Efficacy of memantine in PDD and DLB: an extension study including washout and open-label treatment

Johansson, Camilla; Ballard, Clive; Hansson, Oskar; Palmqvist, Sebastian; Minthon, Lennart; Aarsland, Dag; Londos, Elisabet

doi:10.1002/gps.2516

Cited by 21 publications

(20 citation statements)

References 27 publications

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“…Perhaps this could indicate that patients can benefit from treatment with memantine, but only when it is introduced early in the clinical course. Furthermore, this is in line with the study on the same population by Johansson et al ,19 who noticed a global improvement in the placebo group as well as in the memantine group during the 30 weeks of open-label follow-up, but the change in CGIC was not significant.…”

Section: Discussionsupporting

confidence: 91%

Treatment effect of memantine on survival in dementia with Lewy bodies and Parkinson's disease with dementia: a prospective study

et al. 2014

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ObjectiveTo investigate the effect on survival of treatment with memantine in patients with dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD).Methods75 patients with DLB and PDD were included in a prospective double-blinded randomised placebo-controlled trial (RCT) of memantine, of whom long-term follow-up was available for 42. Treatment response was recorded 24 weeks from baseline and measured by Clinical Global Impression of Change (CGIC). The participants were grouped as responders (CGIC 1–3) or non-responders (CGIC 4–7). The 24-week RCT was followed by open-label treatment and survival was recorded at 36 months.ResultsAfter 36-month follow-up, patients in the memantine group had a longer length of survival compared with patients in the placebo group (log rank x²=4.02, p=0.045). Within the active treatment group, survival analysis 36 months from baseline showed that the memantine responders, based on CGIC, had higher rates of survival compared with the non-responders (log rank x²=6.595, p=0.010). Similar results were not seen in the placebo group.ConclusionsEarly treatment with memantine and a positive clinical response to memantine predicted longer survival in patients with DLB and PDD. This suggests a possible disease-modifying effect and also has implications for health economic analysis. However, owing to the small study sample, our results should merely be considered as generating a hypothesis which needs to be evaluated in larger studies.Trial registration numberISRCTN89624516.

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Section: Discussionsupporting

confidence: 91%

Treatment effect of memantine on survival in dementia with Lewy bodies and Parkinson's disease with dementia: a prospective study

et al. 2014

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“…It is worth noting that the use of mitochondrially-directed antioxidants, calcium chelators/metal protein-binding compounds, NMDA receptor inhibitors, and caspase inhibitors have been developed but have demonstrated modest to no benefit in clinical trials for treating various brain degenerative disorders (Snow, et al 2010) (Johansson, et al 2011) (Bonelli, et al 2006) (Regland, et al 2001) (Sampson, et al 2012). The development of pharmacologically active compounds that can tout protective signaling in neurons poses a paramount challenge due to the compartmentalized nature of PKA signaling pathways in neurons.…”

Section: Resultsmentioning

confidence: 99%

Role of protein kinase A in regulating mitochondrial function and neuronal development: implications to neurodegenerative diseases

Dagda

Banerjee

2015

Reviews in the Neurosciences

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AbstractIn neurons, enhanced protein kinase A (PKA) signaling elevates synaptic plasticity, promotes neuronal development, and increases dopamine synthesis. By contrast, a decline in PKA signaling contributes to the etiology of several brain degenerative diseases, including Alzheimer’s disease and Parkinson’s disease, suggesting that PKA predominantly plays a neuroprotective role. A-kinase anchoring proteins (AKAPs) are large multidomain scaffold proteins that target PKA and other signaling molecules to distinct subcellular sites to strategically localize PKA signaling at dendrites, dendritic spines, cytosol, and axons. PKA can be recruited to the outer mitochondrial membrane by associating with three different AKAPs to regulate mitochondrial dynamics, structure, mitochondrial respiration, trafficking, dendrite morphology, and neuronal survival. In this review, we survey the myriad of essential neuronal functions modulated by PKA but place a special emphasis on mitochondrially localized PKA. Finally, we offer an updated overview of how loss of PKA signaling contributes to the etiology of several brain degenerative diseases.

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“…A total of 20 clinical trials evaluating the efficacy of interventions in PDD were identified . All of these trials assessed pharmacological treatments.…”

Section: Resultsmentioning

confidence: 99%

Outcome Measures for Parkinson's Disease Dementia: A Systematic Review

Holden

Jones

Baker

et al. 2015

Movement Disord Clin Pract

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Background Parkinson’s disease dementia (PDD) is a major cause of morbidity and mortality in Parkinson’s disease (PD), which severely affects patient functioning and quality of life and increases the risk for nursing home admission. Unfortunately, current treatment options for PDD are limited and have only marginal therapeutic effects. As novel treatments are developed, there will be a need to assess their efficacy in well-designed randomized controlled trials. However, there is no consensus on the optimal outcome measures for use in PDD clinical trials. Methods A systematic review of PDD clinical trials and empiric studies of outcome measures used in PDD was performed. Outcome measures were divided into five categories: 1) cognitive; 2) behavioral and mood; 3) activities of daily living and quality of life; 4) global; and 5) caregiver burden. Findings A total of 20 PDD pharmacologic clinical trials were identified. These trials incorporated a broad array of outcome measures, which were used inconsistently across trials. We summarize the psychometric properties and other relevant data on outcome measures used, including their diagnostic utility, inter-rater reliability, test-retest reliability, responsiveness, clinically meaningful change, and availability of alternate forms. Conclusions We have identified the best-evidenced PDD outcome measures in each domain. Further research is needed to assess the validity, reliability, and clinically meaningful change of these measures in PDD to inform the design of future clinical trials and enhance the ability of clinicians, researchers and policy-makers to interpret study results. In addition, the development of outcome measures specific to PDD may be warranted.

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Efficacy of memantine in PDD and DLB: an extension study including washout and open-label treatment

Cited by 21 publications

References 27 publications

Treatment effect of memantine on survival in dementia with Lewy bodies and Parkinson's disease with dementia: a prospective study

Treatment effect of memantine on survival in dementia with Lewy bodies and Parkinson's disease with dementia: a prospective study

Role of protein kinase A in regulating mitochondrial function and neuronal development: implications to neurodegenerative diseases

Outcome Measures for Parkinson's Disease Dementia: A Systematic Review

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