Rightward lateralization of frontal cortex tau pathologies is associated with late‐onset psychosis: A PET study with ¹⁸F‐PM‐PBB3

Abstract Background Several cohort studies have recently reported associations between late‐life psychosis and dementia, and postmortem studies have demonstrated that most individuals with late‐onset schizophrenia and delusional disorder had tau pathologies. The present study was aimed to assess the prevalence and topology of tau pathologies by positron emission tomography (PET) with a specific probe, 18 F‐PM‐PBB3 ( 18 F‐APN‐1607), in patients with late‐onset psychosis (LOP). Method We included LOP patients who experienced the first episode of psychosis after 65 years old and excluded those with dementia. Fourteen patients with LOC (74.2 ± 4.0 years old; 7 females and 7 males)and 16 age‐matched healthy controls (HCs) (72.6 ± 5.7 years old; 9 females and 7 males) underwent PET scans with 18 F‐PM‐PBB3 and an amyloid‐β probe, 11 C‐PiB. The radioprobe retention was calculated as standardized uptake value ratio (SUVR), and the laterality index (LI) of SUVR was estimated as [Left‐Right/(Left+Right)]. We compared 18 F‐PM‐PBB3 SUVRs and LIs in the frontal, temporal, parietal, and occipital cortices between patients and HCs using an independent t ‐test after Bonferroni correction ( p ‐value ≤ 0.05/4). Result All HCs were negative for 11 C‐PiB‐PET. By contrast, unequivocally increased 18 F‐PM‐PBB3 retentions were found in 4 out of 4 11 C‐PiB‐positive patients (100%) and 7 out of 10 11 C‐PiB‐negative patients (70%) with variable localizations. Tau topologies in four 11 C‐PiB‐positive cases were characteristic of Alzheimer’s disease and consisted of limbic predominant (N = 2), medial temporal lobe‐sparing (N = 1), and lateral temporal (N = 1) deposition subtypes. Meanwhile, tau topologies in 7 11 C‐PiB‐negative cases were composed of lateral‐posterior diffuse (N = 3), posterior mild (N = 2), lateral temporal local (N = 1), and progressive supranuclear palsy‐like (N = 1) accumulations. None of the target regions exhibited significant differences in 18 F‐PM‐PBB3 SUVR between patients and HCs, reflecting the heterogeneous distributions of tau deposits in patients. There was significant rightward lateralization of tau pathologies indicated by a reduced LI in the frontal cortex ( P = 0.0093) but not the other cortical regions. Conclusion Our findings indicate that LOP is associated with tau topologies of diverse Alzheimer’s and non‐Alzheimer’s disease subtypes. The rightward lateralization of tau pathologies in the frontal cortex might be involved in the development of psychotic manifestations.