Memantine in Patients with Moderate to Severe Alzheimer's Disease: Meta-Analyses Using Realistic Definitions of Response

Abstract

Background/Aims: We aimed to develop realistic definitions of clinical worsening in advanced Alzheimer's disease (AD) and to use them in a post hoc responder analysis of memantine. Methods: 2,340 patients with moderate to severe AD (Mini-Mental State Examination <20) were included from 9 multicentre, 16- to 28-week, randomised, double-blind, placebo-controlled studies of memantine 20 mg/day versus placebo. Responder meta-analyses were performed, with definitions of response based on minimally important differences (MIDs) on cognitive, functional, and global assessment scales. Validated or established MIDs were used where available; otherwise, MIDs were estimated by a data-driven approach, using data from our moderate to severe AD population. Results: Patients with moderate to severe AD treated with memantine had a lower incidence of worsening from baseline to endpoint than patients treated with placebo, in cognition [24.4 vs. 35.0%; odds ratio (OR) = 0.60; p < 0.001], function (38.1 vs. 43.4%; OR = 0.81; p = 0.01), global status (39.8 vs. 48.6%; OR = 0.70; p < 0.001), and in a combined ‘triple' worsening measure (9.4 vs. 16.1%; OR = 0.54; p < 0.001). Conclusions: New definitions of clinical worsening based on MIDs represent a more realistic functional decline in advanced stages of AD. Results of this new analysis show that memantine reduces the incidence of clinical worsening in key symptomatic domains in moderate to severe AD.

Developing Medications Targeting Glutamatergic Dysfunction in Autism: Progress to Date

“…Memantine is another NMDAR antagonist that has been used to treat Alzheimer’s disease [50]. A retrospective study of memantine in children and adolescents with ASD (N=18; mean age 11.4±3.3; range 6–19 years) showed improvement in Clinical Global Impressions – Improvement (CGI-I) [51].…”

Heteroreceptor Complexes Formed by Dopamine D1, Histamine H3, and N-Methyl-D-Aspartate Glutamate Receptors as Targets to Prevent Neuronal Death in Alzheimer’s Disease

“…The interaction with NR1-1a affects NMDA receptor-mediated excitotoxicity while the interaction with NR2A affects ligand-gated currents. Besides inhibitors of acetyl cholinesterase, the only drug approved for Alzheimer's disease is Namendal R whose active component, memantine, is an allosteric modulator of NMDA receptors [26], which remain one of the main therapeutic targets in this neurodegenerative disease [27]. As heteroreceptor complexes formed by different GPCRs [28] or by combination of GPCR and ionotropic receptors [29] have specific physiological functions and emerge as novel therapeutic targets, the aim of the present paper was to look for heteromers formed by dopamine D 1 , histamine H 3 , and NMDA receptors and to assess their potential as targets in Alzheimer's disease.…”

Clinical experience of the use of memantal in patients with moderate and severe Alzheimer’s disease

“…3), о чем свидетельству-ет снижение медианы суммарного показателя шкалы NPI у больных c 15 [8; 22] Полученные результаты показывают, что меманталь потенциально эффективен и хорошо переносится паци-ентами с умеренной и умеренно тяжелой стадиями БА, что согласуется с выводами различных исследований. Данные метаанализов ряда ранее проведенных исследова-ний [18,19], изучавших эффективность мемантина у больных с умеренной и тяжелой деменцией, показывают однородные результаты, свидетельствующие о сохране-нии когнитивного функционирования пациентов с уме-ренной и умеренно тяжелой деменцией на уровне, пред-шествующем началу лечения, а также о поддержании воз-можностей их физического самообслуживания и об уменьшении выраженности ряда поведенческих и психо-тических симптомов деменции.…”