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Alzheimer’s Disease
A New Concept and New Criteria for Alzheimer’s Disease
a report by
Bruno Dubois,
1
Howard Feldman
2
and Philip Scheltens
3
1. Neurology Department and Inserm U610, Salpêtrière Hospital, Paris; 2. Division of Neurology, University of British Columbia and Vancouver Coastal Health,
Vancouver; 3. Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam
The diagnosis of Alzheimer’s disease (AD) is a two-step process. First, time to diagnosis of AD. It may be assumed that the heterogeneity of
a dementia syndrome, which is defined by impact on social functions MCI has diluted the potential for a significant treatment effect,
or activities of daily living (ADL), is diagnosed. As a consequence, ADL particularly considering that AD is already at work on the brain long
impairment has become the threshold for the diagnosis of dementia before the onset of clinical dementia. However, it is possible to
beyond the identification of a cognitive abnormality. The second step recognise this pre-dementia stage of AD by adopting a
consists of the exclusion of the aetiologies of a different dementia multidimensional approach, identifying:
syndrome using paraclinical investigations, including neuroimaging
and biological tests. AD, therefore, is mainly described in exclusionary •a specific amnestic disorder of the hippocampal type;
terms, with investigations being used to identify other causes of • the atrophy of medial temporal structures – specifically the
dementia – vascular, tumoral and systemic. hippocampus; and
• the specific profile of cerebrospinal fluid biomarkers or of metabolic
This two-step procedure, which relies on the Diagnostic and Statistic neuroimaging changes.
Manual of Mental Disorders IV Text Revision (DSM-IV-TR) and the
National Institute of Neurological and Communication Disorders and An international working group was convened to discuss the
Stroke – Alzheimer’s Disease and Related Disorders Association opportunity to develop a diagnostic framework for AD that would
(NINCDS-ADRDA) criteria, should be revised on the basis of several include the prodromal stages. At the end of this consensus meeting it
arguments. First, the criteria do not take into account the was concluded that it was possible to recognise AD at the prodromal,
unprecedented growth of scientific knowledge concerning the pre-dementia stage with the use of specific memory tests, biomarkers
and neuroimaging investigations. There was no longer a reason to
limit the diagnosis of AD to patients who reached the threshold of full-
blown dementia. Accordingly, it was decided that new criteria be
…the criteria do not take into
proposed that would apply both in the early stages and across the full
account the unprecedented growth
spectrum of the illness.
of scientific knowledge concerning
Proposed Diagnostic Criteria for Probable
the existence of reliable markers of Alzheimer’s Disease
Alzheimer’s disease…
The framework addresses the presentations that are typical of AD. It
excludes atypical presentations – primary progressive aphasia and
visuospatial dysfunction – although it has been demonstrated that
these atypical phenotypes can be associated with post mortem AD
existence of reliable biomarkers of AD that are now available through histological changes. To meet criteria for probable AD, an affected
structural magnetic resonance imaging (MRI), molecular neuroimaging individual must fulfil the core clinical criterion (criterion A) and at least
and cerebrospinal fluid analyses. Nor do they take into account the AD one of the supportive biomarker criteria (see Table 1).
phenotype, which presents in most cases as a progressive amnestic
dementia related to other Alzheimer’s-related changes that involve the
Bruno Dubois is Professor of Neurology and Head of the
medial temporal structures early in the course of disease. Furthermore,
Cognitive Neurology Department and the Alzheimer’s Disease
the episodic memory disorders of AD correlate well with a distribution Centre at the Neurological Institute, Salpêtrière Hospital, Paris.
of neurofibrillary tangles within the medial temporal lobe (MTL) and
He is Director of the Research Unit Inserm U610 and a
member of the Institute of Neurosciences and the European
with the demonstration by MRI of volumetric loss of the hippocampus,
Alzheimer Disease Consortium (Therapeutics and Intervention
the structure known to be critical for episodic memory.
Studies). Dr Dubois is President of the Scientific Committee of
France-Alzheimer and of International Fund Raising for
Alzheimer’s Disease (IFRAD). He is a Consultant for the
In addition, recently developed disease-modifying therapies require Human Frontier Program and an expert of the French Agency of Drugs. He has published studies
early intervention at the prodromal stage before full-blown dementia.
on the central cholinergic systems in rodents and humans and on cognitive neuropharmacology
and neuropsychology in patients with dementia, with special reference to memory and executive
At the moment, the prodromal stage of AD is included under
functions. He is principal or co-investigator of a number of research programmes focusing on
the heterogeneous term mild cognitive impairment (MCI). This
Alzheimer’s disease, mild cognitive impairment and dementia in Parkinson’s disease.
heterogeneity may have contributed to the negative outcomes of
E: bruno.dubois@psl.aphp.fr
clinical trials in which none of the drugs was successful in delaying the
© TOUCH BRIEFINGS 2007 53
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