Brain Scans Link Late-Onset Psychosis to Tau Buildup

A new study from researchers at the National Institute for Quantum Science and Technology has found that hallucinations and delusions appearing for the first time in midlife or later may be linked to brain changes also seen in dementia.

Using positron emission tomography (PET), the 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, compared with about 15% of healthy older controls. Amyloid PET positivity was seen 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. Earlier epidemiological and postmortem studies had suggested a possible link between late-life psychotic symptoms and neurodegeneration, but direct evidence in the living brain had been limited until now.

“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, first author of the study published in Molecular Psychiatry. “This study started from a clinical question: whether hidden biological differences in the brain could explain those differences.”

The team examined 37 patients with psychosis that began after age 40 and 47 healthy older adults, using amyloid PET and the tau PET tracer florzolotau (18F), which can visualize a broad range of tau pathologies in the living brain. 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, which the researchers suggest may affect attention, judgment and problem solving, potentially contributing to psychotic symptoms. Among amyloid-positive patients, greater tau accumulation in the parietal lobe was associated with lower executive function, including planning and controlling attention — suggesting the amount of tau in the brain may help explain some clinical features of late-onset psychosis.

Alzheimer’s diagnosis and treatment increasingly rely on detecting amyloid and tau in the brain, while objective biological tools for hallucinations and delusions have remained limited. The findings may help move late-onset psychosis toward earlier diagnosis and intervention based on measurable brain changes rather than symptoms alone. The researchers hope PET-based assessment could eventually support more personalized treatment, allowing future therapies to be selected according to whether a patient’s symptoms relate to Alzheimer’s-type or non-Alzheimer’s-type tau pathology.