Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease

Gaskell, Helen; Burns, Alistair; Fox, Chris; Maidment, Ian; Pettit, Tor; Wild, Rebecca; McShane, Rupert; Boustani, Malaz

doi:10.1002/14651858.cd006504

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…The fifth case study is a series of E2020 analogues that inhibit the acetylcholinesterase (AChE) activity [34]. Inhibition of AChE could lead to the accumulation of acetylcholine, a neurotransmitter, and research has found that acetylcholine levels are related to many diseases, including Alzheimer’s disease and Lewy body dementia [50,51]. In this case, compound 22 was selected as the template (starting compound) to demonstrate the optimization process (PDB ID: 1b41) [34,52].…”

Section: Methodsmentioning

confidence: 99%

Template-Based de Novo Design for Type II Kinase Inhibitors and Its Extended Application to Acetylcholinesterase Inhibitors

Huang

Chang

et al. 2013

Molecules

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There is a compelling need to discover type II inhibitors targeting the unique DFG-out inactive kinase conformation since they are likely to possess greater potency and selectivity relative to traditional type I inhibitors. Using a known inhibitor, such as a currently available and approved drug or inhibitor, as a template to design new drugs via computational de novo design is helpful when working with known ligand-receptor interactions. This study proposes a new template-based de novo design protocol to discover new inhibitors that preserve and also optimize the binding interactions of the type II kinase template. First, sorafenib (Nexavar ® ) and nilotinib (Tasigna ® ), two type II inhibitors with different ligand-receptor interactions, were selected as the template compounds. The five-step protocol can reassemble each drug from a large fragment library. Our procedure demonstrates that the selected template compounds can be successfully reassembled while the key ligand-receptor interactions are preserved. Furthermore, to demonstrate that the algorithm is able to construct more potent compounds, we considered kinase inhibitors and other protein dataset, acetylcholinesterase (AChE) inhibitors. The de novo optimization was initiated using a template compound possessing a less than optimal activity from a OPEN ACCESSMolecules 2013, 18 13488 series of aminoisoquinoline and TAK-285 inhibiting type II kinases, and E2020 derivatives inhibiting AChE respectively. Three compounds with greater potency than the template compound were discovered that were also included in the original congeneric series. This template-based lead optimization protocol with the fragment library can help to design compounds with preferred binding interactions of known inhibitors automatically and further optimize the compounds in the binding pockets.

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Section: Methodsmentioning

confidence: 99%

Template-Based de Novo Design for Type II Kinase Inhibitors and Its Extended Application to Acetylcholinesterase Inhibitors

Huang

Chang

et al. 2013

Molecules

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“…Pooled results in meta-analysis for cholinesterase inhibitors using the NPI-10 as an outcome measure favored treatment in PDD but not in DLB. When pooling results for PDD, DLB, and cognitive impairment in PD, treatment is favored (Rolinski et al, 2012). An RCT of 550 PD-D patients in 2004 failed to show any significant difference between donepezil and placebo (Dubois et al, 2012).…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Management of visual hallucinations in dementia and Parkinson’s disease

Swann¹,

O’Brien²

2018

Int. Psychogeriatr.

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Objectives:Visual hallucinations are a common symptom in dementia and Parkinson’s disease and have been associated with greater cognitive and functional decline, but optimal management strategies are unclear. We review the frequency and pathogenesis of visual hallucinations in dementia and Parkinson’s disease and examine the evidence base for their management.Design:We undertook a systematic review of the visual hallucinations in dementia, searching studies published between January 1980 and July 2017 using PubMed with the search terms visual hallucinations AND review AND (dementia OR parkinson*).Results:We found 645 articles and screened them for relevance, finally including 89 papers (11 meta-analyses, 34 randomized controlled trials, six other trials and a number of relevant review articles). Only six of the trials reported visual hallucination outcomes separately from other neuropsychiatric symptoms.Conclusions:Atypical antipsychotics were frequently studied, but with the exception of clozapine in Parkinson’s disease dementia, results were equivocal. There was some evidence that acetylcholinesterase inhibitors may help visual hallucinations. Overall, effect sizes for most treatments were small and there were few studies with long term follow up. Treatments need to be carefully weighed up with the risks and reviewed often, and many patients improved without treatment. There is a lack of data regarding visual hallucinations due to the grouping of psychotic symptoms together in commonly used rating scales. The lack of a specific rating scales, or analyzable items within other scales, for visual hallucinations, limited efficacy of current and small evidence base with short follow up are important areas for future studies to address.

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Diagnosis and Management of the Patient with Suspected Dementia in Primary Care

2013

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Dementia is a complex progressive syndrome characterised by impairment of cognition (including memory, language, visuospatial skills and executive function), changes in personality and diminished activities of daily living. The impact of dementia is enormous and poses a huge challenge to patients, their carers, society at large and health systems around the world, in terms of the direct cost of medical care, social care and unpaid care provided by family members and others. In this review, we combine evidence and clinical opinion, using guidelines and reviews from 2006, 2009 and 2010 to present a practical guide for primary care physicians to the diagnosis, treatment and ongoing care of patients with suspected or diagnosed dementia. This review summarises the epidemiology of dementia syndrome, and offers detailed evidence-based advice on recognition of dementia (including subtyping) and responses to it and its associated symptoms. The roles of neuroimaging and biomarkers are discussed, as are both non-pharmacological and pharmacological therapies.

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Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease

Cited by 3 publications

References 23 publications

Template-Based de Novo Design for Type II Kinase Inhibitors and Its Extended Application to Acetylcholinesterase Inhibitors

Template-Based de Novo Design for Type II Kinase Inhibitors and Its Extended Application to Acetylcholinesterase Inhibitors

Management of visual hallucinations in dementia and Parkinson’s disease

Diagnosis and Management of the Patient with Suspected Dementia in Primary Care

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