Handbook of Clinical Neurology, Vol. 118 (3rd series) Ethical and Legal Issues in Neurology J.L. Bernat and R. Beresford, Editors © 2013 Elsevier B.V. All rights reserved

Chapter 20

Ethical issues in the neurology of aging and cognitive decline ERAN KLEIN1* AND JASON KARLAWISH2 Department of Neurology, Oregon Health and Sciences University and Neurology Service, Portland Veterans Administration Medical Center, Portland, OR, USA

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Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

THE ETHICAL CHALLENGES OF PRECLINICAL ALZHEIMER’S DISEASE Neurology is undergoing a revolution whose genesis is a changing approach to defining what is a disease and so, in turn, how a neurologist diagnoses a patient. Increasingly, disease is grounded in measures that foretell future functional decline. Common terms to describe these measures are “biomarkers” and “risk factors.” The former describes measures of pathophysiology and the latter describes measures that predict the probability of a future undesired event, such as functional loss. Alzheimer’s disease is experiencing this revolution. Its definition is expanding from a disease described by a pattern of cognitive deficits that causes progressive functional losses, that is, the dementia syndrome, to include as well “prodromal” and “preclinical” stages defined by biomarkers of the pathology that leads to cognitive and functional losses. Similar changes are occurring with diseases such as Parkinson’s disease and neuromuscular disorders, such as Pompe disease (Ponsen et al., 2010; Laloui et al., 2011; Sperling et al., 2011). This revolution in how neurologists diagnose Alzheimer’s disease will substantially alter the doctor–patient relationship. Once, a neurologist’s relationship with patients was firmly grounded in the practice of “bedside medicine.” This term describes how a clinical encounter begins when the clinician elicits the patient’s chief complaint which, in turn, prompts the clinician to obtain a history of this complaint – a history whose results guide a detailed neurologic exam, and potentially as well, testing such as imaging. The neurologist’s goal was to transform a patient’s story of symptoms, such as forgetfulness, into physical signs that explain the loss of function, and then

to identify the neuroanatomic lesion that explained the patient’s symptoms and physical signs. This practice of bedside medicine progresses from a “history of present illness” to a differential diagnosis, and then to a clinical-pathologic correlation. The neurologist’s capacity to lay bare the final results of this bedside process, “the diagnosis,” in ways that call upon clinically honed skills of narrative and empathy, helps the patient make sense of her illness and, ideally, initiate treatments that relieve her suffering. Increasingly, neurologists are employing a different concept of disease which, in turn, is changing how they approach diagnosis and the ways in which they interact with their patients. The privileged position of the chief complaint as a first step to clinical-pathologic correlation is now being challenged by a medicine oriented to the “preclinical stage.” Instead of identifying for a patient the disease that explains her lived history of suffering, a neurologist takes on an additional or sometimes alternative role in identifying possible future suffering she may face. The emerging concept of “preclinical Alzheimer’s disease” is described by the presence of biomarkers that signify clinically silent neurodegeneration and the future likelihood of cognitive and functional losses. This new model of medicine is called desktop medicine, a term that describes how the medical encounter has moved from the clinician at the bedside of the sick patient to the clinician and patient meeting at a desktop with a networked computer (Karlawish, 2010). Instead of engaging in clinical-pathologic correlation to explain a patient’s chief complaint, the clinician elicits a patient’s risk factors and engages in clinical-actuarial correlation,

*Correspondence to: Eran Klein, M.D., Ph.D., Neurology Service, Portland Veterans Administration Medical Center, 3710 SW US Veterans Hospital Road, PO Box 1034, P3 Neuro Portland, OR 97207, USA. Tel: þ1-503-220-8262 x 53070, E-mail: [email protected]

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a term that describes how a physician assesses how well a patient’s risk factors predict health outcomes and the benefits of reducing those risk factors. Desktop medicine radically restructures the clinician– patient relationship. It reverses the order of the clinical encounter so that it no longer begins with the patient’s complaint, but instead, the clinician’s inquiry into risk factors. It no longer ends with pinpointing a structural lesion that explains a functional problem, but instead, a discussion of risk factors, potential modifiers, and likelihoods of future functional outcomes. The origins of this transformation reflect a general revolution in medicine. Diseases with preclinical stages, such as cardiovascular disease and osteoporosis, are well integrated into the practice of internal medicine and are cited as models by the authors of the preclinical Alzheimer’s disease criteria. These diseases are sufficiently prevalent and their diagnosis, monitoring, and treatment time-consuming that experts in desktop medicine have called for a new approach to the clinical encounter, called “running the numbers first,” a term that describes reviewing relevant measures of desktop diseases prior to eliciting the patient’s chief complaint (Phillips and Twombly, 2008a, b). The transformation has practical value. Diagnosis prior to disability allows neurologists arguably to fulfill a valuable goal of medicine. They can help patients plan their future and offer treatment that delays either the onset of disability or its progression. They can reduce future suffering. And yet, as appealing as this goal is, the practice of desktop medicine presents neurologists with ethical challenges (Karlawish, 2011). What drives a clinical encounter is shifting from the patient’s agenda, inaugurated in the chief complaint, to the clinician’s agenda, inaugurated by the decision to order tests that assess whether a patient is in a “preclinical” state of disease. How should clinicians talk to patients and their families about “preclinical Alzheimer’s disease” and, more generally, about the spectrum of risk of progression from normal cognition to late-stage dementia? Clinicians who pursue desktop approaches to diagnosing Alzheimer’s disease will need to become skilled at engaging in risk-based discussions with patients, a skill that requires balancing ethical principles of respect for autonomy and beneficence. Two approaches can guide this practice. First, in the more mildly symptomatic or seemingly healthy patient the clinician needs to assure that prior to running the numbers and engaging in clinicalactuarial correlation, the patient wants the result and also is prepared to receive it. To make a choice to receive biomarker results, the patient should, following adequate disclosure by the clinician, have the capacity to understand the risks and benefits of Alzheimer’s biomarker testing. These facts will of course vary depending on the person

and the test, but general issues to consider include the potential impact of the test result on the person’s mood, ability to work and obtain insurance, and the impact of the result on family. The second approach is that the more the risk in question is both undesirable and irremediable by available therapies – as is the case with preclinical Alzheimer’s disease and the prodromal stage of mild cognitive impairment, neither of which, at present, has treatment to reduce the likelihood of developing Alzheimer’s disease dementia – the more the clinician has an obligation to engage in pre- and posttest counseling. As part of this counseling, the clinician arguably has a responsibility to assess the patient’s mood. Evidence supports that this approach works. After first-degree relatives of persons with Alzheimer’s disease receive pre-APOE gene test screening for depression and anxiety and those with clinically significant symptoms are excluded from receiving this genetic risk factor assessment, those who receive the results show no clinically significant incidence of anxiety and related neuropsychiatric symptoms (Green et al., 2009). Identifying when and what kind of counseling is needed in predictive testing is a critical challenge for neurologists going forward. Analogous work in other areas of medicine and neurology, such as in genetic testing for Huntington disease, provide a useful model (Hawkins et al., 2011). In addition to assessing how well a patient understands the facts related to a preclinical diagnosis and assuring that the patient is prepared to receive the results, a neurologist needs to assess the patient’s appreciation of these facts. The concept of appreciation refers to applying facts to oneself (Grisso and Appelbaum, 1998a). In pathologic states, such as schizophrenia, appreciation can be impaired when, for example, a person insists on the veracity of false beliefs. But in the case of discussing risk among patients who have an adequate understanding of the facts, are psychologically healthy, and are prepared to receive them, clinicians need to recognize that people can have a very different appreciation of what they think is their actual risk, a difference that cannot simply be explained by a diseased mind or lack of numeracy. The practical manifestation of this is persons who, after learning their risk of developing Alzheimer’s disease dementia (“You said I have a 30% chance over 5 years of developing cognitive problems”), believe they have a different risk (“I think my chance is about half that – more like 15%, no more”) (Linnenbringer et al., 2010). The failure to recognize that a difference may exist between what a patient is told and what the patient thinks is true can lead to problems with patient care such as a lack of adherence or follow-up. To address it, clinicians need to be comfortable with talking about patient values and beliefs.

ETHICAL ISSUES IN THE NEUROLOGY OF AGING AND COGNITIVE DECLINE Preclinical Alzheimer’s disease also presents neurologists with professional challenges. As the locus of control for defining disease moves from the diagnosis made by an expert clinician to biomarker cut-offs that define who is “biomarker-positive,” neurologists’ authority in shaping the prevalence of disease will diminish. Instead, that authority will shift to the researchers who establish biomarker cut-offs. These researchers not only have scientific but also a personal stake in setting these cut-offs, stakes that include their belief in the value of their biomarker and even ownership of the biomarker under the protection of a patent. Small changes in a biomarker cut-off can have a substantial impact on increasing the estimated prevalence of the disease, which, in turn, can increase the perceived urgency of the problem that neurologists will be asked to address in their clinical practice.

SYMPTOMATIC DISEASE AND THE ETHICS OF IMPAIRED DECISION-MAKING Patient autonomy is a fundamental principle of modern medical ethics. Individuals are morally entitled to a say in healthcare and health-related decisions that affect their lives. Decisions about treatment, for instance, are critical moments. Choose quality of life or quantity of time left? Aggressive treatment or conservative wait and see? Participation in clinical research or treatment with standard-of-care therapy? The principle of respect for autonomy recognizes that people differ in what they want out of healthcare and therefore how they would answer these questions. Goals, values, hopes, preferences, dreams, and personalities vary, but all patients are owed the opportunity to make autonomous decisions. But when decision-making autonomy is impaired, or absent, or – as is often the case in neurodegenerative disease – progressively diminishing, how should clinicians approach decisions about health and healthcare? A core skill is assessing decision-making capacity. Decision-making capacity describes the abilities needed to make a choice. Patients with early dementia may have impairments across a range of tasks (or activities) requiring decisions. In the paradigmatic neurodegenerative disease, Alzheimer’s disease, deficits in multiple cognitive domains (e.g., memory, executive function, visuospatial skills) lead to impaired decisionmaking capacity, and typical early difficulties are in driving, managing money and paying bills, and taking medication. Early difficulties can be subtle and intermittent, initially escaping notice. Over time, the difficulties compound; it becomes clear to others, and where insight is preserved, to patients themselves, that something

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more than an oversight or distraction is to blame. Early in dementia the appropriate question is “Does this patient have the capacity to make decision x?” However, ultimately, as dementia progresses to moderate to severe stages, capacity assessments become more global, across a broad range of tasks (e.g., medication management, financial affairs, cooking). “Capacity” and “competence” are used often as interchangeable terms, but they differ in an important respect: competence is a legal term, while capacity is a clinical term. Courts determine competency, either in specific domains (e.g., independent living, finances, or voting) or globally. Capacity, on the other hand, is a clinical determination (American Psychiatric Association, 1998). A capacity assessment does not have the force of law behind it (as a competency determination does), but it should inform legal judgments about competency. Someone with intact decision-making capacity, for instance, with respect to money management, should be left free of family or state oversight. On the other hand, when decision-making capacity is impaired, oversight is warranted. The value of quantifying “decision-making capacity” has obvious appeal. Assessments of overall cognition can be a useful signal of the likelihood that a patient has impaired capacity. For example, the Mini Mental State Exam (MMSE), one of the most common tools that clinicians use to stage dementia, can provide a rough estimate of the likelihood of decisional impairment (Folstein et al., 1975). In patients with Alzheimer’s disease, for instance, lower MMSE scores tend to correlate with judgments of incapacity (Diamond et al., 1989), but acceptable sensitivity and specificity are reached only at the extremes (below 16–18 for incapacity and above 23–24 for capacity) (Etchells et al., 1999). Even better than measures of overall cognition are instruments that specifically operationalize “decision-making capacity,” such as the Capacity to Consent to Treatment Interview (CCTI)) (Marson et al., 1995), the Hopemont Capacity Assessment Interview (HCAI) (Edelstein, 1999), and the MacCarthur Competence Assessment Tool for treatment (MacCAT) and research (Grisso and Appelbaum, 1998b). These instruments assess the capacity of individuals to make particular decisions (Grisso and Appelbaum, 1998a). As an example, the MacCAT measures the four decisional abilities: understanding, appreciation, reasoning, and expression of choice (Appelbaum, 2007). Understanding describes the ability to encode and comprehend relevant information. For example, this might involve demonstrating (in nonidentical words) that one has learned the basic elements of a medical condition (e.g., what Alzheimer’s disease is). Appreciation is the ability to apply general information to oneself in a coherent and meaningful way. This involves not just understanding general information about the disease (e.g., Alzheimer’s

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disease can affect judgment), but grasping the relevance of general information to one’s own particular activities (e.g., “Alzheimer’s disease can affect my personal judgment”). Reasoning is the ability to use information in a comparative manner. This involves weighing consequences, trading off values, and envisioning future possibilities; it involves being able to explain a preference for one choice over another. Expressing a choice is the ability to make one’s choice known so that it can be acted upon. Formal assessment tools permit a neurologist to quantify decision-making capacity. While these tools add methodologic rigor to an assessment that otherwise can be idiosyncratic, different tools that purport to measure the same capacity do not consistently show convergent validity (Moye et al., 2004). In addition, tools are limited in assessing only one slice in time and outside an individual’s usual environment. With these limitations noted, capacity instruments still have value. They provide structure to a clinical interview and documented evidence of impaired decision-making capacity. This evidence is useful not just for clinicians and researchers, but for families struggling to make sense of an individual’s diminishing cognitive abilities. Results help inform family members of areas of cognitive strength and weakness and provide justification when needed for overriding certain patient decisions or abiding by others. For example, an assessment that uncovers that a patient does not appreciate his problems with balancing a cheque book can aid family members as they try to decide whether to respect the patient’s preference to manage her money. In addition, formal capacity assessment tools can be used as a reference point from which to explore other important factors in decision-making, such as the role values play in decision-making of those with dementia (Karel et al., 2010). Assessment of decision-making capacity is important to a number of ethical issues that arise during the symptomatic stage of Alzheimer’s disease; these include disclosure of an Alzheimer’s diagnosis, driving, treatment decision-making, and research participation. Truth-telling is an area of general concern in dementia (Schermer, 2007). The initial disclosure of a diagnosis of dementia can challenge notions of honest patient–clinician communication (Bamford et al., 2004). Patients are morally and legally entitled to know their diagnoses. This has been widely endorsed by the Alzheimer’s Association (2009), the American Medical Association (Guttman and Seleski, 1999), and a consensus statement (Post and Whitehouse, 1995). Though surveys suggest that people want to know about a diagnosis of Alzheimer’s disease (Day et al., 2011), clinicians struggle with when and how, and sometimes if, to disclose a diagnosis directly to patients. Surveys of caregivers suggest that some

physicians do not disclose the diagnosis to the patient (Brodaty et al., 1990), choosing instead to disclose the diagnosis to the family (Holroyd et al., 2002). This is found among generalists (Vassilas and Donaldson, 1998), as well as dementia specialists (Rice and Warner, 1994; Rice et al., 1997; Clafferty et al., 1998), particularly at more advanced stages of disease when comprehension is seriously compromised. The practice of withholding a patient’s diagnosis persists, despite evidence suggesting that most people would want to know about a diagnosis of dementia, at least if asked prospectively (Holroyd et al., 1996). In early dementia, the rationale to inform about a diagnosis derives from the need that patients have to full information in order to make good medical decisions. In later-stage dementia, when independent decision-making is no longer a concern, the need to inform patients of their diagnoses derives from different reasons. Patients are owed respect as persons, and as such the opportunity to understand what is happening to them. While the motivation to protect patients from knowing their diagnosis (and whatever temporary emotional sequelae it may usher in) is understandable, it can be too readily invoked. Sometimes people just want to know why the things that are happening to them are happening and what this portends for the future, even if a partial understanding or a fleeting glimpse of the future is all that is possible. Sometimes respect for personhood requires this. Driving an automobile is an everyday skill but one that relies on proper functioning of a complex range of cognitive abilities (Drazkowski and Sirven, 2011). Accidents, “close calls,” and episodes of getting lost along familiar routes are often early signs of this complex skill breaking down. For many patients and clinicians, the decision to restrict driving can be difficult and contentious. For many, driving is instrumental to health and wellbeing. It provides freedom, independence, and a sense of self, but also access to daily amenities (e.g., groceries), social and public services (e.g., post offices), healthcare (e.g., medical appointments), wellness activities (e.g., gym), and social support (e.g., family). Patients may be reluctant to give up driving voluntarily even when confronted with others’ concerns, typically those of family, about unsafe driving. Not uncommonly, patients lack insight into their disease or how their disease affects driving. Asking patients how they would approach advising a friend about problematic driving or asking patients to imagine how they would “live with” inadvertently injuring a stranger (e.g., a neighbor child) or loved one can be useful exercises for getting patients to reconsider resistance to driving restrictions. When significantly impaired patients refuse to relinquish driving despite clinician reasoning (or persuasion), neurologists must sometimes act paternalistically – favoring the patient’s safety over his

ETHICAL ISSUES IN THE NEUROLOGY OF AGING AND COGNITIVE DECLINE or her expressed wishes to continue driving – and even prioritize the public good over patient interests by taking legal steps (e.g., reporting to the Department of Motor Vehicles) to restrict driving. The American Academy of Neurology has developed a useful guide to help clinicians navigate this challenging area with patients and families (Iverson et al., 2010). Technology allows for the health and activity of individuals with dementia to be monitored from a distance and facilitate independent living. Monitoring can be on-body (e.g., mobile phone or other carried device), infrastructure-mediated (e.g., tracking water or electric use), or in-home ambient sensing (e.g., home-based cameras or motion sensors) (Demiris et al., 2009). Monitoring the activities of individuals with early cognitive impairment is useful for tracking health status and maintaining desired living arrangements (e.g., staying in one’s home). Physiology (e.g., vital signs), function (e.g., mobility around the home), safety (e.g., stove alarms), security (e.g., home alarms), assistance needs (e.g., object locators), or communication (e.g., catching telemarketing fraud) can be remotely monitored by health professionals or family. Technologic monitoring can ease the burden on family and other caregivers, while allowing individuals with dementia to stay longer in their homes. But monitoring is not without cost in terms of loss of privacy, generation of stigma, and reduction in social and caregiver contact (Kang et al., 2010). Care must be taken to balance the embrace of monitoring technology against other means of achieving health and safety goals in this population. Not doing so risks turning the cost of monitoring (e.g., loss of privacy) into just one more thing that those diagnosed with dementia lose. Individuals in early stages of dementia are faced with dementia treatment decisions as well as decisions about how and whether to treat other unrelated medical conditions. Current therapies for dementia carry relatively mild side-effects but also promise correspondingly moderate benefits (Raina et al., 2008). Future therapies, however, may embody a different calculus, with the promise of significant improvement (e.g., symptomatic stabilization or even cure) but also the risk of more serious side-effects (e.g., meningoencephalitis in an early beta amyloid vaccine trial (Orgogozo et al., 2003)). The need for sound decision-making is important as new therapeutic options emerge. Treatment of comorbid medical conditions in patients with dementia raises similar concerns. Should someone with early-stage dementia pursue a hip replacement for degenerative arthritis or a stem cell transplant for a blood disorder? Such decisions are often complicated, requiring the balance of short-term hardship (e.g., surgical recovery) against longer-term benefit. Instruments for decision-making capacity have application to assess whether persons with early-stage dementia

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are able to calculate the risks, weigh future benefits, reason through options, and make decisions. Individuals with dementia who volunteer to participate in research can advance the scientific understanding of their disease. The desire to volunteer derives from various sources, including general altruism, concern for potentially at-risk family members, or belief in scientific progress (Karlawish et al., 2002). But as a result of their cognitive impairments, those with dementia are a vulnerable research population, like other vulnerable populations (e.g., children (Kopelman, 2000), pregnant women (Lyerly et al., 2008), the mentally ill (Dresser, 1996), and the incarcerated (Hoffman, 1999–2000)). The decision to volunteer for research, which involves weighing the costs and benefits of participation, can be affected by cognitive impairments and raise concerns about violating the principle of informed consent (Kim, 2011). Individuals with dementia, particularly early dementia, show interest in research participation and can engage in various aspects of the decision-making processes about participation (Black et al., 2013). Research ethics as a field increasingly recognizes the need to protect participants with dementia from exploitation but at the same time not exclude this population from the personal and public good that can come from research participation (Vellas et al., 2011). Steps to achieve these potentially competing goals include assessing a patient’s capacity to consent, soliciting proxy consent together with patient consent (or assent from patients who cannot consent), and using simple tools such as a one-page summary sheet to help individuals with impairments in cognition provide an informed consent for research participation (Rubright et al., 2010).

ETHICAL ISSUES IN ADVANCED DEMENTIA The transition to advanced dementia leads to a change in the model of clinical care. In mild-stage dementia, as discussed above, the goal of family and medical caregivers is to maximize patient autonomous decision-making, and the operative model is the clinician as facilitator of patient autonomy. But with the transition to advanced stages of dementia, this model is no longer appropriate. Patient dignity and quality of life take precedence in more advanced stages of dementia. What constitutes dignity and quality of life must be highly individualized, but previous patient preferences, deeply held values, and longstanding character traits provide clues to the meaning of dignity for each patient. Family members and friends who have known a patient for years are a critical resource. Those with an intimate knowledge of the patient can give proper interpretation to subtle changes in daily moods or behaviors as a kind of barometer of

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quality of life. The clinical model at this stage of disease is one of clinician as facilitator of patient benefit. Guided by knowledge of who the patient “once was,” the clinician helps family or surrogates make decisions that maximize patient wellbeing and preserve dignity. As dementia advances, family members or other caregivers become decision-makers, a role often described as a “surrogate decision-maker,” which means someone who speaks on behalf of the patient, protecting and promoting that patient’s interests. The designation of a surrogate can be pre-emptive (through a patient’s advance directive) or, as is commonly the case, follows established cultural and legal norms (e.g., spouse, adult child, sibling). In practice, “surrogate decision-making” is a gradual and incremental process that starts well before a patient has “lost capacity.” The de facto surrogate decision-maker is often the person who cares for and knows the patient the best. When conflict arises, legal lines of succession or other legal remedies (e.g., guardianship) can be pursued. A hierarchy of standards for surrogate decisionmaking provides guidance for family and caregivers (Buchanan and Brock, 1989). Substitute judgment, deciding as the patient would have decided, is the preferred standard because a patient’s previous beliefs, values, and character can assist a surrogate in “stepping into the shoes” of the person with dementia to make a decision. When not enough is known or uncertainty persists as to what someone would have wanted, a next best option is for a surrogate to make decisions based on what is believed to be in the patient’s best overall interest (best interest standard). Some studies suggest that older adults prefer less rigid standards of surrogate decision-making, and desire giving surrogates more leeway in decisionmaking (Sehgal et al., 1992). Prior to losing decision-making capacity, a patient can write out an instructional advance directive. These advance directives allow individuals to spell out in their own words what future care or treatment they desire. However, implementing instructional advance directives in dementia can be particularly challenging. People with mild cognitive impairment and early dementia do less advance planning (Garand et al., 2011). The difficulty of adequately anticipating one’s future medical conditions or needs, and formulating one’s wishes in unambiguous terms, undermines the usefulness of instructional advance directives. In practice, instructional advance directives are most useful not in their ability to speak for a person who has lost capacity, to dictate precisely what is to happen, but to speak to a surrogate who must make decisions, to guide that surrogate by affording a better sense of the individual’s priority values and preferences. In addition, over the course of dementia, patients change, including changes in personality and

preferences. Whether these changes constitute a change in personal identity (“Is the person who authored the advance directive the same person who is later subject to it?”) and consequently invalidate an advance directive is unclear. Some individuals make advance directives that severely limit the care their cognitively impaired “future self” will receive, anticipating that this “future self” will have a very poor quality of life. Yet, many individuals who reach later stages of dementia seem relatively content. Deciding how to value the precedent autonomy of the advance directive author against the present well-being of the “pleasantly demented” individual is a subject of ongoing debate (Hughes, 2001). In general, the current wishes and preferences of the individual with advanced dementia, so long as they are reasonable, should be given de facto preference if in conflict with a prior advance directive (Dresser, 1995). Those with advanced dementia can still value certain options over others, even when the ability to give a thorough, rational defense of what is valued has been lost (Jaworska, 1999). Clinicians and families show respect for those with advanced dementia by taking seriously the ability to value, even at last stages of the disease. In the later stages of dementia, surrogate decisionmaking is important to decisions about treatment and research participation, behavior modification, and end-of-life care. Individuals with advanced dementia often are faced with decisions about dementia-related and nondementia-related therapies. Surrogates can face difficult therapeutic decisions. Therapeutic options have costs that must be weighed, and advanced dementia can alter cost–benefit calculations in important ways. A patient with dementia may not be able to understand the side-effects of a procedure or be able to participate fully in postoperative rehabilitation (Di Nino et al., 2010). A patient with advanced dementia may not always benefit from antibiotics for pneumonia if this treatment merely prolongs the dying process (Van der steen et al., 2002). Similarly, preventive care (e.g., influenza vaccine (Jennings, 2011) or cardiac pacemakers (Lampert and Hayes, 2011)) must be assessed in terms of their effect on quality of life in patients with advanced dementia. In general, potentially life-prolonging therapy should be pursued if (1) a previously expressed priority for longevity over comfort has been expressed by the individual and (2) the therapy is not overly burdensome, involving only mild to moderate time-limited discomfort in return for a substantially improved quality and quantity of life. In such cases, complicated, expensive treatment should be treated equivalently to inexpensive, routine treatment (e.g., antibiotics). In advanced dementia, surrogates should be guided not by a goal of prolonging life for the sake of prolonging life, but by a goal of providing a quality

ETHICAL ISSUES IN THE NEUROLOGY OF AGING AND COGNITIVE DECLINE of life that the individual, given previous values and preferences, would find acceptable. Individuals with advanced dementia can be asked to participate (or to continue participation) in clinical research. Although individuals with advanced dementia often do not have the capacity to provide their own informed consent to enroll in a study, they may have preserved capacity to appoint a surrogate to make this decision (Kim et al., 2011). This surrogate must weigh potential harms and benefits, just as he or she would for treatment decisions. For research without a reasonable prospect of benefit to the subjects, but which may advance understanding of the disease and thereby help others, the surrogate’s decision requires a different standard. Enrolling a patient with surrogate consent into such research is permitted only if: (1) the research presents minimal risk or some minor increment over minimal risk; (2) the subject gives assent or lack of dissent; (3) institutional review board approval is obtained; and (4) the surrogate gives consent on the subject’s behalf consistent with the patient’s previous preferences (Wendler and Prasad, 2001). One of the most difficult decisions that surrogates must make is how to control disruptive behavior. Apathy, depression, agitation, anxiety, hallucinations, aberrant motor behavior (e.g., wandering), and disinhibition (e.g., hypersexuality) are common problems in patients with progressive cognitive decline (Lyketsos et al., 2000). Such behaviors can put patient and others’ safety at risk. Bed rails, medications, and locked wards are used to address these challenges, but clearly these carry harms (Tinetti et al., 1991; Miles, 1996). They may mask underlying and potentially reversible causes (e.g., boredom, pain or thirst, infection) of disruptive behavior. For families, coping with such behaviors can be overwhelming, and caregiver burden is tied to the transition to institutional care (Yaffe et al., 2002). Even in institutions experienced in dementia care, where priority is often given to behavioral or environmental interventions for addressing disruptive dementia behaviors, medical interventions (e.g., chemical or physical restraints) are used (Treloar et al., 2010). The tradeoff inherent in aggressive treatment of dementia-related behaviors can be difficult for families and medical personnel. There is often no easy answer to the question of how to address disruptive behaviors in advanced dementia. Chemical restraints, such as the use of antipsychotic medication, have significant downsides, including sedation, fatigue, extrapyramidal symptoms, and increased mortality (Maher et al., 2011). And yet, the failure to reduce disruptive behaviors has consequences, such as expulsion from a care facility. What is in the best interest of the patient? While all individuals deserve to have their preferences respected, the reasonable preferences of someone capable of autonomous decision-making need to be respected in a

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different way (i.e., giving them default legitimacy) than the inconstant preferences of someone with advanced dementia. The way to show respect for the desires of someone with advanced dementia can sometimes be to see these desires for what they often are, cut off from both who the patient once was and from a current grasp of the consequences of fulfilling those desires (e.g., refusing medications leading to exacerbated illness). The way to show respect for the person with dementia can sometimes be for a surrogate to act in his or her best interest. The care of patients with advanced dementia typically engages a model of palliative care (Congedo et al., 2010). These patients experience discomfort but this can be difficult to assess and treat (Sachs et al., 2004). The possibility of over- or undertreating pain is a risk, with life in a “painfree” analgesic fog at one end and constant pain or discomfort at the other. Titrating pain medications in individuals with advanced dementia is a delicate balance with poorly marked guideposts for patients who have lost the ability to communicate their discomfort effectively. In the absence of other evidence, conditions that tend to cause pain in those without dementia (e.g., bone metastases) should be treated similarly in those with dementia. Scheduling medication (rather than relying on patient requests) can be helpful in this regard. Paying close attention to behavioral changes also can help. When there is disagreement about whether the patient is in pain and, if so, how best to treat it, a reasonable approach is to try a course of treatment on and off analgesic therapy with a clear understanding of what kinds of evidence observers are using to assess discomfort. Patients with later-stage dementia often lose the ability to swallow nutrition and hydration, leaving surrogates the decision of whether to pursue medical nutrition and hydration (e.g., feeding tube). Although both physicians (Shega et al., 2003) and surrogates (Mitchell et al., 2000) often see value in enteral nutritional support, evidence suggests that this support does not extend life, reduce respiratory infections through reduction in aspiration, ward off other infections (e.g., skin ulcers) through improvement in nutritional status, or provide a comfortable satiety in individuals with advanced dementia (Finucane et al., 1999). Except in unusual circumstances, artificial nutrition and hydration should not be prescribed to patients with advanced dementia. Nonetheless, eating and being fed have deep symbolic meaning, and rather than immediately refusing a surrogate request for medical nutrition and hydration, a clinician should use a request as an opportunity to explore the surrogate’s understanding of medical nutrition and hydration and discuss with the surrogate what the patient would have considered, and surrogate does now consider, a good death.

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In the United States, Oregon and Washington state permit physician-assisted suicide (PAS). These states enumerate strict standards for capacity as well as restrictions to the “terminal” stages of the disease (e.g., prognosis of 6 months to live) (Steinbrook, 2008). The combination of these two, retained decision-making capacity and proximity to death, effectively eliminate the applicability of PAS to dementia in the American context: Those with retained capacity are not close to death and those who are temporally close to death are in late stages of the disease with absent decision-making capacity. In the Netherlands, where aid in dying has a long medical and legal history, assisted suicide is permitted in early stages of dementia before capacity has been lost and where unavoidable suffering is documented (Berghman, 2010). Advance directives provide an alternative path to PAS in dementia. Advance directives, in principle, can direct others to end life when some clinical state, like advanced dementia, has been reached. Such cases have been documented in the Netherlands (Hertogh et al., 2007), though clinicians show reluctance to participate in this practice (de Boer et al., 2010). Current U.S. state laws do not permit this, and there are good reasons to be wary of such a practice. Familiar practical and epistemic problems with advance directives (as discussed above) come into play. For instance, it is not clear whether the “suffering” of fluctuating disorientation, emotional lability, or loss of memory is the same as the “suffering” used to justify PAS in other circumstances.

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