Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol 9:1118-1127

Pierre & Marie Curie University, Research Centre of the Institute of the Brain and Spinal Cord, UMR, AP-HP, Pitié-Salpêtrière Hospital Group, Paris, France.
The Lancet Neurology (Impact Factor: 21.9). 10/2010; 9(11):1118-27. DOI: 10.1016/S1474-4422(10)70223-4
Source: PubMed


Alzheimer's disease (AD) is classically defined as a dual clinicopathological entity. The recent advances in use of reliable biomarkers of AD that provide in-vivo evidence of the disease has stimulated the development of new research criteria that reconceptualise the diagnosis around both a specific pattern of cognitive changes and structural/biological evidence of Alzheimer's pathology. This new diagnostic framework has stimulated debate about the definition of AD and related conditions. The potential for drugs to intercede in the pathogenic cascade of the disease adds some urgency to this debate. This paper by the International Working Group for New Research Criteria for the Diagnosis of AD aims to advance the scientific discussion by providing broader diagnostic coverage of the AD clinical spectrum and by proposing a common lexicon as a point of reference for the clinical and research communities. The cornerstone of this lexicon is to consider AD solely as a clinical and symptomatic entity that encompasses both predementia and dementia phases.

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Available from: Harald J Hampel, May 24, 2014
    • "It is unlikely that a treatment can be effective in all populations. Dubois and colleagues [251] have suggested a revised definition of AD. One major impact from this new definition applies to the clinical trial design, indicating more targeted subpopulations of AD should be considered. "
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    ABSTRACT: Preclinical studies are essential for translation to disease treatments and effective use in clinical practice. An undue emphasis on single approaches to Alzheimer's disease (AD) appears to have retarded the pace of translation in the field, and there is much frustration in the public about the lack of an effective treatment. We critically reviewed past literature (1990-2014), analyzed numerous data, and discussed key issues at a consensus conference on Brain Ageing and Dementia to identify and overcome roadblocks in studies intended for translation. We highlight various factors that influence the translation of preclinical research and highlight specific preclinical strategies that have failed to demonstrate efficacy in clinical trials. The field has been hindered by the domination of the amyloid hypothesis in AD pathogenesis while the causative pathways in disease pathology are widely considered to be multifactorial. Understanding the causative events and mechanisms in the pathogenesis are equally important for translation. Greater efforts are necessary to fill in the gaps and overcome a variety of confounds in the generation, study design, testing, and evaluation of animal models and the application to future novel anti-dementia drug trials. A greater variety of potential disease mechanisms must be entertained to enhance progress.
    Journal of Alzheimer's disease: JAD 09/2015; 47(4):815-843. DOI:10.3233/JAD-150136 · 4.15 Impact Factor
    • "We followed the approach applied in the construction of an AD model which has been previously described to build a dementia model [5]. Dementia is defined as a long process that starts with the development of brain pathology, either degenerative and/or vascular, not accompanied by clinical manifestations ( " preclinical " ), and that progresses to a mild cognitive impairment (MCI) ( " prodromal " ) stage and, finally, to dementia [14] [15] [16] [17]. Accordingly, in this study, individuals in the general population were divided into three states: healthy, predemented, and demented. "
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    ABSTRACT: Risk and protective factors such as obesity, hypercholesterolemia, physical activity, and hypertension can play a role in the development of dementia. Our objective was to measure the effect of modification of risk and protective factors on the prevalence and economic burden of dementia in the aging Spanish population during 2010-2050. A discrete event simulation model including risk and protective factors according to CAIDE (Cardiovascular Risk Factors, Aging and Incidence of Dementia) Risk Score was built to represent the natural history of dementia. Prevalence of dementia was calculated from 2010 to 2050 according to different scenarios of risk factor prevalence to assess the annual social and health care costs of dementia. The model also supplied hazard ratios for dementia. Aging will increase between 49% and 16% each decade in the number of subjects with dementia. The number of working-age individuals per person with dementia will decrease to a quarter by 2050. An intervention leading to a 20% change in risk and protective factors would reduce dementia by 9% , prevent over 100,000 cases, and save nearly 4,900 million euros in 2050. Switching individuals from a group with a specific risk factor to one without it nearly halved the risk of the development of dementia. Dementia prevalence will grow unmanageable if effective prevention strategies are not developed. Interventions aiming to reduce modifiable risk factor prevalence represent valid and effective alternatives to reduce dementia burden. However, further research is needed to identify causal relationships between dementia and risk factors.
    Journal of Alzheimer's disease: JAD 09/2015; 48(3). DOI:10.3233/JAD-150233 · 4.15 Impact Factor
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    • "In recent times, the term " preclinical AD " has been introduced by the IWG and the NIA-AA groups of investigators to denote individuals who have biomarkers positively supporting ongoing AD pathology, but do not fulfill the operationalized clinical criteria for MCI or dementia [17] [18]. As the field positions itself for upcoming secondary prevention trials, the detection of sensitive indicators, i.e., markers, of preclinical AD is eagerly needed. "
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    ABSTRACT: There is evolving evidence that individuals categorized with subjective cognitive decline (SCD) are potentially at higher risk for developing objective and progressive cognitive impairment compared to cognitively healthy individuals without apparent subjective complaints. Interestingly, SCD, during advancing preclinical Alzheimer's disease (AD), may denote very early, subtle cognitive decline that cannot be identified using established standardized tests of cognitive performance. The substantial heterogeneity of existing SCD-related research data has led the Subjective Cognitive Decline Initiative (SCD-I) to accomplish an international consensus on the definition of a conceptual research framework on SCD in preclinical AD. In the area of biological markers, the cerebrospinal fluid signature of AD has been reported to be more prevalent in subjects with SCD compared to healthy controls; moreover, there is a pronounced atrophy, as demonstrated by magnetic resonance imaging, and an increased hypometabolism, as revealed by positron emission tomography, in characteristic brain regions affected by AD. In addition, SCD individuals carrying an apolipoprotein ɛ4 allele are more likely to display AD-phenotypic alterations. The urgent requirement to detect and diagnose AD as early as possible has led to the critical examination of the diagnostic power of biological markers, neurophysiology, and neuroimaging methods for AD-related risk and clinical progression in individuals defined with SCD. Observational studies on the predictive value of SCD for developing AD may potentially be of practical value, and an evidence-based, validated, qualified, and fully operationalized concept may inform clinical diagnostic practice and guide earlier designs in future therapy trials.
    Journal of Alzheimer's disease: JAD 09/2015; 48(s1). DOI:10.3233/JAD-150202 · 4.15 Impact Factor
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