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Therapeutics designed to treat symptoms or alter the disease course have failed to make an impact, despite substantial investments by governments, pharmaceutical industry, and private donors. These failures in treatment efficacy have led many to believe that symptomatic disease, including both mild cognitive impairment (MCI) and AD, may be refractory to therapeutic intervention. The recent focus on biomarkers for defining the preclinical state of MCI\/AD is in the hope of defining a therapeutic window in which the neural substrate remains responsive to treatment. The ability of biomarkers to adequately define the at\u2010risk state may ultimately allow novel or repurposed therapeutic agents to finally achieve the disease\u2010modifying status for AD. 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MS Cheema AK Mapstone M Zhong X Mhyre TR MacArthur LH et\u00a0al. 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