Systematized delusions in a patient with covert hepatic encephalopathy: A clinicopathological insight into prodromal dementia with Lewy bodies

Late-onset psychosis is an early clinical manifestation of psychiatric-onset prodromal dementia with Lewy bodies (DLB); however, its underlying neuropathology remains poorly understood. Clinicopathological correlations are often limited by the gap between symptom onset and the autopsy.

A 66-year-old man with autopsy-confirmed DLB presented with persistent systematized delusions. After treatment for liver cirrhosis during hospitalization, the patient's physical symptoms improved; however, persecutory delusions developed. The patient was clinically diagnosed with covert hepatic encephalopathy (HE). The delusions were atypical for covert HE, suspecting delusional disorder. His systematized delusions persisted for 3 months until his death, without the development of cognitive decline or Parkinsonism during his lifetime. An autopsy revealed an early transitional type of Lewy body disease with minimal Alzheimer's type II astrocytes indicative of HE. Severe neuronal loss was observed in the locus coeruleus (LC), while the substantia nigra (SN) and nucleus basalis of Meynert (nbM) were preserved. Abundant alpha-synuclein-positive structures were identified in the LC, periaqueductal gray matter, nbM, amygdala, and thalamus, with sparse involvement of the SN, neocortex, peripheral autonomic nervous system, including the heart and gastrointestinal tract.

Selective Lewy body involvement, sparing the SN and neocortex, may explain the isolated psychiatric symptoms in the absence of Parkinsonism or dementia. Systemic conditions such as covert HE may have contributed to the emergence of persistent delusions. This case highlights the need for multidisciplinary approaches that integrate psychosomatic assessments with neuropathological investigations to evaluate late-onset psychosis.