Dataset Information

Memantine Improves Attentional Processes in Fragile X-Associated Tremor/Ataxia Syndrome: Electrophysiological Evidence from a Randomized Controlled Trial.

ABSTRACT: Progressive cognitive deficits are common in patients with fragile X-associated tremor/ataxia syndrome (FXTAS), with no targeted treatment yet established. In this substudy of the first randomized controlled trial for FXTAS, we examined the effects of NMDA antagonist memantine on attention and working memory. Data were analyzed for patients (24 in each arm) who completed both the primary memantine trial and two EEG recordings (at baseline and follow-up) using an auditory "oddball" task. Results demonstrated significantly improved attention/working memory performance after one year only for the memantine group. The event-related potential P2 amplitude elicited by non-targets was significantly enhanced in the treated group, indicating memantine-associated improvement in attentional processes at the stimulus identification/discrimination level. P2 amplitude increase was positively correlated with improvement on the behavioral measure of attention/working memory during target detection. Analysis also revealed that memantine treatment normalized the P2 habituation effect at the follow-up visit. These findings indicate that memantine may benefit attentional processes that represent fundamental components of executive function/dysfunction, thought to comprise the core cognitive deficit in FXTAS. The results provide evidence of target engagement of memantine, as well as therapeutically relevant information that could further the development of specific cognitive or disease-modifying therapies for FXTAS.

SUBMITTER: Yang JC

PROVIDER: S-EPMC4761982 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Memantine, an uncompetitive N-methyl-d-aspartate receptor antagonist, is currently approved by the US Food and Drug Administration for the treatment of moderate to severe Alzheimer's disease. Anecdotal reports have suggested that memantine may improve neurologic and cognitive symptoms of individuals with the neurodegenerative disease fragile X-associated tremor/ataxia syndrome (FXTAS); however, its efficacy and safety in this population have not been assessed in a controlled trial.Individuals with FXTAS aged 34-80 years were enrolled in a randomized, double-blind, placebo-controlled, 1-year trial between September 2007 and August 2012. Inclusion required definite, probable, or possible FXTAS in clinical stages 1-5 according to previously published criteria. Primary outcome measures were the Behavioral Dyscontrol Scale (BDS) score and CATSYS intention tremor severity.Ninety-four participants were randomized from 205 screened; of those, 43 and 45 started treatment with memantine (titrated to 10 mg twice daily) and placebo, respectively. Thirty-four participants receiving memantine and 36 receiving placebo completed the 1-year endpoint assessment (n = 70). Intention-to-treat analysis showed no improvement with respect to intention tremor severity (mean [SD] values with memantine vs placebo: 1.05 [0.73] vs 1.89 [2.19], P = .047) or BDS score (16.12 [5.43] vs 15.72 [3.93], P = .727) at follow-up. Post hoc analyses of participants with early FXTAS (stage ? 3), those with late FXTAS (stage > 3), and those in different age groups (? 65 years and > 65 years) also indicated no significant improvement. More frequent mild adverse events were observed in the placebo group, while more frequent moderate adverse events occurred in the memantine group (P = .007).This randomized, double-blind, placebo-controlled trial of memantine for individuals with FXTAS showed no benefit compared to placebo with respect to the selected outcome measures.ClinicalTrials.gov identifier: NCT00584948.

Dataset Information

Memantine Improves Attentional Processes in Fragile X-Associated Tremor/Ataxia Syndrome: Electrophysiological Evidence from a Randomized Controlled Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets