Using Biomarkers to Predict Memantine Effects in Alzheimer’s Disease: A Proposal and Proof-Of-Concept Demonstration

Article type: Short Communication

Authors: Swerdlow, Neal R.^{a; *} | Kotz, Juliana E.^a | Joshi, Yash B.^{a; d} | Talledo, Jo^a | Sprock, Joyce^{a; d} | Molina, Juan L.^{a; d} | Huisa, Branko^b | Huege, Steven F.^a | Romero, Jairo Alberto^c | Walsh, Michael J.^a | Delano-Wood, Lisa^a | Light, Gregory A.^{a; d}

Affiliations: [a] Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA, USA | [b] Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, CA, USA | [c] Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA | [d] VISN-22 Mental Illness, Research, Education and Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA, USA

Correspondence: [*] Correspondence to: Neal R. Swerdlow, MD, PhD, Distinguished Professor, Department of Psychiatry 0804, UCSD School of Medicine, 9500 Gilman Dr., La Jolla, CA 92093-0804, USA. E-mail: nswerdlow@ucsd.edu.

Abstract: Memantine’s benefits in Alzheimer’s disease (AD) are modest and heterogeneous. We tested the feasibility of using sensitivity to acute memantine challenge to predict an individual’s clinical response. Eight participants completed a double-blind challenge study of memantine (placebo versus 20 mg) effects on autonomic, subjective, cognitive, and neurophysiological measures, followed by a 24-week unblinded active-dose therapeutic trial (10 mg bid). Study participation was well tolerated. Subgroups based on memantine sensitivity on specific laboratory measures differed in their clinical response to memantine, some by large effect sizes. It appears feasible to use biomarkers to predict clinical sensitivity to memantine.

Keywords: Alzheimer’s disease, event-related potentials, memantine, neurocognition, prepulse inhibition

DOI: 10.3233/JAD-215029

Journal: Journal of Alzheimer's Disease, vol. 84, no. 4, pp. 1431-1438, 2021