Alzheimer's & dementia : the journal of the Alzheimer's Association
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In the earliest clinical stages of Alzheimer's disease (AD) when symptoms are mild, clinical diagnosis can be difficult. AD pathology most likely precedes symptoms. Biomarkers can serve as early diagnostic indicators or as markers of preclinical pathologic change. Candidate biomarkers derived from structural and functional neuroimaging and those measured in cerebrospinal fluid (CSF) and plasma show the greatest promise. Unbiased exploratory approaches, eg, proteomics or cortical thickness analysis, could yield novel biomarkers. The objective of this article was to review recent progress in selected imaging and neurochemical biomarkers for early diagnosis, classification, progression, and prediction of AD. ⋯ A number of neuroimaging candidate markers are promising, such as hippocampus and entorhinal cortex volumes, basal forebrain nuclei, cortical thickness, deformation-based and voxel-based morphometry, structural and effective connectivity by using diffusion tensor imaging, tractography, and functional magnetic resonance imaging. CSF Abeta42, BACE1, total tau, and p-tau are substantially altered in MCI and clinical AD. Other interesting novel marker candidates derived from blood are being currently proposed (phase I). Biomarker discovery through proteomic approaches requires further research. Large-scale international controlled multicenter trials (such as the U.S., European, Australian, and Japanese Alzheimer's Disease Neuroimaging Initiative and the German Dementia Network) are engaged in phase III development of the core feasible imaging and CSF biomarker candidates in AD. Biomarkers are in the process of implementation as primary outcome variables into regulatory guideline documents regarding study design and approval for compounds claiming disease modification.
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The fourth Annual Mild Cognitive Impairment (MCI) Symposium, held at the Eden Roc Hotel in Miami Beach Florida on February 24 and 25, 2006, brought together some 150 neuropsychologists, neurologists, and other specialists in the field to discuss the latest research on issues related to the diagnosis and progression of MCI across the broad range of cognitive and functional impairments that comprise its various subtypes. Four mini-symposia were convened on the topics of Cognitive Reserve and MCI, the Genetics and Proteomics of Cognitive Decline, Pathogenesis of Vascular/Metabolic Cognitive Impairment, and Systemic and Psychiatric Considerations in MCI. In addition, 2 keynote addresses were delivered; one on the Rotterdam Study and the other a review of clinical trials in MCI. Participants in the symposium also discussed whether the time has come to revise current diagnostic criteria for Alzheimer's disease.