Inter-individual variability in cognitive aging: Neural mechanisms, reserve processes and malleability of neuroprotective processes

加拿大的老年人口正在迅速增长。到2031年，65岁以上的人将占加拿大人口的25%。因此，了解衰老过程中发生的认知和大脑变化至关重要。值得注意的是，一些老年人对大脑衰老的抵抗力更强。我们的研究团队试图了解这种情况是如何发生的以及为什么会发生。为了回答这些问题，我们将依赖于认知储备模型，该模型提出，尽管存在神经病理学或结构性大脑变化，但大脑激活和/或连接的差异允许一些个体更好地保持认知。第1部分将使用功能性磁共振成像（一种测量大脑激活和大脑区域之间连接的技术）来研究个体间差异的大脑机制。激活和连接将作为老年人的教育水平和他们一生中参与认知刺激活动的函数进行比较。当参与者完成抑制或更新任务时，将测量大脑功能。抑制是指避免不适合手头任务的行为的能力，而更新是指从记忆中删除不再有用的项目的能力。我们将确定大脑激活或连接的差异是否可以防止大脑解剖结构中与年龄相关的变化的不利影响。第二部分将探讨在以后的生活中使用认知训练来建立储备的可能性。我们将研究训练更新或抑制能力引起的大脑变化是否因个人的教育水平或认知参与的终身水平而异。我们还将评估认知训练是否使受教育程度或参与程度较低的人的激活和连接正常化。最后，第3部分将重点讨论迁移，这是一种干预的能力，以提高没有直接训练的能力。发现普遍性非常重要，因为它有助于证明认知训练可以成为改善老年人认知健康和生活质量的相关方法。我们将使用沉浸式虚拟现实作为训练媒介，因为有强有力的证据表明，当训练重现预期转移的条件时，转移是最佳的。我们还将开发一个基于情景特异性诱导技术的程序，该技术涉及对过去经历的详细检索。这将决定在哪些条件下干预措施的效果推广到没有直接培训的任务。总的来说，这项研究计划将有助于了解记忆和大脑如何随着年龄的变化而变化和适应，并为关心其认知健康的加拿大老年人提供新的预防策略。

Canada's population of seniors is growing rapidly. By 2031, people over age 65 will represent 25% of the Canadian population. Understanding the cognitive and brain changes that occur during aging is thus critically important. Remarkably, some older adults are more resistant to brain aging. Our research team seeks to understand how and why this occurs. To answer these questions, we will rely on the cognitive reserve model, which proposes that differences in brain activation and/or connectivity allow some individuals to better maintain cognition despite the presence of neuropathology or structural brain changes. PART 1 will examine the brain mechanisms underlying inter-individual differences using functional magnetic resonance imaging, a technique that measures brain activation and connectivity between brain regions. Activation and connectivity will be compared as a function of older adults' level of education and their participation in cognitively stimulating activities over their lifetime. Brain function will be measured while participants complete inhibition or updating tasks. Inhibition refers to the ability to refrain from an action that is not appropriate to the task at hand, while updating refers to the ability to remove items from memory that are no longer useful. We will determine whether differences in brain activation or connectivity protect against the adverse effects of age-related changes in brain anatomy. PART 2 will examine the possibility of using cognitive training to create a reserve later in life. We will examine whether the brain changes induced by training updating or inhibition capacities differ according to an individual's level of education or lifelong levels of cognitive engagement. We will also assess whether cognitive training normalizes activation and connectivity in people with lower levels of education or engagement. Finally, PART 3 will focus on transfer, which is the ability of an intervention to improve abilities that have not been directly trained. Finding generalizability is of great importance because it helps demonstrate that cognitive training can be a relevant approach to improving cognitive health and quality of life in older adults. We will use immersive virtual reality as a training medium because there is strong evidence that transfer is optimal when the training reproduces the conditions in which transfer is expected. We will also develop a program based on the episodic specificity induction technique, which involves the detailed retrieval of a past experience. This will determine under which conditions the effects of interventions generalize to tasks that have not been directly trained. Overall, this research program will contribute to understanding how memory and the brain change and adapt with age and make novel prevention strategies available for older Canadians concerned about their cognitive health.