Depression is a common mental health issue that affects millions of people around the world. The World Health Organization estimates that more than 280 million people suffer from it. While depression is known for affecting mood and daily life, new research points to a possible connection between depression and a higher risk of Alzheimer’s disease.
Alzheimer’s is the most common type of dementia and leads to serious memory problems as people age. Nearly 55 million people globally are living with Alzheimer’s. It’s one of the top causes of cognitive decline in older adults.
What Is Depression and How Does It Affect the Brain?
Depression is a term often used. But what exactly is it? Clinically, depression is a mood disorder that causes lasting sadness and a loss of interest in things you once enjoyed. It also comes with other symptoms that make everyday life harder.
It’s more than just feeling down — it’s a tough mental health condition that can have profound effects on the brain.
Impact on Brain Structure
Depression doesn’t just change your mood. It can physically alter the brain. Experts says that certain areas of the brain shrink or become less active in people with depression.
The hippocampus, for instance, which is important in memory and learning, often shrinks due to prolonged exposure to stress hormones like cortisol. This shrinkage can make it harder to remember things and focus. These issues are common signs of depression.
Neurotransmitter Imbalance
At the heart of depression is an imbalance of neurotransmitters — chemicals in the brain that transmit signals between nerve cells. Serotonin, dopamine, and norepinephrine are three major neurotransmitters implicated in depression.
Low levels of serotonin, often referred to as the “feel-good” neurotransmitter, are particularly associated with depression. Dopamine, linked to pleasure and reward, also tends to be low, leading to feelings of anhedonia or the inability to experience pleasure.
The Role of Inflammation
Emerging research suggests that inflammation might play a role in depression. Inflammatory cytokines — proteins released by the immune system — can cross the blood-brain barrier and influence brain function. Inflammation in the brain may reduce the production of new neurons (neurogenesis) in the hippocampus, contributing to the symptoms of depression.
Changes in Brain Function
Depression also affects how different parts of the brain communicate with each other. The amygdala, responsible for processing emotions, becomes overactive, which might explain the heightened emotional sensitivity seen in depression.
Meanwhile, the prefrontal cortex (which regulates decision-making and self-control) often becomes less active, making it harder for individuals with depression to make decisions or focus on tasks.
Long-Term Effects
Untreated depression can lead to long-term changes in the brain. Over time, chronic stress and depression can cause neurons to shrink or even die, leading to further cognitive decline. This stresses the importance of early intervention and treatment.
So, How Does Alzheimer’s Disease Develop in the Brain?
Alzheimer’s disease is a devastating condition that gradually erases memories, cognition, and personality. It’s the most common cause of dementia, affecting millions worldwide. But how does it start? And what happens in the brain?
Plaques and Tangles
The hallmark features of Alzheimer’s are amyloid plaques and tau tangles. Amyloid plaques are sticky clumps of protein fragments that accumulate between nerve cells (neurons) in the brain.
These plaques disrupt cell-to-cell communication, leading to cell death. Tau tangles, on the other hand, are twisted fibers of another protein that form inside neurons. These tangles collapse the neuron’s internal transport system, choking off nutrients and causing the neuron to die.
Stages of Development
Alzheimer’s disease develops gradually, often over many years. It typically starts in the hippocampus (the brain’s memory center) before spreading to other regions. Early on, individuals may experience mild memory lapses or confusion — signs of the brain’s gradual decline.
As the disease progresses, it affects the cerebral cortex, responsible for language, reasoning, and social behavior. Eventually, the brain’s ability to perform basic functions, like breathing and swallowing, is compromised.
Genetic and Environmental Factors
The exact cause of Alzheimer’s is still unknown, but it’s believed to result from a combination of genetic, environmental, and lifestyle factors.
The presence of the APOE-e4 gene, for instance, increases the risk of developing the disease. Environmental factors, such as head injuries or exposure to toxins, may also contribute to its development.
Neuroinflammation
Like depression, inflammation plays a significant role in Alzheimer’s disease. Microglia, the brain’s immune cells, become activated in response to the accumulation of amyloid plaques. While they attempt to clear the plaques, their prolonged activation can lead to chronic inflammation, further damaging brain cells and accelerating the disease.
Vascular Contributions
Vascular issues, such as atherosclerosis or high blood pressure, can also contribute to the development of Alzheimer’s. Reduced blood flow to the brain can lead to the death of brain cells, exacerbating the symptoms of Alzheimer’s. This vascular contribution is why maintaining heart health is important in reducing the risk of Alzheimer’s.
But Is There a Link Between Depression and Alzheimer’s?
Depression and Alzheimer’s disease. Two conditions often seen as separate entities, yet recent studies reveal a more complex relationship.
Depression and Amyloid Accumulation in the Aging Brain
Conducted as part of the Harvard Aging Brain Study, this research explored whether emerging depressive symptoms in cognitively unimpaired older adults are associated with early amyloid accumulation — one of the core pathologies of Alzheimer’s disease.
The study followed 154 older adults who were cognitively unimpaired, with mild or no depressive symptoms at baseline. Over an average of 8.6 years, participants underwent annual assessments of depressive symptoms and cognitive performance, along with PET imaging to measure amyloid deposition in specific brain regions.
Key Findings
The results were telling. Increasing depressive symptoms over time were significantly associated with greater amyloid accumulation in brain regions important for emotional regulation, such as the medial orbitofrontal cortex (mOFC), the isthmus cingulate cortex (IC), and the middle frontal cortex (MFC).
Notably, these associations persisted even after controlling for cognitive changes. In simple terms, as depressive symptoms worsened, so did the build-up of amyloid plaques in areas of the brain responsible for managing emotions.
Implications
These findings suggest that depressive symptoms in older adults might be more than just a mental health issue — they could be an early warning sign of Alzheimer’s pathology.
This connection underscores the importance of monitoring mood changes in older adults, not just for their mental health, but also as a potential marker for preclinical Alzheimer’s disease.
Early intervention and treatment of depression could be crucial in delaying or even preventing the onset of Alzheimer’s, highlighting the need for integrated care approaches that consider both cognitive and emotional health.
Stress, Depression, and the Risk of Dementia
This large cohort study, based on data from 1.36 million individuals in Region Stockholm, investigated the combined effects of chronic stress and depression on the risk of developing mild cognitive impairment (MCI) and dementia, including Alzheimer’s disease.
Participants were between 18 and 65 years old at baseline, with diagnoses of chronic stress, depression or both recorded in 2012-2013. The study then tracked the development of dementia and MCI diagnoses from 2014 through 2022.
Key Findings
The study revealed a strong association between both chronic stress and depression with increased risks of Alzheimer’s disease and MCI. Specifically, the odds of developing Alzheimer’s were 2.45 times higher in individuals with chronic stress, 2.32 times higher in those with depression, and a striking 4 times higher in those with both conditions.
Similar trends were observed for MCI, where the odds were 1.87, 2.85 and 3.87 times higher, respectively. Interestingly, when it came to other forms of dementia, only depression showed a significant association, with an odds ratio of 2.39.
Implications
The findings from this study add a crucial layer of understanding to the link between mental health and cognitive decline. The potential additive effect of chronic stress on top of depression is particularly concerning, suggesting that individuals facing both conditions are at significantly higher risk of developing Alzheimer’s.
This emphasizes the importance of addressing both stress and depression early in life, as part of a comprehensive strategy to reduce dementia risk. Moreover, it raises important questions about how chronic stress might accelerate or exacerbate the neurodegenerative processes underlying Alzheimer’s.
Depression as a Precursor to Alzheimer’s
Both studies point to a growing body of evidence that depression — especially when accompanied by chronic stress — might not just be a consequence of Alzheimer’s disease but could play a role in its development. But how?
The Amyloid Hypothesis
One potential explanation lies in the amyloid hypothesis, which posits that the accumulation of amyloid plaques in the brain triggers a cascade of events leading to Alzheimer’s disease.
The first study’s findings suggest that depressive symptoms might be linked to the early stages of amyloid accumulation, particularly in regions involved in emotional regulation. This could mean that depression, or the biological processes associated with it, might accelerate amyloid deposition, pushing the brain further along the path toward Alzheimer’s.
Neuroinflammation and Stress
Another angle to consider is the role of neuroinflammation. Chronic stress and depression are both associated with increased levels of inflammation in the brain, which might contribute to the neurodegenerative processes seen in Alzheimer’s.
The second study’s findings of an additive effect of stress and depression on Alzheimer’s risk support this idea. Chronic stress may exacerbate the inflammatory response in the brain, accelerating the progression from mild cognitive impairment to full-blown dementia.
Early Intervention
These studies show how important it is to step in early. Treating depression and managing stress matters not just for mental health but could also help prevent Alzheimer’s. As we learn more about the connection between mood disorders and dementia, it’s clear we need to take care of both mind and brain.
So, Does Depression Increase the Risk Of Alzheimer’s?
These studies show a clear link between worsening depressive symptoms and early signs of Alzheimer’s. As well as how both chronic stress and depression can significantly raise dementia risk.
Additionally, a review titled “Depression as a Risk Factor for Alzheimer’s Disease” supports this connection. It analyzed 28 studies and found that people with a history of depression are 54% more likely to develop Alzheimer’s.
The review also showed that using clinical methods to diagnose depression provided more consistent results than simply using symptom-based scales. This further highlights the importance of treating depression early to help reduce the risk of Alzheimer’s later on.
Disclaimer: The information provided is for educational purposes and should not replace professional medical advice. Consult your doctor before making any health decisions based on this content.
Can Treating Depression Reduce the Risk of Alzheimer’s?
Yes, treating depression may reduce the risk of Alzheimer’s. Early and effective treatment of depression can potentially mitigate these risks by reducing stress and improving overall brain health.
Cognitive therapies, medications, and lifestyle interventions like exercise and social engagement are key strategies. While more research is needed, managing depression could delay or prevent the onset of Alzheimer’s, especially in individuals at higher risk.
How Can TMS Therapy Help?
Transcranial Magnetic Stimulation (TMS) therapy offers a non-invasive, FDA-approved treatment for depression. Especially in patients resistant to traditional therapies. TMS uses magnetic fields to stimulate specific brain regions, enhancing neuroplasticity and improving mood regulation.
So treating depression with TMS could help lower the risk of Alzheimer’s. It may reduce factors like chronic inflammation and cognitive decline. TMS is especially useful for people who can’t take antidepressants.
It’s a safe alternative that may also support long-term brain health. Because of this, TMS might play a role in lowering the chances of Alzheimer’s. It offers a hopeful option for those concerned about their cognitive future.
Interested in learning more? Contact the TMS Institute of Arizona today to know how TMS therapy can help you manage depression and support your cognitive health.
References:
Munro, C. E., Farrell, M., Hanseeuw, B., Rentz, D. M., Buckley, R., Properzi, M., Yuan, Z., Patrizia Vannini, Amariglio, R. E., Quiroz, Y. T., Blacker, D., Sperling, R. A., Johnson, K. A., Marshall, G. A., & Gatchel, J. R. (2024). Change in Depressive Symptoms and Longitudinal Regional Amyloid Accumulation in Unimpaired Older Adults. JAMA Network Open, 7(8), e2427248–e2427248. https://doi.org/10.1001/jamanetworkopen.2024.27248
Wallensten, J., Ljunggren, G., Nager, A., Wachtler, C., Bogdanovic, N., Petrovic, P., & Carlsson, A. C. (2023). Stress, depression, and risk of dementia – a cohort study in the total population between 18 and 65 years old in Region Stockholm. Alzheimer S Research & Therapy, 15(1). https://doi.org/10.1186/s13195-023-01308-4
