Brain imaging in the study of Alzheimer's disease

Abstract

Over the last 20 years, there has been extraordinary progress in brain imaging research and its application to the study of Alzheimer's disease (AD). Brain imaging researchers have contributed to the scientific understanding, early detection and tracking of AD. They have set the stage for imaging techniques to play growing roles in the clinical setting, the evaluation of disease-modifying treatments, and the identification of demonstrably effective prevention therapies. They have developed ground-breaking methods, including positron emission tomography (PET) ligands to measure fibrillar amyloid-β (Aβ) deposition, new magnetic resonance imaging (MRI) pulse sequences, and powerful image analysis techniques, to help in these endeavors. Additional work is needed to develop even more powerful imaging methods, to further clarify the relationship and time course of Aβ and other disease processes in the predisposition to AD, to establish the role of brain imaging methods in the clinical setting, and to provide the scientific means and regulatory approval pathway needed to evaluate the range of promising disease-modifying and prevention therapies as quickly as possible. Twenty years from now, AD may not yet be a distant memory, but the best is yet to come.

Copyright © 2011 Elsevier Inc. All rights reserved.

Figures

Figure 1

Volumetric MRI in the the detection and tracking of AD, including (i) accelerated rates of atrophy in the hippocampus (Hi) and entorhinal cortex (ERC) regions-of-interest (Mike Weiner, with permission); (ii) accelerated rates of whole brain atrophy using sequential MRIs, as shown in red in a symptomatic AD patient (Nick Fox, with permission); (iii) regional gray matter loss, as shown in this statistical brain map comparing symptomatic AD patients and controls. Reprinted from (Baron et al., 2001), Copyright © 2001 with permission from Elsevier. All rights reserved; and (iv) regional thinning in cerebral cortex, as shown in this statistical brain map comparing symptomatic AD patients and controls. Reprinted with permission from (Du et al., 2007), Copyright © 2007 Oxford University Press. All rights reserved. This figure was reproduced with permission from (Reiman and Langbaum, 2009), Copyright © 2009 Oxford University Press. All rights reserved.

Figure 2

FDG PET in people who are clinically affected by or at increased genetic risk of AD. Characteristic CMRgl reductions (compared to normal controls) are displayed on the medial surface of a brain MRI in clinically affected AD patients and in cognitively normal young adult with one copy of the APOE ε4 allele, the major AD susceptibility gene. Adapted with permission from (Reiman et al., 1996), Copyright © 1996 Massachusetts Medical Society, all rights reserved, and (Reiman et al., 2004), Copyright © 2004 National Academy of Sciences, USA. All rights reserved.

Figure 3

Fibrillar amyloid imaging in the study of AD. Increases in Pittsburgh Compound-B PET measurements of fibrillar amyloid-β in symptomatic AD patients. Adapted with permission from (Reiman et al., 2009; Reiman et al., 2010), Copyright © 2009 National Academy of Sciences, USA. All rights reserved.

Figure 4

Spatial relationships (and postulated causal connections) among the brain regions implicated in i and ii) the Default Mode Network and successful episodic memory retrieval in young adults, iii) the regions preferentially associated with fibrillar amyloid-β deposition, and iv and v) the regions preferentially associated with atrophy and CMRgl decline. Reprinted with permission from (Buckner et al., 2005), Copyright © 2005 Society for Neuroscience. All rights reserved.