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。晚年的孤独感与包括失落在内的不良健康结局有关 认知能力，更大的痴呆症风险和更高的死亡率。然而令人惊讶的是，人们对此知之甚少 孤独会影响成年后的大脑。对大脑的反应可能会产生孤独感 变化，提供潜伏性脑部疾病的早期信号。孤独也可能是一个前置条件或 促进剂，促进神经病变进展，增加痴呆症风险。上一首 MPIS Spreng和Bzdok的研究表明，默认网络是区域的集合 与“社交大脑”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，孤独和神经病理变化可能相互作用，以塑造大脑的进程 衰老和进展为阿尔茨海默病。然而，这些互动的具体性质和方向很差 明白了。该提案的目标是调查孤独和大脑之间的关系 典型衰老和阿尔茨海默病风险人群的结构和功能。本文的研究目的有两个。 目标1中的研究将在大量人群中检验孤独与正常脑老化之间的关系 数据样本(英国生物库)。预期结果包括人群水平的大脑标准轨迹 老龄化和对可归因于孤独经历的“非规范性”变化的估计。AIM 2中的研究 将在局部纵向研究无症状阿尔茨海默病患者孤独感和脑老化之间的关系 老年痴呆症风险增加的老年人队列。这一目标的预期结果是更好地理解 孤独感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的进展。目标1中的研究将使用横断面、人口 神经科学方法(概率层次模型)，以得出大脑老化的标准轨迹。 这些分析将集中在默认网络上，利用高分辨率的皮质和皮质下 由MPI Bzdok开发的分组方案。这些规范的轨迹将允许测量非 标准偏差可归因于老年人群体中的孤独经历。研究项目： 目标2将使用纵向概率层次分析来研究孤独之间的交互作用 在AD风险增加的背景下，大脑老化。参与者将来自当地纵向队列中的老年人 成人患AD的风险增加。这项工作将利用MPI Spreng最近的努力，收集尖端技术 神经成像和行为数据，将作为下一波数据收集的基线 这里。这项研究将促进对孤独如何与大脑结构和功能相互作用的理解 在正常衰老和有症状的AD中。孤独是一种容易处理的社交状况，可以通过 个别或政策层面的干预。更好地理解孤独、大脑 老龄化和疾病最终可能为更好的检测、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