Do stress and depression increase the risk of Alzheimer’s disease? Here’s why there might be a link

Dementia affects more than 55 million people around the world. A number of factors can increase a person’s risk of developing dementia, including high blood pressure, poor sleep, and physical inactivity. Meanwhile, keeping cognitively, physically, and socially active, and limiting alcohol consumption, can reduce the risk.

Recently, a large Swedish study observed that chronic stress and depression were linked to a higher risk of developing Alzheimer’s disease, the most common form of dementia. The researchers found people with a history of both chronic stress and depression had an even greater risk of the disease.

Globally, around 280 million people have depression, while roughly 300 million people experience anxiety. With so many people facing mental health challenges at some stage in their lives, what can we make of this apparent link?

What the study did and found

This study examined the health-care records of more than 1.3 million people in Sweden aged between 18 and 65. Researchers looked at people diagnosed with chronic stress (technically chronic stress-induced exhaustion disorder), depression, or both, between 2012 and 2013. They compared them with people not diagnosed with chronic stress or depression in the same period.

Participants were then followed between 2014 and 2022 to determine whether they received a diagnosis of mild cognitive impairment or dementia, in particular Alzheimer’s disease. Mild cognitive impairment is often seen as the precursor to dementia, although not everyone who has mild cognitive impairment will progress to dementia.

During the study period, people with a history of either chronic stress or depression were around twice as likely to be diagnosed with mild cognitive impairment or Alzheimer’s disease. Notably, people with both chronic stress and depression were up to four times more likely to be diagnosed with mild cognitive impairment or Alzheimer’s disease.

Important considerations

In interpreting the results of this study, there are some key things to consider. First, the diagnosis of chronic stress-induced exhaustion disorder is unique to the Swedish medical system. It is characterised by at least six months of intensive stress without adequate recovery. Symptoms include exhaustion, sleep disturbance and concentration difficulties, with a considerable reduction in ability to function. Mild stress may not have the same effect on dementia risk.

Second, the number of people diagnosed with dementia in this study (the absolute risk) was very low. Of the 1.3 million people studied, 4,346 were diagnosed with chronic stress, 40,101 with depression, and 1,898 with both. Of these, the number who went on to develop Alzheimer’s disease was 14 (0.32%), 148 (0.37%) and 9 (0.47%) respectively.

These small numbers may be due to a relatively young age profile. When the study began in 2012–2013, the average age of participants was around 40. This means the average age in 2022 was around 50. Dementia is typically diagnosed in people aged over 65 and diagnosis in younger ages may be less reliable.

Finally, it’s possible that in some cases stress and depressive symptoms may reflect an awareness of an already declining memory ability, rather than these symptoms constituting a risk factor in themselves.

This last consideration speaks to a broader point: the study is observational. This means it can’t tell us one thing caused the other – only that there is an association.

What does other evidence say?

Many studies indicate that significant symptoms of depression, anxiety and stress are related to higher dementia risk. However, the nature of this relationship is unclear. For example, are depressive and anxiety symptoms a risk factor for dementia, or are they consequences of a declining cognition? It’s likely to be a bit of both.

High depressive and anxiety symptoms are commonly reported in people with mild cognitive impairment. However, studies in middle-aged or younger adults suggest they’re important dementia risk factors too.

For example, similar to the Swedish study, other studies have suggested people with a history of depression are twice as likely to develop dementia than those without this history. In addition, in middle-aged adults, high anxiety symptoms are associated with poorer cognitive function and greater dementia risk in later life.

Why the link?

There are several potential pathways through which stress, anxiety and depression could increase the risk of dementia.

Animal studies suggest cortisol (a hormone produced when we’re stressed) can increase risk of Alzheimer’s disease by causing the accumulation of key proteins, amyloid and tau, in the brain. The accumulation of these proteins can result in increased brain inflammation, which affects the brain’s nerves and supporting cells, and can ultimately lead to brain volume loss and memory decline.

Another potential pathway is through impaired sleep. Sleep disturbances are common in people with chronic stress and depression. Similarly, people with Alzheimer’s disease commonly report sleep disturbances. Even in people with early Alzheimer’s disease, disturbed sleep is related to poorer memory performance. Animal studies suggest poor sleep can also enhance accumulation of amyloid and tau.

We still have a lot to learn about why this link might exist. But evidence-based strategies which target chronic stress, anxiety and depression may also play a role in reducing the risk of dementia.

This article is republished from The Conversation under a Creative Commons license. Read the original article, published on 13 October 2023.

Opinions expressed in Something Borrowed are those of the original authors and do not necessarily reflect those of the Editors, the Editorial Board or the Publisher of Medicine Today.