Why depression increases your risk of dementia and how to deal with it

Telegraph

4 days ago

For the past four decades, my family has grappled with a mystery – can midlife mental health problems actually precipitate the onset of dementia?
Back in the early 1960s, my grandfather suffered the sudden, unexpected loss of his twin brother, a deeply traumatic event from which he never fully recovered. Of course, at that time bereavement counselling or therapy did not really exist, and by all accounts, it left a marked change on his personality.
He began suffering from mood swings, unable to maintain friendships or working relationships. Having previously held a stable job as an architect for more than 20 years, he moved from company to company in a nomadic fashion before eventually being forced to take early retirement. A decade later, he was diagnosed in his mid 60s with Alzheimer's disease.
While I was growing up, my own father described his belief that 'Dad essentially had a nervous breakdown' and would repeatedly wonder aloud as to whether such trauma and the subsequent mental health difficulties had instigated his cognitive decline.
Now, according to a growing number of studies, there is a definite connection between midlife mental health disturbances and the development of dementia. In late May, researchers at the University of Nottingham published a paper which found that depressive episodes across the life course can increase dementia risk, while last year, the prestigious Lancet Commission, which publishes scientific reviews into public health issues, released a new report including depression as one of 14 modifiable risk factors which account for half of all dementia cases.
When I relayed my family's story to Peter Garrard, a consultant neurologist and a professor at St George's University of London, he said that over the years he had seen many cases of people in their 70s and 80s now displaying symptoms of dementia, who had suffered a serious mental health deterioration at some point in midlife.
'A proportion of these people declare absolutely no past history whatsoever of any medical condition,' says Garrard. 'It may have been that they were ashamed of it, they wanted to hide it, and they never went to their doctor in the first place. But if the spouse is there, you can sometimes uncover this past history of five to 10 years of a really deep depression, what they would refer to as a mental or nervous breakdown, typically in their 30s or 40s. I've seen this dozens of times, and I think there must be something biological linking the two.'
So how is depression related to dementia? It turns out that it's a complex picture and one that we're only just starting to understand.
How depression increases dementia risk
As a psychology researcher at the University of Liverpool, and a current research fellow for Alzheimer's Research UK, Amber John has carried out a number of projects in this area.
One of her most interesting findings to date has been that the people more likely to develop dementia in later life tend to be those who have suffered from persistent mental health problems. In contrast, people who have experienced the odd isolated episode of depression are less at risk.
'It's more the chronic problems with depression that seem to be detrimental, especially if they aren't managed,' says John.
There are several reasons why this might be the case. For example, John points out that people who are severely depressed are more likely to struggle to lead a healthy lifestyle in terms of being physically active, sleeping well and maintaining social networks, things which are all known to be generally protective for brain health.
At the same time, the biology of chronic depression itself could also prove toxic to the brain in various ways, with research studies showing for example, that people who suffer from persistent depression tend to have higher levels of neuroinflammation, which can have a toxic effect on brain cells. Another idea relates to the stress hormone cortisol, which is chronically elevated in people with depression, something which John and others say is thought to be driving atrophy or shrinkage of the hippocampus, an area of the brain which is commonly linked with dementia.
'In the long term, high levels of cortisol have been linked to brain shrinkage and cognitive decline,' says Julia Dudley, the head of research at Alzheimer's Research UK. 'But researchers still aren't quite sure and there's more studies going on to look at what's happening, and at what point in our lives this most affects us.'
Why depression or anxiety can sometimes be an early warning sign
In over 65s with no previous history of mental health problems, the sudden onset of depression and anxiety may actually be an early sign that someone is already developing dementia. Garrard can recall various cases of patients in their 80s, later diagnosed with dementia, who initially presented at his clinic with depressive symptoms.
Earlier this year, researchers found that the likelihood of someone experiencing depression steadily increased in the decade prior to a dementia diagnosis, and Jonathan Schott, a neurology professor at University College London, says that in clinics, neurologists now flag sudden-onset cases of anxiety and depression over the age of 65 as a potential warning sign that dementia is brewing.
'It's by no means certain,' he says. 'Clearly there are many reasons for becoming depressed or anxious in later life. But in some cases, it could be related to brain changes occurring in the run-up to dementia. There are two broad causes of dementia – disease of the blood vessels, and then the build-up of abnormal proteins which leads to changes in how brain cells communicate. Basically, the brain is beginning to fail, and one of the manifestations of that is these alterations in mood.'
Because of this, John says that there is a need for better tests which can allow doctors to distinguish cases of late-life depression or anxiety which are solely mood disorders, from instances where it's a more sinister reflection of underlying brain damage. If someone is experiencing early symptoms of dementia, they could be potential targets for future clinical trials of disease-modifying drugs such as the Alzheimer's therapies lecanemab and donanemab, or other experimental medications.
How to deal with midlife depression/anxiety
With mounting evidence linking prolonged midlife mental health problems with later life cognitive decline, experts now feel that addressing these conditions early on might represent a new pathway for reducing dementia risk.
So what can you do if you or a family member are concerned about your mental health and the potential long-term impact on your cognition?
One possibility is antidepressant medication, although the evidence for this when it comes to dementia is currently mixed, and depends on the type of antidepressants. Some research in lab animals has suggested that SSRI drugs may reduce the build-up of the toxic amyloid protein in the brain, a key factor in the progression of Alzheimer's disease. However, another study funded by the Alzheimer's Society found that certain anticholinergic drugs – another class of antidepressants which work by blocking the actions of a particular brain chemical called acetylcholine – may worsen dementia risk, although we still need to learn more.
'It's unclear at the moment whether that's due to the changes in the brain that have already happened before the treatment or the treatment itself,' says Dudley.
John is particularly interested in the potential benefits of midlife psychological therapies for reducing the risk of dementia in the long run. She points to one study she carried out using NHS data from across the country which found that improving symptoms of depression and anxiety in midlifers through psychological therapies seemed to be linked with lower rates of future dementia.
'It provides really encouraging early evidence to suggest that seeking help for mental health symptoms could potentially be a powerful step in terms of protecting our future cognitive health,' she says.
It's impossible to know if modern psychotherapies, had they existed 50 years ago, would have helped my grandfather, and prevented him from ultimately developing Alzheimer's, but there's a chance that they may well have made a difference.
Overall, Dudley says the message is that if anyone is worried they have had depression for a sustained period of time, it's never too late to take action. 'Some people still think that dementia is an inevitable consequence of ageing,' she says. 'But we're learning more and more that's not the case, and it's possible to intervene and reduce your risk.'