Neuropsychiatric symptoms in patients with dementias associated with cortical Lewy bodies: pathophysiology, clinical features, and pharmacological management

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.