Memantine Effects on Verbal Memory in Fragile X-associated Tremor/Ataxia Syndrome (FXTAS): a Double-Blind Brain Potential Study

Neuropsychopharmacology (2014) 39, 27602768

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Memantine Effects on Verbal Memory in Fragile X-associated Tremor/Ataxia Syndrome (FXTAS): a Double-Blind Brain Potential Study

Jin-Chen Yang*,1,2,9, Yu-Qiong Niu1,2,9, Christa Simon1,2, Andreea L Seritan3, Lawrence Chen1,4, Andrea Schneider5,6, Shayan T Moghaddam1,7, Paul J Hagerman5,8, Randi J Hagerman5,6 and John M Olichney*,1,2

1Center for Mind and Brain, University of California Davis, Davis, CA, USA; 2Department of Neurology, University of California Davis,School of Medicine, Sacramento, CA, USA; 3Department of Psychiatry and Behavioral Sciences, University of California Davis, School of Medicine, Sacramento, CA, USA; 4Department of Psychology, University of California Davis, Davis, CA, USA; 5Medical Investigations of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, School of Medicine, Sacramento, CA, USA; 6Department of Pediatrics, University of California Davis, School of Medicine, Sacramento, CA, USA; 7College of Biological Sciences, University of California Davis, Davis, CA, USA;

8Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, CA, USA

Older FMR1 premutation carriers may develop fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder manifesting cognitive deficits that often subsequently progress to dementia. To date, there is no specific treatment available for FXTAS. Studies have demonstrated the premutation-associated overactivation of glutamatergic receptors in neurons. Memantine, a NMDA receptor antagonist approved for treatment of Alzheimers disease, thus was tested in the first placebo-controlled, double-blind, randomized clinical trial in FXTAS. Prior event-related brain potential (ERP) studies in FXTAS found reduced N400 repetition effect, a glutamate-related electrophysiological marker of semantic priming, and verbal memory processes. This substudy of the randomized clinical trial of memantine in FXTAS sought to use the N400 repetition effect to evaluate effects of chronic memantine treatment on verbal memory. Subsequent recall and recognition memory tests for the experimental stimuli were administered to characterize verbal memory. Data from 41 patients who completed the 1-year memantine trial (21 on memantine) and also completed longitudinal ERP studies were analyzed. Results showed treatment-associated benefits on both cued-recall memory and N400 repetition effect amplitude. Importantly, improvement in cued recall was positively correlated with amplitude increase of the N400 repetition effect. The placebo group, in contrast, displayed a significant reduction of the N400 repetition effect after 1 year. These results suggest that memantine treatment may have...