Public Policy Context

Public policy can be categorized as one of three basic types: regulatory, distributive, and redistributive. Regulatory policies impose constraints or restrictions on the actions of groups or individuals: they provide rules of conduct with sanctions backed up by the authority of government. Distributive policies are based on the notion of public goods, e.g., goods and services that benefit all citizens, but which are unlikely to be produced by voluntary acts of individuals alone due to a lack of sufficient resources. Public goods are defined by each society based on how broadly government responsibility is interpreted. Normally, distributive policies provide advantages or benefits to specific segments of society largely through the power of the purse. Considerable governmental activity revolves around the provision of public services, often without undue controversy until scarcity forces trade-offs to be made as to what groups get what goods. Redistributive policies are inherently controversial because they represent efforts by governments to alter the distribution of wealth or property among groups in society. The reallocation of resources can be deliberate such as progressive taxes or result from shift of resources from the young to old or the healthy to unhealthy. It should be emphasized that all policies create winners and losers, although the mechanisms through which gains and losses occur are often subtle. The move of AD to the policy domain brings to the forefront political considerations and divisions and places the resolution of issues in the milieu of interest group politics. Given the huge economic, social, and personal stakes surrounding AD, this is unavoidable.

Government involvement can occur at many points from the research and innovation stages, to placing a technology on the market, to its use by private individuals. Like any policy, it can be permissive, affirmative, regulatory, or prohibitive. The government always has the option of taking no action, thus permitting any actions by the private sector. It can also make affirmative policies that promote or encourage certain activities, for example, government funding of research or provision of services to facilitate more widespread use of a drug or procedure. The question of whether the government ought to be providing such encouragement, and if so how, is a subject of political debate. For instance, should public funds be used to pay for expensive yet unproven interventions for AD patients?

Although regulatory policy can be framed to apply solely to government-supported activities, usually it consists of rules governing activities in both the public and private sectors. For instance, regulation can be used to ensure that standards of safety, efficacy, and liability are adhered to and that marketing of products is fair. While far less common than regulation, prohibitive policies could be implemented that impose legal sanctions on a specific research activity or application such as has been done with human cloning. Another form of prohibitive policy is to preclude public funding of specific areas of research and development.

Another critical issue involves questions of distributive justice, mainly involving the access to services, many of which are costly and are likely to become even more so as treatment options proliferate. While it is premature to speculate about the relative costs and benefits of yet undeveloped AD treatments, cumulatively their cost per case could be high. This also raises questions as to who has priority to these procedures or drugs, whether insurance companies must pay for what are at best experimental treatments, and to what extent a government can or should regulate their use. Will access be equitable and coverage universal, and, if so, how will it be funded? Moreover, what priority should basic research on AD have as compared to health promotion and prevention or care of existing AD patients and provision of dementia-friendly environments? What benefits and opportunity costs does each area of spending hold for the population compared to other spending options? Key policy areas surrounding AD include:

• Research funding. Funding policies are critical for research on the cause of AD, how to prevent it, how to detect it early and accurately, and how to slow, if not, cure it.

• Health care. Payment policy and regulatory functions in Medicare and Medicaid have direct implications for people living with AD who are among the heaviest users of medical care.

• Long-term services and support. Payment policy for nursing homes and strategies to support community living are fundamental for people with mid to late AD. Medicaid is the primary payer for nursing home expenditures resulting in severe budgetary problems, especially for states.

• Public health. Addressing healthy lifestyle and risk factors as well as community readiness are important for a public health approach to managing the growing burden of AD.

• Housing and community services. Critically important for those who wish to remain in their homes are wide range of services including care-giver support, adult day care, and senior centers. They are less costly than nursing home care, but less visible to federal policy makers because they primarily are organized on the local level. Some countries have begun to develop innovative AD-friendly communities.

• Labor. New policies needed to address the challenge of ensuring a competent and adequate workforce, especially for hands-on caregivers, such as personal care assistants, home health aides, and nursing assistants. Currently, about 80 percent of care is provided by family and friends, but this will change in near future.

• Justice and law enforcement. Relevant policies in the legal and law enforcement arena address issues that arise with substituted judgment and the need to provide protection from exploitation, abuse, and neglect. Abuse of AD patients by overworked caregivers is a growing problem.

In summary, some of the major policy issues of AD center on: funding and research priorities; regulating commercial interests; support for informal and formal caregivers; prevention; institutional vs. home care; innovative treatment facilities; and end-of-life issues such as advance directives, treatment abatement, and physician assisted death.

Recent Alzheimer's Policy Activity in the US

The National Alzheimer's Project Act (NAPA) passed unanimously in both Houses of Congress and was signed into law by President Obama in 2011 (Public Law 111-375). NAPA calls for a national strategic plan among federal agencies to address and overcome the rapidly escalating crisis of AD, and mandates the Secretary of the Department of Health and Human Services (HHS) to establish the National Alzheimer's Project to:

1. 1. create and maintain an integrated National Plan to overcome AD;

2. 2. coordinate AD research and services across federal agencies;

3. 3. accelerate the development of treatments that would prevent, halt, or reverse its course;

4. 4. improve early diagnosis and coordination of care and treatment;

5. 5. decrease disparities in AD for ethnic and racial minority populations that are at higher risk;

6. 6. coordinate with international bodies to fight AD globally.

The law also establishes the Advisory Council on Alzheimer's Research, Care, and Services (Advisory Council) and requires the Secretary of DHHS, in collaboration with the Advisory Council, to create and maintain a National Plan to overcome AD. The first National Plan to Address Alzheimer's Disease, released in 2012, recognizes AD as a major public health issue; provides a blueprint for coordinating efforts across the federal government; and outlines concrete goals, strategies, and actions for eliminating the burden of the disease.

Supported by a congressional appropriation beginning in fiscal year 2005, the Centers for Disease Control and Prevention (CDC) established the Alzheimer's-specific segment of the CDC's Healthy Aging Program, referred to as The Healthy Brain Initiative.² The CDC joined with the Alzheimer's Association and other groups, including the National Institute on Aging at the National Institutes of Health (NIH), Administration on Aging, AARP, and other public and private sector organizations to launch the activities of The Healthy Brain Initiative and create a road map to guide a coordinated public health response across agencies and organizations. It offered a ‘synergistic’ model based on several principles: a firm grounding in science; an emphasis on primary prevention; a community and population approach; and a commitment to eliminating disparities.

In addition to enhanced activity at the federal level, plans to strengthen public health efforts to address AD and other dementias have been published in 43 states and D.C. with another 4 states in the process of writing plans.³ Although they vary in emphasis and detail, most address many of the following topics:

• • Increasing awareness of AD among the public.

• • Encouraging earlier detection and diagnosis of AD.

• • Improving individual health care for those with AD.

• • Improving the quality of the health care system for those with AD.

• • Expanding the capacity of the health care system to meet the growing needs of those with AD.

• • Better equipping health care professionals to deal with individuals with AD.

• • Increasing number of health care professionals to deal with the influx of AD patients.

• • Improving services in the home and community to delay and decrease institutionalized care.

• • Improving long-term care, including assisted living, for those with AD.

• • Assisting unpaid AD caregivers.

• • Increasing research funding for AD.

• • Promoting activities that would maintain and improve brain health.

• • Improving data collection regarding AD and its public health burden.

• • Improving public safety and addressing safety-related needs of those with AD.

• • Addressing legal protections for individuals with AD.

• • Improving how government evaluates and adopts policies to help people with AD and their families.

Despite their differences, these public policy statements all call for coordination of resources, better communication, awareness, and essential linkages. However, to achieve the outcomes envisioned in these plans and policies, further action and additional resources are urgently required and must compete with other diseases and spending areas.^{Reference Hoffman4}

Deaths Attributed to AD

An estimated 5.4 million Americans had AD in 2016, 81 percent of whom were age 75 or older. From age 65, the risk of developing AD doubles every 5 years. By age 85, between 25 percent and 50 percent will exhibit signs of AD.^{Reference Sinclair5} When the first wave of baby boomers reaches age 85 in 2031, it is projected that more than 3 million people age 85 and older will have AD. Barring the development of medical breakthroughs to prevent or cure the disease, by 2050 the number of people age 65 and older with AD is expected to nearly triple from 5.2 million to 13.8 million, although previous estimates based on high range projections of population growth suggest that this number could even reach 16 million.⁶

When a person dies, the cause or causes of death are listed on death certificates and filed with a state's Bureau of Vital Statistics. This information is then forwarded to the National Center for Health Statistics of the CDC, which compiles and reports the totals each year as the official US mortality figures and leading causes of death. Based on this process, AD is often listed as the sixth leading cause of death, but new evidence suggests that deaths from AD are considerably higher, and that it is the third leading cause of death in the US.

Underreporting of AD as a cause of death on death certificates is a well-known phenomenon. Some people with the disease never receive a diagnosis while many others have dementia-related conditions, such as aspiration pneumonia, listed as the primary cause of death. Two groups of investigators examined this to discover the full burden of AD. While their estimates of deaths due to AD vary slightly, both groups determined that AD-related mortality rates are several times higher than the official figure. In one study, the researchers combined data from the Chicago Health and Aging Project with US Census data to estimate the number of deaths of older Americans with AD.^{Reference Weuve7} Their findings show that an estimated 600,000 people age 65 and older with AD died in 2010 compared to the CDC's 83,494 figure. A second study found that the number of deaths due to AD in people 75 and older could be six times higher than the official count.^{Reference James, Leurgans, Hebert, Scherr, Yaffe and Bennett8}

AD is the only cause of death among the top 10 that currently cannot be prevented, cured or even slowed. It is also always fatal, with no survivors.⁹ Moreover, while deaths from other major causes are decreasing, deaths from AD have increased significantly. Between 2000 and 2013, deaths attributed to AD increased 71 percent, while those attributed to heart disease decreased 14 percent. It should be noted that this increase of AD deaths reflects both changes in patterns of reporting deaths on death certificates as well as an actual increase in the number of deaths attributable to it. AD is also more prevalent in certain groups, with almost two-thirds being women. Moreover, African Americans have double the risk and Latino Americans 1.5 times the risk of other Americans.¹⁰

The Economic and Social Costs of Alzheimer's Disease

The most striking policy implications of AD relate to cost. Because most cases of AD involve people over 65, Medicare bears the bulk of medical costs of people living with AD who are heavy users of hospital-based care. Similarly, because AD patients frequently require long-term care and outlive their assets, Medicaid pays over 60 percent of nursing home care costs.¹¹ The long duration of illness before death contributes significantly to the impact of AD because much of that time is spent in a state of disability and dependence requiring personal care. Studies indicate that people age 65 and older live an average of 4 to 8 years after a diagnosis of AD, with some up to 20 years, reflecting its slow, insidious progression. On average, a person with AD will spend 40 percent of their total years living in its most severe stage. Nursing home admission by age 80 is expected for 75 percent of people with AD compared with only 4 percent of the general population. Similarly, two-thirds of those who die of AD do so in nursing homes, compared with 20 percent of people with cancer and 28 percent of those dying from all other conditions.¹²

Not surprisingly, AD is the most expensive disease in the US, and it is overwhelming federal and state health care budgets and depleting the life savings of millions of victims and their families.^{Reference Wimo and Prince13} The total national cost of caring for those with AD and other dementias for 2016 was approximately $236 billion. Medicare and Medicaid are expected to cover $160 billion, or 68 percent, of the total health care and long-term care payments with out-of-pocket spending adding $46 billion, or 19 percent of total payments. By 2040, spending on dementia patients is estimated to be $1.2 to $1.6 trillion, if no curative therapies emerge.^{Reference Reid14}

Per-person health care and long-term care payments in 2015 from all sources for Medicare beneficiaries with AD were three times as great as payments for other Medicare beneficiaries in the same age group ($49,126 per person for those with AD compared with $15,550 per person for those without). Total Medicaid spending for people with AD is projected to be $43 billion in 2016 dollars. Total per-person Medicaid payments for Medicare beneficiaries age 65 and older with AD were 19 times as great as Medicaid payments for other Medicare beneficiaries. Much of the difference in payments for beneficiaries with AD is due to the costs associated with long-term care and the greater percentage of people with AD who are eligible for Medicaid. Medicaid paid an average of $26,837 per person for Medicare beneficiaries with AD living in a long-term care facility, compared with an average of $590 for older adults without the diagnosis living in the community or long-term care facilities.¹⁵

As a result, care for elderly people with AD in the last five years of life costs far more than care for other major killers like cancer and heart disease.^{Reference Kelley, McGarry, Gorges and Skinner16} AD and other forms of dementia cost, on average, $287,000 over those five years. This compares with about $175,000 for heart disease and $173,000 for cancer. But health insurance covered about the same amount, approximately $100,000, for each of these diseases, leaving many families of people with AD picking up the difference. In their seminal study of dementia costs, Hurd et al. found that raising the probability of dementia from 0 to 100 percent leads to additional social costs of between $41,689 and $56,290 per person per year, depending on the imputation method used.^{Reference Hurd, Martorell, Delavande, Mullen and Langa17} Furthermore, as noted earlier, because AD can linger for years, or decades in some cases, the cost, both for government insurance programs and for families, is exceedingly high.¹⁸

None of these figures include the heavy costs borne by unpaid informal caregivers. AD affects entire families, because they are likely to be providing direct care and/or financial support. Furthermore, caregivers themselves experience stress on many levels and are at enhanced risk for an array of chronic conditions, family strife, financial strain, and work pressures as well as a range of behavioral health complications. On average, family caregivers spend more than $5,000 a year to care for someone with AD. The financial burden is particularly severe for African-Americans, those with minimal education, and widows. African-Americans have significantly higher costs of care than whites, primarily due to more inpatient care and greater severity of illness. These differences, in turn, may be attributable to later-stage diagnosis, which can lead to higher levels of disability while receiving care; delays in accessing primary care; and a lack of care coordination. Whatever the case, considerably more research is needed to understand the reasons for these health care disparities.¹⁹

Although Medicare provides nearly universal health care coverage for US adults over age 65, it does not cover health-related expenses for those with life-limiting, chronic diseases, such as home care services and non-rehabilitative nursing home care. Thus, while all households face substantial financial risks near the end of life, with AD these uninsured needs are extensive and likely needed for many years of functional decline. AD patients often cannot be left alone because they wander and risk serious injury. Average per-person out-of-pocket payments are highest ($20,207 per person) for individuals living in nursing homes and assisted living facilities and were almost six times as great as the average per-person payments for individuals with AD living in the community.²⁰

Those with AD have more hospital stays, skilled nursing facility stays, and home health care visits than other older people. There are 538 hospital stays per 1,000 Medicare beneficiaries age 65 and older with AD compared with 266 hospital stays per 1,000 Medicare beneficiaries age 65 and older without it. Based on data from the 1998 to 2008 Health and Retirement Study and Medicare, after controlling for demographic characteristics, clinical characteristics, and health risk factors, individuals with AD had a 1.66 times greater risk of having a preventable hospitalization than those without AD.²¹ Similarly, there were 283 skilled nursing facility stays per 1,000 beneficiaries with AD compared with 73 stays per 1,000 beneficiaries for people without it.

Fear of Alzheimer's Disease

Although Americans worry about staying physically healthy as they contemplate old age, losing their mental faculty is their biggest fear. For instance the Research!America Health Poll found that declining health is the number-one concern (37%) about getting older, followed by financial worries (23%) and dependence on others (6%).³⁰ Asked their greatest fear about growing old, they mentioned losing mental capacity twice as often as declining physical ability (62% vs. 29%, respectively). The fear of forgetfulness has made deep inroads into the American psyche. This epidemic of anxiety around memory loss is so strong that many older adults seek help for the kind of dayto-day forgetfulness that once was considered normal.^{Reference Gullettemay31} Draper et al. contend that Alzheimer-phobia, is already evident, especially in developed countries.^{Reference Draper, Peisaha, Snowdond and Brodaty32}

Instead of reducing anxieties about AD or the stigma surrounding it, heightened public awareness has increased fears for many citizens.³³ As noted by Hertogh, “Many people, especially the elderly, are fearful of becoming demented and generally the disease is viewed upon as a humiliating affliction, affecting self and personality. What many of the elderly fear most are the effects of dementia on independence and competence.”^{Reference Hertogh and Burns34} Many more fear AD because they have seen a parent or other relative experience the steady erosion of memory, cognition, and identity as the disease progressed. Now they worry whenever they misplace something or forget a name, and vow that they will do whatever they can to prevent or delay its onset.³⁵

Similarly, a survey by the MetLife Foundation found that people over 55 dread getting AD more than any other disease except cancer. Moreover, over 60 percent were concerned that they may someday have to care for someone with AD. For Garrett, the fear that cancer engendered is being replaced by ‘dementiaphobia’.^{Reference Garrett36} Even the words Alzheimer's or dementia arouse a degree of fear that heart attack, stroke or COPD often do not. Although they all can kill, for many people the fear of losing ‘who one is’ and becoming fully dependent on others is more troubling. It is not only older people who fear AD. A 2015 Harris Poll found that more than 75 percent of millennials, Generation Xers and baby boomers worry about what will happen to their memory as they age.^{Reference Kunkle37}

A British poll found that older people are even more fearful of developing AD than they are of cancer.³⁸ Two thirds of people over the age of 50 fear that they will develop AD, while just one in 10 said they were frightened about getting cancer and just under 4 percent about getting a heart condition. This apprehension is frequently magnified by advocacy groups, manufacturers of purported anti-aging products, and the news media which tend to embellish the horror of AD. It does not help that AD is often characterized in a negative manner, described as ‘dying while alive,’ ‘a slow death,’ or a ‘fate as bad as or worse than death.’ If indeed this has become the model that AD is seen to represent, and for which there is no foreseeable cure, it is not surprising that many people view it with a sense of impending doom and their loss of cognitive self and subsequent loss of autonomy as a dismal fate.^{Reference Gordon39}

As Draper et al. note, however, the lived experience of AD can differ from the imagined experience that many assume.⁴⁰ Although the debilitating impact of AD and the experience of loss and negative emotions cannot be minimized, a literature review of the personal experiences of patients living with it found ‘no solid support to the widespread assumption that AD is necessarily a ‘dreadful state of suffering.’^{Reference de Boer, Hertogh, Droes, Riphagen, Jonker and Eefsting41} Overall, those with early and mid-stage AD have more positive appraisals of their lives than might be expected, and can enjoy human interactions and mental and physical activity, even as the disease progresses. Up to 67 percent of people with mild to moderate AD report a very good or good quality of life.⁴² Sabat challenges the potentially detrimental stereotypes of AD sufferers that they are passive, vegetables, antisocial or irrationally angry. Persons with AD are hardly as disabled as they are socially expected to be and often suffer from ‘learned helplessness,’ as a reaction to such stereotyping.^{Reference Sabat and Innes43}

Despite these findings, the fear of dementia is prevalent and creates a vulnerability to pursue aggressively marketed products, diets, and technologies that promise to prevent it. This summary of two respondents of a study by Kunkle⁴⁴ elucidates this quest for protection from AD. ‘It's my nightmare: the loss of my mind; the inability to recognize people who are dear to me; the ability to think,’ said one 71-year-old man, whose mother had AD. He does everything he can to lower his risk, including working out, reading vociferously, doing crossword puzzles, eating almonds and following the news about possible new treatments. Another interviewee eats blueberries every day, works out for strength and aerobics, does word puzzles and is learning Spanish. Should she develop dementia, she will move to a state that permits euthanasia so that she can die in peace and not to be a burden because there is ‘nothing worse than this disease.’ Although there is nothing detrimental about these individuals' lifestyle choices, their lives have become, in effect, driven by a fear of AD.

Policy Issues in Commercialization and Marketing of AD Products

The fear of AD also has not been lost on a flourishing industry that focuses on products that promise to improve cognition and, in some cases, avert AD or even cure it, despite an absence of scientific evidence. A quick search of AD on the Internet finds hundreds of sites to this end. AD is big business as illustrated by the thousands of items on Amazon.com alone. Moreover, the medicalization of cognitive issues is linked to the availability and profitability of ‘treatment’ options, buoyed by a growing consumerist orientation to health reinforced by enthusiastic media reporting.^{Reference Conrod, Horwitz, Chatterjee and Farah45} Moreover, Internet sites enable consumers to access AD products without the need to visit a doctor, often reinforcing the medicalization of an everyday problem with a new diagnostic category. One example is the emergence of the new disease and susceptibility category of mild cognitive impairment (MCI) that elucidates how blurry the boundaries between what is normal and abnormal cognitive functioning are and how these can shift over time.^{Reference Coveney, Gabe and Williams46}

Both the popular press and, especially, the Internet are predisposed to highly optimistic and oversimplified coverage of all biomedical technologies. In addition, health-oriented magazines and television shows extol the virtues of innovations and the quick fixes or breakthroughs these innovations might offer. By and large, then, media coverage solidifies public trust in the technological fix and stimulates its appetite for new, often expensive, high technology procedures. For instance, Gilbert and Ovadia document many instances of hype and exaggerated coverage of deep brain stimulation (DBS) in scientific journals and the popular press.^{Reference Gilbert and Ovadia47} Even Nature presented DBS findings in an overly optimistic article entitled ‘Brain electrodes can improve learning’ that was quickly followed by highly enthusiastic coverage in television news and the press that headlined ‘Deep stimulation “boosts memory.”’⁴⁸

Direct-to-consumer advertising refers to a variety of marketing practices based on a combination of information and promotion strategies directed at consumers through media such as television (often late night), newspaper and magazine ads, and, of increasing importance, the Internet. Direct-to-consumer advertising in the US has contributed to burgeoning pharmaceutical marketing and sales in the past decades. Although proponents argue it effectively introduces the public to innovations, empowers patients, and provides updated health information directly to potential users, Palmour and Racine view direct-to-consumer marketing of dietary supplements to maintain or enhance cognition as an unhealthy commerce of neuroscience.^{Reference Palmour and Racine49}

The Internet and mass and targeted emails have facilitated marketing of all sorts of products that promise to prevent, slow and even reverse or cure AD that are targeted to anxious seniors. Here are a few excerpts from some of these sales pitches:

1. 1. Discover the cooking oil that repairs memory. During this short video you will also discover how much of this oil you need to take each day to repair and boost memory, increase focus and concentration and prevent and reverse Alzheimer's and dementia. And do it in just 21 days.

2. 2. If you or a loved one has been noticing symptoms of declining brain health such as forgetting your keys, forgetting people's names… Or if there has already been a diagnosis of dementia or Alzheimer's… Then, watch this video to the end and you'll discover just how easy and fast it is to treat any of these illnesses. You're about to discover how for just a couple minutes a day for only 14 days, you can re-program the way your brain works…no more forgetfulness, no more embarrassing senior moments, no ‘fog’ that clouds judgment and creates confusion… Treating any brain issues such as dementia and Alzheimer's, all attained through a single one-of-a-kind method backed up by solid science — no drugs involved.

3. 3. This is a HUGE breakthrough. According to a team of 31 senior scientists at Oxford, Cambridge, and Manchester Universities, Alzheimer's and dementia are caused by common viral infections. Now the good news is that scientists have discovered a way to quickly destroy these Alzheimer's germs. That's probably why many health experts are calling this the health breakthrough of the 21st century. People are using this natural ‘antibiotic’ to kill their Alzheimer's infection in under a month… And data is showing it works for all stages of Alzheimer's and dementia — no matter how severe.

4. 4. Quick and Natural Alzheimer's Cure Could Be Extinct by June 1st, 2017? Over 142 grocery stores affected in your area alone! Stay on this page to find out how to get your hands on this DEMENTIA-ERASING superfood before it runs out. My name is Christine O'Brien. I'm a research assistant for one of America's top doctors, and what I'm about to say may shock you… Evidence has emerged that for at least 3½ years, researchers funded by the U.S. Government have been reversing Alzheimer's disease in their patients. Now perhaps you're thinking… ‘Wait a minute — Alzheimer's and dementia CAN'T be reversed.’ And you're right, that IS the mainstream medical opinion. Yet this elite group of government-funded researchers did it for 9 out of 10 of their patients.

5. 5. A journey that opened my eyes to the sick, predatory, and ultimately deadly practices of the pharmaceutical conglomerates that would eventually lead to the discovery of a completely natural, 100% effective way that could reverse even the most severe cases of Alzheimer's, dementia… No matter whether one suffering was in the very late stages of such a disease, at initial onset, or simply at risk of age related memory loss. It's A Method That's Based on Breakthrough Research Conducted by A Team of Scientists at Yale University…It's already been proven to be effective… And all it takes is the destruction of a simple “evil agent” in your brain… something that until recently was poorly understood by the scientific world, but that has now been pinpointed as the overwhelming cause of almost all memory-destroying diseases. Now in the following 5 minutes I'll tell you exactly what this memory destroying neuro-agent is and give you all the research to support my claims…

6. 6. Dr. Oz suggests eating curry once or twice a week to help prevent Alzheimer's disease.

Moreover, in their quest for a wider market, the brain intervention industry has blurred the line between therapy and enhancement.^{Reference Blank50} If it works for AD patients, it can enhance cognition of healthy people. Dr. Oz says ‘It's the future of the brain’, the World's 11th richest man says that since taking this IQ boosting pill his creativity, problem-solving and focus have increased significantly, and CNN Breaking News reports that this ‘clear-pill’ is so effective, that the government is thinking about banning it. Interestingly, the name of this wonder supplement varies, including Alpha ZXT and Geniux, among others. The ads even include ‘limited edition cover pages’ of magazines such as National Geographic, Forbes and Time extolling the pill that can turn you into ‘the quickest thinker on the planet!’ According to their website, Geniux has been clinically proven to ‘sky-rocket concentration by 312 percent, improve creative thinking, boost energy, enhance memory recall and increase IQ scores by 77 percent.’ Similarly, Alleradd is marketed as a nutritional supplement available online to anyone with a valid credit card who states they are at least 18. Another widely marketed pill is Addium termed ‘Viagra for the brain’ and ‘the most powerful brain enhancer in the world’ by a group of TV ‘doctors’ including Dr. Oz. Interestingly, in almost identical ads, the same compound is called Adderin, Geniux™ (medical name E-Huperzine) and Alpha ZDT!

These types of marketing have led some to call for greater regulation over such direct-to-consumer advertising of brain intervention products.^{Reference Hanrahan51} Certainly, there is a clear regulatory gap for neuro-technologies with non-therapeutic and non-diagnostic commercial purposes. As argued by Racine, van Der Loos and Illes, the commercial development of neuro-technologies deserves greater regulatory attention because of the exceptional ethical considerations they evoke.^{Reference Racine, van Der Loos and Illes52} At the very least, consumer protection against false advertising and to guard against potential long-term safety problems would seem to be especially urgent in the growing commercialized cognitive-product environment. This holds as well for homeopathic drugs and nutritional supplements that are regulated under the Dietary Supplement Health and Education Act of 1996 (DSHEA), which effectively removed them from FDA regulation. Without FDA control, the supplements industry can, in effect, make whatever claims it wants to without having to provide scientific evidence as long as they add a short disclaimer noting the FDA has not reviewed the claims. These lax regulations essentially have created an opportunity to make billions off the placebo effect through aggressive marketing that supplements are “natural” and thus safe and effective despite the fact they can have serious side effects, toxicity, and interactions.^{Reference Bellamy53}

Brain Games

The range of cognitive intervention includes not only pharmacological interventions, but also psychological interventions, such as learned tricks or mental strategies, as well as external technological and institutional structures that support cognition. There are three popular computer-based approaches to improving cognition: brain-training programs, working-memory training, and video-game training. Computer-based cognitive-training software, popularly known as brain games, are assertively marketed, especially to aging adults. Products in this billion-dollar industry include Cogmed, CogniFit, Posit Science, Nintendo's Brain Age and Lumosity, which alone has over 60 million members and strategically advertises even on NPR classical music stations. The promotion of these products entices and reassures a worried public. Consumers are told that playing brain games will reduce cognitive slowing and forgetfulness and fundamentally improve your mind. It is customary for advertising to highlight the benefits in rather abstract terms and reassure consumers that their claims and promises are based on scientific evidence designed by neuroscientists at ‘top universities and research centers.’^{Reference Ghoravshi54} In many instances, however, the cited studies examine something other than the program being advertised, assessing benefits with abstract laboratory tasks rather than everyday ones.^{Reference Boot and Kramer55}

Concerns over the marketing claims by some of these companies led a group of 73 international psychologists, cognitive scientists and neuroscientists to write an open letter accusing them of exploiting customers by making ‘exaggerated and misleading claims’ that are not based on sound scientific evidence. They conclude:

Moreover, cognitive activity takes many forms, and there is currently little evidence suggesting that any software package is best at improving cognition, or that any brain-training product is better than other activities, such as learning a new language or musical instrument, creative writing, or aerobic exercise which comes with a host of physical health benefits.⁵⁷

Physical Interventions

None of the pharmacologic medications available today slows or stops the damage and destruction of neurons that cause AD symptoms and make it fatal.^{Reference Yuan, Tabarak, Yu and Lei58} The six drugs currently approved by the FDA for AD at best temporarily improve symptoms, but the effectiveness varies from person to person. Between 2002-2012, 244 drugs for AD were tested in clinical trials but only one successfully completed the trials and received FDA approval. In 2017, Merck halted the late-stage trial of its highly-touted AD drug verubecestat, after an independent study found that it had ‘virtually no chance’ of working. This came just three months after Eli Lilly announced that it was ending the clinical trial of its AD drug solanezumab, after patients taking it demonstrated no signs of improvement compared to a placebo. It has now been over a decade since a new drug for alleviating the symptoms of AD was made available. Although there have been many successful studies that have cured or reduced memory loss in transgenic lab animals, none have been replicated in humans.^{Reference Cummins59}

The substantial costs and social burden of AD necessitate alternative or complementary therapeutic treatments. In this context, non-pharmacological interventions including ‘non-invasive’ brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), often in combination with cognitive training, have gained increasing attention. TMS employs a coil to deliver brief magnetic pulses to the scalp, inducing electric currents in the targeted areas of the brain. These electrodes send electrical impulses to targeted parts of the brain to alter activity that can regulate abnormal impulses or affect certain cells and chemicals.^{Reference Hsieh60} Compared to TMS, tDCS stimulators are typically inexpensive, battery-operated and portable and have safety advantages, since no serious adverse effects have been reported as a result of this technique.^{Reference Mrakic-Sposta, Rosa, Ferrucci, Mameli and Vergari61} Elder and Taylor evaluated the effects of TMS and tDCS on cognitive and neuropsychiatric symptoms in the major dementias, including AD and MCI, and conclude that both may have potential as interventions for the treatment of symptoms associated with them.^{Reference Elder and Taylor62} Post-rTMS improvements in depression and cognition have been demonstrated in mild-to-moderate, but not severe, AD patients.

Proponents of these techniques argue that the evidence regarding the neuropsychological profile of AD patients justify the application of cognitive rehabilitation at an early stage since some aspects of cognitive functions are preserved until later in AD.^{Reference Cotelli, Manenti, Brambilla, Petesi, Rosini, Ferrari, Zanetti and Miniussi63} It has been shown that a single tDCS session can ameliorate memory deficits in AD patients.^{Reference Ferrucci, Mameli, Guidi, Mrakic-Sposta, Vergari, Marceglia, Cogiamanian, Barbieri, Scarpini and Priori64} Moreover, Boggio et al. found that repeated sessions of anodal tDCS applied bilaterally over the temporal area led to an increase in performance of visual recognition memory tasks in AD patients.^{Reference Boggio, Khoury, Martins, Martins, de Macedo and Fregni65} Marceglia et al., too, found that the abnormal pattern of EEG activity observed in AD during memory processing is partially reversed by applying anodal tDCS.^{Reference Marceglia, Mrakic-Sposta, Rosa, Ferrucci, Mameli, Vergari and Arlotti66} As Meinzer et al. point out, the long pre-clinical phase of AD provides opportunities for potential disease-modifying interventions in prodromal stages.^{Reference Meinzer, Lindenberg, Phan, Ulm, Volk and Flöel67}

Given its simplicity and the amount of research on tDCS, it could become a generalized therapeutic tool, but as Drakos warns, we must beware the commercial exploitation of this technology because if used in the wrong way, it could easily be harmful.^{Reference Drakos68}

Deep brain stimulation (DBS) is a surgical procedure in which electrodes are implanted into targeted areas providing a steady stream of electrical impulses to a part of the brain that regulates memory. Early research indicated that DBS, which is commonly used to treat the symptoms of disorders including chronic pain, major depression, and Parkinson's disease, could slow down or even halt cognitive decline in AD patients.^{Reference Laxton, Tang-Wai, McAndrews, Dotinga and Sauer69} A recent study of 42 patients with mild AD, found that over a 12-month period, those aged 65 and over who received DBS saw ‘a trend toward … benefit on clinical outcomes' and a possible ‘slowing of cognitive decline,’ although younger patients did not benefit from the treatment and may have worsened.^{Reference Novacic70}

During a five-hour surgery in 2015, Kathy Sanford became the first Alzheimer's patient in the US to have a DBS stimulator implanted in her brain as one of up to 10 patients enrolled in a new study.^{Reference Lozano, Fosdick, Chakravarty, Leoutsakos, Munro, Oh, Drake, Lyman, Rosenberg, Anderson and Tang-Wai71} Using a 3-dimensional brain mapping technique called standardized low-resolution brain electromagnetic tomography (sLORETA), Lozano's group found that stimulating the hypothalamus also produced increased brain activity in the hippocampus, a key component in the brain's memory circuitry. As AD progresses, not only does the hypothalamus atrophy, but electrical communication between neurons in the region also gradually becomes impaired. However, after one year there were no significant differences in cognition between the groups, although AD tends to progress slowly and reversing or slowing the neurodegeneration associated with condition may take time to become noticeable. Laxton and Lozano, however, warn that evidence for the use of DBS to treat AD is preliminary and limited, but that further investigation into its potential clinical effects is warranted.^{Reference Laxton and Lozano72}

Despite the uncertain efficacy of these interventions, according to one website, researchers have been studying the benefits of tDCS for years, and the results they've uncovered are ‘astounding’. The Brain Stimulator is the industry leader in tDCS, they trumpet. Products available include the Full Featured Brain Stimulator - Just $90, the Brain Stimulator-Advanced Starter Kit and the Brain Stimulator Travel Model - Only $55. Among the ‘endorsements’ noted are a TV doctor, an article in the New Yorker, and a PBS story. Another example of the marketing of tDCS comes from the Brain Stimulation Clinic that advertises that it is a safe, new, non-invasive procedure which improves attention, memory and learning for both healthy individuals and patients with disabilities. It can be performed at the clinic in Atlanta or self-administered with training and supervision through the Home-Use Program.

Stem Cells

The failure to develop new drugs for AD also intensified attention to stem cells in 2010 when researchers began clinical trials investigating their use for AD. Two phase-I trials on moderate AD patients have been completed and, although they revealed no severe acute or long-term side effects, no significant clinical efficacy was observed. Several studies, which involve more sophisticated study designs using different injection routes and biomarkers such as amyloid positron emission tomography, are planned for mild to moderate AD patients.^{Reference Kang, Yeon, Cho and Suh73} Given preliminary findings, the Alzheimer's Society supports the advancement of stem cell research to help understand the causes of AD and to find new cures if it is balanced with consideration of ethical issues raised by this type of research. The Society supports a legislative environment that allows stem cell research to develop within a strict regulatory framework.^{Reference Thraves74}

Again, despite limited evidence of efficacy, stem cell treatments for AD are being marketed. StemGenex Medical Group provides stem cell therapy to help patients who fail to respond to typical drug treatment, want to reduce their reliance on medication, or want to try stem cell therapy before starting drug treatment.⁷⁵ Similarly, Stem Cell Therapy Plus advertises that it is ‘giving new hope’ to AD patients. ‘Anecdotal evidence shows that the usage of Stem Cell Therapy Plus retards the degenerative process associated with this disease and improves the efficiency of traditional drug treatments…. Unlike traditional Stem Cell Therapy which can only be applied via injection in the selective hospitals/clinics, Stem Cell Therapy Plus delivers stem cells through high-tech bio-active softgel capsules which can be delivered right to your home. All you need to do is to take 1-3 softgel capsules a day at the comfort of your own home.’⁷⁶ The Harvard Stem Cell Institute (HSCI) uses induced pluripotent stem cell technology to direct patient stem cells to become brain cells both affected and not affected by AD. They note that while none of the FDA approved treatments on the market for AD confront the underlying cause of the disease, but merely attempt to alleviate symptoms, by using stem cells HSCI scientists can reveal potential targets for therapeutic intervention by studying the differences between brain cell types, and between those suffering from the disease and those who are healthy.⁷⁷ It should also be noted that, whether stem cells or other physical interventions, any halfway measures that fail to actually treat AD will add to the overall cost of the disease.

Testing for AD, MCI and Predementia

Another area that reflects both the escalating fear of AD and the growth of commercial interests to exploit this fear is pre-symptomatic testing to determine one's risk of developing dementia. Ongoing discoveries in genes, biomarkers, and neuroimaging have the potential to meet the demand for information and provide many advantages possible through early diagnosis, but they also raise ethical issues. Concomitantly, has been the recognition of a predementia diagnosis, MCI which is a condition where an individual has mild but measurable changes in cognitive abilities that are noticeable to the person affected and others, but do not affect the her/his capacity for everyday activities. Approximately 15 to 25 percent of people age 65 or older have MCI, and those with MCI are more likely to develop AD than those without it. A recent review found that an average of 32 percent of individuals with MCI developed AD within 5 years.^{Reference Ward, Tardiff, Dye and Arrighi78} Identifying which individuals with MCI are most likely to develop AD is a major research goal.

In their detailed analysis of the genetics of AD, Alonso Vilatela et al. estimate that the amount of risk of AD attributable to genetics is around 70 percent although others place it lower.^{Reference Alonso, Vilatela and Yescas-Gomez79} Over 100 genes, particularly on chromosomes 9, 10, and 12 have been associated with late-onset AD; while mutations in chromosomes 1, 14, and 21 have been associated with early onset familial AD. Genetic testing has been investigated both in patients with probable AD and in asymptomatic family members. However, for most persons with late-onset AD, there is no reliable genetic predictor of its development. Although persons with one copy of the apolipoprotein E epsilon 4 allele (APOE) have two to five times the risk of AD compared with those who do not carry the gene, the positive predictive value of ApoE-e4 testing in the general population is low, and consensus conferences have been uniform in stating that predictive genetic testing is insufficiently accurate for pre-symptomatic testing.^{Reference Hayden80}

Other recent developments in the identification of biological markers for AD are more promising. Bio-markers include the measurement of levels of total tau protein and other proteins in the blood. Asymptomatic individuals concerned about whether they are susceptible to AD can now arrange for predictive testing, although the tests are not foolproof. The use of these tests has raised ethical issues about pre-symptomatic diagnoses and MCI and about the reactions of patients who undergo such testing.^{Reference Jaret81} Therefore, when researchers recently announced a promising new blood test for AD, reactions were mixed. Most experts welcomed the news, but some worried that, until effective treatments are available, learning that you are likely to develop AD could cause more harm than good. On the positive side, such a test might permit more effective treatment early in the disease progression and motivate people who learn that they are at heightened risk to make healthy changes. Additionally, early detection could allow people to make informed decisions about their care before the symptoms of AD become obstructive – one reason both the Alzheimer's Association and the Alzheimer's Foundation of America support early diagnosis.

On the negative side, a positive result could change a person's outlook on life, making them even more anxious, depressed, and withdrawn and suffer the burden of feeling ashamed. One study found that those who learn they tested positive judge their memories more critically and perform worse on memory tests than those who are not told.⁸² Thus, the stress of learning that you are likely to develop AD could possibly worsen the symptoms of forgetfulness and confusion. Stites and associates found that persons with MCI or AD who were aware of their diagnosis reported lower average satisfaction with daily life, basic functioning, and physical wellbeing, and more difficulties in daily life than those who were unaware, independent of the severity of cognitive impairment. Moreover, those expecting their condition to worsen over time reported greater depression, higher stress, lower quality of daily life, and more cognitive difficulties compared to those unaware of these facts about themselves.^{Reference Stites, Karlawish, Harkins, Rubright and Wolk83} Concern especially is directed toward direct to consumer kits that are readily available commercially that allow wide-scale bio-testing without medical advice or counseling. Furthermore, despite often dramatic headlines announcing a new blood test for AD, for example ‘Alzheimer's disease could be prevented after new blood test breakthrough,’ it is not imminent.^{Reference Knapton84}

Regulatory Status of AD Testing

To date, no FDA-cleared, or regulated, genotyping tests exist, thus, genotyping is generally offered as a laboratory-developed test. Clinical laboratories may develop and validate tests in house and market them as a laboratory service which must meet the general regulatory standards of the Clinical Laboratory Improvement Act (CLIA). In 2012, the FDA approved for the differential diagnosis of AD a brain-imaging technology, Amyvid-PET capable of non-invasively estimating the burden of amyloid plaques. As usual approval for one indication renders the technology a candidate for off-label use based on a physician's judgment. But, what should a physician do if a concerned patient requests off-label use of Amyvid-PET to help her estimate the likelihood that her mild memory complaints are just part of normal aging or are likely to profoundly worsen? Baum summarizes reasons that might justify denial of such a request, including concerns of safety, uncertain benefit, and fair resource allocation, but concludes that there may be certain cases where off-label bio-prediction would be permissible.^{Reference Baum85}

In 2011, the National Institute on Aging and the Alzheimer's Association proposed revised criteria and guidelines for diagnosing AD that include biomarkers. While the diagnostic criteria of the 1984 version were based chiefly on a doctor's clinical judgment, the new criteria incorporate three notable changes. First, they identify two stages of AD: MCI due to AD and dementia due to AD. This contrasts with the earlier criteria where dementia must be apparent. Second, they propose for research purposes criteria for a preclinical phase, occurring before symptoms such as memory loss develop. And third, they incorporate biomarker tests that can indicate the presence or absence of disease, or the risk of developing a disease. Although finding a simple and inexpensive test, such as a blood test, would be ideal for patients and physicians, no test to date has shown the accuracy and reliability needed to diagnose AD based on these criteria.

Similarly, in 1988, the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's and Related Disorders Association defined three diagnostic categories: possible, probable, and definite AD. Definite AD can be confirmed only at autopsy after a brain biopsy confirms the presence of characteristic neurofibrillary tangles. Probable AD is diagnosed clinically when the patient meets core clinical criteria which can be supplemented by tests, including cerebrospinal fluid levels of tau protein or beta amyloid precursor protein.⁸⁶ However, the BlueCross BlueShield Association Technology Evaluation Center (TEC) Assessment concluded that there are insufficient studies to indicate that APOE genotyping provides sufficient sensitivity or specificity to allow genotyping to be used as a diagnostic test in symptomatic individuals. Based on the lack of peer-reviewed literature, genetic testing for AD is considered investigational and, thus, denied coverage by Blue Cross/Blue Shield.⁸⁷ The sensitivity and specificity of genetic testing for indicating which individuals will progress to AD is low, and numerous other factors can affect progression. Moreover, there is no evidence to indicate that genetic testing would change the medical management of the symptomatic patient to improve outcomes. The Joint Practice Guidelines of the American College of Genetics and the National Society of Genetic Counselors do not recommend pediatric testing for AD. Moreover, direct-to-consumer testing of APOE is not advised. Despite these caveats, a growing number of companies are marketing general DNA or specific tests for AD and tapping into the fear of AD.⁸⁸

End-of-Life Decision Making for Alzheimer's Patients

The realities of AD progression, fueled by the fear of AD and its impact on personal autonomy, has also led to considerable apprehension as to how best a person can maintain control over their life process. This has, in turn, leads to a wide array of policy issues, including:

Although there has been a trend towards more acceptance of advance directives for AD over time, they are especially challenging because they involve the authority of the former competent self to govern the welfare of the later, noncompetent self. Critics of advance directives highlight the difficulties in projecting decisions to future states or personal identities of selves that may be drastically different because of physical or mental changes. Furthermore, if the directive includes choosing a proxy, this can result in proxies projecting their own values onto various possible future circumstances when they make decisions for the person. This is problematic because caregivers, especially when burdened by care, tend to report lower scores on quality of life than the patients themselves.⁸⁹ Moreover, Tomlinson and Stott found that health professionals hold more negative views towards assisted dying than patients, the public, and caregivers.^{Reference Tomlinson and Stott90}

Advance directives should be made soon after diagnosis when the person with AD still has the level of judgment and decision-making ability necessary to sign official documents or make medical decisions. Whatever instrument is used, it is important that one understands the range of treatment options available when making decisions to use, withdraw, limit or refuse treatment, especially in the late stage of the disease.⁹¹ These measures range from administering antibiotics to mechanical respiration.

• Antibiotics may be prescribed to treat infections, such as pneumonia and urinary tract, that are common with end-stage AD, but they might not improve the person's condition.

• IV hydration can extend the dying process, but it can physically burden the person by making breathing more difficult. Lack of hydration is a normal part of the dying process and allows a more comfortable death over a period of days.

• Similarly, feeding tubes are sometimes used if a person has difficulty eating or swallowing, but there is no evidence that they offer significant benefits. Moreover, they can result in infections and the need for physical restraints. If artificial nutrition and hydration are started, families will eventually need to decide if or when these treatments should be withdrawn.

• While a respirator can help keep a person who cannot breathe on their own alive, it can cause the body to undergo unneeded stress and cause great discomfort. Thus, many experts discourage CPR for terminally ill patients as it can be painful and traumatic, may leave the person worse off, and is unlikely to prolong life. A DNR order states that no attempts will be made to revive the person.

The Alzheimer's Association points out that refusal or withdrawal of treatment, including tube feeding, antibiotics, CPR or other treatments is not assisted suicide.⁹² Limiting treatments lets the disease take its natural course and supports the person's comfort and dignity. If aggressive medical treatment is refused or withdrawn, a care team should still provide comprehensive physical and emotional care. Instead of seeking a cure or trying to prolong life, palliative care focuses on dignity and quality of remaining life by keeping the person comfortable and pain-free until life ends naturally. It usually excludes medical treatments, tests, and procedures that might cause discomfort.

Table 1 illustrates the possible categories of end-of-life decisions. Passive measures include decisions to withhold or withdraw treatments that might extend a patient's life, while active measures involve direct inducement of death either by providing the means of ending life or assisted suicide. Importantly, these decisions can be voluntary on the part of a competent patient, speculative, or involuntary, against the explicit wishes of the patient. Although passive involuntary could include policies of rationing that deny life-saving resources, involuntary active decisions are presently inconceivable in democracies. Because of the problems discussed above, most such decisions for AD patients fall in the speculative category and will always be open to dispute.^{Reference Smith93}

Table 1.

Categories of End-of-Life Decisions

Source: Blank, 1995: 163.

In the absence of any effective treatments for AD, there is already evidence that persons with MCI and early AD are at risk for suicide or for requesting physician-assisted suicide.⁹⁴ Barak and Aizenberg also observe that suicide attempts are not rare in elderly patients with AD, especially among those with higher levels of daily functioning.^{Reference Barak and Aizenberg95} The ensuing clinical, ethical, and legal dilemmas associated with physician-assisted suicide in the context of AD are a subject of intense debate.^{Reference Humphry and Muramoto96} Clearly, diagnosis has different meanings for different people, who can experience a range of possible reactions. Rabins notes that although about 60 percent of those with AD are unaware that they have a problem, and remain unconvinced of any problem when they are so diagnosed, but, for some, the emotional adjustment is so overwhelming that suicide ensues within months of diagnosis.^{Reference Rabins97}

Active voluntary euthanasia, often termed physician-assisted suicide (PAS), is the active and intentional termination of a patient's life at the explicit request of a patient. Although such practices are highly controversial and illegal in most countries, the laws are more liberal in Belgium, Switzerland, the Netherlands, and an increasing number of US states, such as Oregon, Washington, and Colorado. In 2016, Canada federal legislation permitted PAS for patients with a “serious and incurable illness, disease, or disability” that causes intolerable suffering and in which death was “reasonably foreseeable.” In the Netherlands, where the Euthanasia Act was adopted in 2002, it is legally justified for terminal patents only if the physician is satisfied that the patient's request is voluntary, well-considered, sustained, and well-informed, and that the person is fully competent at the time of the request and perceives his or her situation in terms of unbearable or hopeless suffering. Few experts believe that patients with AD satisfy these criteria and, thus, are ineligible for PAS as the laws are currently written.⁹⁸ At the time when patients are competent to make the decision to end their lives, they often have significantly longer than 6 months left to live, but by the time they have less than 6 months to live, they are often no longer competent by legal standards.^{Reference Guidry99} Although in theory, the Dutch law supports the possibility of having the request substituted by an advanced directive, in practice, this option is difficult to realize, because while an advance directive presupposes a very careful and detailed statement of the wishes, most are very unspecific. Also, most doctors find it unacceptable to perform euthanasia on a person who cannot at that moment express his or her will, nor understand what the physician is about to do.^{Reference de Beaufort and van de Vathorst100}

Given the fear of AD, it is not surprising that in countries where euthanasia or PAS is legal, a growing number of people are drawing up advance directives in which they express the desire to terminate their lives at some stage of the disease. In countries where euthanasia is illegal, clinical experience and anecdotal reports suggest that people are making covert arrangements for some form of assisted suicide in the event of being diagnosed with AD.¹⁰¹ In the Netherlands in 2014, 81 people diagnosed with AD were granted PAS: their doctors either administered the lethal drugs on their request or helped them by handing them the drugs. This was down from 97 in 2013 but substantially higher than other previous years.¹⁰² Almost all these cases involved persons who were in the early stages of the disease, and were considered competent with the capacity to decide about their death. They decided on their death at a stage of their disease when they were still able to make an autonomous choice. Having to decide, while still competent, however, may mean that people die earlier than even they might have preferred, because waiting entails the risk that they will be judged to be incompetent, and then, the opportunity will be gone. The window of opportunity can be narrow and unpredictable.

Another oft-mentioned threat to the voluntariness of a choice for death is the possibility of pressure from family or from society that leads to feelings of a duty to die or to guilt about being alive.¹⁰³ If AD patients are covertly or overtly given the impression that they are a burden to their families and society in general, then their requests to die might not be truly voluntary. In general, those who have severe AD are unable to initiate or carry out the act of killing themselves. Thus, some consider it rational, or at least understandable, for people with less advanced AD to take their own lives even if their quality of life is still relatively good, in the knowledge that in due course (maybe not for some years) they will become more disabled and lack the capacity to affect their own suicide. It is not necessarily the terminal state of severe confusion and total dependence that is feared, but the loss of mental faculties that begin in the earlier stages of the disease.^{Reference McCrae104} For instance, the first person to die using Dr. Kevorkian's ‘suicide machine’ was a 54-year-old woman with early AD, who was said to have persuaded him that her decision was rational and the result of long and careful reflection. Similarly, in 2011, a 64-year-old woman, who had declared for several years that she wanted to be euthanized, was the first documented case of a person with advanced AD to be euthanized in the Netherlands. Until then, patients dying by euthanasia were at very early stages of dementia.^{Reference Kouwenhoven, Raijmakers, van Delden, Rietjens and van Tol105}

The first reported case of a British citizen choosing to end his own life took place at Dignitas assisted suicide center in Switzerland in 2013. The 83-year-old man was in the early stages of AD and wanted to avoid the debilitating process and make certain that his family did not see him suffer. In a survey of 725 British adults at the time, 55 percent agreed to a physician-assisted death for mild and moderate cases and 60 percent for severe cases of AD. Such results show that many see AD as a fate worse than death and anticipate a miserable and humiliating existence with little capacity for resilience and adaptation. The assisted dying campaign, therefore, has focused not on pain, but on perceived loss of dignity. The Kantian view is that dignity derives from autonomy, but this deprives people with advanced AD of a defining quality of human life. An unintended consequence of this rationale for euthanasia is to imply that AD at the terminal stage is undignified. This perception could extend to AD overall, devaluing the status of people with this condition and perpetuating the poor standards of care often found in institutional settings.^{Reference McCrae and Bloomfield106}

Prosporo rejects the prevalent practice of letting an arbitrary infection determine the death of a patient as putting the patient and family through unnecessary suffering.^{Reference Prosporo107} Because infections have varying degrees of severity in how quickly they may be fatal or the pain they incur, euthanasia with advance directive is the most caring means of respecting the interests of patients with end-stage AD. Since AD destroys the neurobiological basis for the access consciousness necessary for moral capacity, the formerly expressed interest should be respected. AD patients are vulnerable to be in ‘Catch 22’ situation because of the difficulty, if not inability, to express their own interests. Moreover, abuse of AD patients is common, ranging from 27.9 to 62.3 percent facing verbal abuse and 3.5 to 23.1 percent physical abuse.^{Reference Dong108} The utmost caution must be taken when deciding treatment options for AD patients to ensure that their interests are adequately regarded.

Johnstone, however, decries the ‘Alzheimerisation’ of the euthanasia debate, arguing that the way AD is portrayed by advocacy groups and the media, as the ‘disease of the century’ that is poised to have a near catastrophic impact on the world's health care system, is having undue influence on the euthanasia debate.^{Reference Johnstone109} This representation of the disease, along with other oft-used terms such as ‘living dead’, a ‘funeral that never ends’ and a ‘fate worse than death’, places AD as a ‘soft target’ in the euthanasia debate because it plays to people's fears of developing the disease and what it symbolizes. It positions AD as something that requires a remedy; that remedy increasingly being pre-emptive and beneficent euthanasia. Johnstone acknowledges that euthanasia is a polarizing and emotive issue, however she warns that the public can be unduly swayed by the way the media and pro-euthanasia groups frame the issue as ‘simply a matter of choice’ often through highly personalized, individual experiences.