Skip to main content
Erschienen in: Journal of Bioethical Inquiry 2/2022

19.03.2022 | Original Research

Should Doctors Offer Biomarker Testing to Those Afraid to Develop Alzheimer’s Dementia?

Applying the Method of Reflective Equilibrium for a Clinical Dilemma

verfasst von: Marthe Smedinga, Eline M. Bunnik, Edo Richard, Maartje H. N. Schermer

Erschienen in: Journal of Bioethical Inquiry | Ausgabe 2/2022

Einloggen, um Zugang zu erhalten

Abstract

An increasing number of people seek medical attention for mild cognitive symptoms at older age, worried that they might develop Alzheimer’s disease. Some clinical practice guidelines suggest offering biomarker testing in such cases, using a brain scan or a lumbar puncture, to improve diagnostic certainty about Alzheimer’s disease and enable an earlier diagnosis. Critics, on the other hand, point out that there is no effective Alzheimer treatment available and argue that biomarker tests lack clinical validity. The debate on the ethical desirability of biomarker testing is currently polarized; advocates and opponents tend to focus on their own line of arguments. In this paper, we show how the method of reflective equilibrium (RE) can be used to systematically weigh the relevant arguments on both sides of the debate to decide whether to offer Alzheimer biomarker testing. In the tradition of RE, we reflect upon these arguments in light of their coherence with other argumentative elements, including relevant facts (e.g. on the clinical validity of the test), ethical principles, and theories on societal ideals or relevant concepts, such as autonomy. Our stance in the debate therefore rests upon previously set out in-depth arguments and reflects a wide societal perspective.
Fußnoten
1
Notably, there is a small difference in pre- and post-test probability because dementia is a relatively common disease
 
2
One could argue that feelings of relief or a confirmation of worries would be simply misplaced in response to receiving a (uncertain) risk status. In the context of clinical practice, however, making a prognosis and assumptions about future health based on risk information would be the exact purpose of testing these biomarkers and is therefore hard to avoid.
 
Literatur
Zurück zum Zitat Anderson, R.M., C. Hadjichrysanthou, S. Evans, and M.M. Wong. 2017. Why do so many clinical trials of therapies for Alzheimer's disease fail? Lancet 390(10110): 2327-2329. Anderson, R.M., C. Hadjichrysanthou, S. Evans, and M.M. Wong. 2017. Why do so many clinical trials of therapies for Alzheimer's disease fail? Lancet 390(10110): 2327-2329.
Zurück zum Zitat Alzheimer Europe. 2017. Discussion paper on ethical issues linked to the changing definitions/use of terms related to AD. Luxembourg: Alzheimer Europe. Alzheimer Europe. 2017. Discussion paper on ethical issues linked to the changing definitions/use of terms related to AD. Luxembourg: Alzheimer Europe.
Zurück zum Zitat Arras, J.D., J.F. Childress, and M. Adams. 2017. Methods in bioethics: The way we reason now. New York, NY: Oxford University Press. Arras, J.D., J.F. Childress, and M. Adams. 2017. Methods in bioethics: The way we reason now. New York, NY: Oxford University Press.
Zurück zum Zitat Barthel, H., and O. Sabri. 2017. Clinical use and utility of Amyloid imaging. Journal of Nuclear Medicine 58(11): 1711-1717. Barthel, H., and O. Sabri. 2017. Clinical use and utility of Amyloid imaging. Journal of Nuclear Medicine 58(11): 1711-1717.
Zurück zum Zitat Baum, M.L. 2016. Patient requests for off-label bioprediction of dementia. Cambridge Quarterly of Healtharec Ethics 25(4): 686-690. Baum, M.L. 2016. Patient requests for off-label bioprediction of dementia. Cambridge Quarterly of Healtharec Ethics 25(4): 686-690.
Zurück zum Zitat Beauchamp, T.L., and J.F. Childress. 2001. Principles of biomedical ethics. 5th ed. New York, N.Y.: Oxford University Press. Beauchamp, T.L., and J.F. Childress. 2001. Principles of biomedical ethics. 5th ed. New York, N.Y.: Oxford University Press.
Zurück zum Zitat Bunnik, E. M, E. Richard, R. Milne, and M.H.N. Schermer. 2018. On the personal utility of Alzheimer’s disease-related biomarker testing in the research context. Journal of Medical Ethics 44(12): 830-834. Bunnik, E. M, E. Richard, R. Milne, and M.H.N. Schermer. 2018. On the personal utility of Alzheimer’s disease-related biomarker testing in the research context. Journal of Medical Ethics 44(12): 830-834.
Zurück zum Zitat Daniels, N. 1979. Wide reflective equilibrium and theory acceptance in ethics. The Journal of Philosophy 76(5): 256-282. Daniels, N. 1979. Wide reflective equilibrium and theory acceptance in ethics. The Journal of Philosophy 76(5): 256-282.
Zurück zum Zitat De Vries, M., and E. Van Leeuwen. 2010. Reflective equilibrium and empirical data: Third person moral experiences in empirical medical ethics. Bioethics 24(9): 490-498. De Vries, M., and E. Van Leeuwen. 2010. Reflective equilibrium and empirical data: Third person moral experiences in empirical medical ethics. Bioethics 24(9): 490-498.
Zurück zum Zitat de Wilde, A., R. Ossenkoppele, W. Pelkmans, et al. 2019. Assessment of the appropriate use criteria for amyloid PET in an unselected memory clinic cohort: The ABIDE project. Alzheimers Dement 15(11): 1458-1467. de Wilde, A., R. Ossenkoppele, W. Pelkmans, et al. 2019. Assessment of the appropriate use criteria for amyloid PET in an unselected memory clinic cohort: The ABIDE project. Alzheimers Dement 15(11): 1458-1467.
Zurück zum Zitat de Wilde, A., M.M. van Buchem, and R.H.J. Otten, et al. 2018. Disclosure of amyloid positron emission tomography results to individuals without dementia: A systematic review. Alzheimers Research and Therapy 10(1): 72. de Wilde, A., M.M. van Buchem, and R.H.J. Otten, et al. 2018. Disclosure of amyloid positron emission tomography results to individuals without dementia: A systematic review. Alzheimers Research and Therapy 10(1): 72.
Zurück zum Zitat Dubois, B., H.H. Feldman, C. Jacova, et al. 2007. Research criteria for the diagnosis of Alzheimer’s disease: Revising the NINCDS-ADRDA criteria. Lancet Neurology 6 (8): 734-746. Dubois, B., H.H. Feldman, C. Jacova, et al. 2007. Research criteria for the diagnosis of Alzheimer’s disease: Revising the NINCDS-ADRDA criteria. Lancet Neurology 6 (8): 734-746.
Zurück zum Zitat Frisoni, G.B., M. Boccardi, F. Barkhof, et al. 2017. Strategic roadmap for an early diagnosis of Alzheimer’s disease based on biomarkers. Lancet Neurology 16(8): 661-676. Frisoni, G.B., M. Boccardi, F. Barkhof, et al. 2017. Strategic roadmap for an early diagnosis of Alzheimer’s disease based on biomarkers. Lancet Neurology 16(8): 661-676.
Zurück zum Zitat Gruters, A.A.A., I. Ramakers, R.P.C. Kessels, et al. 2019. Development of memory clinics in the Netherlands over the last 20 years. International Journal of Geriatric Psychiatry 34(8): 1267-1274. Gruters, A.A.A., I. Ramakers, R.P.C. Kessels, et al. 2019. Development of memory clinics in the Netherlands over the last 20 years. International Journal of Geriatric Psychiatry 34(8): 1267-1274.
Zurück zum Zitat Guerra, U.P., F.M. Nobili, A. Padovani et al. 2015. Recommendations from the Italian Interdisciplinary Working Group (AIMN, AIP, SINDEM) for the utilization of amyloid imaging in clinical practice. Neurological Science 36(6): 1075-1081. Guerra, U.P., F.M. Nobili, A. Padovani et al. 2015. Recommendations from the Italian Interdisciplinary Working Group (AIMN, AIP, SINDEM) for the utilization of amyloid imaging in clinical practice. Neurological Science 36(6): 1075-1081.
Zurück zum Zitat Heister, D., J.B. Brewer, S. Magda, K. Blennow, L.K. McEvoy, and Initiative Alzheimer’s Disease Neuroimaging. 2011. Predicting MCI outcome with clinically available MRI and CSF biomarkers. Neurology 77(17): 1619-1628. Heister, D., J.B. Brewer, S. Magda, K. Blennow, L.K. McEvoy, and Initiative Alzheimer’s Disease Neuroimaging. 2011. Predicting MCI outcome with clinically available MRI and CSF biomarkers. Neurology 77(17): 1619-1628.
Zurück zum Zitat Ismaili M’hamdi, H., and I. de Beaufort. 2018. Forced caesareans: Applying ordinary standards to an extraordinary case. Journal of Medical Ethics 47(4): 233-238. Ismaili M’hamdi, H., and I. de Beaufort. 2018. Forced caesareans: Applying ordinary standards to an extraordinary case. Journal of Medical Ethics 47(4): 233-238.
Zurück zum Zitat Jack, C.R., Jr., D.A. Bennett, K. Blennow et al. 2018. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement 14(4): 535-562. Jack, C.R., Jr., D.A. Bennett, K. Blennow et al. 2018. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement 14(4): 535-562.
Zurück zum Zitat Jansen, W.J., R. Ossenkoppele, D.L. Knol et al. 2015. Prevalence of cerebral amyloid pathology in persons without dementia: A meta-analysis. JAMA 313(19): 1924-1938. Jansen, W.J., R. Ossenkoppele, D.L. Knol et al. 2015. Prevalence of cerebral amyloid pathology in persons without dementia: A meta-analysis. JAMA 313(19): 1924-1938.
Zurück zum Zitat Johnson, K.A., S. Minoshima, N.I. Bohnen 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. Alzheimers Dement 9(1): e-1-16. Johnson, K.A., S. Minoshima, N.I. Bohnen 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. Alzheimers Dement 9(1): e-1-16.
Zurück zum Zitat Koepsell, T.D., and S.E. Monsell. 2012. Reversion from mild cognitive impairment to normal or near-normal cognition: Risk factors and prognosis. Neurology 79(15): 1591-1598.CrossRef Koepsell, T.D., and S.E. Monsell. 2012. Reversion from mild cognitive impairment to normal or near-normal cognition: Risk factors and prognosis. Neurology 79(15): 1591-1598.CrossRef
Zurück zum Zitat Laan, A.L. van der. 2016. Grey matters: Emergent biomarkers and good Alzheimer’s diagnostics. In Emerging technologies for diagnosing Alzheimer's Disease, edited by M. Boenink, H. van Lente, and E. Moors, 103-121. Palgrave Macmillan, London. Laan, A.L. van der. 2016. Grey matters: Emergent biomarkers and good Alzheimer’s diagnostics. In Emerging technologies for diagnosing Alzheimer's Disease, edited by M. Boenink, H. van Lente, and E. Moors, 103-121. Palgrave Macmillan, London.
Zurück zum Zitat Largent, E.A., K. Harkins, C.H. van Dyck, S. Hachey, P. Sankar, and J. Karlawish. 2020. Cognitively unimpaired adults’ reactions to disclosure of amyloid PET scan results. PloS one 15(2): e0229137. Largent, E.A., K. Harkins, C.H. van Dyck, S. Hachey, P. Sankar, and J. Karlawish. 2020. Cognitively unimpaired adults’ reactions to disclosure of amyloid PET scan results. PloS one 15(2): e0229137.
Zurück zum Zitat Le Couteur, D.G., J. Doust, H. Creasey, and C. Brayne. 2013. Political drive to screen for pre-dementia: Not evidence based and ignores the harms of diagnosis. BMJ 347: f5125. Le Couteur, D.G., J. Doust, H. Creasey, and C. Brayne. 2013. Political drive to screen for pre-dementia: Not evidence based and ignores the harms of diagnosis. BMJ 347: f5125.
Zurück zum Zitat Martinez, G., R.W. Vernooij, P. Fuentes Padilla et al. 2017. 18F PET with florbetapir for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database of Systematic Reviews 11: CD012216. Martinez, G., R.W. Vernooij, P. Fuentes Padilla et al. 2017. 18F PET with florbetapir for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database of Systematic Reviews 11: CD012216.
Zurück zum Zitat Martinez, G., R.W. Vernooij, P. Fuentes Padilla et al. 2017a. 18F PET with florbetaben for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database of Systematic Reviews 11: CD012883. Martinez, G., R.W. Vernooij, P. Fuentes Padilla et al. 2017a. 18F PET with florbetaben for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database of Systematic Reviews 11: CD012883.
Zurück zum Zitat Martinez, G., R.W. Vernooij, P. Fuentes Padilla et al. 2017b. 18F PET with flutemetamol for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database of Systematic Reviews 11: CD012884. Martinez, G., R.W. Vernooij, P. Fuentes Padilla et al. 2017b. 18F PET with flutemetamol for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database of Systematic Reviews 11: CD012884.
Zurück zum Zitat McKhann, G., D. Drachman, M. Folstein et al. 1984. Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34(7): 939-944. McKhann, G., D. Drachman, M. Folstein et al. 1984. Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34(7): 939-944.
Zurück zum Zitat Miller, H., J. Tan, J.M. Clayton, A. et al. 2019. Patient experiences of nurse-facilitated advance care planning in a general practice setting: A qualitative study. BMC Palliative Care 18(1): 25. Miller, H., J. Tan, J.M. Clayton, A. et al. 2019. Patient experiences of nurse-facilitated advance care planning in a general practice setting: A qualitative study. BMC Palliative Care 18(1): 25.
Zurück zum Zitat Petersen, R.C., O. Lopez, M.J. Armstrong et al. 2018. Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 90(3): 126-135. Petersen, R.C., O. Lopez, M.J. Armstrong et al. 2018. Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 90(3): 126-135.
Zurück zum Zitat Rabinovici, G.D., C. Gatsonis, C. Apgar, K. et al. 2019. Association of Amyloid Positron Emission Tomography with subsequent change in clinical management among medicare beneficiaries with mild cognitive impairment or dementia. JAMA 321(13): 1286-1294. Rabinovici, G.D., C. Gatsonis, C. Apgar, K. et al. 2019. Association of Amyloid Positron Emission Tomography with subsequent change in clinical management among medicare beneficiaries with mild cognitive impairment or dementia. JAMA 321(13): 1286-1294.
Zurück zum Zitat Rawls, J. 1971. A theory of justice. Harvard university press. Rawls, J. 1971. A theory of justice. Harvard university press.
Zurück zum Zitat ———. 1975. The independence of moral theory. In John Rawls: Collected papers, edited by S.R. Freeman, 286–302. Cambridge, Mass.: Harvard University Press. ———. 1975. The independence of moral theory. In John Rawls: Collected papers, edited by S.R. Freeman, 286–302. Cambridge, Mass.: Harvard University Press.
Zurück zum Zitat Richard, E., B.A. Schmand, P. Eikelenboom, and W.A. Van Gool. 2013. MRI and cerebrospinal fluid biomarkers for predicting progression to Alzheimer”s disease in patients with mild cognitive impairment: A diagnostic accuracy study. BMJ Open 3(6). Richard, E., B.A. Schmand, P. Eikelenboom, and W.A. Van Gool. 2013. MRI and cerebrospinal fluid biomarkers for predicting progression to Alzheimer”s disease in patients with mild cognitive impairment: A diagnostic accuracy study. BMJ Open 3(6).
Zurück zum Zitat Rodriguez-Gomez, O., A. Rodrigo, F. Iradier et al. 2019. The MOPEAD project: Advancing patient engagement for the detection of “hidden” undiagnosed cases of Alzheimer’s disease in the community. Alzheimers and Dementia 15(6): 828-839. Rodriguez-Gomez, O., A. Rodrigo, F. Iradier et al. 2019. The MOPEAD project: Advancing patient engagement for the detection of “hidden” undiagnosed cases of Alzheimer’s disease in the community. Alzheimers and Dementia 15(6): 828-839.
Zurück zum Zitat Schermer, M.H.N., and E. Richard. 2019. On the reconceptualization of Alzheimer’s disease. Bioethics 33(1): 138-145. Schermer, M.H.N., and E. Richard. 2019. On the reconceptualization of Alzheimer’s disease. Bioethics 33(1): 138-145.
Zurück zum Zitat Shaw, L.M., J. Arias, K. Blennow, et al. 2018. Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of Alzheimer’s disease. Alzheimers and Dementia 14(11): 1505-1521. Shaw, L.M., J. Arias, K. Blennow, et al. 2018. Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of Alzheimer’s disease. Alzheimers and Dementia 14(11): 1505-1521.
Zurück zum Zitat Smedinga, M., K. Tromp, M.H.N. Schermer, and E. Richard. 2018. Ethical arguments concerning the use of Alzheimer’s Disease biomarkers in individuals with no or mild cognitive impairment: A systematic review and framework for discussion. Journal of Alzheimer’s Disease 66(4): 1309-1322. Smedinga, M., K. Tromp, M.H.N. Schermer, and E. Richard. 2018. Ethical arguments concerning the use of Alzheimer’s Disease biomarkers in individuals with no or mild cognitive impairment: A systematic review and framework for discussion. Journal of Alzheimer’s Disease 66(4): 1309-1322.
Zurück zum Zitat Smedinga, M., E.M. Bunnik, E. Richard, and M.H. Schermer. 2021. The framing of “Alzheimer’s disease”: Differences between scientific and lay literature and their ethical implications. The Gerontologist 61(5): 746-755. Smedinga, M., E.M. Bunnik, E. Richard, and M.H. Schermer. 2021. The framing of “Alzheimer’s disease”: Differences between scientific and lay literature and their ethical implications. The Gerontologist 61(5): 746-755.
Zurück zum Zitat Somers, C., H. Struyfs, J. Goossens et al. 2016. A decade of cerebrospinal fluid biomarkers for Alzheimer’s disease in Belgium. Journal of Alzheimer’s Disease 54(1): 383-395. Somers, C., H. Struyfs, J. Goossens et al. 2016. A decade of cerebrospinal fluid biomarkers for Alzheimer’s disease in Belgium. Journal of Alzheimer’s Disease 54(1): 383-395.
Zurück zum Zitat Tromp, K., M. Smedinga, E. Richard, M. Perry, and M.H. Schermer. 2021. Views on early diagnosis of Alzheimer’s disease among Dutch physicians: A qualitative interview study. Journal of Alzheimer's Disease 79(2): 917-927. Tromp, K., M. Smedinga, E. Richard, M. Perry, and M.H. Schermer. 2021. Views on early diagnosis of Alzheimer’s disease among Dutch physicians: A qualitative interview study. Journal of Alzheimer's Disease 79(2): 917-927.
Zurück zum Zitat van Maurik, I.S., L.M. van der Kall, A. de Wilde et al. 2019. Added value of amyloid PET in individualized risk predictions for MCI patients. Alzheimers and Dementia 11: 529-537. van Maurik, I.S., L.M. van der Kall, A. de Wilde et al. 2019. Added value of amyloid PET in individualized risk predictions for MCI patients. Alzheimers and Dementia 11: 529-537.
Zurück zum Zitat Van Thiel, G.J.M.W., and J.M. Van Delden. 2016. Reflective equilibrium as a normative empirical model: The case of Ashley X. In Empirical bioethics: Theoretical and practical perspectives, edited by J. Ives, M. Dunn and A. Cribb. Cambridge University Press. Van Thiel, G.J.M.W., and J.M. Van Delden. 2016. Reflective equilibrium as a normative empirical model: The case of Ashley X. In Empirical bioethics: Theoretical and practical perspectives, edited by J. Ives, M. Dunn and A. Cribb. Cambridge University Press.
Zurück zum Zitat Vanderschaeghe, G., J. Schaeverbeke, R. Bruffaerts, R. Vandenberghe, and K. Dierickx. 2017. Amnestic MCI patients’ experiences after disclosure of their amyloid PET result in a research context. Alzheimers Research and Therapy 9(1): 92. Vanderschaeghe, G., J. Schaeverbeke, R. Bruffaerts, R. Vandenberghe, and K. Dierickx. 2017. Amnestic MCI patients’ experiences after disclosure of their amyloid PET result in a research context. Alzheimers Research and Therapy 9(1): 92.
Zurück zum Zitat Wimo, A. 2018. The end of the beginning of the Alzheimer’s Disease nightmare: A devil’s advocate’s View. Journal of Alzheimer’s Disease 64(s1): S41-S46.CrossRef Wimo, A. 2018. The end of the beginning of the Alzheimer’s Disease nightmare: A devil’s advocate’s View. Journal of Alzheimer’s Disease 64(s1): S41-S46.CrossRef
Zurück zum Zitat Zwan, M.D., F.H. Bouwman, E. Konijnenberg, et al. 2017. Diagnostic impact of [(18)F]flutemetamol PET in early-onset dementia. Alzheimers Research and Therapy 9(1): 2. Zwan, M.D., F.H. Bouwman, E. Konijnenberg, et al. 2017. Diagnostic impact of [(18)F]flutemetamol PET in early-onset dementia. Alzheimers Research and Therapy 9(1): 2.
Metadaten
Titel
Should Doctors Offer Biomarker Testing to Those Afraid to Develop Alzheimer’s Dementia?
Applying the Method of Reflective Equilibrium for a Clinical Dilemma
verfasst von
Marthe Smedinga
Eline M. Bunnik
Edo Richard
Maartje H. N. Schermer
Publikationsdatum
19.03.2022
Verlag
Springer Nature Singapore
Erschienen in
Journal of Bioethical Inquiry / Ausgabe 2/2022
Print ISSN: 1176-7529
Elektronische ISSN: 1872-4353
DOI
https://doi.org/10.1007/s11673-022-10167-x

Weitere Artikel der Ausgabe 2/2022

Journal of Bioethical Inquiry 2/2022 Zur Ausgabe