The science of ageing
The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) is a large-scale collaborative research project at the University of Cambridge,
launched in October 2010, with substantial initial funding from the
Biotechnology and Biological Sciences Research Council (BBSRC), followed by support from the Medical Research Council (MRC) Cognition & Brain Sciences Unit (CBU) and the European Union Horizon 2020 LifeBrain project.
The Cam-CAN project uses epidemiological, cognitive, and neuroimaging data to understand how individuals can best retain cognitive abilities into old age.
We show there are at least three distinct aspects of cardiovascular health, and one of these - pulse pressure (systolic - diastolic blood pressure) - is uniquely associated with cognitive decline. This association was stronger for older adults, such that older individuals with higher pulse pressure had greater cognitive decline. Thus maintaining low pulse pressure may help to preserve cognitive function into old age.
Fluid intelligence, the ability to solve novel problems, is essential for effective behaviour but declines steeply with age. We show that this is partly explained by reduced activity in frontoparietal brain regions; however, the link between brain activity and intelligence is buffered by engaging in a wide variety of regular physical activities, which supports exercise as a potential lifestyle factor to help promote successful aging.
Reduction in blood supply to the brain is a hallmark of dementia, but affects the brain and cognition in healthy ageing too. Using MRI to measure the brain's perfusion at rest, we show that maintaining good cerebral perfusion into old age supports brain function during a challenging cognitive task.
By combining MRI data from Cam-CAN with those from other cohorts, we contributed to the largest and first ever growth charts for the human brain.
We know that a special form of adrenaline is important for controlling behaviour, but not how. Here, we used MRI to measure the bit of the brain that makes the adrenaline, and the activity of the brain when inhibiting actions. We show that the ability to control behaviour is related to the connectivity in the frontal lobe of the brain, which is itself regulated by the ability to make adrenaline
Aging is associated with an increase in well-being and improved emotion regulation despite widespread cognitive decline. Using an emotion-regulation task and structural MRI data, we show the robust age-related increases in positivity is associated with integrity of key brain regions.
A neural shift, expressed as decreased occurrence of lower-order brain networks coupled with increased occurrence of higher-order networks, is associated with both increased sleep dysfunction and decreased fluid intelligence.
During actions, older adults show greater activation in the non-dominant motor cortex. This has been suggested to be compensatory for age-related decline in the dominant hemisphere. However we find no evidence to support this, and suggest instead that the hyper-activation reflects inefficient processing or redued interhemispheric inhibition.
The temporal properties of transient brain networks measured during resting-state with MEG are associated with both age and fluid intelligence, and are more consistent with age-related inefficiency than compensation.
Brain function network changes, quantified using dispersion along multi-dimensional gradient maps, were more sensitive to age than traditional network metrics, independent from known morphological changes and scaled with fluid intelligence.
Our findings establish a brain measure of vascular health that can be used to separate vascular signals from neuronal signals in neuroimaging studies, allowing the development of better models of ageing and age-related disorders.
The gene coding a protein called APOE has been implicated in Alzheimer's Disease. However, in a registered report, we found no evidence that the e4 variant of the gene causes faster ageing of cognition or the brain.
We†review the changes that occur in the blood supply to the brain with age, and show how this can affect MRI scans of brain function. The distinction between blood supply and brain function calls for a new way to study how brain changes affect mental processes with age and age-related diseases.
We looked at five separable aspects of people's lifestyles, such as physical and intellectual engagement, and investigated their relationship with crystallised and fluid cognitive abilities. All lifestyle factors significantly predicted age-adjusted cognitive abilities when tested separately. However, when testing simultaneously the independent contributions of different lifestyle factors to cognition, we saw a different pattern, with mental health not making a significant contribution above and beyond the other four lifestyle factors. Our paper highlights the importance of differentiating what we mean by ‚Äėlifestyle‚Äô, and of applying sophisticated statistical tools to further understand the complex relationship between peoples lifestyle choices and healthy cognitive ageing.
‚ÄėMotor learning‚Äô describes our ability to learn new skills, such as playing tennis or riding a bike. In young adults, such motor skill learning uses automatic brain systems, called implicit memory. A new Cam-CAN study shows that as we get older, motor skill learning starts to rely on a different type of memory, called explicit memory, which relies on the hippocampus. Changes in the hippocampus explain why for many people, this type of learning gets more difficult as they get older.
Older people typically report higher levels of emotional well-being despite declines in other cognitive domains such as memory and executive function. We tested age-related changes in emotional reactivity and regulation using functional MRI, showing participants positive, negative and neutral videos and asking them how each one made them feel. Older people showed decreased rather than increased positivity in their reactions, which was linked to reduced brain activity in the middle frontal gyrus, an area associated with successful emotional regulation. Thus age does not always improve emotional regulation.
New research from Bruffaerts and colleauges investigated differences across the adult life-span in perceptual and conceptual processing by comparing neural measures of object processing to behaviour. Using magnetoencephalography (MEG), they showed better neural semantic processing is linked to both higher picture naming accuracy and higher levels of fluid intelligence. These results indicate that maintaining neural responsivity in older age confers benefits in task-related and domain-general cognitive processes.
Juho Str√∂mmer and colleagues at CamCAN found that Physical Activity Energy Expenditure (PAEE) declines with Age (left plot) and partially mediates the relationship between Age and Fractional Anisotropy (FA) - a measure of white matter health - in several brain tracts like corpus collosum (right).
Research by Dr Delia Fuhrmann and colleagues shows that lower diastolic blood pressure, higher systolic blood pressure and higher heart rate are each strongly, and independently, associated with white matter lesion burden and microstructure in the brain. These results highlight the importance of maintaining cardiovascular health for healthy cognitive and brain ageing.
How do we sustain youth-like cognitive abilities despite brain-wide structural loss as we get older? While we know that brain function may play a role in this, it is unclear which aspect of brain function is particularly important, e.g. the extent to which brain regions are activated (functional activity) or the extent to which regions ‚Äútalk‚ÄĚ to each other (functional connectivity). Research by Dr. Tsvetanov and colleagues indicates that functional connectivity, but not functional activity, becomes increasingly important for performance in old age. These insights may facilitate the development of new strategies to support cognitive ability in old age.
Denis Chan and colleagues at the University of Cambridge studied 205 retired individuals from the CamCAN cohort and found that mid-life intellectual, physical and social activities made significant positive contributions to their current cognitive abilities (IQ). The positive effects of mid-life activities also appear to have a protective effect in the face of poor structural brain health.
CamCAN paper wins with paper titled "Challenges in measuring individual differences in functional connectivity using fMRI"
Susanne de Mooij, prof. Rik Henson and Dr. Rogier Kievit investigated whether and when brain connections change with age, and how these changes map onto our cognitive functioning. Using Cam-CAN data, they observed that brain structures become less connected to each other after about 55 years of age. In contrast, the relations between language, memory and reasoning stayed the same across the lifespan. Finally, they found that memory performance becomes less dependent on a white matter network (connecting the hippocampus to other parts of the brain) in later life.
Dr. Alexa Morcom and Prof. Rik Henson investigate the elevated prefrontal cortex activity that is often observed in healthy older adults despite declines in their memory and other cognitive functions. They compare two leading models of brain ageing: that the frontal cortex is either compensating for impairments elsewhere in the brain; or alternatively, that structural or neurochemical changes lead to less efficient and less specific use of resources. Using sophisticated multivariate statistical modelling of the data, the authors present evidence of the latter explanation.
Dr. Darren Price and the Cam-CAN team have shown that age-related delay of the brain‚Äôs response to visual stimulation is partly explained by damage to information-carrying white matter fibres. At the same time, age-related delay to auditory stimulation is partly explained by damage to grey matter in the auditory cortex. This study is the first to find such a relationship providing important clues regarding the biological origins of cognitive decline.
Through new funding from the EU Horizon 2020 framework, Cam-CAN will join 10 other European cohorts in the LifeBrain project to study brain change across the lifespan. The result will be a unique multinational resource of approximately 18,500 individuals that will allow investigation of cognitive and mental health throughout life. The project provides an important example of the benefits of European funding and collaboration.
Cognitive abilities change with age, but why some skills decline and others do not is still not clear. Here, Dr. David Samu and his team used data from the Cam-CAN cohort to show that responsivity of specific sets of brain networks supports different cognitive functions over the lifespan and characterizes preserved cognition in older age. These findings provide insights into why some skills are more vulnerable to age-related decline while others are preserved.
The ability to solve abstract reasoning problems, sometimes known as ‘fluid intelligence’, plays a central role in many day-to-day activities across the lifespan. Dr Rogier Kievit and colleagues at Cam-CAN have studied which mental and neural differences play a role in supporting fluid intelligence. They found that mental speed is especially important. Using MRI they also found that the strength of connections between brain regions plays an important role in supporting both mental speed and agility. Mapping these three interconnected mechanisms using mathematical models will help us better understand healthy cognitive aging.
Our ability to sense the environment is known to decline as we grow older. However, a new Cam-CAN study led by Noham Wolpe finds that the brain‚Äôs motor system compensates for this change by relying more strongly on prediction from prior experience. This adapted combination of sensory information and prediction depends on the age-related differences in grey matter integrity and functional connectivity strength in a key brain network for movement.
Many of us experience memory problems as we grow older, but did you know that different types of memory change at different rates? A recent Cam-CAN study led by Rik Henson shows how age-related differences in three types of memory depend on age-related differences in both the gray-matter integrity of key brain regions and the integrity of white-matter connections between them.
From middle-age, the brains of obese individuals display differences in white matter similar to those in lean individuals ten years their senior, according to new research led by the University of Cambridge. White matter is the tissue that connects areas of the brain and allows for information to be communicated between regions.
Understanding spoken language requires the rapid integration of information at many different levels of analysis. Given the complexity and speed of this process, it is remarkably well preserved with age. Karen Campbell and colleagues challenge the conventional approach to neurocognitive aging by showing that the neural underpinnings of a given cognitive function depend on how you test it.
To better-understand how brain flexibility influences cognition, Kamen Tsvetanov and colleagues first developed techniques to improve measurements of brain function, and then applied those techniques to show that cognitive ability is influenced by brain network flexibility in the frontal cortex. Interestingly, this relationship becomes more important with age, showing that to maintain cognition through the lifespan, brain flexibility is crucial.
Using non-invasive functional Magnetic Resonance Imaging (fMRI) and cutting-edge algorithms, Cam-CAN researchers have developed a new technique to probe the communication patterns between different parts of the human brain. We hope that this technique will give us a clearer picture of how brain connectivity changes during the ageing process, and whether this has a significant effect on cognition.
As greater numbers of us are living longer, it is increasingly important to understand how we can age healthily.
Cam-CAN integrates across different teams of experts in epidemiology, neuroimaging, and cognitive sciences.
Many of our current investigations are focussed on understanding how patterns of activity change and develop gradually over the lifespan.
Although the popular view of ageing is as a process of decline
and decay, new scientific discoveries suggest a very different
view - one in which the brain remains flexible and adaptable
across the lifespan, with many cognitive abilities being
preserved. A major aim of our research is to understand the nature
of these brain-cognition relationships across the lifespan, and to
change the perspective of ageing in the 21st century by
highlighting the importance of abilities that are maintained into
Our research takes a lifespan perspective to understanding how
the mind and brain develop across the adult lifespan in order to
preserve cognitive function. This research will include
participants across the entire adult lifespan, aged 18 and up. Our
aim is to understand how changes in the brain across the adult
lifespan impact on cognitive functions like memory and attention.
Our emphasis will be on determining the extent of neural
flexibility and the potential for neural reorganisation to
preserve cognitive functions.
This research requires the cooperation of researchers and
collaborators across the UK to provide an interdisciplinary view
of the ageing mind and brain. Our core research teams include
members of research groups in Cambridge including the Departments
of Psychology, Public Health and Primary Care, Psychiatry,
Clinical Neurosciences, and Engineering in the University of
Cambridge and the Medical Research Council Cognition and Brain
Sciences Unit. Over 30 project researchers and collaborators will
contribute to a new view of adult development that incorporates
demographic, psychological, physical, and neural measures.
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