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岁以上的人口将占加拿大人口的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，一些老年人对大脑老化的抵抗力更强。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，我们将依靠认知储备模型，该模型提出，大脑激活和/或连接性的差异允许一些人在存在神经病理或大脑结构性变化的情况下更好地维持认知。第一部分将使用功能磁共振成像来研究个体间差异的大脑机制，这是一种测量大脑激活和大脑区域之间连通性的技术。活动和连接性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。抑制指的是避免不适合手头任务的操作的能力，而更新指的是从记忆中删除不再有用的项的能力。我们将确定大脑激活或连通性的差异是否会保护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会因个人的教育水平或终身认知投入水平而有所不同。我们还将评估认知培训是否会使受教育或参与度较低的人的激活和连接正常化。最后，第三部分将侧重于迁移，这是一种干预能力，以提高未经直接培训的能力。找到概括性是非常重要的，因为它有助于证明认知训练可以是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培训媒介，因为有强有力的证据表明，当培训再现预期迁移的条件时，迁移是最佳的。我们还将开发一个基于情节特异性诱导技术的程序，该技术涉及对过去经验的详细检索。这将决定在哪些条件下，干预措施的效果适用于未直接培训的任务。总体而言，这项研究计划将有助于了解记忆和大脑如何随年龄变化和适应，并为关心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.