The findings were stark: nearly 50 per cent of the LLMD group showed significant tau protein accumulation in the brain, compared to just 15 per cent in the control group
Mood disorders such as depression, bipolar disorder, or mania appearing after the age of 40 may be early indicators of underlying neurodegenerative diseases like dementia, a new study has revealed.
Conducted by researchers at the National Institutes for Quantum Science and Technology (QST), Japan, the study highlights growing evidence that late-life mood disorders (LLMDs) can precede cognitive and motor symptoms by several years, suggesting they could serve as early warning signs of conditions such as Alzheimer’s and other tau-related diseases.
Published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, the study explored the neurological changes in 52 individuals diagnosed with LLMDs and 47 healthy controls. Using advanced positron emission tomography (PET) scans with two tracers, researchers assessed tau and amyloid protein accumulations—two biomarkers strongly linked with neurodegeneration.
The findings were stark: nearly 50 per cent of the LLMD group showed significant tau protein accumulation in the brain, compared to just 15 per cent in the control group. Similarly, about 29 per cent of those with mood disorders had detectable levels of amyloid deposits, whereas this was observed in only 2 per cent of the control participants.
To further confirm these observations, researchers examined 208 autopsy cases and found a markedly higher prevalence of tau-related brain pathologies in individuals who had experienced mood disorders in later life. These included both Alzheimer’s and non-Alzheimer’s tauopathies, suggesting a broader connection between psychiatric symptoms and neurodegenerative disease mechanisms.
“Because most of the participants with LLMDs in our study had no or only mild cognitive decline, these results support growing evidence that neurodegenerative diseases can initially manifest as psychiatric symptoms,” said Dr. Shin Kurose of QST. The PET scans revealed notable tau accumulation in the frontal regions of the brain—areas associated with emotional regulation and executive cognitive function. This anatomical pattern helps explain why mood disturbances may be among the first visible signs of an evolving neurodegenerative condition.
Importantly, the autopsy data showed that mood symptoms preceded the onset of motor or cognitive symptoms by an average of 7.3 years. This latency provides a potential window for early detection and intervention.
Researchers said the ability to identify these psychiatric symptoms as possible precursors of dementia could shift clinical practices. “Early recognition of depression or bipolar disorder in individuals over 40 could lead to timely interventions, possibly even with disease-modifying therapies,” the team noted.
Currently, late-life mood disorders are often treated independently of cognitive concerns, but this research underscores the need for a more integrated approach. Clinicians may need to screen older patients with new-onset mood disturbances for underlying neurodegenerative processes, especially when cognitive symptoms are not yet pronounced. The study also emphasizes the urgent need for more research into the links between psychiatric and neurodegenerative conditions, and how imaging and biomarker-based tools can aid early diagnosis. As the global burden of dementia continues to rise, particularly in aging populations, the findings carry significant implications for public health. Recognizing and addressing LLMDs as early warning signs could improve outcomes and open up new avenues for intervention before irreversible brain damage occurs.
