- Late-life mood disorders (LLMDs) are mental health issues that first occur or recur at an older age.
- Past research shows that people with an LLMD may be at a higher risk of developing dementia.
- A new study found that people with LLMDs have larger amounts of the proteins beta-amyloid and tau in their brains than those with no late-onset mental health issues.
- Researchers also found that these abnormal brain protein levels can be detected years before traditional dementia symptoms first appear.
Late-life mood disorders (LLMDs) are mental health issues, such as depression and bipolar disorder, that first occur or recur at an older age.
In addition to having an impact on a person’s quality of life, past research shows that people with an LLMD may be at a higher risk for developing dementia.
“We often encounter cases in clinical practice where patients who develop mood disorders later in life — after the age of 40 — eventually progress to dementia,” Keisuke Takahata, MD, PhD, chief researcher at the National Institutes for Quantum Science and Technology in Japan, told Medical News Today. “
This has led to the shared clinical impression that such mood disorders may, in some cases, represent early symptoms of neurodegeneration. Previous postmortem brain studies also suggest that depression and dementia that occur in old age share common pathologies. However, the underlying pathophysiological mechanisms [have] remained unclear,” he explained.
Takahata is the co-lead author of a new study published in
Researchers also found that these abnormal brain protein levels can be detected years before traditional dementia symptoms first appear.
For this study, researchers recruited 99 adult study participants — 52 participants had an LLMD over the age of 40, and 47 participants acted as age-matched healthy controls.
Participants received positron emission tomography (PET) scans using two different tracers to detect the presence of beta-amyloid and tau in the brain.
Additionally, scientists analyzed brain tissue samples from 208 autopsy cases of various neurodegenerative diseases.
At the study’s conclusion, researchers found that about 50% of participants with LLMDs had tau accumulation and 29% had amyloid deposits, versus 15% and 2%, respectively, in the control group.
“It suggests that mood disorders can emerge many years — over seven on average — before the typical symptoms of dementia are recognized. In other words, psychiatric symptoms such as depression or mania may be the first clinical indicators of an ongoing neurodegenerative process. Acknowledging this possibility could help shift the clinical mindset to consider dementia in the differential diagnosis of new-onset mood disorders in older adults.”
— Keisuke Takahata, MD, PhD
Takahata and his team also discovered that these abnormal protein amounts could be detected years before traditional cognitive symptoms appeared, with mood symptoms preceding cognitive or motor symptoms by an average of 7.3 years in autopsy cases.
“This finding highlights that mood symptoms can appear well before the clinical onset of dementia, sometimes by more than seven years,. It suggests that we should consider mood disorders — especially those with late onset — as possible prodromal features of neurodegenerative dementias. This perspective has important implications for earlier diagnosis and proactive monitoring of at-risk individuals.”
— Keisuke Takahata, MD, PhD
“Our results reinforce the emerging paradigm in which diagnoses of Alzheimer’s disease (AD) and non-AD tauopathies are increasingly informed by objective molecular markers, rather than relying solely on clinical symptoms,” he continued. “It also underscores the potential utility of PET biomarkers in identifying at-risk individuals at a much earlier stage — perhaps even before they meet the criteria for mild cognitive impairment.”
“We plan to follow individuals with late-life mood disorders over time using longitudinal PET imaging with both tau and amyloid tracers,” Takahata added. “This approach will allow us to track the progression of pathological changes and relate them to the emergence of cognitive or neurological symptoms. By doing so, we hope to clarify which patients are truly in a prodromal phase of dementia and which may follow a more stable psychiatric course.”
MNT had the opportunity to speak with Richard A. Bermudes, MD, board certified psychiatrist, associate physician in the School of Medicine Department of Psychiatry and Behavioral Sciences at the University of California, Davis, chief medical officer of BrainsWay, and founder of Empathy MindCare, about this study, who commented the findings both validate what’s been seen clinically, and fundamentally reframes late-life depression treatment.
“This isn’t just about treating mood symptoms anymore — we’re potentially intervening in the earliest stages of neurodegeneration,” Bermudes explained. “The finding that 50% of late-life mood disorder patients showed tau pathology compared to only 15% of Healthy controls means we’ve been underestimating the stakes.”
The importance of early detection and diagnosis“Early detection transforms everything in neurodegenerative disease, and this study positions mood symptoms as potentially our best early biomarker. By the time we see obvious cognitive decline, we’ve lost years of intervention opportunity — but if depression or mania after age 40 signals underlying pathology seven-plus years before cognitive symptoms, we have an unprecedented therapeutic window.”
— Richard A. Bermudes, MD
“We need to change clinical practice to embrace comprehensive treatment approaches immediately,” Bermudes added. “The evidence supports aggressive, multimodal intervention for late-life depression, and we have demonstrated safety and remarkable efficacy in older adults.”
MNT also spoke with Gary Small, MD, chair of psychiatry at Hackensack University Medical Center in New Jersey, about this study.
“Symptoms of mood and neurodegenerative disorders overlap, particularly for older adult. Untreated depression increases the risk for dementia, and patients with Alzheimer’s disease and other forms of dementia show a high rate of depression.”
— Gary Small, MD
“These new findings are consistent with previous research showing a link between amyloid and tau accumulation in the brain and mood disorders,” Small said. “Numerous studies indicate that early detection and intervention is an important strategy for neurodegenerative diseases. It is easier to protect a healthy brain than to attempt to repair neural damage once it becomes extensive.”
“Future studies using amyloid and tau PET as well as other neurodegenerative biomarkers in both mood and cognitive disorders will elucidate early detection and prevention strategies,” he added.
