Introduction
Dementia, by impairing a person's ability to make decisions for themselves, raises ethical issues that differ as the disease progresses from biomarker-based risk status to early clinical symptoms to more severe stages. Keeping this in mind, the present review analyzes ethical issues at each of these stages.
We begin with the topic of prevention: how do scientific developments that have increased our understanding of early dementia risk factors raise ethical questions related to prevention trials, disclosure of risk status, and protection from stigma and discrimination? These issues have become salient as research trials aim to intervene earlier in the dementia's disease course. While the first part of the paper focuses on issues related to prevention, the second part of the paper is prompted by the fact that these prevention efforts, though promising, are in their early stages. As a result, research continues to enroll not only cognitively intact persons who are at risk for dementia, but also persons with cognitive impairment that threatens their ability to consent. Therefore, the second part of the paper focuses on treatment and research protections for persons with dementia whose decision-making capacity may be compromised, and proper ways to balance the benefits of enabling access to treatments and research options against challenges raised by a person's impaired ability to choose these options for themselves. Finally, the third section recognizes that despite efforts to prevent dementia and treat the symptoms and clinical course, there are still many people living with dementia, raising ethical challenges related to living with dementia and its associated impairments.
The review focuses on these issues for two reasons. First, the distinct stages of dementia's progression raise distinct sets of ethical issues: the questions that accompany dementia's pre-clinical stages differ from those that accompany its severe clinical manifestations. Second, while ethical analyses of dementia often focus on the person with dementia's participation in clinical care or in research studies, persons spend the majority of their time engaged in activities outside these medical settings. There are thus important ethical questions about the effect of dementia on these daily, non-medical activities that range from how to protect persons at risk for dementia from unjust employment discrimination to protecting the right to vote. Focusing on these two goals, the present review analyzes the existing literature and highlights newly emergent ethical questions.
“Preclinical” dementia: the ethics of risk
The discovery of biomarkers associated with the pathophysiology of Alzheimer's disease (AD) and other neurodegenerative diseases has begun to transform how researchers and clinicians define these diseases. These transformations, in turn, are beginning to reshape the contours of the ethical challenges that clinicians and patients face.
For Alzheimer’s, the most common cause of dementia, substantial evidence supports that the pathophysiological process begins long before a person becomes a patient with observable signs and symptoms (Sperling et al., Reference Sperling2011). In 2011, a work group from the National Institute on Aging and Alzheimer's Association summarized this research in order to propose guidelines for a novel stage of AD called “preclinical Alzheimer's disease.” The work group strongly emphasizes that the framework is “not intended to serve as diagnostic criteria for clinical purposes,” a move that is “currently unwarranted because many individuals who satisfy the proposed research criteria may not develop the clinical features of AD in their lifetime” (Sperling et al., Reference Sperling2011). A separate working group of predominantly European researchers has advanced a category called “asymptomatic at risk for Alzheimer's disease” and they make similar arguments about the role of biomarkers in defining this stage and the current “research only” status of the category (Dubois et al., Reference Dubois2014). Yet the presence of brain, blood, genetic, and cerebrospinal fluid-based biomarkers raises interesting ethical questions about moving the boundaries of AD from the beside of the patient with dementia, to the desktop of the person who learns her biomarker results. As Alzheimer's begins to conform to this “desktop medicine” model of disease (Karlawish, Reference Karlawish2010) – with disease defined by a dimensional risk of impairment rather than a categorical pathology – three ethical questions emerge.
First, what are the ethical implications of a shift in the focus of research trials from testing interventions in patients with symptomatic Alzheimer's to testing interventions in clinically asymptomatic patients with biomarker-based risk? Second, how can persons at high risk for dementia be protected from the stigma and discrimination that accompanies most forms of irreversible cognitive decline? Third, if effective treatments for Alzheimer's and other dementias remain elusive, what is the clinical and social utility of knowing one's risk status?
Risk-benefit ratios in Alzheimer's prevention trials
Recently, researchers have undertaken several major efforts at “secondary prevention” of Alzheimer's and other dementias: trials with the goal of preventing cognitive decline in persons who have already begun to exhibit genetic or brain-based signs of the dementia disease process (Peters et al., Reference Peters, Lynn Beattie, Feldman and Illes2013; Sperling et al., Reference Sperling, Karlawish and Johnson2013; Reference Sperling2014). These trials were prompted by the fact that clinical trials that test interventions in patients with symptomatic forms of dementia – for instance, compounds targeting beta-amyloid – have failed to affect the conditions’ progression. These results have prompted a call to test compounds in patients who do not yet exhibit observable symptoms of memory loss but who do exhibit biomarker-based risk factors. The logic is that intervention prior to neurodegeneration will prove more effective than intervening when people already have suffered substantial loss of neurons.
The prevention trials raise three sets of ethical questions. First, and arguably the most important, is that in some of the trials, participants will learn their dementia risk status in order to understand why they are eligible for enrollment and the benefits the trial may offer (Sperling et al., Reference Sperling, Karlawish and Johnson2013). As we discuss below, this ethical challenge means that prevention trials will need to develop careful procedures to minimize the harms that can accompany disclosure of risk information. Second, some proportion of participants in prevention trials may have never progressed from the biomarker-positive status that qualifies them for trial enrollment to the clinical symptoms that trial interventions aim to prevent. As a result, the risk that interventions pose to this subset of biomarker-positive persons who would have never progressed to clinical dementia should be included in the trial's general risk/benefit ratio. Finally, prevention trials have the ethical benefit of enrolling persons with sufficient cognitive capacity to weigh the trial's risks and benefits for themselves (Sperling et al., Reference Sperling, Karlawish and Johnson2013). This means that the participant himself can weigh the ethical issues at stake in prevention trials – disclosure of biomarker status; assessing the benefits versus harms of early intervention – as he makes his enrollment decision.
Stigma and discrimination
The fact that persons may learn about their risk status from prevention trials or other sources raises questions about the consequences of learning risk results. The impairments associated with AD and other dementias often evoke stigma, which largely takes the form of “social distancing” from those with progressive cognitive impairment (Werner, Reference Werner2006). Will persons in dementia's “preclinical” stages who are “marked” with a potential diagnosis but who lack the diagnosis’ cognitive and behavioral symptoms be subject to similar levels of stigma and social distancing as persons whose disease label is accompanied by observable, disease symptoms? Framed differently, do persons react with negative stereotypes, emotions, and behaviors to the disease label of Alzheimer's itself, or are they reacting to various assumptions embedded in that label – such as ideas about the certainty of a person's decline into a state of severe cognitive incapacity? Research addressing this question suggests that it is not the AD label itself that elicits stigma, but instead, the label's association with expectations of certain future decline (Johnson et al., Reference Johnson, Harkins, Cary, Sankar and Karlawish2014). These findings suggest that one way to minimize potential stigma is to emphasize that persons diagnosed with pre-clinical AD will experience a range of clinical trajectories that do not uniformly converge upon a severe form of Alzheimer’s.
In addition to stigma and distancing in social relationships, persons at risk for AD and other dementias – especially if the disease is diagnosed before retirement – also may fear discrimination by employers and various types of insurance providers (Prince and Berkman, Reference Prince and Berkman2012; Arias and Karlawish, Reference Arias and Karlawish2014). The prevention trials we discussed previously may result in a person's amyloid risk status being documented into his or her medical record (Arias and Karlawish, Reference Arias and Karlawish2014). Existing legislation designed to protect persons from insurance and employment discrimination does not adequately protect persons who may have their AD risk status revealed by neuroimaging and other non-genetic tests. For instance, although the 2008 Genetic Information Non-Discrimination Act (GINA) prevents employers and health insurance companies from discriminating against persons at risk for a disease until the disease manifests itself, a positive biomarker test result could count as a disease manifestation (Kostiuk, Reference Kostiuk2012; Prince and Berkman, Reference Prince and Berkman2012; Arias and Karlawish, Reference Arias and Karlawish2014). This would leave persons unprotected from insurance discrimination on the basis of their risk status, since it is also unclear whether biomarker-indicated AD risk counts as a pre-existing condition for which the Affordable Care Act (ACA) prevents insurers from charging higher rates. Furthermore, GINA does not apply to disability, life and long term insurances, arguably the kinds of insurance a person at elevated risk for dementia would want (Prince and Berkman, Reference Prince and Berkman2012; Arias and Karlawish, Reference Arias and Karlawish2014). Likewise, it remains unclear whether being at risk for dementia qualifies as a disability protected from employment discrimination under the Americans with Disabilities Act (ADA) (Arias and Karlawish, Reference Arias and Karlawish2014). The ADA has expanded to include disabilities like HIV infection characterized by system-damaging physiological impairment rather than observable physical or mental impairment. Under this reasoning, AD risk should qualify since a positive biomarker test result indicates impairment to one's neurological system, but case law has yet to affirmatively establish such a protection (Arias and Karlawish, Reference Arias and Karlawish2014).
From the standpoint of persons with dementia risk, this lack of protection is worrisome since it increases their chance of insurance denial or higher insurance premiums. However, insurers concerned with the financial ramifications of adverse selection – for instance, long-term care insurers who fear that persons who are at high dementia risk will be more likely to seek out insurance, making the insurance's coverage pool less balanced between those who will and those who will not end up utilizing long-term care – are more critical of protections that keep patients’ risk information private. Indeed, evidence suggests that those who learn that they are at higher genetic risk for Alzheimer's report an increased interest in long-term care insurance, showing that insurers’ adverse selection fears may be well-founded (Taylor et al., Reference Taylor2010).
The unsettled law in the areas of insurance and employment discrimination leads to tension between different goals a person at risk for AD or other dementias may have. Out of a desire to contribute to generalizable knowledge about dementia or for the prospect of preventing dementia's onset, they may want to participate in trials that test risk-reduction therapies. Yet records of their trial participation may result in negative insurance and employment consequences. Improved legal protections for this population, combined with thoughtful research designs that better mask a person's risk status, can ease this tradeoff (Arias and Karlawish, Reference Arias and Karlawish2014). In addition, reforms of the long-term care insurance marketplace should focus on balancing insurers’ needs for a financially sustainable coverage pool with patients’ interest in remaining eligible for affordable insurance regardless of their risk status.
The utility and downsides of risk information
The previous section highlighted one potential downside of learning one's dementia risk status: stigma and discrimination. What are other benefits and downsides of learning one's risk status, especially in the absence of effective preventative or treatment measures? While further research is needed, one important finding thus far is that people's perceptions of the benefits and downsides of risk information often change once they receive a risk assessment. In the case of pre-clinical AD, clinicians should be concerned that certain patients may be psychologically harmed by information that they are “biomarker positive.” Yet clinicians must weigh the risks of harm against possible benefits of disclosure, which include a person's ability to plan for his future and to decide on whether to participate in prevention trials that recruit persons at elevated risk for AD or other dementias (Grill et al., Reference Grill, Karlawish, Elashoff and Vickrey2013).
The results of the Risk Evaluation and Education for Alzheimer's Disease (REVEAL) study suggest that the experience of psychological harms can be reduced. Participants in REVEAL who received their genotype-specific risk did not have more anxiety, depression, or test-related distress compared to participants who received age, family history, and sex-based risk information (Green et al., Reference Green2009). However, the study excluded persons who screened positive for clinically significant depression, anxiety and suicidality, and prior to receiving their Apolioprotein E (ApoE) result, which indicates genetic risk, eligible participants underwent a “pre-test” model of education and counseling. Translating this experience to biomarker disclosure suggests a model for clinicians to safely disclose a biomarker result to an adult.
Notably, as objective as biomarker data may be, people who receive that data use it in ways that are arguably deeply subjective and unique. In REVEAL, perceptions of the benefits and drawbacks of genotype-based risk information did change after testing was conducted. After they received genotype-based risk information, participants were less likely to believe that testing was useful for seeking information about preventative measures and potential treatments, had increased fears of employment discrimination, and had increased recognition that the test does not give them a definitive answer about whether they will get AD or not (Christensen et al., Reference Christensen, Roberts, Uhlmann and Green2011).
The FDA's 2012 approval of the amyloid imaging compound Florbetapir shifts the conversation about clinical risk disclosure from discussions about disclosing genotype-based risk to discussions about disclosing risk based on imaging disease pathophysiology. As analyses of brain-based biomarkers migrate from research into clinical care, clinicians will have to develop skills in how to communicate and explain this information to patients in a way that minimizes harms and maximizes benefits. As to who should learn about their risk status, clinicians appear to believe that disclosure has a better benefit-harm ratio for persons who are experiencing mild cognitive impairment than persons who are cognitively normal. A survey of clinicians and research staff who participated in the Alzheimer's Disease Neuroimaging Initiative (ADNI) found broad support for disclosure of amyloid results to persons with mild cognitive impairment, with 73% supporting disclosure, but more mixed opinions about disclosure to cognitively normal persons, with 58% supporting disclosure (Shulman et al., Reference Shulman, Harkins, Green and Karlawish2013).
The researchers in the ADNI sample are likely more knowledgeable about brain-based biomarker information than the average clinician. Yet even these professionals called for more guidance about how to disclose amyloid results and more research on how disclosure might affect patient well-being (Shulman et al., Reference Shulman, Harkins, Green and Karlawish2013). New prevention trials such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4 study) are appropriately developing standardized processes for disclosing risk information and measuring the impact of disclosure on various psychological and cognitive outcomes (Sperling et al., Reference Sperling2014). This empirical data on the consequences of disclosure is important for ethics questions about the advisability of disclosure.
Challenges about AD risk disclosure have a unique feature. Once, doctors largely controlled a patient's access to risk information. Now, consumers have increased power to conduct risk assessment in the absence of trained physicians and counselors. As of a 2011 review, nine companies provide direct to consumer genetic risk assessments for Alzheimer’s; one company provides direct to consumer testing for vascular dementia (Dvoskin and Kaufman, Reference Dvoskin and Kaufman2011). In addition, some companies with questionable expertise have begun to market neuroimaging directly to healthy consumers for the purposes of “diagnosing” disorders such as autism (Nuffield Council on Bioethics, 2010; O’Connell et al., Reference O’Connell2011), a service that could expand to include Alzheimer's risk. As a result, physicians may increasingly encounter patients who take risk assessments into their own hands and seek physician help with interpreting the results or determining a treatment plan.
Research into dementia: cognitive impairments and the capacity to consent to research
While questions about the ethics of risk center on dementia's consequences for cognitively normal or mildly symptomatic persons, some proportion of these persons will develop dementia that results in considerable cognitive impairment. This impairment raises ethical questions about how to balance the promise of research to improve outcomes for this population with protections due to their vulnerability. From the 1950s to the 1990s, several national and international codes – the Declaration of Helsinki, the Belmont Report, the “Common Rule,” and others – set forth guidelines for the regulation of research, including its independent review, the risk-benefit profile for potential enrollees, fair subject selection so that vulnerable populations are not targeted for risky research, and goals for research's scientific and social value (Emanuel et al., Reference Emanuel, Wendler and Grady2000). Focusing on the Common Rule, the most widely-used guideline for US research practice, the guidelines require that “additional safeguards” be put in place for “vulnerable subjects,” but fails to precisely specify what these safeguards ought to entail (Karlawish, Reference Karlawish2003; Department of Health and Human Services, 2009). In this section, we focus on two questions that can provide greater specificity. First, assuming that respect for persons entails allowing persons to make their own decisions about research participation, how is the capacity and competency to enroll in research defined and assessed for persons with dementia? Second, if a person with dementia is deemed not competent to consent to research participation, who can consent for them and to what type of research? These questions remain important since amidst the prevention efforts discussed in the “Preclinical” dementia section, research continues to enroll persons with symptomatic dementia whose cognitive impairment raises difficult questions about consent.
Capacity to consent to research: the process and challenges of assessment
For an investigator to decide which persons with dementia can consent to research, the investigator should assess the person's decision-making abilities, which are: understanding (the ability to comprehend relevant information), appreciation (the ability to apply that information to one's own situation), reasoning (the ability to compare decision options and infer potential consequences of choosing an option), and expression of choice (the ability to communicate a stable choice) (Applebaum and Roth, Reference Appelbaum and Roth1982). Assessing these four abilities, investigators then make a judgment about whether the person is able to make the decision in question (Karlawish et al., Reference Karlawish, Casarett and James2002).
To inform this judgment, researchers can use the MacArthur Competency Assessment Tool for Clinical Research (MacCAT-CR), a semi-structured interview that assesses a person's performance on each of the four decision-making abilities (Applebaum and Grisso, Reference Appelbaum and Grisso2001; Karlawish et al., 2008a). Studies of AD patients’ capacity to consent show that the likelihood of being judged capable of consent depends on the risks of the research and the overall severity of the patient's cognitive impairment: the riskier the research and the more severe a patient's dementia, the more likely a patient is judged not capable of consent (Kim et al., Reference Kim, Caine, Currier, Leibovici and Ryan2001; Karlawish et al., Reference Karlawish, Casarett and James2002; Kim et al., Reference Kim, Caine, Swan and Appelbaum2006).
Yet, just as research shows that for many neurological and psychiatric diagnoses, the presence of a diagnosis does not automatically render a person incapacitated (Kim, Reference Kim2010), studies suggest that a diagnosis of AD or other dementia should not be taken as determinative of a person's incapacity. Among persons with very mild AD as denoted by a Mini-Mental State Exam (MMSE) above 24, more than half are capable of consent and among those with moderate AD, most are not capable of consent (Karlawish et al., 2008a). Patients between these two groups – those in the mild stage of disease – are variable in their performance (Kim and Caine, Reference Kim and Caine2002). These and other studies demonstrate that a diagnosis of mild to moderate Alzheimer's cannot be used as an automatic judgment of incapacity to consent to research. Instead, the investigator must look at the patient's severity of overall cognitive impairment and assess that patient's decisional capacity.
How to conduct research with decisionally-impaired participants
What should researchers do when they find a patient lacks the capacity to consent to research? This question is deeply contentious. At one extreme is the position that research studies should exclude all persons who lack the capacity to consent, a position that fails on two ethical counts. First, there is some subset of research studies that offer some prospect of benefit to participants; excluding persons who lack the capacity to consent may hinder the legitimate interests of those persons in improved clinical outcomes. Second, one aspect of ethical research is the scientific validity of a study: research must not only protect potential participants from excess risk or from exploitation, research should also have scientific and social value (Emanuel et al., Reference Emanuel, Wendler and Grady2000). If dementia studies only include the subset of patients who retain the competency to consent, the study's sample is likely non-representative of the broader dementia population, a fact that undermines the study's external validity (Kim, Reference Kim2011). Therefore, this extreme position is ethically untenable.
An alternative position recognizes four approaches that can justify enrolling persons who lack the capacity to consent to research: respecting assent/dissent, seeking informed consent from a proxy, following the instructions in a research advance directive, and following Institutional Review Board (IRB) restrictions on the types of studies that can enroll persons incapable of giving consent.
Assent/dissent
The concept of respecting assent or dissent originated in the context of research with children, and researchers have adapted the concepts to dementia research. Researchers who seek to enroll adult participants who lack the capacity to consent can allow those participants the opportunity to assent or dissent. Black proposes definitions of assent/dissent in the context of dementia research that address the particular challenges of dementia patients – for instance, agitation that is associated with dementia and that causes resistance to care (Black et al., Reference Black, Rabins, Sugarman and Karlawish2010). Assent can be defined as an affirmative agreement to participate expressed verbally or a nonverbal indication of willingness to cooperate with the study's procedures both at the time of study initiation and throughout the study's course (Black et al., Reference Black, Rabins, Sugarman and Karlawish2010). Dissent can be defined as a verbal or nonverbal indication of unwillingness to participate in the study's procedures and the person does not need to give a reason for why they are dissenting; in addition, a person can assent to some particular procedures and dissent to others (Black et al., Reference Black, Rabins, Sugarman and Karlawish2010). However, respecting assent/dissent alone is viewed as a thin protection for a person who lacks the capacity to consent. Typically, it is paired with seeking informed consent from a proxy.
Proxy decision-making
The US Common Rule for the protection of human research subjects allows for proxy consent, granting a “legally authorized representative” the power to offer research consent for a person with cognitive impairments or other vulnerabilities (Karlawish, Reference Karlawish2003; Department of Health and Human Services, 2009). Although the law typically offers little explicit guidance on who can serve as the representative or the conditions that allow a proxy (Appelbaum, Reference Appelbaum2002; Saks et al., Reference Saks, Litt, Dunn and Wimer2008), the argument that under certain circumstances a person may decide that another person can be in research has substantial ethical warrant. The ethical argument for allowing proxy decision-making relies on analogy and empirical data. Analogically, we allow families to make many clinical decisions on behalf of non-competent patients, even clinical decisions that engage substantial risks. Empirically, most people facing decisional impairments trust persons close to them to make good research-related decisions (Wendler et al., Reference Wendler, Martinez, Fairclough, Sunderland and Emanuel2002; Karlawish et al., Reference Karlawish, Rubright, Casarett, Cary, Ten Have and Sankar2009; Kim et al., Reference Kim, Kim, Langa, Karlawish, Knopman and Appelbaum2009) and persons with dementia may retain the capacity to appoint a proxy even if they have lost the capacity to make research decisions (Kim et al., Reference Kim, Karlawish, Kim, Wall, Bozoki and Appelbaum2011).
One of the more contentious issues in proxy consent is what evidence should guide the standard that a proxy follows when deciding whether to enroll the person in their care? One guideline – the substituted judgment standard – asserts that proxies should make the decision the patient would have made if he or she was capable of making a decision (Karlawish, Reference Karlawish2003). Yet in real-life cases, research proxies often use a “best interest” standard, framing their decisions in terms of what they think is best for the patient rather than what the patient would have necessarily consented to him or herself (Sugarman et al., Reference Sugarman, Cain, Wallace and Welsh-Bohmer2001). In addition, older adults generally support that their proxy can exercise leeway over the older adult's research advance directive (Karlawish et al., Reference Karlawish, Rubright, Casarett, Cary, Ten Have and Sankar2009). This concept of leeway refers to allowing a proxy the freedom to choose what he or she thinks is best rather than follow the instructions in a research advance directive.
Restrictions on the type of research
Even if most persons are willing to grant proxies the leeway to consent to research that poses greater-than-minimal risk and that offers no prospect of direct benefit, safeguards should be put in place to circumscribe the types of studies to which dementia patients can consent.
One way to create a narrower class of studies is on the basis of risk. Karlawish (Reference Karlawish2003), building on recommendations from the National Bioethics Advisory Commission, proposes a two-step model of risk assessment that IRBs could undertake for studies involving cognitively impaired adults: first, assess the risks of each study component relative to the potential benefit of that component. Second, for components that offer no benefit, assure that the risks of that component are no more than minimal and that these risks are balanced by important knowledge to be gained.
Other approaches to narrowing the types of research include a “necessity” requirement – only enroll persons who lack the capacity to consent if such populations are necessary for the research – and a “subject's condition” requirement – only enroll cognitively impaired persons in research that matches the cause of their cognitive impairment (see Wendler and Prasad, Reference Wendler and Prasad2001 for a review of how national/institutional guidelines incorporate these requirements). Yet “necessity” and “subject's condition” requirements can have counterintuitive consequences – for example, they can prevent dementia patients with a co-morbidity like cancer from enrolling in research that offers benefits for their co-morbidity but no benefits for their dementia. This suggests that risk/benefit thresholds may be more promising safeguards for research with persons with dementia.
Research advance directives or a patient preference predictor
Even if one restricts the types of studies permitted to enroll persons with dementia, there will still be a range of studies where persons with dementia are eligible to enroll but there are questions about whether enrollment is a good decision for that patient. When proxies confront these decisions, research advance directives can assist their decision. A patient, prior to cognitive impairment, specifies categories of research he would agree or object to, the balance of benefits and risks he would tolerate, and what researchers should do if the person exhibits distress or dissent (Wendler et al., Reference Wendler, Martinez, Fairclough, Sunderland and Emanuel2002). Yet as with advanced directives for medical treatment, the gap between theoretical support for the documents – 89% of participants in one study expressed support for research advance directives – and practically filling one out – only 16% of the participants had filled out a research advance directive a year later – remains large (Wendler et al., Reference Wendler, Martinez, Fairclough, Sunderland and Emanuel2002). While some have hypothesized that clinical developments in dementia – for instance, its rising prevalence and the ability to detect risk earlier based on genetic and biomarker data – may facilitate the uptake of research advance directives (Pierce, Reference Pierce2010), investigators who conduct dementia research themselves reiterate the value of gaining a proxy decision-maker's input on research projects (Jongsma and Vathorst, Reference Jongsma and Vathorst2015). Their rationale is that it is often difficult to anticipate the range of research options a patient with dementia will have, and that even when a patient has a research advance directive, investigators still feel more comfortable having a proxy decision-maker's input on enrollment (Jongsma and Vathorst, Reference Jongsma and Vathorst2015).
Surveying this low rate of advance directive uptake, and also noting that proxies report difficulty and distress in making decisions for incapacitated patients, some have proposed a “patient preference predictor” tool for patients who lack capacity (Rid and Wendler, Reference Rid and Wendler2014). This tool would take characteristics of a patient (e.g. gender; religiosity) and create estimates about which course of action regarding two sets of decisions – treatment and research – the incapacitated patient is likely to endorse. Proxies and clinicians could use these estimates as strong guidance when making decisions for the incapacitated patient.
Responding to this proposed tool, some have argued for the continued relevance of proxy decision-makers. These commentators claim that persons grant their proxies significant considerable leeway in making decisions not because they think these proxies will predict what they would have chosen with a high degree of accuracy. Instead, it is because the patient trusts his proxy to discern what is good for the patient in a situation that is difficult for the patient himself to ever anticipate and about which he may not have stable, well-formed preferences (John, Reference John2014; Kim, Reference Kim2014). If we take the trust persons place in proxies seriously, and if IRBs limit the risk of research procedures performed on incapacitated patients, the rarity of research advance directives and difficulty predicting a person's precise wishes for when they lack capacity should not necessarily be considered large ethical problems.
Many of these approaches are complementary – for example, IRBs can regulate the risk of any research involving persons with dementia and persons facing dementia can appoint trusted proxy decision-makers. A combination of ethical safeguards can help strike the appropriate balance between beneficently allowing valuable research on dementia to go forward and respecting the autonomy of persons with dementia.
Living with dementia: clinical treatment, care support, and civic rights and privileges
Despite efforts to prevent dementia and to conduct research that alleviates its impairments, short of a cure for AD and other dementias, we will have to learn to live with the many ethical issues that clinicians, patients and families face as a result of disabling cognitive impairments. In this section, we discuss three common ethical challenges presented by dementia, and its associated cognitive and behavioral impairments: treatment decisions, caregiving, and decisions about whether to exercise various civic privileges such as driving and rights such as voting. While we initially focus on ethical issues related to medical care for dementia, the latter two parts show that dementia raises important questions extending beyond the medical realm that touch on how dementia affects relationships, employment, and civic rights and privileges.
Clinical treatment
Empirical studies into persons with dementia's capacity to make treatment decisions have three key findings with corresponding ethical implications. First, patients with mild to early moderate stage AD should not be presumed incompetent to make decisions about clinical treatment; some proportion of patients, in particular those with a higher degree of insight into their condition and mild stage dementia, are competent to make treatment decisions (Karlawish et al., Reference Karlawish, Casarett, James, Xie and Kim2005). Second, at some point decision-making competence is clearly lost, pointing to the importance of early diagnosis and diagnostic disclosure so patients can communicate their treatment preferences in advance (Karlawish et al., Reference Karlawish, Casarett, James, Xie and Kim2005). Third, patients want to be involved with treatment decision-making to the extent that their abilities allow, pointing to the importance of involving these patients even if one does not allow them to make the final treatment decision (Hirschman et al., Reference Hirschman, Joyce, James, Xie and Karlawish2005).
Once patients lose the ability to make decisions for themselves about treatment, other ethical dilemmas emerge. Three particular forms of treatment have prompted scrutiny. First are the use of antipsychotics to alleviate the behavioral and psychological symptoms (e.g. aggression, delusions, agitation) sometimes associated with Alzheimer's and other dementias. In 2005, the FDA issued a black box warning for atypical antipsychotics about the drugs’ mortality risks for elderly persons with dementia, but the medications continue to be widely prescribed, largely due to the absence of alternatives (Crystal et al., Reference Crystal, Olfson, Huang, Pincus and Gerhard2009). Some commentators argue that antipsychotics are ethically appropriate when a dementia patient suffers from distress with no treatable physical or environmental cause (Treloar, Reference Treloar2010), but that antipsychotics should not be a routine first treatment for disruptive but not distressed patients.
The second treatment-related ethical dilemma is the appropriate way to feed patients whose dementia has progressed to a point where severe difficulties with chewing and swallowing arise. As Volicer and Simard (Reference Volicer and Simard2015) discuss in the present issue, tube feeding can fail to help a patient's survival, is uncomfortable, and can deprive patients of positive contact with caregivers that occurs during the hand feeding process. In addition, one survey of older adults’ attitudes towards dementia-related treatments found that 49% indicated that they did not want parenteral/enteral tube feedings under any circumstances, and 45% only wanted the tube feedings if it was a temporary measure (Gjerdingen et al., Reference Gjerdingen1999). As a result, both ethical analysis and empirical evidence of patient attitudes point towards hand feeding over tube feeding when possible.
Finally, in addition to ethical debates about specific life-sustaining interventions such as tube feeding, there are important general debates about how to respect the autonomy of persons with dementia to choose treatments in line with their preferences and values. Should we give weight to the preferences and values that a person with dementia expresses in his or her impaired state or should we give weight to the preferences and values a person with dementia expressed before the onset of her illness (Jaworska, Reference Jaworska1999)? These questions become particularly important when a person experiences a shift in preferences regarding life-sustaining interventions. For example, a person who was deeply religious before the onset of dementia may have expressed that withholding aggressive, life-saving treatment would be unacceptable and discordant with his religious beliefs. After developing a certain severity of dementia, the person may lose his religious values and repeatedly ask for life-saving measures to be withheld because aggressive treatment causes him pain (Jaworska, Reference Jaworska1999). Conversely, in a case Menzel and Chandler-Cramer (2014) pose, a person may create an advance directive stating that he or she wants food and water withheld at a certain point in his disease progression; yet when his disease reaches that stage, he may seem to truly value continued survival and caregivers may be distressed by the prospect of following his earlier stated wishes to withhold food and water. Which “self” and which set of preferences ought to be honored: the “then”-self or the “now”-self?
Some argue that respecting a person with dementia means respecting the values they expressed before the onset of the illness and its capacity-damaging impact (Dworkin, Reference Dworkin1993). So for first case above, we should continue to provide aggressive treatment because doing so is in line with the set of values the person expressed when he still retained a clear sense of his values, goals, and interests. For the second case above, since the person autonomously expressed an interest in discontinuation of treatment at a certain disease stage, those wishes should be followed.
Others argue for the opposite position: heeding past values that the person with dementia no longer endorses does not do the person good. Therefore, you should heed the person with dementia's present values (Dresser, Reference Dresser1986). Ultimately, a middle-ground position that recognizes how the person with dementia blends their then-self and now-self may be preferable: caregivers and clinicians should acknowledge that persons with dementia may have new values that are worthy of respect; and when these new values come into conflict with values the person once held, perhaps the person's comfort and well-being should be prioritized. Likewise, for decisions about then-self versus now-self preferences regarding life-sustaining treatment, a balance can be struck between recognizing the person's clearly held wishes regarding the aggressiveness of end-of-life care while also recognizing that one should not prematurely end of the life of a person with dementia who continues to find great enjoyment in his or her daily experiences (Menzel and Chandler-Cramer, 2014).
Non-clinical care and assistance
While medical care is one aspect of living with dementia, the disease's impairments create substantial difficulties with the activities of daily living, ranging from getting out of bed to grocery shopping to feeding (Ory, Reference Ory, Hoffman, Yee, Tennstedt and Schulz1999). The ethics of caregiving for persons with dementia are framed differently depending on one's disciplinary vantage point. Economists applaud the cost-savings of persons cared for by family members in the home rather than in institutional settings: one estimate finds savings of $30,000 per year per dementia patient to the US healthcare system for every patient cared for in the home and another estimates that a one-month delay in nursing home entrance saves the US healthcare system over $1 billion annually (Rice et al., Reference Rice1993; Leon et al., 1998). Meanwhile, psychologists document the clinical depression and anxiety that can stem from the burdens of caregiving (Schulz et al., Reference Schulz, O’Brien, Bookwala and Fleissner1995). Sociologists wonder if family caregiving is a form of “work” that ought to be financially compensated or subsidized (Zelizer, Reference Zelizer2010). Ethicists point to questions of global justice raised by the mass migration of paid care workers from less affluent countries to more affluent countries (Eckenwiler, Reference Eckenwiler2009). What is clear from these diverse stances is that caregiving for a person with dementia is not simply a private matter. Instead, while it begins with the obligations (if any) that children and spouses have for caring for persons with dementia, it engages the obligations (if any) that governments have for subsidizing home-based care for citizens with dementia. Guidance for operationalizing this obligation begins with an essential moral position: the experience of being a caregiver creates a role akin to that of a patient because the caregiver effectively takes on the patient's illness experience together with decision-making and providing care (Karlawish, Reference Karlawish2014). Just as the patient's sick role creates obligations for care, it follows that the healthcare system must provide educational, psychological and social support to caregivers.
While these debates discuss ways to support caregivers, other discussions falling under the heading of person-centered care discuss the proper ways that caregivers ranging from family members to paid nursing home staff can respect the unique personhood of each individual with dementia (Brooker, Reference Brooker2003). An important element of person-centered care is not only acknowledging the person with dementia's physical needs – such as nutrition and toileting – but also acknowledging the person with dementia's psychosocial needs to feel a sense of belonging within a supportive community and to feel respect in their interactions with others (Kitwood, Reference Kitwood1997; Edvardsson et al., Reference Edvardsson, Winblad and Sandman2008). Specific caregiving approaches that adopt a person-centered care philosophy include incorporating biographical knowledge of the person with dementia into interactions with them – for instance, sharing photographs and music that help affirm the experiences the person with dementia has had (Kontos, Reference Kontos2005) and enabling people to live in surroundings that are as homelike as possible with photographs and pleasant auditory stimuli (Cohen-Mansfield and Werner, Reference Cohen-Mansfield and Werner1998). These changes can be adopted in both informal family settings and more formal institutional settings.
Civic privileges and rights: driving and voting
Person-centered dementia care focuses on viewing the individual with dementia as more than just a clinical patient; it emphasizes viewing the person with dementia in the context of roles they have taken on within their community and their day-to-day interactions with others. In this section, we discuss dementia's effect on two important rights and privileges that enable people to maintain these community roles and interactions: driving and voting.
Driving
Driving is one aspect of a person with dementia's non-clinical life, and for many persons, is synonymous with mobility and independence. Losing one's driving privileges is perceived to place a large burden on one's caregivers and can lead to social isolation and clinical depression (Ragland et al., Reference Ragland, Satariano and MacLeod2005). Yet driving is a state-granted privilege that one must lose access to if one poses sufficient risks, raising questions of how physicians and caregivers for persons with dementia should prevent the risks posed by incompetent drivers while protecting the interests of dementia patients who retain the competency to drive.
Persons in the moderate to severe stages of dementia present documented safety problems if allowed to drive (Lucas-Blaustein et al., Reference Lucas-Blaustein, Filipp, Dungan and Tune1988). However, for those in dementia's very mild to mild stages, driving ability is variable and should be assessed on a case-by-case basis (Drachman and Swearer, Reference Drachman and Swearer1993; Dubinsky et al., Reference Dubinsky, Stein and Lyons2000). Unfortunately, physicians who treat persons with dementia lack a clinical measure that can assess whether a patient is capable of driving with the same precision as an on the road driver's assessment: scores on the MMSE are not generally a good predictor of which persons with mild dementia retain the capacity to drive; neuropsychological tests assessing visuospatial skills and executive functioning, and especially road and simulation-driving tests, are better measures (Brown and Ott, Reference Brown and Ott2004). For patients and families hesitant to spend time and money on a driving evaluation, clinicians can emphasize that just as periodic assessments of a car's mechanical safety are important – and in fact many governments mandate periodic automobile inspections – periodic assessments of a driver's competency should also play an important role.
Even if a physician is able to determine that a persons with dementia may pose a driving risk, physicians face a patchwork of often-confusing state laws on whether they should report the patient's condition to a Department of Motor Vehicles: some laws obligate physicians to report impaired driving, while others make this reporting optional; some laws shield physicians from legal liability for breaking confidentiality if they report a patient, while other laws offer no such protection and others can hold physicians who don't report potentially risky drivers liable for accidents (Bacon et al., Reference Bacon, Fisher, Morris, Rizzo and Spanaki2007). As the label of AD moves to milder and even pre-clinical stages, mandatory reporting laws will need to be revisited to address whether they are overly restrictive.
Voting
While the dementia literature has paid a large amount of attention to the civic privilege of driving, the relationship between dementia and the civil right of voting has only recently received critical scrutiny (Karlawish et al., Reference Karlawish2004). While driving is a privilege, and states can err on the side of revoking this privilege when safety is potentially threatened, voting is a right and states should err on the side of protecting this right. Advances are needed to ensure the preservation of this right for persons with dementia while ensuring the voting system's integrity: the courts need standardized, voting-specific assessments of capacity and clear legislative guidance on how these assessments should be implemented (Karlawish et al., Reference Karlawish2004), and the practice of mobile polling should be more widely adopted.
Recently, researchers have tackled the issue of how to assess the capacity to vote, building on a 2001 federal district court decision – Doe v. Rowe – that specifies that a person is considered incompetent to vote only if they “lack the capacity to understand the nature and effect of voting such that they cannot make an individual choice” (Doe, Reference Doe2001). The researchers created a 3–4 minute questionnaire – the Competence Assessment Tool for Voting (CAT-V) – that operationalizes these criteria, testing a person's understanding of the nature of voting and their ability to choose a candidate (Applebaum et al., Reference Appelbaum, Bonnie and Karlawish2005). To be implemented ethically, this form of voting-specific capacity assessment needs to be supplemented by several developments: state laws consistent with the Doe criteria, fair procedures that specify who can conduct these assessments (e.g. judges in states that have laws that remove the right to vote from persons who lack the capacity to vote), and public education about the dangers of blanket, diagnosis-based exclusions on the right to vote (Karlawish et al., Reference Karlawish2004).
The capacity to vote is not essential to preserving a credible voting system. Some countries and states in the US, such as Canada and Vermont, have no criteria that a person be competent to vote. Instead, they focus on providing disabled voters access to the polls and appropriate assistance to complete a ballot. In long term care settings, the majority of voters use so-called “absentee ballots” instead of going to a polling station and most need assistance to complete their ballot (Karlawish et al., 2008b). Voting systems that bring election officials to long term care facilities, a practice known as mobile polling, assure that voters receive assistance that minimizes fraud and undue influence (Bovbjerg and Jenkins, Reference Bovbjerg and Jenkins2009). Compared to voting assistance provided by long term care staff, such as the activities director, mobile polling has been shown to increase patient dignity, reduce staff anxiety and minimize concerns about voter fraud (Karlawish et al., Reference Karlawish, Sabatino, Markowitz, Rubright, Klem and Boruch2011).
Conclusion
The same cognitive impairments that make dementia clinically troubling lead to difficult ethical issues as diverse as how persons at risk for dementia should be protected from insurance discrimination to which types of research enrolling persons with dementia are ethically acceptable (Strech et al., Reference Strech, Mertz, Knüppel, Neitzke and Schmidhuber2013). The present review focused on two themes among these diverse areas.
First, expanding the boundaries of dementias such as Alzheimer's to include asymptomatic but at-risk persons generates new ethical questions. For instance, what should persons be told about their risk? How can research in this population balance potential benefits of early intervention with potential harms of stigma and discrimination? Answering these questions requires empirical data on topics such as the effect of risk information disclosure on psychological well-being or how anti-discrimination law applies to persons with abnormal biomarkers but normal daily functioning. One promising direction for addressing these questions is to take an integrative approach to analyze the ethical, legal, and social implications of dementia research advances (Presidential Commission for the Study of Bioethical Issues, 2014), which can include incorporating ethics-related data collection into the design of a dementia research study itself. For example, one clinical trial in cognitively normal older adults will examine the psychological and cognitive impact of informing participants of their amyloid PET results, in addition to its primary goals of testing the effects of an investigational therapy on memory loss progression (Sperling et al., Reference Sperling2014). This kind of integration can help ethical analysis keep pace with research advances.
Second, we emphasized how dementia raises a set of ethical questions broader than decisions about medical research and medical care. There are a range of issues that impact persons with dementia and that clinicians, bioethicists, and researchers in allied fields should discuss: health policy questions about insurance coverage for long-term care (Levitsky, Reference Levitsky and Hudson2010); political questions about voting, driving, and other civic rights and privileges; economic questions about balancing an employer's right to a safe and productive workforce with an employee's rights to avoid discrimination on the basis of their dementia risk. These questions require the expertise of a range of non-medical disciplines, from law to economics to health services research to political theory.
Conflicts of interest
None.
Description of author's roles
R. Johnson and J. Karlawish designed the review and wrote the paper.
Acknowledgments
Jason Karlawish is supported by NIA AG01024, CDC Healthy Brain Research Network [U48-DP-00553-01S3] and the Marian S. Ware Alzheimer Program.
