April 14 - 15, 2016
The redefinition of Alzheimer’s disease and its social and ethical consequences
- Milne Richard, University of Cambridge
- Badger Shirlene, University of Cambridge, Dr Senior Research Associate
- Jason Karlawish, University of Pennsylvania, Professor of Medicine, Medical Ethics and Health Policy, and Neurology
Alzheimer’s disease is an increasingly pressing social, political and economic concern. However, despite significant investment in multiple candidate therapeutics, research has as yet failed to discover effective disease-modifying therapies. One explanation for this failure has been that interventions are being tested too late in the disease process. Consequently, researchers increasingly emphasise the need to identify and then intervene in the neurodegenerative process at an earlier stage. New guidelines restructuring the course of Alzheimer’s disease have been produced in both Europe and the USA. Guidelines from the National Institute of Ageing-Alzheimer’s Association workgroup (Albert et al. 2011; Sperling et al. 2011), along with those outlined by the International Working Group (2007, 2014) establish criteria for a preclinical or “at risk” stage of AD that precedes the onset of symptoms.
The symposium will bring together social scientists and ethicists conducting research on the scientific practices associated with the redefinition of Alzheimer’s disease or in closely related fields. Over two days, from a range of disciplinary perspectives, we will explore the boundary between the clinical and research uses of biomarkers and how, as this boundary shifts, it changes how we study, care for and, as a society, approach Alzheimer’s disease.
Symposium sessions will explore three key dimensions of the redefinition of Alzheimer’s disease, featuring empirical and theoretical papers presenting work conducted on Alzheimer’s disease and cognate areas.
1. The ethical, legal and social implications of preclinical diagnosis
Early diagnosis coupled with an effective intervention promise to reduce the burden of persons living in the severe stages of the disease, but this strategy also presents ethical, legal and social challenges in the short, intermediate and long term. These include how to conduct research that requires enrolling cognitively healthy but biomarker positive individuals, and the consequences of the redefinition of disease categories. More widely, they include issues related to the potential stigma associated with preclinical AD, and the implications for insurance and employment.
2. The translational challenges of biomarker-based criteria
The translation of biomarkers from research to clinical settings presents differing challenges in the short and long-term. Biomarkers are currently framed as a research tool, primarily to establish endpoints for pharmaceutical trials. As such, they are not validated for clinical use. However, research tests may be included in clinical records, rendering the boundary between research and clinical applications increasingly porous (CDCIG 2010; Johnson et al. 2013). In addition, research use may lead to changes in clinical practice where challenges include the ‘scale-up’ of new practices of diagnosis and intervention, and their translation into policy and practice, engaging issues of value and the cost we are willing to bear to attain it.
3. Biomarkers, the normal and the pathological
As biomarkers to enter into clinical practice, they will begin to transform how we think about the borders between health and disease and what constitutes ‘normal’ ageing and cognition. As in other disease areas (Greene 2007), this will contribute to the creation of new market spaces and new approaches to prevention and therapy, including the emergence of personalised ‘theranostics’. This enmeshed relationship between a biological diagnostic marker and therapy has wider implications for the social and cultural infrastructure that defines and sustains a disease. It raises questions about the relationship between disease and the owners of markers used to both define and treat it, and issues of quality, access and equity associated with the tools and expertise required in clinical practice, raising questions of access, equity and quality.
The symposium will contribute to establishing a community of established and early career researchers working in this area, identifying key areas of ethical concern, highlighting sites at which social scientific investigation and intervention is most needed, and suggesting new directions for research, practice and policy. It will bring together researchers involved in work on the ethical and social implications of several major Alzheimer’s research initiatives, including the MRC Dementias Platform UK (DPUK), the IMI European Prevention of Alzheimer’s Disease project (EPAD) and the US Anti-Amyloid treatment in Asymptomatic AD (A4) project. It will build on and extend prior meetings including the Fundació Pasqual Maragall’s 2014 symposium on the ethics of research on presymptomatic, “at risk” and prodromal AD.
Albert, Marilyn S. et al. 2011. “The Diagnosis of Mild Cognitive Impairment due to Alzheimer’s Disease: Recommendations from the National Institute on Aging-Alzheimer's Association Workgroups on Diagnostic Guidelines for Alzheimer's Disease.” Alzheimer’s & dementia : the journal of the Alzheimer's Association 7(3):270–79.
CDCIG. 2010 Cochrane Dementia Group Response to Proposal for New Diagnostic Criteria https://dementia.cochrane.org/news/cochrane-dementia-group-response-proposal-new-diagnostic-criteria
Dubois, Bruno et al. 2007. “Research Criteria for the Diagnosis of Alzheimer’s Disease: Revising the NINCDS–ADRDA Criteria.” The Lancet Neurology 6(8):734–46.
Dubois, Bruno et al. 2014. “Advancing Research Diagnostic Criteria for Alzheimer’s Disease: The IWG-2 Criteria.” Lancet Neurology 13(6):614–29.
Greene, Jeremy A. 2007. Prescribing by Numbers: Drugs and the Definition of Disease. Johns Hopkins University Press.
Johnson, Keith A. et al. 2013. “Appropriate Use Criteria for Amyloid PET: A Report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association.” Alzheimer’s & Dementia : the journal of the Alzheimer's Association 9(1):e – 1–16.
Karlawish, Jason. 2011. “Addressing the Ethical, Policy, and Social Challenges of Preclinical Alzheimer Disease.” Neurology 77(15):1487–93.
Karlawish J: How Are We Going To Live With Alzheimer's Disease? Health Affairs 33(4): 541-546, April 2014.
Kim SYH, Karlawish J, Berkman B.: Ethics of Genetic and Biomarker Test Disclosures in Neurodegenerative Disease Prevention Trials. Neurology in press.
Leibing, Annette. 2014. “The Earlier the Better: Alzheimer’s Prevention, Early Detection, and the Quest for Pharmacological Interventions.” Culture, Medicine and Psychiatry 38(2):217–36.
Lock, Margaret. 2013. The Alzheimer Conundrum: Entanglements of Dementia and Aging. Princeton: Princeton University Press.
Sperling, Reisa A. et al. 2011. “Toward Defining the Preclinical Stages of Alzheimer’s Disease: Recommendations from the National Institute on Aging-Alzheimer's Association Workgroups on Diagnostic Guidelines for Alzheimer's Disease.” Alzheimer’s & Dementia : the journal of the Alzheimer's Association 7(3):280–92.