Data from clinicopathologic and biomarker studies have converged to support the view of Alzheimer’s disease (AD) as a continuum, with pathology developing decades prior to the onset of cognitive symptoms which culminate as dementia at the end stage of the disease. This concept is impacting disease nomenclature, diagnostic criteria, prognostic potential, and clinical trial design. Revisions to diagnostic criteria to incorporate biomarker results have recently been proposed in order to increase the confidence of AD as the underlying etiology of a clinical impairment and to permit a diagnosis of AD across the disease continuum, eventually perhaps in the asymptomatic period. Individuals in this preclinical stage are receiving intense focus as a targeted population for secondary prevention trials aimed at identifying disease-modifying therapies that have the best chance of preserving normal cognitive function. The goal is to bring validated biomarkers to clinical practice for the purpose of disease diagnosis, prognosis, and evaluation of therapeutic efficacy once disease-modifying treatments become available. Realization of this goal requires worldwide biomarker standardization efforts, consensus among researchers and clinicians regarding the clinical utility of assessing biomarkers in patient care settings, and eventually the endorsement and adoption of such procedures and practices into global health care systems. 1. The Crisis of AD Alzheimer’s disease (AD) is the most common cause of dementia, accounting for up to 70% of all dementia cases, and is now estimated to be the third leading cause of death, after heart disease and cancer [1]. Since advanced age is the strongest risk factor for AD, increased life expectancy and the aging of the “baby boomer” generation are leading to dramatic increases in AD incidence. AD currently affects 5.2 million people in the United States (US), with projected estimates reaching 13.8 million (115 million world-wide) by the year 2050 (http://www.alz.org/documents/national/world_alzheimer_report_2010.pdf). The lifetime risk for AD dementia for a 65-year-old person is currently estimated to be ~10.5%, with prevalence doubling every 5 years after age 65, reaching nearly 50% by age 80. In the US alone, the costs for care associated with AD in 2013 were more than $200 billion, with projected annual costs surpassing $1 trillion by the year 2050 (http://www.alz.org/alzheimers_disease_facts_and_figures.asp#cost). At present there are no effective treatments that will prevent the disease, halt its progression, or delay its onset.
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