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Introduction

Published online by Cambridge University Press:  12 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

The last few years have seen considerable progress in revisions of clinical diagnostic criteria for dementia. In relation to Alzheimer's disease (AD), the focus of this particular debate, the original McKhann criteria were described in 1984 (McKhann et al., 1984) and represented a landmark in their field, allowing accurate categorisation of a type of dementia that was indeed shown subsequently by validation studies to largely represent AD. The criteria distinguished between “probable” AD, which despite its name was the highest level of clinical certainty available, “possible” AD, when there were variations in the course and presentation or the presence of another comorbidity that could be the cause of dementia, and “definite” AD for which autopsy validation was necessary. The impact of these criteria cannot be overestimated. Most of what we know regarding the natural history, and certainly the therapeutic response (and sadly non-response) of AD, is based upon cohorts diagnosed with these criteria, and most usually the probable Alzheimer type. Validation studies have shown reasonably good, and clinically applicable, sensitivity for the criteria of around 80%, but specificity has been lower, at around 70% (Knopman et al., 2001). This low specificity is an issue, largely because of the lack of any positive features for ruling AD in (they have largely, though somewhat unfairly, been labelled criteria of exclusion). In addition, the low specificity is in part because the criteria often also include conditions that were not well defined or even recognised in the 1980s as separate disorders. For example, dementia with Lewy bodies, subcortical ischaemic vascular dementia, and various subtypes of frontotemporal dementia, which have now been shown to have distinct clinical, pathological and, in some cases, genetic components.

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. 174 - 175
Copyright
Copyright © International Psychogeriatric Association 2012

The last few years have seen considerable progress in revisions of clinical diagnostic criteria for dementia. In relation to Alzheimer's disease (AD), the focus of this particular debate, the original McKhann criteria were described in 1984 (McKhann et al., 1984) and represented a landmark in their field, allowing accurate categorisation of a type of dementia that was indeed shown subsequently by validation studies to largely represent AD. The criteria distinguished between “probable” AD, which despite its name was the highest level of clinical certainty available, “possible” AD, when there were variations in the course and presentation or the presence of another comorbidity that could be the cause of dementia, and “definite” AD for which autopsy validation was necessary. The impact of these criteria cannot be overestimated. Most of what we know regarding the natural history, and certainly the therapeutic response (and sadly non-response) of AD, is based upon cohorts diagnosed with these criteria, and most usually the probable Alzheimer type. Validation studies have shown reasonably good, and clinically applicable, sensitivity for the criteria of around 80%, but specificity has been lower, at around 70% (Knopman et al., 2001). This low specificity is an issue, largely because of the lack of any positive features for ruling AD in (they have largely, though somewhat unfairly, been labelled criteria of exclusion). In addition, the low specificity is in part because the criteria often also include conditions that were not well defined or even recognised in the 1980s as separate disorders. For example, dementia with Lewy bodies, subcortical ischaemic vascular dementia, and various subtypes of frontotemporal dementia, which have now been shown to have distinct clinical, pathological and, in some cases, genetic components.

Tremendous progress has also been made in the area of biomarkers. At the time of the 1984 criteria, progressive atrophy on computed tomography imaging was really the only biomarker that had been described, and was incorporated in the 1984 criteria. Now, the situation has been transformed, with cerebrospinal fluid, tau and amyloid, multiple magnetic resonance (MR) biomarkers including serial whole-brain hippocampal atrophy on MR; temporoparietal hypometabolism on fluorodeoxyglucose-positron emission tomography (FDG-PET) or hypoperfusion on SPECT, and most recently amyloid PET imaging, to list but a few of the best validated biomarkers (Sinha et al., 2012). Undoubtedly, others will emerge over time and despite the robustness of many of the aforementioned biomarkers, there remains interest in finding cheap, simple, and reliable alternatives, most especially those that could be easily collected, so for example blood biomarkers would represent a major advance.

On the background of these two major developments, demonstrating that the original 1984 McKhann criteria have limited specificity together with the advance in knowledge regarding biomarkers that can increase the certainty of AD diagnosis, various revisions to the clinical diagnostic criteria for AD have been proposed. Those of the International Working Group (IWG) of Dubois and colleagues (2007; 2010) represented a key step in arguing that the diagnosis of AD should be brought forward before the global cognitive impairment, or dementia, stage and also suggesting that biomarkers should be used to support the diagnosis. Similarly, a National Institute on Aging–Alzheimer's Association (NIA–AA) workgroup reformed and, under Guy McKhann's leadership, published revised proposed criteria for AD (McKhann et al., 2011). Other associated workgroups also proposed criteria for mild cognitive impairment due to AD (Albert et al., 2011) and most controversially of all asymptomatic or preclinical AD (Sperling et al., 2011). The publication of these various sets of criteria has caused considerable interest, but also controversy. How valid and reliable are they? Do they really represent a major advance over current criteria? How should they be used: are they strictly criteria for research or should we be using them in the clinic?

In view of these key issues, we decided to commission a debate between Bruno Dubois, Serge Gautier, and Jeff Cummings, who make the case for the utility of the new research diagnostic criteria for AD, focussing on the IWG criteria though similar arguments apply to the NIA–AA criteria, and Helen Chiu and Henry Brodaty who argue from a number of different areas including technical, ethical, and social that use of these criteria more widely may be premature. I hope you enjoy this very timely and topical debate.