How a 76-year-long study has allowed a better understanding of brain health and dementia risk


By Nicola Williams | Friday 28 October 2022

How does our health and circumstances in early and midlife affect our brain health in later life?

Researchers at University College London (UCL) led by Alzheimer’s Research UK’s Chief Medical Officer, Prof Jonathan Schott, are helping answer this question in a study called Insight 46, which has lasted 76 years so far.

Their aim: to find out how various factors in early and midlife affect brain health in people living in their eighth decade and onwards.

To do this, Prof Schott’s team are studying a unique group of volunteers. Insight 46 participants were all born in the same week in 1946 and have been taking part in a larger, ongoing health study, run by the Medical Research Council (MRC), since they were born. What sets Insight 46 apart from the rest of the MRC study is that the UCL researchers are specifically looking at the volunteers’ brain health and dementia risk.

What the UCL team has found has significant implications for the way we understand and study brain health.

Creating a map of the brain at 70 years old

Over the course of the study, the participants have had regular brain scans, blood tests and memory and thinking tests. The results of these have been paired with other health data collected throughout the participants’ lives. Combined, this information has allowed the researchers to create a ‘map’ of an average 70-year-old brain and they have used it to understand which aspects of people’s lives are linked to changes in their brain – for example its size and whether there is any build-up of a protein called amyloid, a hallmark of Alzheimer’s disease.

So, what have they found?

Rising blood pressure- especially in mid-life- could lead to poorer brain health at age 70

A key finding from Insight 46, published in 2019, is that people with high blood pressure in midlife tend to have slightly smaller brains and slightly more blood vessel damage by the time they’re 70. Smaller brains and blood vessel damage are indicators of poorer brain health and can increase people’s risk of dementia in later life.

As well as people’s overall blood pressure, the study also looked at whether changes in blood pressure across a person’s life affected their brain health. It did: participants who had higher blood pressure at age 46, compared to when they were 36, had slightly smaller brains at around age 70.

Taken together, these findings – that high or increasing blood pressure from as early as 36 years old could impact someone’s brain size nearly four decades later – show clearly how looking after our health in midlife can protect our brains as we age.

Off the back of these findings, and the initial investment from Alzheimer’s Research UK, the UCL team secured a $7 million grant from the US to further investigate the effects of heart health on the brain.

Childhood scores on memory and thinking tests can predict scores at age 70

As part of the original MRC study, Insight 46 volunteers took memory and thinking tests when they were eight years old. Researchers then explored whether these test results could predict the same people’s scores on similar tests more than 60 years later.

In a study published in 2019 the researchers found that the higher a person’s memory and thinking ability in childhood, the better their scores in later life too. However, the story doesn’t end there…

A separate study looked at lifelong hobbies and social activities in people from the original MRC 1946 study group, the same group from which Insight 46 participants were chosen.  People from the MRC study who regularly took part in physical and social activities in mid-life had better memory and thinking in later life, even if they performed poorly on tests when they were eight.

This suggests that the brain’s ability to cope and keep working, even in the face of damage from diseases like Alzheimer’s, can boost brain health into later life.

Knock-on effects of head injuries in mid-life could affect brain health at age 70

In March 2021, the Insight 46 team found that head injury resulting in loss of consciousness is linked to poorer brain health, memory and thinking in later life.

People who, during their 50s or earlier, had a head injury which caused them to lose consciousness, subsequently scored lower than expected on memory and thinking tests at age 70. The team also saw that these people had very subtle changes in brain structure – these were not direct markers of dementia, but the team suggested that the changes could indicate that the person may be more susceptible to dementia in the future.

This adds more evidence linking head injury and head impacts to poorer brain health. Often, there’s not much that people can do about head injuries, but the latest evidence demonstrates that it is important to protect ourselves where possible, for instance by minimising the risk of head impact in sports.

Insight 46 hasn’t found links between lifelong risk factors and amyloid protein levels in the brain

The build-up of a protein called amyloid in the brain is a key feature of Alzheimer’s disease. It causes damage to nerve cells and contributes to symptoms including a decline in memory and thinking. Despite this link, the UCL team have not seen higher amyloid levels in the brains of Insight 46 participants who had midlife high blood pressure or head injury.

This is interesting, as it suggests that factors like blood pressure could have important effects on brain health on their own, rather than causing damage resulting from raised amyloid levels.

Evidence from Insight 46, along with other studies, now suggests that amyloid is not the only driving factor in the diseases that cause dementia – brain health and dementia risk are affected by multiple different factors and physical processes in the brain.

That’s one reason why Alzheimer’s Research UK doesn’t just focus on one approach and instead funds research into prevention and new treatments, targeting different mechanisms.

As the Insight 46 team continue to monitor participants as they age, they are looking at other ways to assess brain health. This includes looking at levels of tau, a protein that forms toxic tangles in nerve cells in people with Alzheimer’s.

So, what has Insight 46 taught us about brain health?

Insight 46 has proven to be a landmark study, opening up new research opportunities and contributing to evidence surrounding brain health and dementia risk. The study has helped determine not only what factors influence brain health, but when in a person’s life these factors have the most impact.

Research studies like Insight 46, alongside other studies into dementia risk factors, have helped us shape our Think Brain Health campaign, which aims to raise awareness of dementia risk factors we may be able to influence.

Whilst there’s no sure-fire way to prevent dementia completely, Think Brain Health brings together key findings from research including how we can all take steps to better protect our brain health.

One of three key messages from the campaign is ‘Love Your Heart’- the Insight 46 studies into cardiovascular health certainly support the idea of looking after our heart health to protect our future brain health.

This is just the start – Prof Schott and his colleagues at UCL will continue to follow the Insight 46 participants, and we expect more important findings to come.

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About the author

Nicola Williams