Education and cancer-related cognitive decline during aging

摘要 癌症相关认知衰退(CRCD)是不断增长的人群中高度恐惧和普遍存在的结果 更年长的癌症幸存者。众所周知，教育可以预测老年人的认知功能更好，而且 大大降低了痴呆症的风险，但在老年癌症的普通人群中基本上是未知的 幸存者。几乎所有CRCD研究都是在受过高等教育的研究人群的临床环境中进行的， 因此，通常不太适合将教育作为慢性传染性疾病风险修正因素来评估教育的效果。这 是限制我们了解慢性阻塞性肺病在人群中的负担或预测因素的主要证据差距吗？ 水平。这项拟议的研究利用了认知储备理论，该理论假设认知储备 允许个人保持认知功能，尽管积累了大脑病理和认知侮辱。 我们的中心假设是，教育和相关的认知储备标记物会改变记忆率 与新的癌症诊断和化疗收据相关的变化，这可能是对认知的侮辱， 在中后期生活中。我们将研究CRCD在中老年癌症中的病程是否发生改变 具有较高认知储备的幸存者(通过教育、计算、职业技能、社交能力来衡量 参与)，相对于低储备和年龄匹配的无癌成年人。具体目标是 为了：1)根据教育，确定与新的癌症诊断相关的记忆改变率 和癌前诊断认知储备的相关标志物，以及2)决定记忆改变率 与接受化疗有关，总体上，并根据教育和相关的癌前标志物 诊断认知储备。我们将使用具有全国代表性的美国健康和退休组织的数据 研究并链接了1998-2016年的医疗保险数据。分段线性混合模型将估计内存 在新的癌症诊断和治疗前后认知储备标志物水平的变化， 并以年龄匹配的无癌成年人为对照组。主要的创新是：1)我们使用纵向 先前CRCD临床研究中无法获得的癌前诊断数据；2)a 具有全国代表性的大型研究人群，在教育和其他认知方面存在不同的差异 储备标记，允许结果的概括性；3)我们将丰富的HRS数据与联邦医疗保险索赔联系起来 数据作为癌症治疗信息的黄金标准；4)我们对认知储备理论的利用 从阿尔茨海默氏症和痴呆症领域帮助理解CRCD现象。架起了 癌症和老龄化流行病学，我们的结果将：1)促进对CRCD的理解，这是一个至关重要的 对癌症患者及其家人的结果，以及2)加强对癌症患者及其家人的神经认知影响的了解 教育和认知储备的机制，通过评估认知储备是否适用于这种非 痴呆的神经病理现象。这项研究是实现我们长期目标的第一步。 了解和改善不断增长的老年癌症幸存者群体的认知老化结果。

ABSTRACT Cancer-related cognitive decline (CRCD) is a highly feared and prevalent outcome for the growing population of older cancer survivors. Education is known to predict better cognitive function in older adults generally and substantially reduces dementia risk, but is largely unexplored in the general population of older cancer survivors. Almost all CRCD studies are conducted in clinical settings with highly educated study populations, and thus are often not well suited to evaluate the effects of education as a CRCD risk-modifying factor. This is a major evidence gap limiting our understanding of the burden or predictors of CRCD at the population level. The proposed research leverages the cognitive reserve theory, which postulates that cognitive reserve allows individuals to maintain cognitive function despite accumulating brain pathology and cognitive insults. Our central hypothesis is that education and related cognitive reserve markers will modify the rate of memory change associated with a new cancer diagnosis and chemotherapy receipt, which may be cognitive insults, in mid-to-later life. We will investigate whether the course of CRCD is altered in middle-aged and older cancer survivors with high cognitive reserve (measured by education, numeracy, occupational skill, social engagement), relative to those with low reserve and age-matched cancer-free adults. The specific aims are to: 1) determine the rate of memory change associated with a new cancer diagnosis, according to education and related markers of pre-cancer diagnosis cognitive reserve, and 2) determine the rate of memory change associated with chemotherapy receipt, overall and according to education and related markers of pre-cancer diagnosis cognitive reserve. We will use data from the nationally representative US Health and Retirement Study and linked Medicare data from 1998-2016. Segmented linear mixed models will estimate memory change prior to and after a new cancer diagnosis and treatment across levels of cognitive reserve markers, with age-matched cancer-free adults as a comparison group. Key innovations are: 1) our use of longitudinal pre-cancer diagnosis data that have been previously unavailable in prior clinic-based studies of CRCD; 2) a large nationally-representative study population with diverse variation in education and other cognitive reserve markers that allows generalizability of results; 3) our linkage of the rich HRS data to Medicare claim data as a gold standard for information on cancer treatments; 4) our leveraging of cognitive reserve theory from the Alzheimer’s and dementia field to help understand the phenomenon of CRCD. Bridging the fields of cancer and aging epidemiology, our results will: 1) advance understanding of CRCD, a critically important outcome to cancer patients and their families, and 2) enhance understanding of the neurocognitive effects of education and mechanisms of cognitive reserve, by evaluating whether cognitive reserve applies to this non- dementia neuropathological phenomenon. This research is a first step towards achieving our long-term goal of understanding and improving cognitive aging outcomes in the growing population of older cancer survivors.