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Characterising brain network differences during scene perception and memory in young adult APOE-e4 carriers: multi-modal imaging in ALSPAC

描述年轻成人 APOE-e4 携带者场景感知和记忆过程中大脑网络差异的特征：ALSPAC 中的多模态成像

基本信息

批准号：
MR/N01233X/1
负责人：
Kim Graham
金额：
$ 181.01万
依托单位：
CARDIFF UNIVERSITY
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FN01233X%2F1
关键词：
Characterising brain network differences during

项目摘要

Approximately 850,000 people in the UK have dementia; by 2025, this will increase to over one million, and by 2050 is projected to exceed 2 million. The annual financial cost of neurodegenerative disease to the UK economy is over £24 billion and rising; yet delaying dementia onset by just 5 years could reduce these costs by half. The earlier that potential interventions can be implemented, therefore, the greater the benefit for improving health and the greater the opportunity to reduce the economic and societal burden of dementia. Key to knowing when and in whom to apply preventative interventions is the identification of at-risk individuals prior to the onset of age-related cognitive decline. Here, we view 'vulnerability' to poorer cognitive health in later life as not exclusively related to 'aging', but instead, to the accumulation of risks across the lifespan. This account predicts that some of the cognitive and brain differences evident in later life can be predicted by early life factors, and lends itself to the study of young healthy individuals who are at heightened risk of age-related cognitive decline via possession of genes associated with cognitive disorders of ageing. In this research proposal, we focus on the potential influence of one such common semi-dominant risk allele, APOE-e4, by asking: (a) whether healthy APOE-e4 carriers in early adulthood show selective brain and behavioural differences (compared to non-carriers) that are consistent with the early cognitive and anatomical markers of detrimental aging, and (b) how such early life effects may be moderated by cognitive reserve, gender and lifestyle factors.A large-scale neuroimaging study will be undertaken in young adults from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, including novel application of 7T MRI which allows detailed assessment of key brain structures in the medial temporal lobe (e.g., hippocampus). This approach, which is founded on strong pilot evidence for early life brain network changes in young APOE e4 carriers (particularly during scene perception and memory) will identify the circumstances under which such cognitive changes in young at-risk individuals are seen, ask whether these brain network alterations are linked to behavioural performance (e.g., successful perception and memory), and determine how this early life cognitive vulnerability may be moderated by gender, lifestyle and cognitive reserve.

英国约有85万人患有痴呆症;到2025年，这一数字将增加到100多万，到2050年预计将超过200万。神经退行性疾病对英国经济的年度财务成本超过240亿英镑，而且还在上升;然而，将痴呆症的发病时间推迟5年就可以将这些成本降低一半。因此，越早实施潜在的干预措施，对改善健康的好处就越大，减少痴呆症的经济和社会负担的机会就越大。了解何时以及在谁身上应用预防性干预措施的关键是在年龄相关的认知能力下降开始之前识别出有风险的个体。在这里，我们认为“脆弱性”在以后的生活中认知健康状况较差，并不完全与“衰老”有关，而是与整个生命周期的风险积累有关。这个帐户预测，在以后的生活中明显的一些认知和大脑差异可以通过早期生活因素来预测，并适合于研究年轻健康个体，他们通过拥有与衰老认知障碍相关的基因而面临与年龄相关的认知下降的风险。在这项研究提案中，我们关注一种常见的半显性风险等位基因APOE-e4的潜在影响，通过询问：（a）健康的载脂蛋白E-e4携带者在成年早期是否表现出选择性的大脑和行为差异（与非携带者相比）与有害衰老的早期认知和解剖学标志物一致，以及（B）认知储备如何调节这种早期生命效应，性别和生活方式因素将在来自Avon父母和儿童纵向研究（ALSPAC）队列的年轻人中进行大规模神经成像研究，包括7 T MRI的新应用，其允许详细评估内侧颞叶中的关键脑结构（例如，海马）。这种方法建立在年轻APOE e4携带者早期生活脑网络变化（特别是在场景感知和记忆期间）的强有力的试点证据基础上，将确定年轻高危个体中观察到这种认知变化的情况，询问这些脑网络变化是否与行为表现有关（例如，成功的感知和记忆），并确定这种早期生活认知脆弱性如何受到性别，生活方式和认知储备的调节。