Investigating the impact of loneliness on brain aging and pre-symptomatic Alzheimer's disease progression

项目摘要（Spreng/Bzdok，麦吉尔大学） 项目摘要。晚年的孤独感与健康状况不佳有关， 认知能力，更大的痴呆风险和更高的死亡率。然而令人惊讶的是， 孤独会影响老年人的大脑孤独的感觉可能会出现在回应大脑 变化，提供了一个早期的信号，隐匿性脑疾病。孤独也可以是先行词， 促进剂，促进神经病理变化的进展，增加痴呆风险。先前 MPIs Spreng和Bzdok的工作表明，默认网络，即区域集合， 与“社会脑”紧密重叠，选择性地易受孤独和阿尔茨海默病的影响 （AD）。这表明，孤独和神经病理学变化可能相互作用，塑造大脑的过程， 衰老和进展为AD。然而，这些相互作用的具体性质和方向是很差的， 明白该提案的目标是调查孤独与大脑之间的关系 结构和功能在典型的老龄化和个体的风险为AD。有两个研究目标。 目标1中的研究将在大量人群中考察孤独与正常大脑老化之间的关联 数据样本（UK Biobank）。预期结果包括人群水平的大脑正常轨迹 老龄化和估计的“非规范”的变化归因于孤独的经验。研究目的2 将在当地纵向研究中， AD风险升高的老年人队列。这一目标的预期结果是更好地理解 孤独的纵向变化如何与大脑结构和功能的纵向变化相互作用， 影响症状前AD进展。目标1中的研究将使用横断面、人群 神经科学方法（概率分层模型），以获得大脑老化的规范轨迹。 这些分析将集中在默认网络上，利用高分辨率皮层和皮层下 由MPI Bzdok开发的parcellation方案。这些规范性轨迹将允许测量非 在老年人群体中归因于孤独体验的规范偏差。研究 目标2将使用纵向概率分层分析来研究孤独感与 和大脑衰老的关系参与者将来自当地的老年人纵向队列， AD风险升高的成年人。这项工作将利用MPI Spreng最近的努力， 神经成像和行为数据，将作为下一波数据收集的基线 这里.这项研究将进一步了解孤独感如何与大脑结构和功能相互作用 在正常衰老和症状前AD中。孤独是一种易驾驭的社会状态，可以通过 个人或政策层面的干预。更好地理解孤独与大脑之间的关系 衰老和疾病可能最终为更好的检测、监测和干预铺平道路。 ! 1

Project Summary (Spreng/Bzdok, McGill University) Project Summary. Feelings of loneliness in later life are associated with poor health outcomes including loss of cognitive ability, greater dementia risk, and higher mortality rates. Yet surprisingly little is known about how loneliness impacts the brain in older adulthood. Feelings of loneliness may arise in response to brain changes, providing an early signal of insipient brain disease. Loneliness may also be an antecedent or accelerant, promoting the advance of neuropathological changes and increasing dementia risk. Previous work from MPIs Spreng and Bzdok has demonstrated that the default network, an assembly of regions closely overlapping the `social brain', is selectively vulnerable to both loneliness and Alzheimer's disease (AD). This suggests that loneliness and neuropathological changes may interact to shape the course of brain aging and progression to AD. However, the specific nature and direction of these interactions is poorly understood. The goal of the proposal is to investigate the relationship between loneliness and brain structure and function in typical aging and in individuals at risk for AD. There are two research aims. Studies in Aim 1 will examine associations between loneliness and normal brain aging in a large population data sample (UK Biobank). Anticipated outcomes include population-level normative trajectories of brain aging and estimates of `non-normative' change attributable to the experience of loneliness. Studies in Aim 2 will examine associations between loneliness and brain aging in pre-symptomatic AD in a local longitudinal cohort of older adults at elevated risk for AD. The anticipated outcome for this Aim is a better understanding of how longitudinal changes in loneliness interact with longitudinal changes in brain structure and function to influence pre-symptomatic AD progression. Studies in Aim 1 will use cross-sectional, population neuroscience methods (probabilistic hierarchical modeling) to derive normative trajectories of brain aging. These analyses will focus on the default network, drawing upon a high resolution cortical and subcortical parcellation scheme developed by MPI Bzdok. These normative trajectories will allow measurement of non- normative deviations attributable to the experience of loneliness in a population of older adults. Studies in Aim 2 will use longitudinal probabilistic hierarchical analyses to investigate interactions between loneliness and brain aging in the context of elevated AD risk. Participants will be from a local longitudinal cohort of older adults at elevated risk for AD. This work will leverage recent efforts by MPI Spreng, to collect cutting edge neuroimaging and behavioral data that will serve as a baseline for the next wave of data collection proposed here. This research will advance understanding of how loneliness interacts with brain structure and function in normal aging and pre-symptomatic AD. Loneliness is a tractable social condition, modifiable through individual or policy-level interventions. Greater understanding of the relationships between loneliness, brain aging, and disease may ultimately pave the way for better detection, monitoring, and interventions. !1