Critical appraisal of the long-term impact of memantine in treatment of moderate to severe Alzheimer&amp;rsquo;s disease

Puangthong, Umamon; Hsiung, Ging-Yuek Robin

doi:10.2147/ndt.s5021

Cited by 7 publications

(1 citation statement)

References 68 publications

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“…Furthermore, Aβ induces LTD and excitotoxicity mediated by NMDARs receptors [20] . The importance of glutamate signalling via NMDARs as a causative event of dementia in AD is further demonstrated, by findings that memantine -a low affinity antagonist for NMDARs- results in behavioural improvement in AD model transgenic mice and is used as treatment of moderate AD [21] , [22] , [23] . This raises the possibility that the effects of Aβ could be due to an agonist action on NMDARs [24] .…”

Section: Introductionmentioning

confidence: 99%

Amyloid-β Acts as a Regulator of Neurotransmitter Release Disrupting the Interaction between Synaptophysin and VAMP2

et al. 2012

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BackgroundIt is becoming increasingly evident that deficits in the cortex and hippocampus at early stages of dementia in Alzheimer’s disease (AD) are associated with synaptic damage caused by oligomers of the toxic amyloid-β peptide (Aβ42). However, the underlying molecular and cellular mechanisms behind these deficits are not fully understood. Here we provide evidence of a mechanism by which Aβ42 affects synaptic transmission regulating neurotransmitter release.Methodology/FindingsWe first showed that application of 50 nM Aβ42 in cultured neurones is followed by its internalisation and translocation to synaptic contacts. Interestingly, our results demonstrate that with time, Aβ42 can be detected at the presynaptic terminals where it interacts with Synaptophysin. Furthermore, data from dissociated hippocampal neurons as well as biochemical data provide evidence that Aβ42 disrupts the complex formed between Synaptophysin and VAMP2 increasing the amount of primed vesicles and exocytosis. Finally, electrophysiology recordings in brain slices confirmed that Aβ42 affects baseline transmission.Conclusions/SignificanceOur observations provide a necessary and timely insight into cellular mechanisms that underlie the initial pathological events that lead to synaptic dysfunction in Alzheimer’s disease. Our results demonstrate a new mechanism by which Aβ42 affects synaptic activity.

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Section: Introductionmentioning

confidence: 99%

Amyloid-β Acts as a Regulator of Neurotransmitter Release Disrupting the Interaction between Synaptophysin and VAMP2

et al. 2012

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Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia

Parsons

Lim

Loy

et al. 2021

Cochrane Database of Systematic Reviews

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BackgroundDementia is a progressive syndrome characterised by deterioration in memory, thinking and behaviour, and by impaired ability to perform daily activities. Two classes of drug -cholinesterase inhibitors (donepezil, galantamine and rivastigmine) and memantine -are widely licensed for dementia due to Alzheimer's disease, and rivastigmine is also licensed for Parkinson's disease dementia. These drugs are prescribed to alleviate symptoms and delay disease progression in these and sometimes in other forms of dementia. There are uncertainties about the benefits and adverse e ects of these drugs in the long term and in severe dementia, about e ects of withdrawal, and about the most appropriate time to discontinue treatment.Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia (Review)

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Memantine augmentation in clozapine-refractory schizophrenia: a randomized, double-blind, placebo-controlled crossover study

Veerman¹,

Schulte²,

Smith

et al. 2016

Psychol. Med.

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BackgroundDysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia.MethodClozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale.ResultsWhen compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient.ConclusionsIn patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.

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Critical appraisal of the long-term impact of memantine in treatment of moderate to severe Alzheimer’s disease

Cited by 7 publications

References 68 publications

Amyloid-β Acts as a Regulator of Neurotransmitter Release Disrupting the Interaction between Synaptophysin and VAMP2

Amyloid-β Acts as a Regulator of Neurotransmitter Release Disrupting the Interaction between Synaptophysin and VAMP2

Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia

Memantine augmentation in clozapine-refractory schizophrenia: a randomized, double-blind, placebo-controlled crossover study

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