Multiple pathologies underlying a very late‐onset schizophrenia‐like psychosis

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AbstractBackgroundVery late‐onset schizophrenia‐like psychosis term was recently introduced and includes schizophrenia, delusional disorders, and paranoid psychosis after 60 years. More than 60% of cases are due to secondary causes, mostly neurodegenerative diseases. We described clinical, neuropathological, and radiological findings of a woman with psychotic symptoms preceding cognitive impairment.MethodClinical data were obtained by interview with a next of kin. Both hemispheres were fixed in 4% buffered paraformaldehyde within 15 hours of death. The following samples from both fixed hemispheres were embedded in paraffin: middle and inferior frontal, middle and superior temporal, superior frontal and anterior cingulate gyri, angular gyrus, insula, visual cortex, hippocampal formation at the level of the lateral geniculate body, amygdala, basal ganglia at the level of the anterior commissure, thalamus, midbrain, brainstem, and cerebellar cortex and dentate nucleus. All areas were stained with hematoxylin and eosin (H&E), and immunohistochemistry with antibodies against β‐amyloid (4G8), phospho‐tau (AT8), phospho α‐synuclein (81A), phospho TDP‐43, and p62.ResultA 69‐year‐old woman started with visual and auditory hallucinations and delusions, followed by cognitive impairment and hyperorality. Three years later, she became bedridden and died at 73. Postmortem 7T MRI showed diffuse cortical atrophy more prominent in the temporal cortex and anterior hippocampus. Unfixed brain 887g weight. Macroscopy depicted cortical brain atrophy with enlargement of the lateral ventricles, depigmentation moderate of substantia nigra, and severe of locus coeruleus. Microscopy showed bilateral hippocampal sclerosis. At immunohistochemistry: diffuse Lewy‐type pathology corresponding to Braak stage 6 of PD‐related pathology, Braak staging VI for AD, amyloid deposits in diffuse, cored, and perivascular plaques in cortical and subcortical areas (CERAD B and Thal 5), and neuronal, glial TDP‐43 inclusions were found in cortical and limbic areas corresponding to LATE 3 and Staging 6.ConclusionLate‐onset psychosis is associated with frontotemporal involvement and is frequently observed in those with C9orf72 mutation. Co‐pathologies may influence clinical and neuropsychiatric presentation and disease progression in mixed dementias.