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会发生变化，这就是所谓的“大脑老化”。这些变化导致反应时间、记忆力和注意力受损，并对人们的工作或照顾自己的能力产生负面影响。老年人患某些脑部疾病的风险也更高，尤其是痴呆症。然而，大脑老化对人的影响并不是一致的；一些人比其他人更早体验到大脑老化的负面后果。了解这种变异性的原因将使我们能够确定消极大脑老化的风险因素。为了理解这些个体差异，我们需要一种衡量它们的方法。为了做到这一点，我开发了一种大脑老化的生物标记物(即生物学测量)，它基于对人们大脑的磁共振成像(MRI)扫描。这使我们能够根据一个人的大脑结构准确地预测他的实际年龄。然后，我可以测量一个人的大脑相对于他们的年龄看起来有多典型，并识别出那些大脑看起来相对于他们的实际年龄来说是异常老还是异常年轻的人。使用这种方法，我已经证明，大脑看起来更老了，与认知和身体功能较差有关，而且死亡风险也更高。我将在英国生物库的研究中测量大脑年龄。这是有史以来进行的最大规模的核磁共振研究，为确定影响大脑老化方式的因素提供了独特的机会。我建议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、锻炼)与积极或消极的脑老化有关的因素。测试特定的遗传因素是否与大脑老化有关，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，在环境中，基因只会在特定的环境条件下导致较差的大脑健康。设计软件来估计大脑不同区域或大脑功能的不同方面的大脑老化，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，确定这些因素是否可以改变，并确定重要的遗传影响。从长远来看，我的方法可以对患者进行筛查，以确定个人认知能力下降和痴呆症的风险，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.