Education and cancer-related cognitive decline during aging

摘要 癌症相关的认知能力下降（CRCD）是一个高度担心和流行的结果，人口不断增长 老年癌症幸存者众所周知，教育通常可以预测老年人更好的认知功能， 大大降低痴呆症的风险，但在老年癌症的一般人群中， 幸存者几乎所有的CRCD研究都是在临床环境中进行的，研究人群受过高等教育， 因此，通常不适合评估教育作为CRCD风险修正因素的影响。这 是一个主要的证据缺口，限制了我们对CRCD在人群中的负担或预测因素的理解 水平这项研究利用了认知储备理论，该理论假设认知储备 允许个体维持认知功能，尽管累积了大脑病理和认知损伤。 我们的中心假设是，教育和相关的认知储备标记将修改记忆的速度 与新的癌症诊断和接受化疗相关的变化，可能是认知损害， 在中年到晚年的生活中。我们将研究CRCD的过程是否在中老年癌症中改变 具有高认知储备的幸存者（通过教育、计算能力、职业技能、社交能力 参与），相对于那些低储备和年龄匹配的无癌症成年人。具体目标是 1）根据教育程度，确定与新癌症诊断相关的记忆变化率 和癌前诊断认知储备的相关标志物，以及2）确定记忆改变的速率 与接受化疗相关，总体和根据教育和癌前相关标志物 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基金会的数据， 研究并链接1998-2016年的医疗保险数据。分段线性混合模型将估计记忆 在新的癌症诊断和治疗之前和之后，认知储备标志物水平的变化， 与年龄匹配的无癌症成年人作为对照组。主要创新是：1）我们使用纵向 先前基于临床的CRCD研究中无法获得的癌前诊断数据; 2）a 在教育和其他认知方面存在不同差异的大型全国代表性研究人群 储备标记，允许结果的普遍性; 3）我们将丰富的HRS数据与Medicare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来帮助理解CRCD的现象。在以下领域架起桥梁 癌症和衰老流行病学，我们的研究结果将：1）推进对CRCD的理解，这是一个至关重要的 癌症患者及其家属的结果，以及2）加强对神经认知影响的理解， 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 痴呆神经病理学现象这项研究是实现我们长期目标的第一步 了解和改善日益增长的老年癌症幸存者人群的认知老化结果。

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.