Journal Article

Ushering in the study and treatment of preclinical Alzheimer disease

Chen, Kewei, Tariot, Pierre N., Langbaum, Jessica B., Lopera, Francisco, Quiroz, Yakeel T., Reiman, Eric M., Ayutyanont, Napatkamon, Fleisher, Adam S., Caselli, Richard J.

2013

Overview

The pathological underpinnings of Alzheimer disease (AD) are now known to begin up to two decades before manifestation of clinical disease, and intervention during preclinical AD stages is increasingly recognized as key to therapeutic success. Here, Eric Reiman and colleagues discuss strategies to study changes in the brain and bodily fluids that precede clinical AD, focusing in particular on genetic at-risk individuals, who might be suitable candidates for secondary prevention trials. Researchers have begun to characterize the subtle biological and cognitive processes that precede the clinical onset of Alzheimer disease (AD), and to set the stage for accelerated evaluation of experimental treatments to delay the onset, reduce the risk of, or completely prevent clinical decline. In this Review, we provide an overview of the experimental strategies, and brain imaging and cerebrospinal fluid biomarker measures that are used in early detection and tracking of AD, highlighting at-risk individuals who could be suitable for preclinical monitoring. We discuss how advances in the field have contributed to reconceptualization of AD as a sequence of biological changes that occur during progression from preclinical AD, to mild cognitive impairment and finally dementia, and we review recently proposed research criteria for preclinical AD. Advances in the study of preclinical AD have driven the recognition that efficacy of at least some AD therapies may depend on initiation of treatment before clinical manifestation of disease, leading to a new era of AD prevention research. Key Points The pathogenic cascade of Alzheimer disease (AD) is thought to begin at least one to two decades prior to cognitive impairment Disappointing results of several AD drugs in late-stage trials have suggested the need for early therapeutic intervention, calling for development of biomarkers and sensitive cognitive measures of preclinical disease The best established measurements for detection and tracking of preclinical and clinical AD include MRI, fluorodeoxyglucose PET, amyloid PET, and cerebrospinal fluid measures of amyloid-β 42 , total tau, and phospho-tau Studies of individuals with inherited AD can provide insights into cognitive and biomarker changes that precede clinical manifestation of AD, and are suitable candidates for ongoing monitoring and early-intervention strategies We are entering an era of AD prevention research, with a number of preclinical AD treatment trials in the planning stages or under way for several at-risk, cognitively unimpaired populations

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 692/308/2778 / 692/699/375/365/1283 / 692/700/1421/65 / Alzheimer Disease - diagnosis / Alzheimer Disease - therapy / Alzheimer's disease / Amyloid beta-protein / Biomarkers / Biomarkers - analysis / Brain Chemistry / Drug therapy / Genetic aspects / Health aspects / Humans / Medical imaging / Medicine / Medicine & Public Health / Neurology / Older people / Prodromal Symptoms / review-article / Risk Factors