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Neuropsychiatric Symptoms in Patients with Dementias Associated with Cortical Lewy Bodies: Pathophysiology, Clinical Features, and Pharmacological Management

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An Erratum to this article was published on 01 July 2014

Abstract

Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) are synucleinopathies that lead to neurodegeneration and dementia. Although they result in symptoms common to Alzheimer’s disease, they are associated with early emergence of parkinsonism and high frequency of neuropsychiatric symptoms, most commonly hallucinations and delusions. This review summarizes the current understanding of the underlying biology of neuropsychiatric symptoms in DLB and PDD and the evidence base for treatment to address them. Disruption to cholinergic and serotonergic neurotransmission and synapse activity are highlighted as primary pathological factors in neuropsychiatric symptoms, particularly loss of key neurotransmitter functions, alterations to neuronal receptors in the serotonergic pathway, and regionally specific structural changes that are linked to specific symptoms. Review of options for pharmacological treatment of neuropsychiatric symptoms suggests that the best evidence for the value of treatment is for cholinesterase inhibitors, with an indication that people with visual hallucinations are particularly likely to benefit. Evidence for the benefits of antipsychotics other than clozapine is limited, and there are serious safety concerns about the use of antipsychotics in these patients. Evidence to support other pharmacological interventions is very preliminary. Nonpharmacological approaches based on person-centered care and cholinesterase inhibitors should be considered as the first-line treatment for neuropsychiatric symptoms except in extreme cases.

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Acknowledgements

We thank the NIHR Biomedical Research Unit for Dementia and the NIHR Biomedical Research Centre for Mental Health at King’s College London/South London and Maudsley NHS trust for supporting the involvement of Clive Ballard, Paul Francis, and Anne Corbett in the writing of the manuscript.

Conflict of interest

Professor Clive Ballard has received research grants from Lundbeck and Acadia pharmaceutical companies and honoraria and consultancy fees from Lundbeck, Acadia Novartis, Bristol Myer Sqibb, and Bial pharmaceutical companies and from Tapestry consultancy agency within the past 3 years.

Dag Aarsland has received research support and honoraria from H. Lundbeck, Novartis Pharmaceuticals, and GE Health.

Paul Francis has received research grants from Lundbeck pharmaceutical company and fees for consultancy or speaking from Lundbeck and Novartis pharmaceutical companies. He has also received payment related to expert witness testimony related to cases involving Novartis and Janssen Alzheimer Immunotherapy. None of this work is directly relevant to the submitted manuscript.

Anne Corbett has received speaking and consultancy honoraria from Lundebck, Bial, Novartis, and Acadia pharmaceuticals. None of this work is directly relevant to this manuscript.

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  1. Wolfson Centre for Age-Related Diseases, King’s College London, Wolfson Building, Guy’s Campus, London, SE1 1UL, UK

    Clive Ballard, Paul Francis & Anne Corbett

  2. Karolinska Institutet Alzheimer’s Disease Research Centre, Novum, Karolinska Institutet, Stockholm, 141 86, Sweden

    Dag Aarsland

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  1. Clive Ballard
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Correspondence to Clive Ballard.

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Ballard, C., Aarsland, D., Francis, P. et al. Neuropsychiatric Symptoms in Patients with Dementias Associated with Cortical Lewy Bodies: Pathophysiology, Clinical Features, and Pharmacological Management. Drugs Aging 30, 603–611 (2013). https://doi.org/10.1007/s40266-013-0092-x

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