Publications by authors named "Laura D Gamble"
Background: Dysregulated amino acid metabolism creates cancer-specific vulnerabilities. Neuroblastoma tumors have dysregulated arginine metabolism that renders them sensitive to systemic arginine deprivation. Arginase therapy has been proposed as a therapeutic approach for neuroblastoma treatment and has a favorable safety profile in pediatric cancer patients, however optimal therapeutic combinations remain unexplored.
View Article and Find Full Text PDFIntroduction: People living alone with neurodegenerative conditions face unique difficulties in maintaining independence and accessing appropriate health and social care support. Consolidating current understanding regarding these unique difficulties would better inform health and social care services and enable more tailored and appropriate service delivery. The proposed scoping review will summarise evidence from studies that provide evidence about people with dementia, Parkinson's disease, Huntington's disease or motor neurone disease who live alone.
View Article and Find Full Text PDFAssociations of objective and perceived social status with well-being in dyads of people with dementia and their caregivers: findings from the IDEAL programme.
Soc Psychiatry Psychiatr Epidemiol
June 2025
Purpose: Social status is related to disparities in health and well-being outcomes in people with dementia (PwD). Few studies have explored the interpersonal influence of social status of PwD on the well-being of their caregiver, or vice versa. We investigated this relationship using measures of objective and perceived (subjective) social status.
View Article and Find Full Text PDFThe cell-permeable iron chelator M606 inhibits MYCN-driven neuroblastoma via an E2F3-mediated response.
Proc Natl Acad Sci U S A
June 2025
Despite Myc oncoproteins being major causal factors in human cancer, they remain "undruggable." The oncogene is one of the most powerful prognostic markers for the childhood cancer neuroblastoma and represents an important target for developing novel therapeutics. Here, we report the finding and characterization of M606, a selective small molecule inhibitor of MYCN, which was identified by screening a diverse chemical library.
View Article and Find Full Text PDFBackground: The concept of cognitive reserve may explain inter-individual differences in susceptibility to neuropathological changes. Studies suggest that experiences over a lifetime impact on cognitive reserve, and it is hypothesised that following a dementia diagnosis, greater reserve levels are linked to accelerated disease progression.
Objective: To investigate the longitudinal impact of cognitive reserve on cognitive and functional abilities, physical activity and quality of life in people with dementia.
Article Synopsis
- This study examines what factors contribute to people with dementia and their caregivers that could lead to a higher likelihood of moving into a care home.
- Data from 1545 individuals with dementia and 1305 caregivers were analyzed over a 24-month period using modified Poisson regressions.
- Key findings indicated that older age, specific types of dementia, lack of spousal support, and cognitive difficulties significantly increased the risk of transitioning to institutional care, suggesting that promoting daily functional skills could help delay this transition.*
Article Synopsis
- MYCN oncogene amplification is linked to aggressive childhood neuroblastoma, but a study found a germline mutation in Runx1t1 that can prevent tumor development associated with MYCN.
- This mutation affects a conserved zinc finger domain and reduces the risk of neuroblastoma by inhibiting cell growth and reversing hyperplasia, which is a precursor to tumor formation.
- RUNX1T1 is part of a transcriptional repression complex that impacts chromatin accessibility without directly regulating MYCN, and its silencing affects other cancers, indicating its broader significance in tumor biology.
Article Synopsis
- The study explored how quality of life differs among various types of dementia, focusing on 1555 people with mild-to-moderate dementia and their carers over six years.
- Results indicated that individuals with Parkinson's disease dementia or dementia with Lewy bodies reported the lowest quality of life, particularly at the time of diagnosis.
- While self-rated quality of life remained stable over time, informant ratings decreased significantly, emphasizing the need for more attention to the needs of those with specific types of dementia.
Living Alone With Mild-to-Moderate Dementia Over a Two-Year Period: Longitudinal Findings From the IDEAL Cohort.
Am J Geriatr Psychiatry
November 2024
Article Synopsis
- - The study compares the experiences of individuals with dementia living alone versus those living with others over a two-year period, using data from the British IDEAL cohort.
- - Findings reveal that those living alone tended to have better cognitive abilities and made more use of in-home care, but reported poorer physical and mental health outcomes, leading to higher rates of transitioning to residential care.
- - The research suggests a need for support that targets both functional abilities and psychosocial challenges for individuals with dementia living alone to help them maintain their independence.
Longitudinal Trajectories of Stress and Positive Aspects of Dementia Caregiving: Findings From the IDEAL Programme.
J Gerontol B Psychol Sci Soc Sci
August 2024
Objectives: Understanding what influences changes over time in caregiver well-being is important for the development of effective support. This study explores differences in trajectories of caregiver stress and positive aspects of caregiving (PAC).
Methods: Caregivers of community-dwelling individuals with mild-to-moderate dementia at baseline from the IDEAL cohort were interviewed at baseline (n = 1,203), 12 months (n = 917), and 24 months (n = 699).
Article Synopsis
- - The study investigates the health conditions of spousal caregivers for people with dementia, assessing how these conditions affect the caregivers' stress, positive experiences, and social networks over a two-year period.
- - Findings indicate that caregivers report an increase in health conditions, particularly among older individuals and those providing extensive daily care, which relates to stress levels and changes in social networks.
- - The research emphasizes the need to address caregivers' health issues to reduce stress and maintain social connections, pointing out that many caregivers face significant health challenges while managing their responsibilities.
Background: Most people with dementia have multiple health conditions. This study explores (1) number and type of health condition(s) in people with dementia overall and in relation to age, sex, dementia type, and cognition; (2) change in number of health conditions over two years; and (3) whether over time the number of health conditions at baseline is related to social isolation, loneliness, quality of life, and/or well-being.
Methods: Longitudinal data from the IDEAL (Improving the experience of Dementia and Enhancing Active Life) cohort were used.
Article Synopsis
- * Findings show that individuals with dementia from minority ethnic backgrounds report a lower quality of life and higher loneliness, while their carers experience greater stress and poorer relationship quality compared to their white counterparts.
- * The research highlights the need for further studies with larger sample sizes to better understand the unique challenges faced by specific minority ethnic groups in the context of dementia care.
Dyadic influences on awareness of condition in people with dementia: findings from the IDEAL cohort.
Front Aging Neurosci
December 2023
Article Synopsis
- The study explores the differences in how caregivers and individuals with dementia perceive the difficulties experienced due to dementia, focusing on caregiver and dyadic characteristics that may influence these perspectives.
- Data from 1,038 community-dwelling individuals with mild-to-moderate dementia and their spouse/partner caregivers were analyzed using the RADIX checklist, revealing that caregivers generally reported more difficulties than the individuals with dementia themselves.
- Higher caregiver stress levels were linked to greater differences in reported difficulties and were also influenced by the caregiver's sex and the dementia partner's mood, indicating that caregiver assessments could provide insights into awareness of the condition and the dynamics of caregiver stress.
Article Synopsis
- A study tested a new model of resilience in 1,222 caregivers of individuals with mild-to-moderate dementia, examining factors like self-efficacy, optimism, and self-esteem to see if they predict resilience better.
- Results showed that older age, being male, and caregiving for older dementia patients correlated with higher resilience, while caregiver self-efficacy and optimism did not significantly impact resilience levels.
- The conclusion suggests that caregiving demands can affect resilience, indicating that future studies should explore the link between caregiver resilience and the care needs of dementia patients.
Introduction: Impaired cognition and instrumental activities of daily living (iADL) are key diagnostic features of dementia; however, few studies have compared trajectories of cognition and iADL.
Methods: Participants from the IDEAL study comprised 1537, 1183, and 851 people with dementia, and 1277, 977, and 749 caregivers at baseline, 12 and 24 months, respectively. Addenbrooke's Cognitive Examination-III and Functional Activities Questionnaire were used to measure cognition and iADL, respectively.
Article Synopsis
- Researchers developed and validated a questionnaire called the My Life Questionnaire to measure how people with mild-to-moderate dementia experience 'living well'.
- A co-production group of nine individuals with dementia helped shape the questionnaire through workshops, initially generating 230 items, which were narrowed down to a final 10-item version after extensive testing.
- The final questionnaire showed strong reliability and validity, indicating it effectively correlates with quality of life and well-being, while negatively correlating with depression, making it suitable for different settings.
Article Synopsis
- - The study investigated how personality traits relate to the perception of 'living well' for people with dementia and their caregivers over two years, looking at the Five-Factor model (neuroticism, conscientiousness, extraversion, openness, agreeableness).
- - Data from 1487 individuals with dementia and 1234 caregivers were analyzed, revealing that high neuroticism negatively impacted 'living well' scores at the beginning, while traits like conscientiousness and extraversion had a positive effect.
- - Results showed that while personality traits influenced initial perceptions of 'living well,' overall scores remained stable over time, indicating that personality may not significantly impact changes in these perceptions.
Article Synopsis
- Research on the social, cultural, and economic capital of people with dementia is limited, highlighting the need for thorough examination of these factors.
- The study analyzes data from over 1,500 individuals with dementia, assessing their social, cultural, and economic capital at baseline and its impact on quality of life and well-being over 2 years.
- Results indicated four distinct groups based on their capital levels, with disparities in quality of life, showing that those with higher capital reported better well-being, while those with very low capital experienced significantly poorer outcomes.
The extent to which people with dementia are involved in everyday decision-making is unclear. We explored informant-rated involvement of people with dementia in everyday decision-making over 2 years and whether functional, behavioral, and psychological factors related to the person with dementia and the caregiver explain variability in involvement of people with dementia in everyday decision-making. We used IDEAL data for 1182 people with dementia and their caregivers.
View Article and Find Full Text PDFObjective: We explored (1) social, cultural, and economic capital in spousal carers of people with dementia; (2) profiles of carers with different levels of capital; (3) whether the identified profiles differ in levels of stress and positive experiences of caring, and likelihood of depression over time.
Methods: Baseline (2014-2016), 12-month, and 24-month follow-up data were analyzed for 984 coresident spousal carers of people with dementia. We assessed social, cultural, and economic capital, stress, positive experiences of caring, depression.
"Living Well" Trajectories Among Family Caregivers of People With Mild-to-Moderate Dementia in the IDEAL Cohort.
J Gerontol B Psychol Sci Soc Sci
October 2022
Article Synopsis
- The study aims to understand how caregivers' ability to "live well" changes over time and what factors influence these changes, with the goal of improving caregiver support.
- Researchers analyzed data from spouse caregivers of individuals with mild-to-moderate dementia over three time points, focusing on their quality of life, well-being, and satisfaction.
- Results indicated a slight decrease in the "living well" scores among caregivers, identifying three distinct groups based on their initial scores and changes, highlighting the need for targeted support for caregivers showing signs of decline.
Article Synopsis
- The study investigates how COVID-19 social restrictions affected caregivers of individuals with dementia in the UK, focusing on access to support and perceived caregiving burden.
- It compared two groups: one assessed before the pandemic and another assessed before and during the pandemic, evaluating their well-being, coping abilities, and other related factors.
- Findings indicate that, despite initial concerns, caregivers during the pandemic coped better and maintained similar levels of well-being and quality of life compared to those before the pandemic, showing a more positive outlook over time.
Article Synopsis
- Many individuals with dementia remain undiagnosed, which delays access to necessary support services and planning for both patients and families.
- The study analyzed data to uncover demographic traits and neuropsychiatric symptoms linked to undiagnosed dementia, highlighting common patterns in this population.
- Results show that better cognitive function, higher education levels, and living in deprived areas reduce the likelihood of diagnosis, while symptoms like depression and sleep issues are prevalent among undiagnosed individuals.
Article Synopsis
- - The study investigates how well people with dementia (PwD) understand their own ability to perform daily activities, using discrepancy scores between self-reports and informant ratings.
- - Data from 1,227 PwD and their informants showed that smaller discrepancies indicate greater self-awareness, correlating with factors like depression, neuroticism, and the amount of care provided.
- - The findings suggest that identifying PwD with smaller discrepancy scores can help target them for interventions aimed at enhancing their independence.