The Medical clinics of North America
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Med. Clin. North Am. · May 2013
ReviewApplying the IWG research criteria in clinical practice: feasibility and ethical issues.
One of the strengths of the IWG criteria was to reconceptualize the diagnosis of AD, from a clinical-pathologic diagnosis to a clinical-biologic one, which can be performed in vivo. The diagnosis should, therefore, be implemented in the clinical stage of the disease, relying on the essence of the new IWG diagnostic criteria in the recognition of this dual aspect of AD: a specific clinical presentation that is related to a well-defined underlying pathology. ⋯ From an ethical perspective, the governing principle for early prodromal diagnosis should be autonomy, because the decision of wishing to know or not to know should be performed individually by a competent individual. Furthermore, the potential benefit of an early diagnosis may be mediated through an autonomous decision.
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Med. Clin. North Am. · May 2013
ReviewRelevance of magnetic resonance imaging for early detection and diagnosis of Alzheimer disease.
Hippocampus volumetry currently is the best-established imaging biomarker for AD. However, the effect of multicenter acquisition on measurements of hippocampus volume needs to be explicitly considered when it is applied in large clinical trials, for example by using mixed-effects models to take the clustering of data within centers into account. The marker needs further validation in respect of the underlying neurobiological substrate and potential confounds such as vascular disease, inflammation, hydrocephalus, and alcoholism, and with regard to clinical outcomes such as cognition but also to demographic and socioeconomic outcomes such as mortality and institutionalization. ⋯ From a neurobiological point of view, the main determinants of cognitive impairment in AD are the density of synapses and neurons in distributed cortical and subcortical networks. MRI-based measures of regional gray matter volume and associated multivariate analysis techniques of regional interactions of gray matter densities provide insight into the onset and temporal dynamics of cortical atrophy as a close proxy for regional neuronal loss and a basis of functional impairment in specific neuronal networks. From the clinical point of view, clinicians must bear in mind that patients do not suffer from hippocampus atrophy or disconnection but from memory impairment, and that dementia screening in asymptomatic subjects should not be used outside of clinical studies.
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Med. Clin. North Am. · May 2013
ReviewThe application of cerebrospinal fluid biomarkers in early diagnosis of Alzheimer disease.
This article gives an updated account of the clinical application of cerebrospinal fluid (CSF) biomarkers for Alzheimer disease (AD). The clinically most relevant biomarkers, total tau, phospho-tau and Aβ42 are discussed, and how they may be used, together with other diagnostic investigations, to make a predementia diagnosis of AD. Recent findings in sporadic and genetic preclinical AD are also discussed and, more specifically, what the biomarkers have taught us on the sequence of events in the pathogenic process underlying AD.