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.