Study Links Late-Life Mood Disorders to Tau and Amyloid Pathology

A groundbreaking study has revealed a significant association between late-life mood disorders (LLMDs) and the presence of tau and amyloid pathology, suggesting that these mood disorders may serve as early warning signs of neurodegenerative diseases such as Alzheimer's disease (AD). The research, led by Dr. Keisuke Takahata, MD, PhD, and PhD student Shin Kurose from the National Institutes for Quantum Science and Technology in Japan, was published in the journal Alzheimer's & Dementia on June 9, 2025.

The study included 52 participants diagnosed with LLMDs and 47 healthy controls. It utilized positron emission tomography (PET) imaging to assess brain pathology, revealing that approximately 50% of LLMD participants exhibited tau accumulation compared to only 15% of the control group. Furthermore, the prevalence of amyloid deposits was significantly higher among those with LLMDs, with 28.8% showing detectable amyloid compared to just 2% in the control group.

Dr. Takahata emphasized the clinical implications of these findings, stating, "Our results support the evidence that neurodegenerative diseases can initially manifest as psychiatric symptoms, rather than cognitive decline alone." This assertion aligns with previous studies, including one by Dr. Agnès Singh-Manoux published in JAMA Psychiatry in 2017, which indicated that depressive symptoms could precede dementia-related cognitive disorders by as much as 28 years.

The study also stratified results by specific mood disorders, finding that 60% of participants with late-life depression and 40.5% with late-life bipolar disorder exhibited tau accumulation. Autopsy analysis of 208 cases further corroborated these findings, showing a higher prevalence of tau-related pathologies among individuals who had experienced late-life mood disorders.

Moreover, researchers noted that tau accumulation was concentrated in the frontal regions of the brain, areas crucial for emotional regulation and cognitive function. This suggests a potential neurological mechanism linking mood disorders to cognitive decline. Notably, mood symptoms were observed to precede any cognitive or motor symptoms associated with dementia by an average of 7.3 years.

The implications of this research extend beyond academic inquiry; they suggest new avenues for early detection and intervention strategies for LLMDs. According to Dr. Kurose, the tracer molecules used in PET imaging could act as biomarkers for identifying individuals at risk of developing neurodegenerative diseases, paving the way for potential disease-modifying treatments targeting tau pathologies.

Despite the promising findings, the study also highlights the need for further research to clarify the biological mechanisms connecting LLMDs with neurodegenerative diseases, particularly for conditions like late-life bipolar disorder that have been less studied in this context. Dr. Takahata and his team concluded that future research should focus on longitudinal imaging studies to refine diagnostic and therapeutic approaches for individuals suffering from late-life mood disorders.

This research marks a significant step forward in understanding the complex interplay between psychiatric conditions and neurodegenerative diseases, potentially transforming how clinicians approach treatment and early intervention for older adults experiencing mood disorders.