The new AD definitions and the ethical implications of the way we represent health and disease
2016: Ethical issues linked to the changing definitions/use of terms related to Alzheimer’s disease
The new and changing definition of Alzheimer’s disease
In 1906, Dr Alois Alzheimer fi rst described the symptoms and the amyloid plaques and neurobrillary tangles in the brain, which have come to be considered as the hallmarks of Alzheimer’s disease (AD). Now, more than a hundred years later, the exact causes of AD are still unknown and a cure is not available.
However, signifi cant progress has been made in understanding AD and especially in biomarker research. A biomarker is a biological substance (e.g. a protein that may or may not be detected in a body fl uid) or a structure (such as some changes in size in specifi c parts of the brain) that is considered as a “mark” indicative of a disease. Biomarkers can change, appear or disappear during the development of a particular pathology. They can be detected through tests and technologies such as neuroimaging (brain scans) and through the analysis of cerebrospinal fl uid (CSF – a body fl uid found around the brain and spine) and blood.
Signs of abnormal changes in the brain associated with AD can now be detected long before the occurrence of any symptoms of AD dementia. These recent advances are also leading to a radical change in the way that AD is conceptualised (i.e. as a manifestation of the disease which can be observed before the occurrence of any symptoms of dementia). In this fi rst section of the discussion paper, we provide a brief overview of the developments which led to this new way of understanding AD. A more detailed explanation can be found in Appendix 2.
In 1984, the “NINCDS-ADRDA” criteria for AD were proposed by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (McKhann 1984). These criteria permit a probable clinical diagnosis of AD that can be confi rmed as defi nite only aft er the person’s death if an autopsy is performed and the plaques and tangles mentioned earlier are observed. These criteria therefore result in a long period of uncertainty because the definite diagnosis of AD can only be made aft er a post mortem analysis of the person’s brain. Furthermore, researchers have shown that these criteria have low accuracy (Hyman & Trojanowski 1997; Beach et al. 2012) and that only 70% of diagnoses were correct, the others being false positive or false negative cases.
The last decade of research has been a testimony to changes in the conceptual approach to AD. Two main research groups comprised of world-renowned scientists and clinicians specialised in AD have been developing criteria aiming at improving AD diagnosis and related research. The fi rst is the International Working Group (IWG and IWG2) led by Dubois et al. (2007, 2014 & 2016) and the second is the National Institute on Aging and the Alzheimer’s Association (NIA-AA) (see Jack et al., McKhann et al., Albert et al. and Sperling et al., all in 2011). Despite a few diff erences, both research groups agree that AD should be considered as a continuum. Both groups also agree on the importance of biomarkers in the procedure leading to a potential diagnosis of AD dementia. In order to reach a consensus on the diagnostic criteria and harmonisation of standards for research, IWG and IWG2 developed and recently revised a new consensus lexicon to unify all defi nitions, stages and processes (Dubois et al. 2010 & 2016). According to this new lexicon, the defi nition of AD has been extended to encompass the full spectrum of the disease, including both pre-dementia (preclinical and prodromal AD or MCI due to AD) and dementia phases and its diagnosis can be established in vivo (in a living person).
The term “AD pathology” is used to refer to the changes in the brain underlying AD, irrespective of the stage or phase (i.e. with or without dementia). The following table summarises the diff erent stages/syndromes along the AD continuum (adapted from the lexicon by Dubois et al. 2010 & 2016). The preclinical terminology is currently only proposed for use in the context of research. The other terms are used in the context of diagnosis and research.
To facilitate discussion, in this paper, we will refer to the IWG and NIA-AA collectively as “the new AD model” and specify “IWG” or “NIA-AA”, if necessary, to distinguish between the two approaches. AD dementia is the most advanced of three phases described in the new AD continuum model. We will therefore use the term “AD dementia” whenever referring to dementia due to AD. Most of the ethical issues addressed in this report are related to the conceptualisation of AD as a continuum and to the subsequent extension of the term AD to include a preclinical phase and a pre-dementia phase. The use of the term “AD dementia” in relation to diff erent diagnostic approaches and defi nitions should therefore not be problematic. We would like to emphasise that our use of the newly developed terms related to AD in this discussion paper is for the purpose of refl ecting on potential ethical issues they raise. Our use of the new terms in this document should therefore not be interpreted as an unquestioning acceptance of them or of the AD models on which they are based.
Representations of health and disease
At first glance, questions regarding concepts of health and disease seem to refer to purely scientifi c facts. Whether a specifi c condition is a disease or a particular person is aff ected by it seems to be just a matter of objective natural, biological or medical states that leave little room for interpretation or even controversy. However, it is important to acknowledge that conceptual representations of disease also have evaluative and normative implications as well as individual and social consequences: they are based on certain value judgments and decisions and aff ect the ways we perceive and treat ourselves and others (Fulford 1989). Therefore changes in their defi nition and/or use deserve ethical attention and refl ection.
In general, concepts of health and disease are based on theoretical assumptions and defi nitional decisions that require justifi cation (e.g. the decision to set the cut-off value defi ning hypertension at around 140/90 rather than 135/90 or 145/95 mmHg). They rely on certain common standards of normality, functioning, wellbeing or human fl ourishing. Some philosophical theories suggest that these standards of health and disease are ultimately individual or social values and norms. From this perspective, being healthy means having the ability to pursue certain acknowledged vital goals and having a disease accordingly translates into being in an individually undesirable or socially deviant state that calls for corrective measures (Nordenfelt 1995).
Furthermore, assigning the label “disease” also has many far-reaching and morally ambivalent practical consequences. We have specifi c expectations towards people who are ill and oft en treat them diff erently. Having a disease or being ill confers certain moral and legal rights and responsibilities, for example regarding personal behaviour (e.g. we are usually more indulgent and considerate vis-avis people with health conditions), working life (e.g. sick leave, sickness benefi ts etc.), coverage of healthcare costs (health insurance) or legal liabilities (Parsons 1951). Sometimes, disease labels can also be used to stigmatise people or discriminate against them as in the case of HIV/AIDS or certain psychiatric disorders (Goff man 1963).
The history of Alzheimer’s disease (AD) provides an example of changing views with social and moral consequences. When Alois Alzheimer fi rst described the “peculiar disease of the cerebral cortex” that was later named aft er him, the case he had in mind was an instance of what we now call early onset AD dementia. Consequently, for a long time, AD dementia was by defi nition a rather rare disease aff ecting people between 45 and 65. Since the 1970s, however, scientists, politicians and activists have made eff orts to eliminate the age criterion. In 1980, AD dementia was included in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) as a diagnostic category without any age restriction (Ballenger 2006a, 101–112).
When the age criterion for AD dementia was dropped, older people who had previously been vaguely described as “senile” increasingly found themselves confronted with a specifi c medical diagnosis. This conceptual shift had many consequences. On one hand, it facilitated a general re-evaluation of ageing. Mental deterioration or diminished control were no longer considered signs of an age-associated weakness of character or moral degeneration, or as part of normal ageing. Instead, they were increasingly recognised as symptoms of a distinct medical condition. This was one reason why the elimination of the age criterion was actively supported and applauded by prominent senior advocates. However, replacing senile dementia with AD dementia did not eradicate stigma and age discrimination. “Alzheimer’s” became a concept associated with derogative labels like “living death” or “empty shells” (Ballenger 2006b). Moreover, the “medicalisation” of senility (i.e. linking what was previously described as senility to a medical diagnosis of AD dementia) may have increased the tendency to pathologise old age, to neglect the role of psychological and social factors and to prioritise medical research and treatment over care or social support (Bond 1992).
Since conceptual questions regarding health and disease do not just refer to objective scientifi c facts, but also to certain interpretative and evaluative matters, the current changes in the defi nition of AD need critical refl ection in view of their ethical implications and consequences. This refl ection becomes particularly relevant insofar as the newly introduced early stages are not only employed as methodologically useful conceptual constructs in neuroscientifi c research, but increasingly fi nd their way into clinical practice and diagnostic procedures (Schicktanz et al. 2014). The fact that there are diff erent evolving terminologies in the United States and in Europe underlines the need for clarifi cation and standardisation. Aft er all, these terminologies can have diff erent practical and ethical implications, some of them rather far reaching. Thus, taking the NIA-AA terminology literally, a person without any clinical symptoms but an increased risk of developing MCI due to AD or AD dementia (based on having a positive biomarker specifi cally for AD) actually already counts as having (a “preclinical” stage of) the disease (Sperling et al. 2011, 282).
In general, the defi nition of earlier stages of AD without any clinical symptoms amounts to a considerable expansion of the concept. It becomes possible to be classifi ed as having AD without showing any symptoms of dementia such as memory loss. This could have serious consequences for the people concerned (e.g. stress, insecurity, worries about insurance, self-stigmatisation and depression). It could also spread stigma to larger groups of the population who now count as diseased, turning them into patients and their whole demeanour into potential psychological and behavioural symptoms. At the same time, however, learning that larger segments of the general population could be aff ected might also promote a normalisation and thus a de-stigmatisation of AD.
Furthermore, the defi nition of stages of AD prior to AD dementia seems to be part of a general trend: Health and disease are no longer simply two discrete, mutually exclusive states; they become a matter of graduation, of probabilities, of risk factors that need to be identifi ed, calculated and controlled (Karlawish 2011). This might help reduce the tendency to oversimplify notions of health and disease and thus also alleviate stigma (since there is no clear distinction but rather a continuum between people with and without dementia). However, it could also promote a view in which developing the disease becomes a sign of personal failure (e.g. of a reckless lifestyle or failure to take preventive measures) and people are eventually blamed for having AD, which may in turn increase the likelihood of stigmatisation (Weiner, Perry & Magnusson 1988). In any case, the knowledge that many people might have “silent” AD might lead to increased stigma, with any instance of forgetfulness being perceived as a sign of dementia and suggesting the need for treatment.
Finally, the concept of AD is no longer limited to expert biomedical discourses, but is increasingly being adopted and integrated into public imagination and popular culture, gaining multiple new interpretations, evaluations and functions in a variety of cultural domains (e.g. literature, visual arts, fi lm and the media). Therefore, changing biomedical conceptions of AD are not just a question aff ecting scientifi c research or healthcare. They may have great infl uence on public representations of the condition as well (Swinnen & Schweda 2015), hence the importance of involving the public in debates surrounding the changing defi nitions of AD.
Last Updated: Friday 17 February 2017