Dear Editor,

Recently, the US Food and Drug Administration (FDA) approved two anti-amyloid antibodies for the treatment of patients with early Alzheimer's disease (AD), with a third expected to be approved soon.¹ These drugs are designed to remove amyloid-β peptides from the brains of patients in the early stages of AD to slow down cognitive decline. The use of anti-amyloid immunotherapy has raised several ethical issues, mostly centered around the dimensions of beneficence, nonmaleficence, and informed consent. We consider another potential area of concern related to the principle of human dignity.

The modest benefits and associated risks of recently FDA-approved anti-amyloid antibodies aducanumab and lecanemab^2-4 have generated reluctance among some clinicians in prescribing these drugs to individuals with cognitive impairment, who may not fully grasp the nuances of potential benefits and harm. Due to ongoing scientific progress, it is increasingly likely that anti-amyloid immunotherapies will become more effective in slowing down cognitive decline, be safer, and lead to better long-term outcomes.⁵ In this scenario, are there other ethical objections to the routine use of these interventions worth considering?

We argue that there is still reason to pause on deontological grounds. A motivation for seeking anti-amyloid immunotherapy, despite known risks, is the fear of losing one's dignity. We contend that routinely offering anti-amyloid immunotherapy based on this motivation is questionable. Several moral frameworks, such as forms of deontological ethics, virtue ethics, and certain cultural and religious worldviews, maintain that human dignity is inherent to all human beings and not clearly contingent upon cognitive abilities or any external factors.⁶ According to this view, cognitive impairment or any reduction in cognitive abilities does not diminish a person's inherent dignity.

If preserving someone's dignity as a motivation to use anti-amyloid immunotherapy were to be widely adopted in the public narrative, this may inadvertently result in a shift in collective thinking about the value of individuals with compromised cognition. If the prevailing justification for pursuing such interventions becomes the preservation of dignity, there is a hidden risk that those who choose not to pursue these interventions—for whatever reasons—may be tacitly regarded as having inferior worth and lower dignity than others. The presumption that compromised cognition categorically entails a loss of dignity is also at odds with the medical ethic of care, which supports difference and upholds respect for all persons, regardless of their (in)capacity.⁷

One objection might emphasize that the term “dignity” is to be understood differently in these contexts. Patients with AD are sometimes treated in undignified ways and may animate fear of cognitive decline. The dignity with which one is treated ought not to be linked to one's cognitive capacities in determining a person's moral status. Instead, dignity should be based on an individual's inherent worth, regardless of their cognitive status. Moreover, while expressions of personhood may indeed change with shifting cognitive capacities, intrinsic dignity is still preserved throughout the course of disease.^{8, 9}

A second objection could be that there are indeed other motivations to seek anti-amyloid immunotherapy, including the desire to preserve autonomy and independence, at least temporarily. These are reasonable ethical considerations for the use of these interventions, as they do not risk implicitly imposing value judgements on others. When considering these factors, one must carefully weigh potential benefits against associated risks and burdens, including the possibility that autonomy and independence may unexpectedly be detrimentally impacted rather than safeguarded following intervention.

亲爱的编辑，

最近，美国食品和药物管理局（FDA）批准了两种抗淀粉样蛋白抗体用于治疗早期阿尔茨海默病（AD）患者，第三种预计很快就会获得批准。¹这些药物旨在清除 AD 早期患者大脑中的 β 淀粉样肽，以减缓认知能力下降。抗淀粉样蛋白免疫疗法的使用引发了一些伦理问题，主要集中在善意、非恶意和知情同意方面。我们考虑与人类尊严原则有关的另一个潜在关注领域。

^{最近 FDA 批准的抗淀粉样蛋白抗体 aducanumab 和 lecanemab 2-4}的适度益处和相关风险导致一些临床医生不愿意向认知障碍患者开出这些药物，因为他们可能无法完全掌握潜在益处和危害的细微差别。由于不断的科学进步，抗淀粉样蛋白免疫疗法越来越有可能在减缓认知能力下降方面变得更有效、更安全，并带来更好的长期结果。⁵在这种情况下，对于常规使用这些干预措施是否存在其他值得考虑的伦理反对意见？

我们认为，基于义务论的理由，仍有理由暂停。尽管存在已知的风险，但寻求抗淀粉样蛋白免疫疗法的动机是担心失去尊严。我们认为，基于这种动机而常规提供抗淀粉样蛋白免疫疗法是值得怀疑的。一些道德框架，例如义务论伦理学、美德伦理学以及某些文化和宗教世界观，都认为人类尊严是所有人所固有的，而不明显取决于认知能力或任何外部因素。⁶根据这一观点，认知障碍或认知能力的任何下降都不会削弱一个人固有的尊严。

如果将维护某人的尊严作为使用抗淀粉样蛋白免疫疗法的动机在公共叙事中得到广泛采用，这可能会无意中导致对认知受损个人价值的集体思维发生转变。如果采取此类干预措施的普遍理由成为维护尊严，那么就存在一个隐藏的风险，即那些选择不采取这些干预措施的人（无论出于何种原因）可能会被默认为比其他人具有较低的价值和较低的尊严。认知受损肯定会导致尊严丧失的假设也与医疗护理伦理相矛盾，医疗伦理支持差异并维护对所有人的尊重，无论其能力如何。⁷

一种反对意见可能强调“尊严”一词在这些情况下应有不同的理解。 AD 患者有时会受到不尊重的对待，并可能引发对认知能力下降的恐惧。一个人所受到的尊严不应与决定一个人道德地位的认知能力挂钩。相反，尊严应该基于个人的内在价值，无论其认知状态如何。此外，虽然人格的表达确实可能随着认知能力的变化而改变，但内在的尊严在整个疾病过程中仍然得到保留。^{8, 9}

第二个反对意见可能是，寻求抗淀粉样蛋白免疫疗法确实有其他动机，包括希望至少暂时保持自主和独立。这些是使用这些干预措施的合理道德考虑，因为它们不会隐含地将价值判断强加于他人的风险。在考虑这些因素时，必须仔细权衡潜在收益与相关风险和负担，包括干预后自主性和独立性可能意外受到不利影响而不是得到保障的可能性。