Decision making and dementia: from mechanisms to clinical trials

决策和痴呆：从机制到临床试验

• 批准号: MC_UU_00030/14
• 负责人: James Rowe
• 金额: $ 157.75万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00030%2F14
• 关键词: Decision; making; dementia; mechanisms; clinical

For people with dementia and related conditions, the changes in memory and behaviour not only affect quality of life but also survival. We study the causes and potential treatments of the changes in behaviour and thinking that affect people with dementia. Rather than look only at the root cause of disease (which is often not known), we look at what is happening in the human brain to change behaviour. In practical terms this could be a better basis for treatment than trying to reverse the effects of faulty genes or unknown environmental triggers. We work with people with different conditions, including Alzheimer’s disease and frontotemporal lobar degeneration, and those with the risk of dementia because of faulty genes of ageing. Part 1 of the research aims to understand and restore behaviour, including the actions one takes and the decisions that lie behind those actions. Apathy and impulsivity are of particular interest. These two problems paradoxically often come together. They point to a worse prognosis. And they have possible treatments to hand. We use computational models of the brain to study how decisions are made in the brain, about what to do and what not to do. We link these models to actual brain function (physiology) and brain chemistry (pharmacology). With these methods, we explain why people differ in their symptoms and response to treatment. We call this precision medicine: precision not in terms of gene or molecules of the brain, but precision of the chemical, physiological and cognitive processes underlying dementia. Part 2 looks at brain function more closely. We use very big sets of data from collaborations (eg. MRC Dementias Platform UK and BIOFIND consortium), and specialist studies at the CBU (eg. Cambridge Centre for Ageing and Neuroscience and scans from people with Alzheimer’s disease, frontotemporal dementia, Progressive Supranuclear Palsy). We use these data to understand how and when dementia begins, and combine different types of brain scanning to explain the biological causes of dementia in people. This leads naturally to ways to target treatments at those most likely to respond.

对于患有痴呆症和相关疾病的人来说，记忆和行为的变化不仅影响生活质量，还会影响生存。我们研究影响痴呆症患者行为和思维变化的原因和可能的治疗方法。我们不是只研究疾病的根本原因(这通常是未知的)，而是研究人类大脑中正在发生的改变行为的事情。实际上，与试图逆转缺陷基因或未知环境诱因的影响相比，这可能是一个更好的治疗基础。我们与患有不同疾病的人合作，包括阿尔茨海默病和额颞叶变性，以及那些由于衰老基因缺陷而有患痴呆症风险的人。研究的第一部分旨在了解和恢复行为，包括一个人采取的行动以及这些行动背后的决定。冷漠和冲动是特别令人感兴趣的。自相矛盾的是，这两个问题经常出现在一起。他们指出了更糟糕的预后。而且他们手头有可能的治疗方法。我们使用大脑的计算模型来研究大脑是如何做出决定的，关于做什么和不做什么。我们将这些模型与实际的大脑功能(生理学)和脑化学(药理学)联系起来。通过这些方法，我们解释了为什么人们的症状和对治疗的反应不同。我们称之为精准医学：精确度不是基于大脑的基因或分子，而是痴呆症背后的化学、生理和认知过程的精确度。第二部分更详细地研究了大脑的功能。我们使用来自协作的非常大的数据集(例如，MRC Dementias Platform UK和BIOFIND财团)，以及CBU的专家研究(例如，剑桥老龄化和神经科学中心和阿尔茨海默病、额颞叶痴呆、进行性核上性麻痹患者的扫描结果。我们使用这些数据来了解痴呆症是如何以及何时开始的，并结合不同类型的大脑扫描来解释人类痴呆症的生物学原因。这自然导致了针对那些最有可能有反应的人进行治疗的方法。

项目成果

Distinct components of cardiovascular health are linked with age-related differences in cognitive abilities

心血管健康的不同组成部分与年龄相关的认知能力差异有关

• DOI: 10.17863/cam.92263
• 发表时间: 2023
• 作者: King D

Neurodegenerative disease of the brain: a survey of interdisciplinary approaches.

• DOI: 10.1098/rsif.2022.0406
• 发表时间: 2023-01
• 期刊: Journal of the Royal Society, Interface

Differential synaptic loss in ß-amyloid positive versus ß-amyloid negative corticobasal syndrome

β-淀粉样蛋白阳性与β-淀粉样蛋白阴性皮质基底综合征的突触丧失差异

• DOI: 10.17863/cam.107505
• 发表时间: 2024
• 作者: Holland N

Reliability of dynamic causal modelling of resting state magnetoencephalography

静息态脑磁图动态因果模型的可靠性

• DOI: 10.1101/2023.10.16.562379
• 发表时间: 2023
• 作者: Jafarian A

Distinct components of cardiovascular health are linked with age-related differences in cognitive abilities.

• DOI: 10.1038/s41598-022-27252-1
• 发表时间: 2023-01-18
• 期刊: Scientific reports
• 影响因子: 4.6