Late-life mood disorders may signal neurodegenerative diseases

Depression and bipolar disorder of late beginning can be more than just mental health conditions. The growing evidence suggests that these late-life mood disorders (LLMDs) can not only be risk factors, but rather early warning signals from neurodegenerative diseases such as dementia, even when they appear clearly years before memory loss or other cognitive symptoms.

Unfortunately, scientists have difficulty understanding the relationship between LLMDS and the development of dementia at biological level. Although previous research connections suggested between specific disorders such as depression in late life and Alzheimer’s disease, the specific neurological mechanisms involved usually remain unclear. This knowledge gap is particularly pronounced for bipolar disorder in late life, which has rarely been investigated with regard to dementia. In addition, restrictions in the brain’s imaging technology have prevented researchers from detecting all different types of abnormal proteins that may underlie these disorders.

Against this background, a research team led by Dr. Shin Kurose and Dr. Keisuke Takahata of the National Institutes for Quantum Science and Technology (QST), Japan, an extensive study conducted into the brain changes related to LLMDS. Their paper, published in Alzheimer & Dementia: The Journal of the Alzheimer’s Association on 9 June 2025, investigates the presence of abnormal tau protein-a characteristic of various neurodegenerative diseases-in brains of people with late lifepression and bipolar disorder. The study became the co-author of Dr. Makoto Higuchi, also from QST, and Dr. Masaki Takao from the National Center of Neurology and Psychiatry.

The researchers used advanced brain image techniques to examine 52 participants with LLMDS and 47 healthy checks. They used a positronemissietoMography (PET) scan with the help of two different tracers, which can detect different forms of tau protein and amyloid beta accumulation, important proteins associated with Alzheimer’s disease and other neurodegenerative diseases. To validate their findings, they also analyzed brain tissue samples from 208 autopsy cases, in which they investigate the relationship between late-life mood symptoms and the subsequent development of neurodegenerative diseases.

The results were striking: about 50% of the participants with LLMDs showed Tau accumulation in their brains, compared to only about 15% of healthy checks. Similarly, almost 29% of the participants with LLMD’s detectable amyloid deposits versus only 2% of the checks. The autopsy findings further supported these results, which demonstrated a considerably higher prevalence of various Tau-protein-related pathologies in people who had experienced mania or depression in late life. “Because most participants with LLMDS in our study had no or mild cognitive decline, these results support the proof that neurodegenerative diseases, including the Tau-related pathologies of Alzheimer’s and non-Alzheimer’s, can initially manifest themselves as psychiatric symptoms“Dr. Kurose emphasizes.

Another remarkable discovery was that many participants showed Tau accumulation in the frontal areas of the brain, which is crucial for emotional regulation and cognitive function. The study also showed that these abnormal proteins could be detected for years before traditional cognitive symptoms of dementia appeared. As revealed by the autopsy cases, mood symptoms preceded cognitive or motor symptoms on average 7.3 years. “In general, our findings strongly suggest that TAU-PET scans can detect different TAU ​​pathologies that underlie dementia in patients with LLMDs“Concluded Dr. Takahata.

The insights discovered in this study have important implications for clinical practice, because some cases of depression in late life and bipolar disorder can probably benefit from an evaluation for underlying neurodegenerative diseases. Timely identification of these disorders would make previous intervention possible with disease -modifying treatments. In addition, the researchers also emphasize the value of the tracer molecules used in their PET scans as effective biomarkers for detecting these various TAU-related pathologies in living patients.

With a bit of happiness, these efforts will help to strengthen our understanding of how neurodegenerative diseases first manifest, which leads to earlier diagnosis and possibly better results.