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Commentary

Published online by Cambridge University Press:  13 November 2012

John T. O'Brien
John T. O'Brien*
Affiliation:
Department of Psychiatry, University of Cambridge, Level E4 Box 189, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK Email: john.obrien@medschl.cam.ac.uk

Extract

Dubois, Gauthier, and Cummings argue strongly and coherently for the need for revision of the Alzheimer's diagnostic accuracy and the many benefits to moving to a new diagnostic system. What they propose represents a fundamental paradigm shift in our field, moving Alzheimer's disease from a clinic-pathological to a clinic-biological entity, and separating the diagnosis of Alzheimer's disease from Alzheimer's dementia. In other words, recognising that people can have Alzheimer's disease for many years before they develop the global cognitive decline needed to fulfil current clinical criteria for dementia. The new diagnostic criteria are strongly supported by a very large body of research over the last 25 years and seek to advance the previous McKhann et al. (1984) criteria by, in particular, enhancing diagnostic specificity since, for the first time, CSF and imaging biomarkers are needed to “rule in” rather than simply rule out other disorders. The authors emphasise that these are research criteria and that they require validation and further investigation of clinical utility, whilst also pointing out that they have already been implemented in current Phase 2 clinical studies. Such a parallel introduction of criteria to our field whilst validation is ongoing is nothing new for psychiatry, or indeed dementia, and the same happened for the original Alzheimer's disease criteria as well. Dubois, Gauthier, and Cummings end with a stated aspiration to move the criteria from research to clinical settings, and by doing so hopefully increase the accuracy of the clinical diagnosis of Alzheimer's disease and ultimately improve patient care.

Information

Type
FOR DEBATE: IS VERY EARLY DIAGNOSIS OF AD USING THE NEW CRITERIA BENEFICIAL FOR PATIENTS?
Information
International Psychogeriatrics , Volume 25 , Issue 2 , February 2013 , pp. 181 - 184
Copyright
Copyright © International Psychogeriatric Association 2012

Dubois, Gauthier, and Cummings argue strongly and coherently for the need for revision of the Alzheimer's diagnostic accuracy and the many benefits to moving to a new diagnostic system. What they propose represents a fundamental paradigm shift in our field, moving Alzheimer's disease from a clinic-pathological to a clinic-biological entity, and separating the diagnosis of Alzheimer's disease from Alzheimer's dementia. In other words, recognising that people can have Alzheimer's disease for many years before they develop the global cognitive decline needed to fulfil current clinical criteria for dementia. The new diagnostic criteria are strongly supported by a very large body of research over the last 25 years and seek to advance the previous McKhann et al. (Reference McKhann, Drachman, Folstein, Katzman, Price and Stadlan1984) criteria by, in particular, enhancing diagnostic specificity since, for the first time, CSF and imaging biomarkers are needed to “rule in” rather than simply rule out other disorders. The authors emphasise that these are research criteria and that they require validation and further investigation of clinical utility, whilst also pointing out that they have already been implemented in current Phase 2 clinical studies. Such a parallel introduction of criteria to our field whilst validation is ongoing is nothing new for psychiatry, or indeed dementia, and the same happened for the original Alzheimer's disease criteria as well. Dubois, Gauthier, and Cummings end with a stated aspiration to move the criteria from research to clinical settings, and by doing so hopefully increase the accuracy of the clinical diagnosis of Alzheimer's disease and ultimately improve patient care.

In a thoughtful and very carefully argued piece, Chiu and Brodaty acknowledge and agree that there have been major and fundamental developments in the research field in relation to biomarkers, but raise some extremely important issues that need to be addressed before the criteria can be more widely applied in clinical practice. From a nosological perspective, they ask whether Alzheimer's disease can really be a disease when there are no signs or symptoms, which would be the case if the diagnosis is pushed back to the “preclinical” phase. They highlight the potential over-reliance on biomarkers, particularly as biomarkers may be abnormal for 20 years before the onset of symptoms, question how multiple pathologies will be taken into account, argue the need for better standardisation of biomarkers and the need for them to be more widely (and cheaply) available and argue that there is a need in ongoing research to demonstrate the “added value” of the new criteria and use of biomarkers over current clinical practice. The practical difficulties of the high cost of using investigations and ethical issues over the labelling of those with preclinical disease are eloquently addressed. Finally, Chiu and Brodaty conclude by cautioning against the widespread adoption of the criteria without the appropriate validation studies and the need for financial, ethical, and practical issues to be properly addressed.

Like many of the thoughtful debates we have carried in the pages of this journal, the two sides appear to start from very different perspectives but arrive at some common ground. Both articles argue that the new criteria represent a potential advance, that there are issues that need to be addressed and that the criteria are currently for research rather than clinical practices. Thus, all authors seem to agree on the direction of travel, the main difference appears essentially to be that Dubois, Gauthier, and Cummings are occupying the outer lane, arguing for a fast and rapid pace of movement from research to clinical use, whilst Chiu and Brodaty feel that if the key issues that they eloquently highlight are not properly addressed first, then more harm than good may result. As usual, the final arbiter of the strength or otherwise of the different arguments is you, our highly valued readers.

Conflict of interest

J. O'Brien has acted as a consultant to Bayer Healthcare, GE Healthcare, and received research funding from Lilly. B. Dubois has acted as a consultant for Lilly. S. Gauthier has acted as consultant to Affiris, Astellas, Astra-Zeneca, Bayer, Baxter, BMS, Elan, Epix, ExonHit, GE Health Care, Janssen-Cilag, Lundbeck, Lilly, Merz, Myriad, Neurochem, Novartis, Pfizer, Sanofi-Aventis, Schering-Plough, Servier, Sonexa, UBC, Wyeth. J. Cummings, H. Chiu, and H. Brodaty have no conflict of interest.

Description of authors’ roles

J. O'Brien wrote the introduction and the commentary. B. Dubois, S. Gauthier, J. Cummings, H. Chiu, and H. Brodaty contributed to the writing of the paper.

References

Aizenstein, H.-J.et al. (2008). Frequent amyloid deposition without significant cognitive impairment among the elderly. Archives of Neurology, 65, 1509–1517.CrossRefGoogle ScholarPubMed
Albert, M. 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 and Dementia, 7, 270–279.CrossRefGoogle ScholarPubMed
Alzheimer's Disease International (2009). World Alzheimer Report. London: Alzheimer's Disease International.Google Scholar
Ballard, C.et al. (2011). Alzheimer's disease. Lancet, 377, 1019–1031.CrossRefGoogle ScholarPubMed
Blacker, D. (2010). Beyond the dawning of the age of biomarkers. American Journal of Geriatric Psychiatry, 18, 955–958.CrossRefGoogle ScholarPubMed
Boustani, M.et al. (2005). Implementing a screening and diagnosis program for dementia in primary care. Journal of General Internal Medicine, 20, 572–577.CrossRefGoogle ScholarPubMed
Bouwman, F.-H.et al. (2010). New research criteria for the diagnosis of Alzheimer's disease applied in a memory clinic population. Dementia and Geriatric Cognitive Disorders, 30, 1–7.CrossRefGoogle Scholar
Chiu, H. F. and Lam, L. C. (2007). Relevance of outcome measures in different cultural groups – does one size fit all? International Psychogeriatrics, 19, 457–466.CrossRefGoogle ScholarPubMed
Draper, B., Peisah, C., Snowdon, J. and Brodaty, H. (2010). Early dementia diagnosis and the risk of suicide and enthusiasm. Alzheimer's and Dementia, 6, 75–82.CrossRefGoogle Scholar
Dubois, B.et al. (2007). Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria. Lancet Neurology, 6, 734–746.CrossRefGoogle ScholarPubMed
Dubois, B.et al. (2010). Revising the definition of Alzheimer's disease: a new lexicon. Lancet Neurology, 9, 1118–1127.CrossRefGoogle ScholarPubMed
Frisoni, G. B., Winblad, B. and O'Brien, J. T. (2011). Revised NIA-AA criteria for the diagnosis of Alzheimer's disease: a step forward but not yet ready for widespread clinical use. International Psychogeriatrics, 23, 1191–1196.CrossRefGoogle Scholar
Galluzzi, S.et al. (2010). The new Alzheimer's criteria in a naturalistic series of patients with mild cognitive impairment. Journal of Neurology, 257, 2004–2014.CrossRefGoogle Scholar
Giaccone, G.et al. (2011). New lexicon and criteria for the diagnosis of Alzheimer's disease. Lancet Neurology, 10, 298–299.CrossRefGoogle ScholarPubMed
Gomar, J. J.et al. (2011). Utility of combinations of biomarkers, cognitive markers, and risk factors to predict conversion from mild cognitive impairment to Alzheimer disease in patients in the Alzheimer's Disease Neuroimaging Initiative. Archives of General Psychiatry, 68, 961–969.CrossRefGoogle ScholarPubMed
Hort, J., Bartos, A., Pirttila, T. and Scheltens, P. (2010a). Use of cerebrospinal fluid markers in diagnosis of dementia across Europe. European Journal of Neurology, 17, 90–96.CrossRefGoogle Scholar
Hort, J.et al. (2010b). EFNS guidelines for the diagnosis and management of Alzheimer's disease. European Journal of Neurology, 27, 1236–1248.CrossRefGoogle Scholar
Humpel, C. and Marksteiner, J. (2009). Peripheral biomarkers in dementia and Alzheimer's disease. In Ritsner, M. S. (ed.), The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes (pp. 3–12). Dordrecht: Springer.CrossRefGoogle Scholar
Isaac, M., Vamvakas, S., Abadie, E., Jonsson, B., Gispen, C. and Pani, L. (2011). Qualification opinion of novel methodologies in the predementia stage of Alzheimer's disease: cerebrospinal fluid related biomarkers for drug affecting amyloid burden – regulatory considerations by European Medicines Agency focusing in improving benefit/risks in regulatory trials. European Neuropsychopharmacology, 21, 781–788.CrossRefGoogle ScholarPubMed
Jack, C. R.et al. (2011). Introduction to the recommendations from the National Institute on Aging–Alzheimer's Association workgroup on diagnostic guidelines for Alzheimer's disease. Alzheimer's and Dementia, 7, 257–262.CrossRefGoogle Scholar
Klunk, W. E. (1998). Biological markers of Alzheimer's disease. Neurobiology of Aging, 19, 145–147.CrossRefGoogle ScholarPubMed
Knopman, D. S.et al. (2001). Practice parameter: diagnosis of dementia (an evidence-based review). Neurology, 56, 1143–1153.CrossRefGoogle ScholarPubMed
Mattsson, N.et al. (2012). Age and diagnostic performance of Alzheimer disease CSF biomarkers. Neurology, 78, 468–476.CrossRefGoogle ScholarPubMed
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E. M. (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, 939–944.CrossRefGoogle ScholarPubMed
McKhann, G. M.et al. (2011). The diagnosis of dementia 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 and Dementia, 7, 263–269.CrossRefGoogle ScholarPubMed
Murray, A. D.et al. (2011). The balance between cognitive reserve and brain imaging biomarkers of cerebrovascular and Alzheimer's disease. Brain, 134, 3687–3696.CrossRefGoogle Scholar
Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) (2001). Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Lancet, 357, 169–175.CrossRefGoogle Scholar
Oksengard, A. R.et al. (2010). Lack of accuracy for the proposed “Dubois criteria” in Alzheimer's disease: a validation study from the Swedish Brain Power Initiative. Dementia and Geriatric Cognitive Disorders, 30, 374–380.CrossRefGoogle ScholarPubMed
Organization for Economic Co-operation and Development (OECD) (2011). Health Care Resources: CT Scanners Per Million Population and MRI Units Per Million Population. Available at: www.oecd.org/health/healthdata; last accessed 4 October 2012.Google Scholar
Schmand, B.et al. (2011). Value of neuropsychological tests, neuroimaging, and biomarkers for diagnosing Alzheimer's disease in younger and older age cohorts. Journal of American Geriatrics Society, 59, 1701–1710.CrossRefGoogle ScholarPubMed
Sinha, N., Firbank, M. and O'Brien, J. T. (2012). Biomarkers in dementia with Lewy bodies: a review. International Journal of Geriatric Psychiatry, 27, 443–453.CrossRefGoogle ScholarPubMed
Sperling, R. 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 and Dementia, 7, 280–292.CrossRefGoogle ScholarPubMed
The World Bank (2012). Indicators: Gross National Income Per Capita, Atlas Method (Current US $). Available at: http://data.worldbank.org; last accessed 4 October 2012.Google Scholar
Wharton, W. B.et al. (2011). Epidemiological neuropathology: the MRC cognitive function and aging study experience. Journal of Alzheimer's Disease, 25, 359–372.CrossRefGoogle ScholarPubMed
WHO (2004). Atlas: Country resources for neurological disorders. Available at: www.who.int/mental_health/neurology/epidemiology/en/index.html; last accessed 4 October 2012.Google Scholar
WHO (2005). Mental Health Atlas. Available at: www.who.int/mental_health/evidence/mhatlas05/en/index.html; last accessed 4 October 2012.Google Scholar