Solving the Dementia Dilemma: Part 2
Written by Coco Newton
In my previous article, I laid out the intricacy and uncertainty of a dementia diagnosis. This condition is a leading cause of death in the UK and is caused by diseases which we now know develop in midlife. Consequently, it is still detected far too late and there is no firm consensus on how to approach detecting it earlier, even with recent innovations in blood test biomarkers.
The pressure to solve this diagnosis dilemma is immense. In a matter of months, we will see a controversial decision taken on whether newly developed Alzheimer’s treatments should be made available on the NHS (controversial because the treatments are of questionable benefit to patients, at best providing a few more months of symptom-free living and at worst triggering serious side-effects. They also risk eclipsing the more-than-third of dementia cases not due to Alzheimer’s disease).
But if we’re not careful, we could also easily slip into a future of dementia screening practices that serve neither patients nor clinicians. Drug developers are desperate to make up for decades of lost revenue after thousands of failed clinical trials in dementia, and they will lobby hard for these new treatments.
Rather than scramble to implement an imperfect early diagnosis approach, I suggested in Part 1 that we should instead focus on a completely different approach; the potential to prevent dementia through lifelong protection and awareness of brain health.
A new focus on brain health
One of my favourite brain health research avenues involves a committed group of swimmers at Hampstead open-air lido in London, who regularly undergo a hypothermic body-temperature cooling to 34C – all in the name of fun.
Compared to non-swimmers, researchers have found that this group shows elevated levels of the RBM3 “cold-shock” protein in their blood. In previous studies with mice, a similar increase in RBM3 halted the effect of Alzheimer’s on brain cells. In fact, when artificially introduced into the brains of mice, RBM3 restored previously lost brain cells and their connections.
The researchers behind this discovery are now trying to develop a drug that mimics the RBM3 effect [source]. There is, however, another vital message to take from this finding: there are environmental factors that can biologically protect our brain health. Epidemiological evidence supports this message: although the total number of dementia cases is increasing as people age, the expected proportion of those older people getting dementia is dropping – by 13% each decade since 1995 in the Western world [source].
Dementia prevention is not just possible, it’s already underway. But why? Besides some zealous swimmers in Hampstead, what else are we doing that could possibly be harnessed to influence our brain health?
Lifestyle and environment
To understand influences, we must first define brain health. Somehow, talking about heart or kidney health is more intuitive: we can ‘visualise’ cholesterol affecting how clear our arteries are, or ‘track’ the dehydration that impacts urine production. We understand what these organ systems do. But the brain does everything: walking, talking, feeling, breathing, remembering, decision-making, giving us our sense of selves. These are all complex evolutions not even the neuroscience community fully understands.
It helps, instead, to think about what the brain is: a highly regulated network of millions of electrically charged brain and immune cells, interspersed with around 400-miles of blood vessels, that together use up about 20% of your daily energy intake. Brain health fundamentally is the ability of those brain cells to keep communicating with each other – enabling us to function at our full potential.
This requires good vascular health for plenty of oxygen and glucose-rich blood flow; no nasty chemicals from smoking, drugs or air pollution blocking connections between brain cells; a balanced concentration of elements in the surrounding fluid from a good diet and exercise; and, ideally, lots of use through cognitive stimulation. Aside from these general guidelines, the question over which factors are more influential remains open.
Take the recent study from the UK Biobank initiative for example. With over 40,000 volunteers, the study identified type 2 diabetes, air pollution and increased alcohol intake as the top three midlife lifestyle risk factors for faster rates of brain health decline with age [source]. It is, however, quite difficult to detangle the causality of these factors from other features of lifestyle – is diabetes itself such a large risk factor (high blood sugar levels might damage brain cells) or is it other intermediary factors that put people at risk for diabetes, such as diet and exercise?
A diet rich in vegetables, olive oil, vitamin D and low in ultra-processed food promotes brain cell and vascular health, which several large-scale studies have shown is associated with a reduced risk of age-related decline in cognitive function. Similarly, we have extensive data for the role of exercise. A meta-analysis of data, totalling over 250,000 older adults, showed that higher vs lower physical activity levels over a ten-year period were associated with a 20% reduced risk in future all-cause dementia [source]. Yet we don’t all need to start training for a marathon to reap the benefits – an average daily step count of just 9,826 is apparently optimal for reducing future dementia risk [source].
Lifestyle is complexly interwoven into the picture, then, even when research prioritises specific factors. And beyond the oft-cited ‘diet and exercise’ tropes, there are also lesser known, but perhaps equally important, lifestyle and environment factors.
Did you know that staying in school longer as a youth is associated with a reduced risk of dementia? This is likely because we build up more brain connections and thus have bigger ‘cognitive reserves’ against future brain insults. Similarly, being bilingual is a great form of cognitive stimulation and has been associated with a delayed onset of dementia symptoms. Should the design of our education curriculums consider long-term brain health benefits?
Social participation is becoming an increasingly well-recognised protective factor for brain health too. People that report perceptions of loneliness, dissatisfaction with social relationships, or less social support can be anywhere between 20-70% more likely to develop dementia. Relatedly, midlife hearing loss appears to be a risk factor – perhaps because it increases social isolation. This may be mediated through cognitive reserve again: regardless of how many brain cells we have, being social promotes the maintenance of connections between them. The Netherlands is leading the charge on this insight, where senior residence homes such as ‘Humanitas’ offer students free accommodation in exchange for some of their time being spent interacting with the older co-residents.
Most recently, it’s been shown that viral infections could play a role in dementia risk, potentially through triggering brain inflammation. In 2022, researchers established a novel link between prior infection with the Epstein-Barr virus and increased risk for multiple sclerosis. This prompted a large-scale international effort systematically investigating the link between different virus exposures over 15 years and brain health outcomes across several national biobanks (totalling 400,000 people across Europe). Over 22 associations were identified, the strongest being between influenza and increased risk for five of the six neurodegenerative conditions examined: generalised dementia, Alzheimer’s disease, ALS (a form of motor neuron disease), Parkinson’s disease and vascular dementia [source]. This last finding is striking. Most viruses flagged in the research are largely preventable through vaccination. Would vaccination uptake rates increase if people knew the potential impact on their risk for dementia, and should national flu vaccine programmes begin earlier than the age of 65?
Genetics
Unlike lifestyle and environmental factors, we can’t modify our genetic risk for dementia (for now at least). But even that is not quite the end of the story.
Only 2-5% of dementia cases can be traced to inheritance of a single gene mutation (‘familial dementia’). These cases are rare, early-onset and aggressive forms of Alzheimer’s, or fronto-temporal dementia, and there is currently nothing one can do to prevent it.
The remaining majority of the cases, however, are multiply determined. This means that the aggregation of many tiny gene variations, either inherited or acquired during life, can determine your genetic risk for dementia. This is known as a ‘polygenic risk score’.
Although studies show mixed findings about the usefulness of this score in predicting dementia, there is one steadfast observation gaining recognition: your lifestyle choices could balance out your polygenic risk.
In a major study, researchers assigned nearly 200,000 people a genetic and a lifestyle risk score for dementia, and examined if they could predict who developed dementia over an 8-year period [source]. Unsurprisingly, the high genetic and high lifestyle risk group showed the highest number of dementia cases. In the high genetic but low lifestyle risk group, however, there were far fewer dementia cases – a 32% reduction. Should we be screening the general population for genetic dementia risk scores to promote the uptake of lifestyle interventions in those who need it most?
There’s even more excitement brewing around the genetics of dementia. One of the largest kindreds of ‘familial dementia’ mutation carriers can be found in the rural mountain regions of Columbia, where individuals with the gene are sadly doomed to dementia before their 50th birthday.
Or that’s what researchers thought until a few years ago, when they came across a local woman in her seventies who, according to genetic records, should have been living with dementia for the past 30 years – except she wasn’t [source].
They subsequently discovered that she had a second mutation, in a totally different gene, that had somehow protected her brain function from the vast amounts of toxic protein accumulation evident on several of her brain scans. What’s more, the researchers have since identified at least ten more individuals in the kindred, all with slightly different secondary protective mutations. The researchers are now working on isolating the protective proteins from these mutations, which could pave the way for a whole new development programme of preventative drugs.
Brain health equity
I’d like to note that this article is not attempting to place blame on people with dementia for how they live their life or claim that it is somehow their fault and responsibility. How can it be, when so much of this information is only now becoming properly understood?
If everyone could have access to a healthy Mediterranean diet and time to regularly exercise in pollution-free environments, stay in education and learn multiple languages, pay for additional vaccinations, be as social as possible as they age, and never drink alcohol or smoke – I likely wouldn’t be writing this article.
Not only is there very little awareness of these factors, but social injustice means that there is also an illusion of choice concerning them. You will be disproportionately at risk of dementia based on your ethnicity, gender, socio-economic gradients, sexual identity, and religious beliefs. How can we empower all people to states in which they command their lifestyles and environments?
It’s also important to highlight that most data presented in this article comes from research participants that were most likely white, Western, and educated above the national average. To generalise these findings, our research communities must be far more intentional about who we recruit.
Putting it all into practice
Armed with this new understanding of how we can influence our brain health, how do we move forward?
I began this article with the epidemiological observation that the age-expected incidence of dementia is declining, and then presented the possible lifestyle and environment factors that could explain this. The problem is that it is probably all of them - and which is more important is dependent on each individual.
On the one hand, we are entering an era of personalised protection of our brain health, especially as we begin to unveil the interaction between genetics and lifestyle. This means we need individual measures of risk. But on the other hand, many of the things that can influence our brain health traditionally fall under the remit of population-level public health policy acts. And per-person public health spending, at least in the UK, has decreased by a quarter since 2015 [source: OHE whitepaper, 2023].
I believe that decentralising management of our brain health with digital health tools could be a solution, in the same way that Zoe does for our diets and Apple Watch for our heart health. Not only could this empower people to measure and track their exposure to different lifestyle and environment risk factors, but it helps them experiment with different interventions to see what works well for them.
Pairing self-management with new large-scale initiatives that answer some of the questions I’ve posed, like the need for better equity, factoring in brain health considerations into educational policy, extending national vaccination programmes, introducing genetic screening, or coming up with savvy multi-generational living solutions, could help society to reset our mindset around brain health and dementia.
Self-management of brain health might also go some way towards solving the diagnosis dilemma we face today – it will enable better community-based awareness of signs and symptoms that ensure timely intervention.
So what are these digital health tools I mention?
Well, to learn that you’ll just have to keep up with the E-Lab blog to see how my start-up progresses.
Coco Newton
Coco is a neuroscientist and entrepreneur driven by a vision to make dementia preventable. Since completing a PhD focused on improving the sensitivity of dementia diagnostic assessments, she has pivoted as a Schmidt Science Fellow into health systems design and engineering to better understand the broader complexity and human perspective of dementia. Alongside research positions at Cambridge, UCL, and TU Delft in the Netherlands, Coco is currently a King's E-Lab Research Associate where she is building a brain health start-up.