Abstract

Psychiatric symptoms are frequent in neurocognitive disorders and dementias. Psychotic symptoms, mainly hallucinations and delusions, may appear in up to 50% of cases, influencing morbidity and mortality. Genetic, neurobiological, and environmental factors are involved in their onset. We conducted a narrative review of primary articles developed in humans that analyzed the genetic and neurobiological basis of psychosis in dementias. Evidence suggests that there are genetic risk variants for presenting psychosis in dementia. How genetic variants are related to schizophrenia, dementia, and other neurodegenerative disorders is under discussion. Candidate gene studies have found COMT, SLC6A4, APOE, HTR2A, and HTR2C genetic variants are associated with psychosis in dementia, while genome-wide association studies have shown variants located in ENPP6 y SUMF1. Epigenetic studies are scarce but have detected differences in the methylome of people with dementia and psychosis. On the other hand, alterations of the cholinergic, serotonergic, dopaminergic, and gabaergic neurotransmitter systems and the excitatory-inhibitory balance have been described in dementia. From a functional and anatomical point of view, there are alterations in several regions, mainly in the frontal area and other sensory processing and integration areas. Finally, we describe the influence of cognitive alterations in the genesis and maintenance of delusions and discuss the phenomenological overlap with confabulations. Multiple genetic, neurobiological, structural, and cognitive factors influence the occurrence of delusions and hallucinations in persons with dementia. Further research is needed to understand the pathophysiology of psychosis in dementias. This approach would support the understanding of psychosis as a transdiagnostic entity.