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

研究孤独对大脑衰老和阿尔茨海默病症状前进展的影响

• 批准号: 10774062
• 负责人: Danilo Bzdok
• 金额: $ 13.47万
• 依托单位: MCGILL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10774062
• 关键词: Acute; Administrative Supplement; Adult; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Behavior; Behavioral; Biological Markers; Brain; Chronic; Collection; Data; Data Collection; Data Set; Disease; Disease Progression; Elderly; Feeling; Funding; Goals; Impaired cognition; Individual; Infrastructure; Loneliness; Longitudinal Studies; Measures; Modeling; Plasma; Population; Registered nurse; Research; Research Design; Risk; Social Distance; Structure; Time; aging brain; biobank; blood-based biomarker; cognitive ability; cohort; dementia risk; innovation; mortality; neuropathology; novel marker; pandemic disease; pandemic impact; parent grant; poor health outcome; post-pandemic; programs

R01AG068563 Administrative Supplement (PI: Spreng R.N.) 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. Loneliness may be an antecedent or accelerant, promoting the advance of neuropathological changes and increasing dementia risk. The goal of the parent grant is to investigate the relationship between loneliness and brain structure and function in typical aging and in individuals at risk for AD. We are examining these associations in a large population dataset (UK Biobank, parent grant AIM 1) as well as in a local, longitudinally followed cohort of older adults at elevated risk for AD (parent grant AIM 2). However, pandemic-related social distancing restrictions were imposed between the two longitudinal datapoints for the parent grant, complicating our proposed analysis plan for AIM 2. We know that loneliness among older adults increased significantly during the pandemic. As these acute impacts of the pandemic are wholly coincident with our longitudinal study design, it is now challenging to isolate these from our originally hypothesized associations between loneliness and presymptomatic AD progression over time. The goal of the administrative supplement is to leverage the data collection infrastructure in place for the parent grant to collect an additional time point of data in this cohort. This will provide two post-pandemic timepoints of brain, behavior and loneliness data (Supplementary Aim 1), enabling us to model and isolate the acute and more chronic impacts of the pandemic from normal, longitudinal changes originally predicted in the parent grant. In addition, we will take advantage of recent innovations in plasma-based biomarkers of AD pathology to derive novel markers of AD- risk in our cohort (Supplementary Aim 2). Importantly, these markers of AD risk will be temporally aligned with proposed brain and behavioral data collection in Supplementary Aim 1. As described in the parent grant AIM 2, this program of research will advance our understanding of how loneliness interacts with brain structure and function in pre-symptomatic AD. The Administrative Supplement is critically necessary to achieve this goal, enabling us to measure, model and characterize the acute, and hopefully exceptional, impacts of the pandemic from normally occurring age- and disease-related changes that were the central focus of the parent grant. 1

R 01 AG 068563行政补充（PI：Spreng R.N.） 项目摘要。晚年的孤独感与健康状况不佳有关， 认知能力丧失，痴呆风险增加，死亡率升高。然而令人惊讶的是， 孤独是如何影响老年人的大脑的孤独可能是一个先行者或促进剂， 促进神经病理改变的进展，增加痴呆风险。家长的目标 格兰特是调查孤独和大脑结构和功能之间的关系， 老年人和有AD风险的个体。我们正在一个大型人口数据集中检查这些关联 (UK Biobank，父母资助AIM 1）以及当地的，纵向随访的老年人队列， AD风险升高（父母资助AIM 2）。然而，与流行病相关的社交距离限制 强加在父母补助金的两个纵向数据点之间，使我们提出的分析复杂化 AIM 2计划。我们知道，在大流行期间，老年人的孤独感显著增加。作为 大流行的这些急性影响与我们的纵向研究设计完全一致，现在 很难将这些与我们最初假设的孤独感和 症状前AD随时间的进展。行政补充的目标是利用 数据收集基础设施到位，供母基金收集额外时间点的数据， 这个cohort。这将提供大流行后两个时间点的大脑、行为和孤独数据 （补充目标1），使我们能够模拟和隔离的急性和慢性影响的 大流行从正常的纵向变化最初预测在母公司补助金。此外，我们将采取 最近在AD病理学的基于血浆的生物标志物中的创新以衍生AD的新标志物的优势- 我们队列中的风险（补充目标2）。重要的是，这些AD风险的标志物将在时间上与 补充目标1中建议的大脑和行为数据收集。如母基金AIM中所述 2，这项研究计划将促进我们对孤独如何与大脑结构相互作用的理解 并在症状前AD中发挥作用。行政补编是实现这一目标的关键 目标，使我们能够衡量，建模和描述的急性，希望例外，影响， 流行病从正常发生的年龄和疾病相关的变化，这是父母的中心重点， 格兰特. 1

项目成果

Age differences in functional brain networks associated with loneliness and empathy.

• DOI: 10.1162/netn_a_00293
• 发表时间: 2023
• 期刊: NETWORK NEUROSCIENCE
• 影响因子: 4.7
• 作者: Mwilambwe-Tshilobo, Laetitia;Setton, Roni;Bzdok, Danilo;Turner, Gary R. R.;Spreng, R. Nathan
• 通讯作者: Spreng, R. Nathan

Longitudinal changes in hippocampal texture from healthy aging to Alzheimer's disease.

• DOI: 10.1093/braincomms/fcad195
• 发表时间: 2023
• 期刊: Brain communications
• 影响因子: 4.8

Trips and neurotransmitters: Discovering principled patterns across 6850 hallucinogenic experiences.

• DOI: 10.1126/sciadv.abl6989
• 发表时间: 2022-03-18
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Ballentine G;Friedman SF;Bzdok D
• 通讯作者: Bzdok D

From Precision Medicine to Precision Convergence for Multilevel Resilience-The Aging Brain and Its Social Isolation.

• DOI: 10.3389/fpubh.2022.720117
• 发表时间: 2022
• 期刊: FRONTIERS IN PUBLIC HEALTH
• 影响因子: 5.2
• 作者: Dube, Laurette;Silveira, Patricia P.;Nielsen, Daiva E.;Moore, Spencer;Paquet, Catherine;Cisneros-Franco, J. Miguel;Kemp, Gina;Knauper, Baerbel;Ma, Yu;Khan, Mehmood;Bartlett-Esquilant, Gillian;Evans, Alan C.;Fellows, Lesley K.;Armony, Jorge L.;Spreng, R. Nathan;Nie, Jian-Yun;Brown, Shawn T.;Northoff, Georg;Bzdok, Danilo
• 通讯作者: Bzdok, Danilo

Deep learning identifies partially overlapping subnetworks in the human social brain.

• DOI: 10.1038/s42003-020-01559-z
• 发表时间: 2021-01-14
• 期刊: Communications biology
• 影响因子: 5.9
• 作者: Kiesow H;Spreng RN;Holmes AJ;Chakravarty MM;Marquand AF;Yeo BTT;Bzdok D
• 通讯作者: Bzdok D