title: The evolution of preclinical Alzheimer's disease: implications for prevention trials.
abstract: As the field begins to test the concept of a "preclinical" stage of neurodegenerative disease, when the pathophysiological process has begun in the brain, but clinical symptoms are not yet manifest, a number of intriguing questions have already arisen. In particular, in preclinical Alzheimer's disease (AD), the temporal relationship of amyloid markers to markers of neurodegeneration and their relative utility in the prediction of cognitive decline among clinically normal older individuals remains to be fully elucidated. Secondary prevention trials in AD have already begun in both genetic at-risk and amyloid at-risk cohorts, with several more trials in the planning stages, and should provide critical answers about whether intervention at this very early stage of disease can truly bend the curve of clinical progression. This review will highlight recent progress in cognitive, imaging, and biomarker outcomes in the field of preclinical AD, and the remaining gaps in knowledge.
authors.affiliation: Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Aging Brain Study, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: reisa@rics.bwh.harvard.edu.
authors.forename: Reisa
authors.initials: R
authors.lastname: Sperling
authors.affiliation: Harvard Aging Brain Study, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mormino
authors.affiliation: Harvard Aging Brain Study, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Johnson
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D035843:Biomedical Research / Q000379:methods*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D059906:Neuroimaging
chemical_list: D014150:Antipsychotic Agents