¹National Institutes for Quantum Science and Technology, Advanced Neuroimaging Center, Institute for Quantum Medical Science, Chiba, Japan, ²Graduate School of Medicine, Kyoto University, Department of Psychiatry, Kyoto, Japan, ³Keio University School of Medicine, Department of Neuropsychiatry, Tokyo, Japan, ⁴Jikei University Graduate School of Medicine, Department of Psychiatry, Tokyo, Japan, ⁵Nara Medical University, Department of Psychiatry, Nara, Japan, ⁶Shimofusa Psychiatric Center, Department of Psychiatry, Chiba, Japan, ⁷Institute of Science Tokyo, Department of Psychiatry and Behavioral Sciences, Tokyo, Japan, ⁸National Institutes for Quantum Science and Technology, Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, Chiba, Japan

Background: Late-onset psychosis (LOP) has distinct clinical features compared to younger-onset psychosis. While previous postmortem and epidemiological studies have suggested a link between the neural substrates of LOP and neurodegenerative processes, particularly tauopathies, research examining tau accumulation in the living brain of patients with LOP remains limited.

Aims & Objectives: This study aimed to investigate the putative neuropathology of LOP by combining amyloid PET and tau PET with Florzolotau (18F) (¹⁸F-florzolotau), which can detect various tauopathies in vivo.

Method: Thirty-seven patients with LOP (mean age = 69.9 years) and 47 controls underwent PET with ¹¹C-PiB and ¹⁸F-florzolotau to evaluate amyloid beta and tau accumulation. Multivariate analysis of covariance (MANCOVA) was performed to examine the effects of diagnosis on standardized uptake value ratios (SUVRs) of ¹⁸F-florzolotau for four gray matter regions (frontal, temporal, parietal, and occipital cortices), controlling for age and sex. Correlations between these SUVRs and total scores of Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) were investigated.

Results: Patients showed a significantly higher proportion of amyloid positivity (13 patients versus one control). MANCOVA demonstrated significant effects of diagnosis on ¹⁸F-florzolotau SUVRs (p = 0.004), and post-hoc analyses showed a higher SUVR in the parietal cortex of the patients. The diagnostic effects on SUVRs remained significant when MANCOVA was restricted exclusively to amyloid-negative participants (p = 0.002). There were no significant correlations between SUVR values in these regions and total MMSE or FAB scores.

Discussion & Conclusions: This in vivo clinical PET study suggests a potential association between the neuropathology of LOP and diverse tau pathologies. These findings contribute to a better understanding of the pathogenesis of LOP, and may facilitate the development of molecular-targeted therapeutic interventions.