促进老年癌症幸存者的认知健康

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Introduction

Good news: the 5-year survival rate for a number of cancers, including breast, prostate, and thyroid, is now at least 90% (National Cancer Institute [NCI], 2021). The median age of cancer diagnosis is 66 years, meaning that an increasing number of older adults will live as cancer survivors (NCI, 2018). However, for older adults with cancer, overlooking the physiological impacts of cancer treatment and its biological aging effects may be equally detrimental to overall quality of life, morbidity, and mortality (Mandelblatt et al., 2021). One particularly distressing side effect of treatment is cancer-related cognitive impairment (CRCI).

CRCI is functionally characterized as impairments in short-term and working memory, attention, executive function, or processing speed (Lange et al., 2019). Formally, the International Cognition and Cancer Task Force defines CRCI based on cognitive testing: specifically, scores ≥2 standard deviations below age-based norms in any cognitive domain (Bartels et al., 2021). Changes in cognition experienced by patients with cancer have multiple causes, spanning physiological (i.e., side effects of treatment) and nonphysiological (e.g., psychosocial) mechanisms. Anxiety, depression, and fatigue experienced by some patients may simultaneously contribute to CRCI (Hervey-Jumper & Monje, 2021). Furthermore, CRCI impacts multiple aspects of life: financial stability, social relationships, and the ability to function independently (Boykoff et al., 2009). Although most research has focused on CRCI in breast cancer, it is a common experience across colorectal, testicular, and prostate cancers as well (Janelsins et al., 2014). Adults who are older, more frail, or have lower cognitive reserve are particularly at risk for cognitive decline related to cancer treatment (Ahles et al., 2010; Hurria et al., 2011).

In addition to its impact during treatment, CRCI may have long-term effects on cognition, such as accelerated cognitive aging and a higher risk of future dementia, including Alzheimer's disease (Roderburg et al., 2021). Although the direct relationship between cancer and Alzheimer's disease remains unclear, we know that cognitive impairment is experienced by patients diagnosed with cancer, regardless of cancer type, in up to 30% of patients prior to treatment, 75% during treatment, and continues post-treatment in up to 35% of cancer survivors (Jansen et al., 2011). Once referred to as “chemobrain” and perceived as a limited, temporary side effect of cancer treatment, CRCI is now understood to encompass subjective as well as objective cognitive changes that can persist as long as 20 years post-treatment (Deprez et al., 2012; van der Willik et al., 2018). Recent findings, such as an investigation of patients with lung cancer and melanoma, demonstrate a strong likelihood that autoantibodies affect cognitive dysfunction, underscoring the role of inflammation (Bartels et al., 2019; Bartels et al., 2021). Notably, the apolipoprotein E (APOE) genotype APOE4 is also associated with a higher risk of CRCI (Ahles et al., 2003; Guida et al., 2019). As the scientific evidence grows, it is increasingly clear that assessment of CRCI, and a thoughtful response to its impacts, are critically important aspects of providing comprehensive cancer care for older adults.

When our patients voice concerns about changes in memory or cognition, reassurances that “this is only temporary” may not be helpful, particularly if CRCI does not resolve quickly. Instead, we may serve our patients best by not dismissing memory or cognitive changes; rather, we can extend the conversation to inquire more about symptom severity and how such changes are affecting our patients' lives. Our first inclination should be, “Tell me more.” When oncology patients describe changes in cognition, it may be valuable to provide an initial cognitive screening, such as the Mini-Cog, as an appropriate next step, followed by referral for neuropsychological testing if warranted as a way to document changes and justify future supportive services (Mandelblatt et al., 2021). Furthermore, enhancing knowledge regarding the promotion of cognitive health in aging can directly inform patient care as nurses are often the first point of contact for patients in the clinical setting.

Improving cognitive outcomes in older cancer survivors is likely to require a multifactorial approach. Currently, the most effective approaches to prevent cognitive impairment and dementia (including Alzheimer's disease) are those that target modifiable risk factors across the life course. In their 2020 report, the Lancet Commission identified 12 such factors that could prevent or delay up to 40% of dementia cases (Livingston et al., 2020). Among these are factors that influence multiple aspects of health, including management of hypertension, obesity, and depression. Preventing delirium; addressing sensory impairments, such as vision or hearing loss; and promoting physical activity are notably important for older cancer survivors as polypharmacy and fatigue are commonly experienced (Shahrokni et al., 2017). Multiple large-scale studies have demonstrated potential of interventions with medical and lifestyle components to reduce dementia risk. For example, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) trial found that targeting vascular risk along with cognitive training led to cognitive benefits in at-risk older adults (Kivipelto et al., 2013; Rosenberg et al., 2018). Overall, a holistic model of prevention, intervention, and care is needed to improve cognitive outcomes in aging and reduce the individual and societal impact of dementia (Olivari et al., 2020). Regardless of the outcome of cognitive screening, patient reports of CRCI should prompt further assessment and consideration. Unmet mental health needs of older adult patients undergoing cancer treatment may also influence CRCI (e.g., cognitive symptoms of depression). Addressing anxiety or depression experienced with cancer can greatly improve patients' ability to sustain continued treatment, improve outcomes, and preserve daily functionality—an important component of cognitive health.

Identifying individuals at higher risk for cognitive decline supports our ability to target interventions with precision and, ideally, maximize benefits at individual and societal levels. As with older adults who have underlying cardiovascular risk factors, those with CRCI may be another group who would benefit from tailored lifestyle interventions to promote cognitive health. The understanding of CRCI has expanded tremendously from a temporary side effect of cancer treatment, creating moments of “fuzzy memory,” to a complex cascade of physiological and anatomical changes that may persist beyond cancer treatment. When older adults report cognitive changes during cancer treatment, nurses are best positioned to ensure that follow-up evaluation and supportive services are arranged to enable the best outcomes possible.

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简介

好消息：包括乳腺癌、前列腺癌和甲状腺癌在内的一些癌症的5年生存率现在至少为90%（国家癌症研究所[NCI]，2021）。癌症诊断的中位年龄是66岁，这意味着越来越多的老年人将作为癌症幸存者活着（NCI, 2018）。然而，对于患有癌症的老年人来说，忽视癌症治疗的生理影响及其生物老化效应可能同样不利于整体生活质量、发病率和死亡率（Mandelblatt等人，2021）。治疗的一个特别令人痛苦的副作用是癌症相关的认知障碍（CRCI）。

       CRCI在功能上表现为短期和工作记忆、注意力、执行功能或处理速度的损害（Lange等人，2019）。从形式上看，国际认知和癌症工作组根据认知测试对CRCI进行了定义：具体来说，在任何认知领域的得分都要比基于年龄的标准值低≥2个标准差（Bartels等人，2021）。癌症患者经历的认知变化有多种原因，横跨生理（即治疗的副作用）和非生理（如社会心理）机制。一些病人经历的焦虑、抑郁和疲劳可能同时导致CRCI（Hervey-Jumper & Monje, 2021）。此外，CRCI影响生活的多个方面：经济稳定、社会关系和独立运作的能力（Boykoff等人，2009）。虽然大多数研究集中在乳腺癌的CRCI，但它也是结肠直肠癌、睾丸癌和前列腺癌的常见经历（Janelsins等人，2014）。年龄较大、体质较弱或认知储备较低的成年人特别容易出现与癌症治疗有关的认知衰退（Ahles等人，2010；Hurria等人，2011）。

       除了治疗期间的影响外，CRCI还可能对认知产生长期影响，如加速认知老化和未来患痴呆症（包括阿尔茨海默病）的风险更高（Roderburg等人，2021）。尽管癌症和阿尔茨海默病之间的直接关系仍不清楚，但我们知道，被诊断为癌症的患者，无论其癌症类型如何，在治疗前有高达30%的患者出现认知障碍，在治疗期间有75%的患者出现认知障碍，在治疗后有高达35%的癌症幸存者继续出现认知障碍（Jansen等人，2011）。CRCI曾经被称为 "化学脑"，并被认为是癌症治疗的有限的、暂时的副作用，现在被理解为包括主观以及客观的认知变化，在治疗后可以持续20年之久（Deprez等人，2012；van der Willik等人，2018）。最近的研究结果，如对肺癌和黑色素瘤患者的调查，表明自身抗体影响认知功能障碍的可能性很大，强调了炎症的作用（Bartels等人，2019；Bartels等人，2021）。值得注意的是，脂蛋白E（APOE）基因型APOE4也与CRCI的高风险有关（Ahles等人，2003；Guida等人，2019）。随着科学证据的增加，越来越清楚的是，对CRCI的评估，以及对其影响的深思熟虑的回应，是为老年人提供全面癌症护理的至关重要的方面。

       当我们的病人对记忆或认知的变化表示担忧时，"这只是暂时的 "的保证可能没有帮助，特别是如果CRCI不能迅速解决。相反，我们最好不要忽视记忆或认知的变化；相反，我们可以扩大谈话范围，更多地询问症状的严重程度以及这些变化对病人生活的影响。我们的第一个倾向应该是，"告诉我更多"。当肿瘤患者描述认知方面的变化时，作为一个适当的下一步，提供初步的认知筛查，如Mini-Cog，如果有必要的话，可以转诊到神经心理学测试，作为记录变化和证明未来支持性服务的一种方式（Mandelblatt等人，2021）。此外，增强有关促进老年认知健康的知识可以直接为病人护理提供信息，因为护士往往是临床环境中病人的第一接触点。

       改善老年癌症幸存者的认知结果可能需要一个多因素的方法。目前，预防认知障碍和痴呆症（包括阿尔茨海默病）最有效的方法是那些针对整个生命过程中可改变的风险因素。柳叶刀委员会在其2020年的报告中确定了12个这样的因素，可以预防或推迟多达40%的痴呆症病例（Livingston等人，2020）。其中包括影响健康的多个方面的因素，包括高血压、肥胖症和抑郁症的管理。预防谵妄；解决感官障碍，如视力或听力损失；以及促进身体活动，对于老年癌症幸存者来说是明显重要的，因为他们通常会有多药和疲劳的经历（Shahrokni等人，2017）。多项大规模的研究表明，包含医疗和生活方式的干预措施有可能降低痴呆风险。例如，芬兰预防认知障碍和残疾的老年干预研究（FINGER）试验发现，针对血管风险与认知训练一起导致高危老年人的认知益处（Kivipelto等，2013；Rosenberg等，2018）。总的来说，需要一个预防、干预和护理的整体模式来改善老龄化的认知结果，减少痴呆的个人和社会影响（Olivari等人，2020）。无论认知筛查的结果如何，患者对CRCI的报告应促使其进一步评估和考虑。接受癌症治疗的老年患者未得到满足的心理健康需求也可能影响CRCI（例如，抑郁症的认知症状）。解决因癌症而产生的焦虑或抑郁，可以极大地提高患者持续治疗的能力，改善疗效，并保持日常功能--这是认知健康的一个重要组成部分。

       识别认知能力下降风险较高的个体，有助于我们精确地采取干预措施，最好是在个人和社会层面上实现利益最大化。与有潜在心血管风险因素的老年人一样，患有CRCI的人可能是另一个群体，他们将受益于定制的生活方式干预，以促进认知健康。人们对CRCI的理解已经从癌症治疗的暂时性副作用，即产生 "模糊记忆 "的时刻，扩展到癌症治疗后可能持续存在的一系列复杂的生理和解剖学变化。当老年人报告在癌症治疗期间出现认知变化时，护士最能确保后续评估和支持性服务的安排，以实现可能的最佳结果。