NIHRDataInsights/HRCSData huggingface dataset:
Title: Brain white matter imaging and cognitive ageing in the Lothian Birth Cohort of 1936: II
Funder: Medical Research Council

Abstract: Background: During the calendar years 2008-2011, MRC contributed cash-limited funds to the Disconnected Mind project team, for staff to analyse data from the first wave of brain magnetic resonance imaging (MRI) studies in the Lothian Birth Cohort 1936 (LBC1936). This has been done and has provided a cutting-edge examination of the brain?s white matter in over 725 people in the LBC1936. With further discussion with the relevant MRC programme manager (Rob Buckle) we have been permitted to apply for a similar complement of staff to analyse the next wave of brain imaging data in the Lothian Birth Cohort 1936, to cover the calender years 2011-2013. All other costs will be met by Age UK. Science: In this proposal we seek to characterize longitudinal changes in brain white matter structure in old age, and to investigate relationships between brain biological ageing and cognitive ageing in a unique cohort of subjects in whom cognitive data are available in both youth and across old age, and who have just completed a first wave of detailed brain imaging. The average age of the cohort, which is ideal to study ageing affects, the narrow age range, longitudinal MRI, genetic and lifestyle information, and the availability of life-long measures of cognitive ability provide an unparalleled opportunity to study relationships between brain structural and cognitive ageing.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: PREDICTING MRI ABNORMALITIES WITH LONGITUDINAL DATA OF THE WHITEHALL II SUBSTUDY
Funder: Medical Research Council

Abstract: The programme will combine multi-modal imaging and cutting edge analysis of brain structure, brain perfusion, white matter integrity and brain function with a rich longitudinal data set, the Whitehall II cohort. Twenty-five year antecedent vascular and metabolic risk trajectories and morbidity, antecedent levels of physical and mental activity, baseline cognitive performance levels and 15-year slopes of memory decrement over time, history of depressed mood, genotype, and measured resilience will be used to model brain changes in 800 subjects. Hypotheses are predicated on the assumption that the brain responds adaptively to any age or illness-related lesion with compensating functional reorganization and repair that result in the restitution of cognitive and mental function and behaviour. Damage to this ?scaffolding structure?, e.g. by widespread vascular damage to executive brain networks, will lead to decompensation of function, and result in clinical presentation with e.g. dementia or depression. We would thus predict that highly functioning individuals may show structural or functional lesions in e.g. hippocampal networks, associated with an increase in activity in scaffolding (e.g. executive) networks. We further predict that such active protective mechanisms will be dependent on such antecedents as vascular risk related behaviour and (mental) activity, in addition to other factors less amenable to treatment and prevention. The presence of detailed and frequently sampled cohort data in the Whitehall II study allows for a unique prospective analysis of the effects of socio-demographic, physical and behavioural factors on brain integrity, and a powerful study design strategy that makes it possible to compare the two extreme expressions of a clinical feature (e.g. depression with first onset in the 60s versus no depressive symptoms over at least 25 years), by controlling and stratifying for potential confounders, such as the conventional variables age, gender and occupational level, but also crucial mechanistic factors, such as vascular risk. Short of a prospective interventional study this will be the most effective and efficient way of establishing time directed associations between socially important variables and brain structure and function in older age. Considering the crucial importance that the growing group of active over 60 year olds will have in society, and the effect that a small shift from disabled to able people will have in this part of society, this is important research.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Testing for material-specific effects in long-term memory: evidence from amnesia and functional neuroimaging.
Funder: Medical Research Council

Abstract: Long-term memory (LTM) is a critical part of our ability to maintain social interactions and navigate accurately in our environment; not surprisingly, therefore, loss of LTM - common to many neurological disorders (dementia, epilepsy, stroke) - can have a significant impact on independent living and general well being. The high frequency of memory impairment after brain damage also has a major financial cost to society, and a key goal for cognitive and clinical neuroscience therefore, is (a) to understand the genesis of memory impairment, (b) to elucidate the functional role of brain regions considered necessary for memory and (c) to use this scientific knowledge to make progress aimed at intervention after memory impairment. The proposed project contributes to these important questions by undertaking novel experiments aimed at identifying how two brain regions within the medial temporal lobe (MTL), the hippocampus and perirhinal cortex, contribute to memory for exemplars from different visual categories (faces, objects and scenes). It addresses novel data emerging from patient experiments in which amnesic patients with hippocampal damage do not show a global deficit in LTM (as predicted by most models), but instead reveal memory difficulties that are modulated by category (good memory for faces despite poor memory for scenes, Taylor et al., 2007). Such material-specific differences are not easily explained by current theories of human LTM, and there is an urgent need for more research aimed at obtaining further data to help refine these models. The experiments proposed here involve neuropsychological and neuroimaging approaches (the latter in both patients and healthy controls) to ask under what circumstances the hippocampus and perirhinal cortex contribute to memory for different visual categories. A unique strength of the proposal is the application of the three main paradigms used in the field to measure LTM (relational processing, memory confidence and source memory); this means that we can test key hypotheses from all existing models, and ensures that we obtain definitive evidence about the role of the hippocampus and perirhinal cortex in visual memory. This knowledge is then used to undertake an experiment aimed at asking whether we can improve verbal memory in amnesia by stressing encoding of object features. This experiment has significant translational potential, and provides a stepping stone to further work aimed at remediating some of day-to-day difficulties experienced by amnesic individuals.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Spontaneous Social Cognition: Mechanisms and Development
Funder: Medical Research Council

Abstract: Cognitive neuroscience studies have revealed that several cortical and subcortical structures in the human brain, collectively referred to as the social brain, are functionally specialized for social cognition. A fundamental question about the social brain is how it processes a fluid and rapidly changing social world. To perform this function, the social brain has to be fast, spontaneous and on-line. One of the best examples of spontaneous social cognition is the eye contact effect, a phenomenon in which perceived eye contact spontaneously modulates social cognition. Recently I proposed the fast-track modulator (FTM) model to explain the eye contact effect, and the aim of the current proposal is to investigate the neural and cognitive mechanisms underlying, and the development of, this effect. Firstly, I will test the prediction derived from the FTM model that subcortical regions of the brain initially detect eye contact, then modulate the key structures of the social brain. I will record eye movement and cortical activities of healthy adults when they spontaneously process eye contact, with experimental tasks specifically designed to test the predictions derived from the FTM model. I will also assess the eye contact effect in patients with a lesion in a key structure of the subcortical route. Secondly, I will test the prediction derived from the FTM model, that infants are born with widespread and non-specific cortical processing of social stimuli such as eye contact, which is then modulated by input from the postnatal environment to develop more specialized and effective processing of social stimuli. To do this I will assess the neural correlates of the eye contact effect in young infants, examine how the familial and cultural environment modulate development of the eye contact effect, and examine how developmental disorders such as autism, which affect the development of social interaction, affect development of the eye contact effect. Findings from these projects will shed new light on the cognitive, neural and developmental basis of spontaneous social cognition. Such an understanding is essential if we are to understand how the human brain adapts to the social environment and achieves complex social communication rapidly, spontaneously and on-line. It will also help us understand how the familial and cultural environment, as well as developmental disorders such as autism, affect its development.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Investigating the Relationship between Puberty and Cognitive Brain Development
Funder: Medical Research Council

Abstract: Adolescent brain development is a rapidly emerging field, with structural and functional MRI studies suggesting dramatic development during early adolescence of brain regions involved in social cognition, self-awareness and risk-taking. These findings have marked implications for behaviours of health risk (e.g. substance use, sex, violence) and have begun to influence health policy internationally. The timing of this development coincides with pubertal events. It is unclear whether these changes relate solely to advancing chronological age, or to the biological changes of puberty. The key aims of the project are: 1.To elucidate whether pubertal stage is associated with changes in brain structure, and performance on and brain activity during social cognition and risk-taking tasks, independently of chronological age. We will do this in two populations i) typically developing adolescents within a narrow age band incorporating all pubertal stages and ii) a clinical sample of individuals with constitutional pubertal delay compared to post-pubertal age-matched controls. 2.To investigate whether identified changes in performance, brain structure and functional activity are associated with risky behaviours and depression in adolescence. The research objectives are: 1.To investigate how risk-taking task performance changes with normal puberty in typically developing adolescents aged 12-13 years. 2.To assess the functional activity during risk-taking and social cognition tasks in 13 year olds at different pubertal stages using fMRI. 3.To evaluate grey and white matter volumes of brain structures in 13 year olds at different pubertal stages using MRI; to assess how identified structural and functional differences are related. 4.To repeat these MRI/fMRI studies using a clinical sample of 15-16 year old boys with non-pathological constitutional pubertal delay and post-pubertal same-age controls 5.To investigate the association between self-reported risk-taking, self-harming behaviours and depressive symptoms and brain structure and performance and brain activity during social cognition and risk-taking tasks In order to achieve these objectives, three studies will be undertaken. Study 1:A behavioural study investigating the change in risk-taking behaviours with pubertal development in healthy male and female participants aged 12-14. Study 2:An MRI/fMRI study assessing risk-taking and social emotion processing in healthy male age-matched participants at differing stages of puberty Study 3:An MRI/fMRI study using identical paradigms to study 2, comparing 15-16 year old boys with constitutional delay of puberty to their post-pubertal, age-matched peers. Understanding links between adolescent neurodevelopment and puberty has clear implications for both clinical medicine in adolescence and for public policy relating to adolescent risk behaviours.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Over three years for developing and trialling a novel intervention for children and adolescents with chronic pain: attention and interpretation bias modification training
Funder: Action Medical Research

Abstract: Background_x000D_ Chronic pain is pain lasting at least three months and persisting beyond normal healing time. European studies have reported that 25 per cent of children and adolescents experience chronic pain. This debilitating health problem affects many areas of life and puts children and their families under huge strain. It can lead to mood disorders, sleep disturbance, absence from school and deter young people from participating in hobbies and other social activities they would normally enjoy. The impact of chronic pain on daily life tends to increase with age and if untreated, can result in long-term physical and mental health problems which place a significant burden on healthcare resources. There is an urgent need to target chronic pain before adulthood. Current treatments are often ineffective and new, innovative treatment tools focussing on the perception of pain and pain-related anxiety may provide greater opportunities for treating this condition. _x000D_The research project_x000D_ It has been found that people with chronic pain can have what is known as an 'attention bias' towards pain-related information. This means that they are acutely aware of anything in their environment to do with pain, including pain-related words. This heightened awareness contributes to anxiety about their condition and may exacerbate pain symptoms and disability. The researcher will also investigate interpretation biases, the tendency to draw negative conclusions from ambiguous situations and consequently expect negative outcomes. These biases are thought to maintain and even cause problems _x000D_The proposed research aims to develop and trial a novel, easy-to-deliver treatment tool for young people with chronic pain. This tool is a computerised training task designed to shift attention away from pain-related words. Studies in adults with chronic pain have shown that using this computerised task can improve mood and pain symptoms Miss Heathcote will investigate whether the treatment tool is also effective in young people with chronic pain. Breaking the links between pain and anxiety or negative interpretations could decrease disability, for example, patients may be more willing to accept physiotherapy treatment. During the study, most of the training will be carried out in the clinic, but it would be possible to install computerised training at home making treatment for chronic pain more accessible.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Mechanistic assessment of the acute and chronic cognitive effects of flavanol/anthocyanin intervention in humans
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Dietary-derived flavanols and anthocyanins have been shown to enhance cognition in humans and animals. These beneficial effects have been attributed to their potential to influence peripheral and cerebral blood flow. This proposal is designed to test the hypothesis that the impact of (-)-epicatechin and delphinidin at dietary levels (1mg/kg body weight) on neuro-cognitive function is mediated by eNOS/nNOS derived NO production and resultant changes in regional brain blood delivery. Acute and chronic changes in cerebral blood flow in response to intervention will be assessed using a Siemens MAGNETOM Trio 3.T scanner to investigate the regional selectivity of cerebral blood flow during cognitive testing. Concurrently, the involvement of prolonged, augmented NO synthesis on cognitive improvements induced by flavanol/anthocyanin intake will be investigated as follows: 1) by testing neuro-cognitive outcomes and brain fMRI following flavanol/anthocyanin administration with or without systemic NOS-inhibition, via by i.v. infusion of L-N G-mono-methyl-arginine (L-NMMA; 1 mg.kg-1 per min-1 over 3 min); 2) by multivariate regression analysis, to assess correlations between behavioural parameters, peripheral (FMD) and cerebral (MRI) blood perfusion and circulating flavanol/anthocyanin metabolites using HPLC with electrochemical and MS detection; 3) by measurement of the circulating NO pool using gas-phase chemiluminescence and the activity of NAPDPH oxidase (enzymatically), as markers of NO status (production: eNOS/nNOS; destruction: NOX generated superoxide); and 4) by assessment of acute temporal nature of cognitive improvements following NOS inhibition (NOS inhibition should not affect cognitive improvements between 4-6h. Lastly, the longer term effects of flavonoid supplementation and the sustained effects of such an intervention will be addressed by examining whether cognitive improvements are maintained after a 12 week secession of treatment.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Centre for Cognitive Ageing & Cognitive Epidemiology
Funder: Biotechnology and Biological Sciences Research Council

Abstract: The Centre will: (1) elucidate the routes to the vulnerable ageing brain; (2) find mechanisms by which lower cognitive ability makes the body vulnerable to ill health; (3) provide an outstanding environment for interdisciplinary research training. In research training: Mentor a new cohort of post-doctoral scientists. Expand our cohort of interdisciplinary PhD students. Expand our training of medical scientists. In cognitive epidemiology: Expand it to include non-cognitive traits. Conduct individual participant meta-analyses. Use new datasets to test mechanistic hypotheses. In cohort work on cognitive ageing: Expand work on the Lothian Birth Cohorts and Edinburgh type 2 Diabetes Study. Test genetic and environmental influences on cognitive change from childhood to old age and in old age. Test determinants of cognitive change across 10 years in type 2 diabetes. Conduct longitudinal genome-wide methylation studies. Conduct genome-wide expression studies. Test associations between the human brain connectome and cognitive functions. Lead international consortia on GWAS, exome chip, and methylation studies of cognition, novel brain imaging and other phenotypes. In experimental work on cognitive ageing: Complete regulatory approval for Alzheimer diagnostic tests. Use brain imaging to explore why some cognitive functions are preserved with age. Identify cognitive signatures that identify those likely to convert to dementia. Explore the relationship between the design and use of digital memory systems and our research on age-impaired forgetting and multitasking. In mechanisms of cognitive ageing: Investigate how stress and glucocorticoids influence cognitive ageing and test therapeutic strategies. In cerebral small vessel disease test the importance of vascular integrity, inflammation and oxidative stress for ageing brain integrity. Understand how brain injury occurring in the context of acute systemic illness can alter cognitive decline.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES;1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING)
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Associations between brain computed tomography (CT) abnormalities and delirium: a study in 3300 older emergency medical patients
Funder: Dunhill Medical Trust

Abstract: Delirium is a severe deterioration in mental status affecting 20% of acutely hospitalised older people. Delirium is serious, being associated with patient distress, higher morbidity and mortality, and new institutionalisation. However, delirium remains under-researched. In particular, the critical question of relationships between brain abnormalities and delirium is largely unaddressed. Small studies have shown that brain atrophy on magnetic resonance imaging (MRI) is associated with delirium. Infeasibility and high cost of MRI restrict its application in larger, population-representative delirium studies. Computed tomography (CT) scans are much more commonly done clinically and validly detect atrophy and moderate-severe white matter abnormalities (WMLs). We will test the hypotheses that brain atrophy and WMLs on CT scans are associated with delirium. Analysis will use an existing prospectively collected linked dataset for 3300 older people admitted as a medical emergency comprising: CT scans, validated delirium assessments (1/3 have delirium), dementia status, and multiple other clinical variables.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: MENTAL HEALTH;NEUROLOGICAL
Title: Ethnic inequalities in access to dementia diagnosis and good quality care in the United Kingdom
Funder: Dunhill Medical Trust

Abstract: For people with dementia, early diagnosis and good quality mental and physical health care improve life quality. US studies suggest that people with dementia from minority ethnic groups are diagnosed later and receive worse care. In our previous Dunhill Medical Trust funded study, we found that more deprived UK people with dementia were less likely to receive treatment. We plan to build on this to investigate for the first time in a national sample whether there is inequality between the UK’s ethnic groups in likelihood of receiving a dementia diagnosis and the healthcare received by people with dementia. THIN is the largest, representative, epidemiological dataset for dementia (70,000 dementia patients from UK primary care); we will investigate ethnic differences in dementia diagnosis rates (2007-2015), dementia drug prescribing, primary care consultations and preventative healthcare (2013-15); and how these vary by gender, socio-economic and age groups, UK country and time.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: MENTAL HEALTH;NEUROLOGICAL