Chiba, Japan — Hallucinations and delusions that appear for the first time in midlife or later are often treated as psychiatric symptoms whose biological cause is unclear. The study , published online in Molecular Psychiatry on August 2, 2026, suggests that, for many patients, these symptoms may be linked to brain changes also seen in dementia.
Using positron emission tomography, or PET, the research team found that about 65% of patients who developed psychosis after age 40 showed abnormal buildup of tau, a protein associated with Alzheimer's disease and other forms of dementia. By comparison, tau PET positivity was seen in about 15% of healthy older controls. The study also found amyloid PET positivity in 35% of patients, compared with 2% of controls.
The findings provide the first in vivo evidence that diverse tau-related brain changes may be involved in late-onset psychosis. Until now, earlier epidemiological and postmortem studies had suggested a possible relationship between late-life psychotic symptoms and neurodegeneration, but direct evidence in the living brain had been limited.
"Patients can show the same symptoms, such as hallucinations or delusions, but their clinical course and response to treatment can be very different," said Manabu Kubota, the study's representative researcher. "This study started from a clinical question: whether hidden biological differences in the brain could explain those differences."
Late-onset psychosis can place a heavy burden on patients, families and caregivers, especially in aging societies. People who first experience hallucinations or delusions in midlife or later may not always receive medical care, and their symptoms can be difficult to diagnose and manage using psychiatric evaluation alone.
To look for biological signs of disease, the team examined 37 patients with psychosis that began after age 40 and 47 healthy older adults. They used amyloid PET and QST's tau PET tracer florzolotau (18F), which can visualize a broad range of tau pathologies in the living brain.
The PET scans revealed not only a higher rate of tau positivity among patients, but also diverse patterns of tau buildup. Some patients showed amyloid-positive patterns consistent with Alzheimer's disease, while others showed amyloid-negative patterns, suggesting non-Alzheimer's disease types of tau-related neurodegeneration.
In amyloid-negative patients, tau accumulation was especially notable in posterior brain regions, including the parietal and occipital lobes. The researchers suggest that tau buildup in these regions may affect higher cognitive functions such as attention, judgment and problem solving, potentially contributing to psychotic symptoms.
The study also linked tau buildup with cognitive function. Among amyloid-positive patients, greater tau accumulation in the parietal lobe was associated with lower executive function, which includes abilities such as planning and controlling attention. This suggests that the amount of tau in the brain may help explain some clinical features seen in late-onset psychosis.
Alzheimer's disease diagnosis and treatment increasingly rely on detecting amyloid and tau in the brain. By contrast, objective biological tools for hallucinations and delusions have remained limited. The new findings may help move late-onset psychosis toward earlier diagnosis and intervention based on measurable brain changes rather than symptoms alone.
In the longer term, the researchers hope that PET-based assessment could support more personalized treatment. If doctors can identify whether a patient's symptoms are related to Alzheimer's-type or non-Alzheimer's-type tau pathology, future therapies may be selected or developed according to the patient's underlying disease process.
REFERENCE
DOI: http://doi.org/10.1038/s41380-026-03749-3
About National Institutes for Quantum Science and Technology, Japan
The National Institutes for Quantum Science and Technology (QST) was established in April 2016 to promote quantum science and technology in a comprehensive and integrated manner. The new organization was formed from the merger of the National Institute of Radiological Sciences (NIRS) with certain operations that were previously undertaken by the Japan Atomic Energy Agency (JAEA).
QST is committed to advancing quantum science and technology, creating world-leading research and development platforms, and exploring new fields, thereby achieving significant academic, social, and economic impacts.
About Dr. Manabu Kubota
Dr. Kubota is a Board-Certified Psychiatrist who completed his PhD at Kyoto University conducting neuroimaging research on schizophrenia. He subsequently worked at University Medical Center Utrecht in the Netherlands, where he expanded his MRI research, before moving to the National Institutes for Quantum Science and Technology (QST) in Japan to conduct clinical PET studies on neuropsychiatric diseases. Since 2020, he has been based at Kyoto University, continuing his neuroimaging research alongside clinical duties. He has received several awards and has published numerous peer-reviewed articles, including two in JAMA Psychiatry and one previous article in Molecular Psychiatry.
