Revision of the criteria for Alzheimer's disease: A symposium (original) (raw)
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International Psychogeriatrics, 2011
In clinical medicine, diagnostic criteria are not only useful everyday tools for the practicing physician, but also represent a conceptual concentrate of the understanding of the etiology and pathophysiology of diseases at a given point in time. Although different sets of diagnostic criteria for Alzheimer's disease (AD) have been developed, the most widely used and best validated by clinico-pathological study to date are the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke – Alzheimer's Disease and Related Disorders Association) criteria which were published in 1984 (McKhann et al., 1984). These criteria are largely based on the exclusion of other conditions that may cause dementia and can be succinctly but fairly summarized as defining AD as an “acquired progressive cognitive, behavioral, and functional impairment with no other obvious cause”. Clearly, the NINCDS-ADRDA criteria were etiology- and pathophysiology-agnostic in that they f...
Alzheimer's & Dementia, 2011
Population studies strive to determine the prevalence of Alzheimer dementia but prevalence estimates vary widely. The challenges faced by several noted population studies for Alzheimer dementia in operationalizing current clinical diagnostic criteria for Alzheimer's disease (AD) are reviewed. Differences in case ascertainment, methodological biases, cultural and educational influences on test performance, inclusion of special populations such as underrepresented minorities and the oldest old, and detection of the earliest symptomatic stages of underlying AD are considered. Classification of Alzheimer dementia may be improved by the incorporation of biomarkers for AD if the sensitivity, specificity, and predictive value of the biomarkers are established and if they are appropriate for epidemiological studies as may occur should a plasma biomarker be developed. Biomarkers for AD also could facilitate studies of the interactions of various forms of neurodegenerative disorders with cerebrovascular disease, resulting in "mixed dementia".
Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria
The Lancet Neurology, 2007
The NINCDS-ADRDA and the DSM-IV-TR criteria for Alzheimer's disease (AD) are the prevailing diagnostic standards in research; however, they have now fallen behind the unprecedented growth of scientifi c knowledge. Distinctive and reliable biomarkers of AD are now available through structural MRI, molecular neuroimaging with PET, and cerebrospinal fl uid analyses. This progress provides the impetus for our proposal of revised diagnostic criteria for AD. Our framework was developed to capture both the earliest stages, before full-blown dementia, as well as the full spectrum of the illness. These new criteria are centred on a clinical core of early and signifi cant episodic memory impairment. They stipulate that there must also be at least one or more abnormal biomarkers among structural neuroimaging with MRI, molecular neuroimaging with PET, and cerebrospinal fl uid analysis of amyloid β or tau proteins. The timeliness of these criteria is highlighted by the many drugs in development that are directed at changing pathogenesis, particularly at the production and clearance of amyloid β as well as at the hyperphosphorylation state of tau. Validation studies in existing and prospective cohorts are needed to advance these criteria and optimise their sensitivity, specifi city, and accuracy.
Alzheimer's disease (AD) has traditionally been defi ned as a type of dementia, and criteria have been provided by the National Institute of Neurological and Communicative Disorders and Stroke -Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) [1], the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) , and the 10th revision of the International Classifi cation of Diseases (ICD-10) . Of these sets of criteria, the NINCDS-ADRDA criteria were most widely used in dementia research. Th ere were several notable aspects of these criteria: (a) patients had to have cognitive defi cits and functional compromise severe enough to meet criteria for dementia, (b) a confi rmed diagnosis depended on postmortem examination, (c) the most accurate diagnosis that the clinician could make for the living patient was 'probable AD' , (d) other possible causes of cognitive impairment had to be excluded by the clinician, and (e) the cognitive defi cits were not oper ationa lized for characteristics or severity. When applied by expert clinicians, these criteria have an 80% positive predictive value and a 60% negative predictive value for the accurate clinical diagnosis of AD when compared with postmortem examination .
Alzheimer's & Dementia, 2011
The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some diseasemodifying therapies may be most efficacious.