Brain imaging and cognitive ageing in the Lothian Birth Cohort 1936: III

As human populations age across the planet, increasingly significant resources will be needed to manage and care for some older people. Cognitive ageing, the process by which some cognitive abilities decline in older age, is of particular concern, leading as it does to reduced quality of life, loss of independence, and, in its later stages, increased risk of dementia. Characterising the biological causes of cognitive ageing is therefore important if we are to reduce the burden of ageing at both the individual and societal level.

In this proposal we request funds to collect and analyze brain magnetic resonance imaging (MRI) and carotid artery Doppler ultrasound data from participants of the Lothian Birth Cohort 1936. They are a large group of relatively healthy community-dwelling subjects in their late seventies. This cohort is unique in having cognitive data from youth (a well-validated measure of IQ obtained at age 11 years), and repeat cognitive testing, brain imaging, genetic, epigenetic, lifestyle, psychological, social and other important information obtained from ages 70, 73, 76 years, and to be collected at age 79.

By undertaking a third wave of brain MRI and carotid ultrasound scanning, we will have detailed imaging data spanning most of the eighth decade of life (73 to 79 years) during which risk of dementia increases. Longitudinal imaging data obtained at three time points in older age is rare and will allow a thorough exploration of changes in brain structure with age (e.g. loss of brain grey and white matter), how these changes relate to cognitive ability measured across the whole life course, and what factors (e.g. genetics, diet, exercise, etc.) are most responsible for these changes. Understanding these relationships is an important step in helping to develop strategies to slow age-related cognitive decline, and in characterising what role cognitive ageing plays in heralding dementia.

The present application is for minority funding for a project that also has funding from Age UK for the collection of the cognitive, medical, biomarker, and psychosocial data and their collation and analyses.

Studying the changes in brain structure that accompany older age may be useful for understanding cognitive ageing and reducing the risk of dementia in the elderly. We seek funds to acquire a 3rd wave of brain MRI and a 2nd wave of carotid Doppler ultrasound data from the Lothian Birth Cohort 1936, a large group of relatively healthy subjects in their late seventies. This cohort has a wide range of phenotypic data available from older age (at 70, 73, 76; 79 to be done) including cognitive, genetic, epigenetic, lifestyle, etc. Uniquely, they also have a measure of childhood intelligence from age 11. These subjects have already undergone brain MRI at ages 73 and 76, and vascular imaging at age 73. Repeat brain MRI and ultrasound scanning at age 79 will provide multi-time-point longitudinal imaging data across the eighth decade of life. This will be used to investigate associations between older age brain structure, vascular, genetic and other risk factors, and cognitive ability across the life course.

This 3rd wave of brain MRI will be undertaken on the same GE 1.5T clinical scanner as used in the first two examinations. The imaging protocol will consist of structural, diffusion tensor (DT), magnetization transfer (MT) and quantitative T1-mapping sequences. The structural scans will be analyzed to provide measures of brain atrophy, cortical thickness and white matter hyperintensity volume. The DT, MT and T1 data will be used to segment a range of major white matter tracts and provide measures of the integrity of these structures.

These imaging data will be analyzed using methods such as structural equation and longitudinal latent growth curve modelling to examine associations, both cross-sectionally and longitudinally, with cognitive, genetic, epigenetic, lifestyle, and other phenotypic data to provide insights into the factors driving non-pathological cognitive ageing. The carotid Doppler ultrasound data will be used as outcome and predictor variables.

Key beneficiaries from this project will be older people and older people's groups, carers, health and social care practitioners and policymakers, academics and the wider public. A knowledge exchange (KE) strategy is already in place and has an excellent track record of engagement with these diverse groups. CCACE has a dedicated KE Officer (funded by the University of Edinburgh) and one of his main foci is the Lothian Birth Cohort 1936. This is an unusual resource and ensures regular and effective public engagement and KE activity. We have also co-developed a formal Joint Impact Plan with our primary funders, Age UK. This is a detailed framework for current and future KE activities which reflects our mutual ambitions to realise the potential for impact beyond academia throughout the lifetime of the project period. We are committed to maintaining our successful KE strategy to improve understanding of cognitive and brain ageing and identifying which potentially preventable factors affect brain health and cognitive function.

For older people, carers and public health providers, our research has the potential to lead to interventions to prevent or ameliorate age-related cognitive decline and provides clinical benefits through the development of methods for more accurate diagnosis of dementia. For third sector organisations, our research will provide benefits in terms of advice and support they can offer to older people who are concerned about cognitive ageing and brain health. It is hoped that our findings will ultimately contribute to future healthcare policy, which will ideally serve to prolong the amount of time in old age during which individuals remain cognitively healthy and independent.

We will continue to proactively engage directly with policy makers at a national and local government level and indirectly through our 3rd sector close partners such as Age UK, Age Scotland and Alzheimer Scotland and public sector organisations such as NHS Health Scotland and Edinburgh City Council. Age UK's direct engagement with older people is critical to successful exchange of Disconnected Mind-generated knowledge with the public. This is particularly pertinent for medium and short-term impact. Research findings so far signal that in the future, people will be able to take informed decisions to influence their own brain and cognitive health and that there are significant messages for public health (e.g. physical fitness and brain white matter integrity). Lifestyle factors, controllable physical factors and social factors are most likely to be the focus of Age UK's KE activity. Regular contact between Age UK and the research team allows Age UK to disseminate new findings to the wider Age UK family through audience-appropriate Insight and Evidence briefings. These, in turn, allow various parts of Age UK to use this knowledge for the benefit of older people in the form of services, products and influencing activities. These include publications such as overview articles for the general public and for policy makers and through co-produced key stakeholder workshops which aim to raise awareness of brain and cognitive ageing and their determinants.

As well as our joint work with charities, we will continue to engage with policy makers through Cross-party Groups, committees, policy-focussed meetings, networking events and consultations. We will also seek to engage policy makers through our programme of stakeholder workshops. We will continue to engage with schools, families and the media using presentations, workshops, museum and science festivals, our presence on policy committees, art collaborations (previous examples include theatre, portraits, short films and a CCACE-published book of short stories) and via our established online following. CCACE has been particularly successful in engaging individuals and groups through integrated online content.