow was found in both temporal lobes involving the hippocampus. Conclusion:Administration of 2.5 mg/kg of LEV in patients without any history of epilepsy leads to changes in rCBF in areas known to be affected in the early stages of AD. These areas may be the focus of the epileptiform activity. Larger studies are needed to confirm the current findings.

Keywords: Alzheimer’s disease, arterial spin labeling MRI, epilepsy, epileptiform activity, levetiracetam, randomized controlled trial

DOI: 10.3233/JAD-220614

Journal: Journal of Alzheimer's Disease, vol. 93, no. 3, pp. 939-948, 2023