Psychology. Depression or late-onset bipolar disorder: warning signs of Alzheimer's disease?

Mood disorders in older adults, such as depression and bipolar disorder, may be prodromal manifestations of degenerative dementia.

A team of scientists explored this further by looking at levels of tau and beta-amyloid proteins in 52 people with mood disorders and 47 healthy participants.

As a reminder, these are the two main markers of Alzheimer's disease. Brain tissue from 208 autopsies was also analyzed to validate the neuroimaging. The results were published in the journal Alzheimer's and Dementia on June 9, 2025.

According to this work, conducted by the National Institute for Quantum and Radiological Sciences and Technology (Japan), 50% of participants with bipolar disorder or depression had an abnormal accumulation of the tau protein in the brain, compared to 15% in the control group.

The accumulation of tau protein was particularly concentrated in areas of the brain crucial for the regulation of cognitive functions.

In detail, the imaging revealed that 60% of participants who had late-life depression, and 40.5% of those who suffered from bipolar disorder, had an accumulation of tau protein.

Regarding beta-amyloid, the figures were 36% in depressed participants, 22% in bipolar participants, and 2% in healthy controls. The accumulation of tau and beta-amyloid proteins was equivalent between patients who had active psychiatric disorders and those who had experienced them.

Analysis of autopsies confirmed these findings, showing higher tau protein levels in people who had experienced manic or depressive episodes. Specifically, mood disorder symptoms preceded cognitive impairment associated with dementia by an average of 7.3 years.

"Since participants with depression or bipolar disorder did not exhibit any cognitive impairment, our results support the evidence that neurodegenerative diseases may initially manifest as psychiatric symptoms," explained Shin Kurose, a doctoral student at QST, as quoted by Patient Care Online.

Thus, in some patients, late-onset mood disorders could be a sign of an incipient neurodegenerative process. Based on the results of this study, the researchers believe that an abnormal presence of tau protein could be sought during brain imaging tests in patients who experienced their first depressive or manic episode after the age of 40 or 50. This would make it possible to intervene even before the first signs of cognitive decline appear.

Source: Alzheimer's and Dementia, patient Care,