Mood Disorders After 40 Could Signal Early Dementia, Finds Study

Mood disorders such as depression, mania, or bipolar disorder occurring after the age of 40 may be more than psychiatric issues-they could be early indicators of neurodegenerative diseases, according to a new study published in the journal Alzheimer’s and Dementia. Researchers from the National Institutes for Quantum Science and Technology (QST), Japan, suggest that late-life mood disorders (LLMDs) could precede the cognitive decline typically associated with conditions like Alzheimer’s disease.

To explore this potential link, the researchers studied 52 individuals diagnosed with late-life mood disorders and compared them with 47 healthy controls. Using advanced brain imaging, including positron emission tomography (PET) scans with two types of tracers, they assessed the presence of tau protein and amyloid beta—both biomarkers of neurodegenerative diseases.

The results were striking. Approximately 50% of individuals with late-life mood disorders showed abnormal tau protein accumulation in their brains, compared to only 15% of healthy controls. Similarly, amyloid deposits were detected in nearly 29% of the late-life mood disorders group but only 2% of the control group. The study also analyzed 208 autopsy cases, confirming a significantly higher prevalence of tau-related pathologies among individuals who had experienced late-life mood symptoms.

“Because most of the participants with late-life mood disorders in our study had no or mild cognitive decline, these results support the evidence that neurodegenerative diseases, including Alzheimer’s and non-Alzheimer’s tau-related pathologies, can initially manifest as psychiatric symptoms,” said Dr. Shin Kurose from QST. The study also found that tau accumulation often occurred in the brain's frontal regions—areas key to mood regulation and executive function.

Perhaps most notably, autopsy data revealed that mood symptoms preceded noticeable cognitive or motor symptoms by an average of 7.3 years. This suggests that mood disorders after midlife may offer a critical window for early diagnosis.

The researchers emphasized that recognizing late-life depression or mania as potential early signs of neurodegenerative disease could pave the way for earlier intervention with disease-modifying treatments—potentially changing the trajectory of conditions like Alzheimer’s.

Reference: Kurose S, Moriguchi S, Kubota M, et al. Diverse tau pathologies in late-life mood disorders revealed by PET and autopsy assays. Alzheimer's Dement. 2025; 21:e70195. https://doi.org/10.1002/alz.70195