The role of loneliness in cognitive decline and risk for dementia

项目摘要/摘要 孤独感在老年人中非常普遍，并与患上 痴呆症，特别是阿尔茨海默病(AD)。最近的证据表明，孤独与 认知功能减退和神经生物学改变的加速，包括AD的堆积 神经病理、神经退行性变和脑源性神经营养因子(BDNF)水平降低。然而， 大多数先前的研究依赖于单一时间点的横断面设计或孤独感评估，并且 因此不能检查关系的时间顺序或方向性。因此，它仍然是 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。在提议的项目中，我们将通过以下方式解决这一关键差距：检查纵向 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 将孤独与痴呆症风险联系起来的机制(目标2)。为了实现这些目标，我们将利用密集的 来自已建立的爱因斯坦老化研究(EAS)的纵向数据和生物样本，其中包括 从布朗克斯通过系统的概率抽样招募的不同的老年人样本(年龄为≥70岁) 县登记选民名单。这些参与者已经完成了最多4次年度评估浪潮，包括 为期16天的生态瞬时评估(EMA)突发、血液样本采集和临床评估 适用于轻度认知障碍(MCI)。每项评估的血液样本都进行了生物标志物分析。 AD神经病理(淀粉样蛋白-β，Tau)、神经退行性变(神经丝光)和BDNFVal66Met 遗传多态。拟议的项目将通过分析每个人血浆中BDNF的水平来增加这一点 评估浪潮。该项目的结果将对告知孤独是否是一种敏感因素具有重要意义 认知功能障碍的早期指标或干预措施的可行目标，以降低认知功能下降的风险 痴呆症。这将是第一次研究孤独感与生物标志物之间的纵向关系。 AD、神经退行性变和BDNF在人类中的作用，以确定导致增加的神经生物学机制 孤独个体认知功能减退与痴呆症风险。

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.