Ushering in the study and treatment of preclinical Alzheimer disease

Abstract

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.

Figures

Figure 1

Reconceptualizing Alzheimer’s Disease

Figure 2

Well Established Brain Imaging Techniques in the Detection and Tracking of AD

Figure 3

Hypothetical dynamic biomarkers of the AD pathological cascade

Figure 4

Temporal link between amyloid deposition and onset of AD dementia With permission from Chris Rowe, reprinted from