Japanese PET Study Suggests Late-Onset Psychosis May Be Linked to Neurodegenerative Pathology

A nuclear medicine imaging study conducted by a Japanese research team has shown that many adults who experience psychotic symptoms such as hallucinations and delusions for the first time after age 40 have abnormal protein deposits in the brain associated with Alzheimer's disease and other neurodegenerative disorders.

The study included 37 patients with late-onset psychosis and 47 age-matched healthy controls. The researchers used the amyloid PET tracer ^11C-PiB and the tau protein PET tracer ^18F-florzolotau to assess the accumulation of β-amyloid and tau proteins in the participants' brains.

The results showed that among patients with late-onset psychosis, the β-amyloid positivity rate was 35.1% (13 of 37 cases), significantly higher than the 2.1% (1 of 47 cases) in the control group; the tau protein positivity rate was 64.9% (24 of 37 cases), compared with 14.9% (7 of 47 cases) in the control group. The research team believes these data provide in vivo imaging evidence for the association between late-onset psychosis and neurodegenerative pathology.

Further analysis revealed that some patients had concurrent β-amyloid and tau protein deposition, exhibiting features consistent with Alzheimer's disease-related pathology; other patients showed tau protein deposition without β-amyloid positivity, suggesting the possible presence of non-Alzheimer's disease-related tauopathy. In β-amyloid-negative patients, tau protein accumulation was predominantly observed in the parietal and occipital regions. The study also found that among β-amyloid-positive patients, higher parietal tau protein burden was associated with lower scores on frontal lobe executive function assessments.

The researchers noted that although patients with late-onset psychosis may present with similar hallucination or delusion symptoms, the underlying brain pathology, clinical progression, and treatment response may differ. PET molecular imaging holds promise for providing more objective assessment evidence for such patients, helping to distinguish Alzheimer's disease-related psychotic symptoms from manifestations associated with other neurodegenerative diseases, and supporting early diagnosis and individualized treatment strategies.