Modelling brain ageing using neuroimaging to improve brain health in older adults

随着年龄的增长，我们的大脑在结构和功能上都发生了变化，即所谓的“大脑老化”。这些变化会损害反应时间、记忆力和注意力，并对人们的工作或照顾自己的能力产生负面影响。老年人也更容易患某些脑部疾病，特别是痴呆症。然而，大脑老化对人们的影响并不一致;有些人比其他人更早经历大脑老化的负面后果。了解这种变化的原因将使我们能够识别大脑负老化的风险因素。为了理解这些个体差异，我们需要一种测量它们的方法。为此，我开发了一种“生物标志物”（即，这是一种基于磁共振成像（MRI）扫描人脑的大脑老化生物学测量方法。这使我们能够准确地预测一个人的实际年龄从他们的大脑结构。然后，我可以测量一个人的大脑在他们的年龄中看起来有多典型，并确定那些大脑在他们的实际年龄中看起来异常年老或年轻的人。使用这种方法，我已经证明，拥有一个“看起来更老”的大脑与认知和身体功能较差以及死亡风险较高有关。我将在英国生物银行的研究中测量大脑年龄。这是有史以来规模最大的MRI研究，为确定影响大脑衰老方式的因素提供了独特的机会。我提出的工作有四个主要目标：1。确定个人（年龄、性别、种族）、生活方式和环境（例如，饮食、吸烟、运动）与积极或消极脑老化相关的因素.测试特定的遗传因素是否与大脑衰老有关，帮助我们理解为什么大脑健康问题可以遗传。探索基因与环境之间的相互作用，在某些环境条件下，基因只会导致更差的大脑健康。设计软件来估计大脑不同区域的大脑老化，或者大脑功能的不同方面，如血流和神经连接。这项研究将帮助我们了解是什么影响大脑老化的方式，以确定这些因素是否是可修改的，并确定重要的遗传影响。从长远来看，我的方法可以筛选人们，以确定认知能力下降和痴呆症的个体风险，并帮助设计更好的临床试验，旨在保护老化的大脑。

As we get older, our brain undergoes changes to both its structure and its function, so-called 'brain ageing'. These changes cause impairments to reaction time, memory and concentration and have a negative impact on people's ability to work or look after themselves. Older people are also more at risk of certain brain diseases, particularly dementia. However, brain ageing does not affect people uniformly; some people experience the negative consequences of brain ageing much earlier than others. Understanding the reasons for this variability will allow us to identify risk factors for negative brain ageing. To understand these individual differences we need a way of measuring them. To do this I have developed a 'biomarker' (i.e., biological measure) of brain ageing, which is based on magnetic resonance imaging (MRI) scans of people's brains. This allows us to accurately predict a person's actual age from the structure of their brain. I can then measure how typical an individual's brain looks for their age and identify individuals whose brains look unusually old or young for their actual age. Using this approach, I have shown that having an 'older-appearing' brain is linked to poorer cognitive and physical functioning, as well as a higher risk of death. I will measure brain-age in the UK Biobank study. This is the largest MRI study ever conducted and provides a unique opportunity to identify factors that influence the way brains age. My proposed work has four main goals:1. To identify personal (age, gender, ethnicity), lifestyle and environmental (e.g., diet, smoking, exercise) factors related to positive or negative brain ageing.2. To test whether specific genetic factors relate to brain ageing, helping us to understand why brain health problems can be inherited.3. To explore the interactions between genes and the environment, where genes only cause poorer brain health under certain environmental conditions.4. Design software for estimating brain-ageing in different regions of the brain, or in different aspects of brain function, such as blood flow and neural connectivity.This study will help us understand what influences the way brains age, to establish whether these factors are modifiable and to determine important genetic influences. In the long-term, my approach could screen people to determine individual risk for cognitive decline and dementia, and help design better clinical trials of treatments aimed at protecting the ageing brain.