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HomeA FocusBrain Health Crossword — ACROSS: Risk factors (9) DOWN: Stress scenarios (27)

Brain Health Crossword — ACROSS: Risk factors (9) DOWN: Stress scenarios (27)

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EN-CROSSWORD A crossword puzzle
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One third of dementia cases might be prevented if brain health is improved throughout life by targeting 9 risk factors, reports a Lancet Commission. A separate US study identifies 27 stress scenarios that significantly age the brain. Finally, a large-scale and robust UK trial finds that the more people do word puzzles, the better their brain function in later life.

For the first time, the new report, co-authored by University College London researchers, models the impact of risk factors at all stages of life, and quantifies the potential contribution of hearing loss and social isolation as risk factors for dementia.

The Lancet Commission on dementia prevention, intervention, and care combines the expertise of 24 international experts to provide a comprehensive review of the disease including 10 key messages to help improve dementia care. The latest estimates suggest that the cost of dementia is $818bn a year and there are around 47m people living with dementia globally. The number of people affected is set to almost triple to 131m by 2050, with the number of cases increasing most in in low- and middle-income countries.

“Acting now will vastly improve life for people with dementia and their families, and in doing so, will transform the future of society,” says lead author Professor Gill Livingston (UCL psychiatry). “Although dementia is diagnosed in later life, the brain changes usually begin to develop years before, with risk factors for developing the disease occurring throughout life, not just in old age. We believe that a broader approach to prevention of dementia which reflects these changing risk factors will benefit our ageing societies and help to prevent the rising number of dementia cases globally.”

The report models the impact of nine health and lifestyle factors at various stages in life, including staying in education until over the age of 15 years old, reducing high blood pressure, obesity and hearing loss in mid-life (45-65 years old), and reducing smoking, depression, physical inactivity, social isolation and diabetes in later life (over 65 years old). The estimates show the proportion of all dementia cases that could be prevented if the risk factors were fully eliminated.

The study estimates that removing these factors could prevent one in three cases of dementia (35%). Comparatively, finding a way to target the major genetic risk factor, the apolipoprotein E (ApoE) ε4 allele, would prevent less than one in 10 (7%) cases.

Of the 35% of all dementia cases that could potentially be prevented, the three most common risk factors that could be targeted were increasing education in early life (estimated to reduce the total number of dementia cases by 8% if all people continued education until over the age of 15), reducing hearing loss in mid-life (reducing the number of cases by 9% if all people were treated) and stopping smoking in later life (reducing the number of cases by 5% if all people stopped smoking).

Not completing secondary education in early life may raise dementia risk by reducing cognitive reserve – a resilience to cognitive decline caused by the brain strengthening its networks and therefore continuing functioning in later life despite damage.

Preserving hearing in mid-life may help people to experience a cognitively rich environment and build cognitive reserve, which may be lost if hearing is impaired. However, this research is at an earlier stage and could also be a result of social isolation and depression caused by hearing loss, or occur at the same time as brain degeneration that causes dementia. In later life, stopping smoking will be important to reduce exposure to neurotoxins, and improve cardiovascular health which, in turn, affects brain health.

To help reduce dementia risk, the researchers suggest public health interventions including building cognitive reserves by increasing the number of children who complete secondary education, and, in later life, engaging in mentally stimulating activities (such as a combination of engaging in a hobby, going to the cinema, restaurants or sporting events, reading, doing volunteer work, playing games and having a busy social life). In addition, protecting hearing and treating hearing loss in mid-life may be an important way to prevent dementia, but it is not yet clear if hearing aids counteract the cognitive damage caused by this.

Other interventions likely to benefit are increasing physical activity, reducing smoking rates, and treating high blood pressure and diabetes. The researchers note that such interventions are already available, safe and have other health benefits, but in order to have the greatest impact they should be incorporated into society.

“Society must engage in ways to reduce dementia risk throughout life, and improve the care and treatment for those with the disease. This includes providing safe and effective social and health-care interventions in order to integrate people with dementia within their communities. Hopefully this will also ensure that people with dementia, their families and caregivers, encounter a society that accepts and supports them.” says co-author Professor Lon Schneider, Keck School of Medicine of the University of Southern California.

While interventions for these risk factors would not delay, prevent, or cure all dementia cases, there is much to gain, with other studies suggesting that dementia prevalence would be halved if its onset were delayed by five years, and that a 10% reduction in the prevalence of the seven health and lifestyle factors could reduce worldwide dementia prevalence by more than a million cases.

The authors note some limitations within their estimates, including that they do not take into account diet and alcohol intake, and some estimates could not be based on global data as such data were not available. They also note that some risk factors may also have an impact during other stages of life, for instance lifelong learning (beyond childhood education) may also be beneficial.

Summary 1
Acting now on dementia prevention, intervention, and care will vastly improve living and dying for individuals with dementia and their families, and in doing so, will transform the future for society.

Jill Livingston, Andrew Sommerlad, Vasiliki Orgeta, Sergi G Costafreda, Jonathan Huntley, David Ames, Clive Ballard, Sube Banerjee, Alistair Burns, Jiska Cohen-Mansfield, Claudia Cooper, Nick Fox, Laura N Gitlin, Robert Howard, Helen C Kales, Eric B Larson, Karen Ritchie, Kenneth Rockwood, Elizabeth L Sampson, Quincy Samus, Lon S Schneider, Geir Selbæk, Linda Teri, Naaheed Mukadam

Summary 2
Today, nearly 50 million people worldwide have dementia, with this figure projected to increase to 75 million by 2030 and to 132 million by 2050,1 largely driven by population ageing. Dementia causes not only disability and dependency for individuals affected by the disorder, but can also have a profoundly detrimental effect on family and other carers, who are at high risk of developing depression and anxiety disorders.2 The cost of caring for people with dementia is more than US$800 billion per year globally, rising to $2 trillion by 2030.

Stress scenarios that increase dementia risk:

We've known for a while now that stress and dementia are intricately linked, but the nuances of such a clear risk factor have been somewhat vague.

Until now, that is. Net Doctor reports that scientists at the University of Wisconsin School of Medicine and Public Health have identified the 27 scenarios that are so upsetting they put enough strain on the body to cause long-term health problems and significantly age the brain, taking the link between stress and dementia to a whole new level.

The research team asked 1,320 people from the US aged in their 50s and 60s to undergo memory and problem-solving tests to assess mental ability, followed by questionnaires about their lifetime stress levels. Not only did the results show greater lifetime stress to be clearly linked with poorer cognition later in life, but the scientists were also able to identify trends in experience.

For children and teenagers, experiences like having to repeat a year of school, being expelled or growing up with an addict parent were found to be particularly damaging to the brain whilst, for adults, losing a job, the death or a parent or spouse, long-term unemployment and joining the army were also found to have negative consequences. It was concluded that such events had the equivalent effect on the brain as four years of ageing, while experiencing more than one traumatic event seemed to have a cumulative effect on long-term health.

Dr Carol Routledge, director of research at Alzheimer's Research UK, said: "Stressful life events can turn our lives upside down for a time and though most people can eventually return to an even keel, we can't be sure how psychological stress and worse could impact the workings of the brain over time. There is a growing realisation that events and experiences throughout life can impact the brain decades later."

In addition, a second study – also by the University of Wisconsin – found that the places we live can also impact our brain health, with the poorest areas suffering the most. Dr Amy Kind, of the University of Wisconsin, said: "This study provides evidence to suggest that living in a neighbourhood challenged by poverty, low education, unemployment and / or sub-standard housing may increase risk of Alzheimer's disease."

While these studies undoubtedly provide valuable insight into the ways in which stress and dementia are linked, experts say that simply moving to the suburbs and enjoying a peaceful retirement will not necessarily help. Dr Doug Brown, director of research and development for Alzheimer's Society, said: "We know that prolonged stress can have an impact on our health. However, it remains to be established whether these stressful life events can lead to an increased risk of dementia. Studying the roles of stress is complex. It is hard to separate from other conditions such as anxiety and depression, which are also thought to contribute towards dementia risk."

He added: "However, the findings do indicate that more should be done to support people from disadvantaged communities that are more likely to experience stressful life events."
Other life events that were found to significantly impact an individual's brain health included sexual and physical assault, divorce, legal difficulties, severe financial loss or the loss of home through natural disaster.

Background: Prevalence of Alzheimer’s disease and cognitive impairment is rising, and the greatest burden falls upon historically disadvantaged communities. Despite substantial evidence for racial disparities in later life cognitive health, underlying pathways are unclear and the cognitive impact of lifelong adversity remains underexplored. Stressful experiences cluster and accumulate across the life course, potentially fomenting cognitive health disparities. We examined relationships between lifetime stress and cognition among African American and non-Hispanic white adults in the longitudinal Wisconsin Registry for Alzheimer’s Prevention (WRAP) study.
Methods: Participants (N=1,320) reported lifetime stressful experiences and completed comprehensive neuropsychological testing. Cognitive outcomes included two executive function factor scores (Speed & Flexibility and Working Memory) and four memory scores (Immediate Memory, Verbal Learning & Memory, Visual Learning & Memory, and Story Recall). The key predictor of interest was a Lifetime Stress index score (sample range=0-17 experiences). Mixed-effects regression models, including socioeconomic and health covariates, were utilized to assess effects of lifetime stress in each cognitive domain. We stratified by race to explore between-group differences in stress-cognition relationships.
Results: Average age (mean=58.1, SD=6.5), years of education (mean=16.2, SD=2.8), and APOEε4 carrier proportion (38.5%) did not differ by race. However, African Americans (n=82) reported significantly more (mean=4.5) stressful experiences during their lifetime than non-Hispanic whites (n=1,232; mean=2.8, p<.001). In fully adjusted models including the full sample, lifetime stress partially attenuated negative relationships between African American race and both domains of executive function. Stratification revealed that cognitive detriment associated with lifetime stress in non-Hispanic whites is significantly potentiated among African Americans, for whom it is the strongest measured predictor of Speed & Flexibility (p=0.002) and Working Memory (p=0.03).
Conclusions: We found that lifetime stress is associated with poorer later-life cognition, particularly executive function, and contributes to racial disparities therein. Even within a small, highly-educated sample, African Americans report experiencing more stressful events and exacerbated stressor-associated cognitive dysfunction, with each reported experience equivalent to more than four years of cognitive aging. Our findings reaffirm the effect of stress on cognitive health and disparities, and emphasize the need to expand within-group, lifecourse-based strategies as we strive to eliminate disparities through targeted interventions.

Megan Zuelsdorff; Carey E Gleason; Amy J Kind; Rebecca L Koscik; Sterling C Johnson; Ozioma C Okonkwo

UK study on word puzzles and cognition:

The more regularly people report doing word puzzles such as crosswords, the better their brain function in later life, a large-scale and robust online trial has found.

Experts at Wesnes Cognition Ltd, Reading, UK, University of Exeter Medical School, Exeter and King's College London analysed data from more than 17,000 healthy people aged 50 and over, submitted in an online trial. In research presented at the Alzheimer's Association International Conference (AAIC) 2017, the team asked participants how frequently they played word puzzles such as crosswords.

The study, one of the largest of its kind, used tests from the CogTrackTM and PROTECT online cognitive test systems to assess core aspects of brain function. They found that the more regularly participants engaged with word puzzles, the better they performed on tasks assessing attention, reasoning and memory.

From their results, researchers calculate that people who engage in word puzzles have brain function equivalent to ten years younger than their age, on tests of grammatical reasoning speed and short-term memory accuracy.

Keith Wesnes, professor of cognitive neuroscience at the University of Exeter Medical School, said: "We found direct relationships between the frequency of word puzzle use and the speed and accuracy of performance on nine cognitive tasks assessing a range of aspects of function including attention, reasoning and memory. Performance was consistently better in those who reported engaging in puzzles, and generally improved incrementally with the frequency of puzzle use. For example, on test measures of grammatical reasoning speed and short-term memory accuracy, performing word puzzles was associated with an age-related reduction of around 10 years. We now need to follow up this very exciting association in a clinical trial, to establish whether engaging in puzzles results in improvement in brain function."

The study used participants in the PROTECT online platform, run by the University of Exeter and Kings College London. Currently, more than 22,000 healthy people aged between 50 and 96 are registered in the study, which is planning further expansion. The online platform enables researchers to conduct and manage large-scale studies without the need for laboratory visits. PROTECT is a 10-year study with participants being followed up annually to enable a better understanding of cognitive trajectories in this age range. PROTECT is funded by the Alzheimer's Society and the National Institute for Health Research (NIHR) Bioresource, including through its NIHR Clinical Research Network (CRN).

Clive Ballard, professor of age-related diseases at the University of Exeter Medical School, said: "We know that many of the factors involved in dementia are preventable. It is essential that we find out what lifestyle factors really make a difference to helping people maintain healthy brains to stop the soaring rise of the disease. We can't yet say that crosswords give you a sharper brain – the next step is to assess whether encouraging people to start playing word games regularly could actually improve their brain function."

Dr Doug Brown, director of research of Alzheimer's Society, said: "We know that keeping an active mind can help to reduce decline in thinking skills. This new research does reveal a link between word puzzles, like crosswords, and memory and thinking skills, but we can't say definitively that regular 'puzzling' improves these skills. To be able to say for sure, the crucial next step is to test if there are benefits in people who take up word puzzles. In the meantime our top tips to reduce the risk of developing dementia are keeping physically active, avoiding smoking and eating a healthy balanced diet."

Background: Lifestyle is becoming recognised to play a role in preserving cognitive function with ageing. Here the relationship between engagement with word puzzles and major aspects of cognitive function are evaluated in older adults.
Methods: The 10-year PROTECT study began in 2015 ( and has over 20,000 participants aged 50 and over. Participation is entirely remote, without clinic visits, various on-line assessments being completed, including lifestyle questionnaires and from the CogTrackTM and PROTECT cognitive test systems, assessing attention, information processing, working and episodic memory. This analysis concerned the 6 possible answers to the question: “How frequently do you engage in word puzzles, e.g. crosswords?” (More than once a day, Once a day, Once a week, Once a month, Occasionally, Never).
Results: On study entry participants were invited to perform the cognitive tests on up to 3 occasions over a 7-day period. Data from up to 17,690 participants (72.2% female) aged 50 to 96 years (mean 61.7, SD 7.2) were available. There were 14 outcome measures from 9 tasks, and the average score per participant over the completed sessions was calculated. ANCOVAs were conducted, the main effect being the frequency of engaging in word puzzles (6 levels), with age, gender, education and sessions completed fitted as covariates. Highly significant differences between the various responses were identified for each measure (p<0.0005). The pattern in every case was for the quality of performance to be lowest for those who responded ‘Never’, and for all but 2 measures for this group to be significantly different from every other one. As the frequency of reported usage increased, so did quality of performance, these improvements being incremental for measures from 7 tasks. On a pattern separation task, both speed and accuracy were significantly superior for the neurogenesis sensitive stimuli. The effect sizes of the differences between the 2 extreme scores were in the small to medium range for measures from 7 tasks.
Conclusions: The frequency of word puzzle use is directly related to the quality of cognitive function on a range of major cognitive domains in this large population aged up to 96 years.

Keith Wesnes; Helen Brooker; Anne Corbett; Laura McCambridge; Clive Ballard
Helen Frankish, Richard Horton

[link url=""]University College London material[/link]
[link url=""]The Lancet Commisions article summary[/link]
[link url=""]The Lancet article summary[/link]

[link url=""]Net Doctor report[/link]
[link url=""]University of Wisconsin School of Medicine and Public Health material[/link]
[link url=""]AICC 2017 abstract[/link]

[link url=""]University of Exeter material[/link]
[link url=""]AAIC 2017 abstract[/link]

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