The role of loneliness in cognitive decline and risk for dementia

孤独在认知能力下降和痴呆风险中的作用

• 批准号: 10646826
• 负责人: Jennifer Elise Graham-Engeland
• 金额: $ 8.02万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646826
• 关键词: Acceleration; Address; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Animal Model; Behavioral; Biological; Biological Markers; Blood specimen; Brain-Derived Neurotrophic Factor; Cerebrum; Clinic; Cognitive; Collection; Country; County; Data; Data Set; Dementia; Development; Disease; Early Diagnosis; Ecological momentary assessment; Elderly; Foundations; Future; Genetic Polymorphism; Health; Human; Impaired cognition; Incidence; Income; Individual; Intervention; Life; Light; Link; Loneliness; Longevity; Measurement; Mediating; Nerve Degeneration; Neurobiology; Neurodegenerative Disorders; Outcome; Parents; Participant; Pathway interactions; Phenotype; Plasma; Probability Samples; Risk; Risk Factors; Risk Reduction; Role; Sampling; Series; Serum; Specific qualifier value; Time; age group; aged; cognitive change; cognitive function; cohort; dementia risk; design; human old age (65+); improved; lonely individuals; mild cognitive impairment; multilevel analysis; neurobiological mechanism; neurofilament; neurogenesis; neuropathology; pre-clinical; programs; psychosocial; recruit; response; tau Proteins

PROJECT SUMMARY/ABSTRACT Loneliness is highly prevalent among older adults and is associated with substantially increased risk for dementia, particularly Alzheimer’s disease (AD). Recent evidence indicates that loneliness is associated with accelerated rates of cognitive decline and neurobiological changes including accumulation of AD neuropathology, neurodegeneration, and lower levels of brain-derived neurotrophic factor (BDNF). However, most prior studies have relied on cross-sectional designs or assessment of loneliness at a single timepoint, and thus are not able to examine the temporal ordering or directionality of relationships. As a consequence, it remains unclear whether loneliness is a risk factor for, or an indicator of, cognitive and neurobiological changes that are associated with dementia. In the proposed project we will address this critical gap by: examining the longitudinal bidirectional relationships between loneliness and cognitive function (Aim 1), and exploring neurobiological mechanisms linking loneliness with dementia risk (Aim 2). To address these aims, we will leverage intensive longitudinal data and biological samples from the established Einstein Aging Study (EAS), which includes a diverse sample of older adults (aged ≥70 years) recruited via systematic probability sampling from the Bronx County Registered Voter list. These participants have completed up to 4 annual assessment waves that include a 16-day ecological momentary assessment (EMA) burst, collection of blood samples, and in-clinic assessment for mild cognitive impairment (MCI). Blood samples from each assessment have been analyzed for biomarkers of AD neuropathology (amyloid-β, tau), neurodegeneration (neurofilament light [NfL]), and BDNF Val66Met genetic polymorphism. The proposed project will add to this by analyzing BDNF levels in plasma from each assessment wave. The outcomes of the project will be significant in informing whether loneliness is a sensitive early indicator of cognitive dysfunction or a viable target for intervention to reduce risk for cognitive decline and dementia. This will be the first study to examine the longitudinal relationships of loneliness and biomarkers of AD, neurodegeneration, and BDNF in humans, to identify neurobiological mechanisms contributing to increased cognitive decline and dementia risk of lonely individuals.

项目总结/摘要 孤独症在老年人中非常普遍，并且与以下风险的显著增加相关： 痴呆症，特别是阿尔茨海默病（AD）。最近的证据表明，孤独与 认知能力下降和神经生物学变化（包括AD累积）的速度加快 神经病理学、神经变性和较低水平的脑源性神经营养因子（BDNF）。然而，在这方面， 大多数先前的研究依赖于横截面设计或在单个时间点对孤独感的评估， 因此不能检查关系的时间顺序或方向性。因此， 目前尚不清楚孤独是否是认知和神经生物学变化的风险因素或指标， 与痴呆症有关。在拟议的项目中，我们将通过以下方式解决这一关键差距： 孤独和认知功能之间的双向关系（目标1），并探索神经生物学 将孤独与痴呆风险联系起来的机制（目标2）。为了实现这些目标，我们将利用密集 纵向数据和生物样本从建立爱因斯坦老化研究（EAS），其中包括一个 通过系统概率抽样从布朗克斯招募的老年人（年龄≥70岁）的多样化样本 县登记选民名单。这些参与者已完成最多4轮年度评估，包括 为期16天的生态瞬时评估（EMA）爆发、血液样本采集和诊所内评估 轻度认知障碍（MCI）。对每次评估的血样进行生物标志物分析 AD神经病理学（淀粉样蛋白-β，tau），神经变性（神经丝轻[NfL]）和BDNF Val 66 Met 遗传多态性该项目将通过分析每个人血浆中的BDNF水平来补充这一点。 评估波。该项目的结果将在告知孤独是否是一种敏感的 认知功能障碍的早期指标或降低认知功能减退风险的可行干预目标， 痴呆这将是第一个研究孤独和生物标志物的纵向关系的研究。 AD、神经退行性变和BDNF，以确定有助于增加AD的神经生物学机制。 孤独个体的认知能力下降和痴呆风险。