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.

Introduction

Alzheimer's disease (AD) is the most common cause of cognitive impairment in older people. When one considers the impact of AD on patients and families and the growing number of people living to older ages, there is a need to understand the progressive brain changes associated with the development of AD. There is also an urgent need to find treatments to slow down, stop, reduce the risk of, or completely prevent AD symptoms as soon as possible. Brain imaging techniques have had a profound impact on the scientific study of AD; they are expected to play growing roles in the clinical setting, and they are expected to play critical roles in the effort to find effective AD-modifying and prevention therapies.

In the last 20 years, there has been an explosion of interest in the development and use of brain imaging techniques for the scientific study, early detection, tracking, treatment and prevention of AD. This interest is reflected by the growing proportion of imaging researchers who attend and present their data at the major AD meetings, the development of imaging techniques to measure fibrillar amyloid-β deposition (a cardinal neuropathological feature of AD (Braak and Braak, 1991, Hardy and Selkoe, 2002)) in the living human brain (Klunk et al., 2004), the role that imaging studies have already played in the reconceptualization of AD (Sperling et al., 2011), the extraordinary opportunities researchers have to help in the scientific fight against this devastating disease, and the challenges the field continues to face along the way.

In this article, we review the best established brain imaging measurements for the detection and tracking of AD, and we note several other important imaging measurements, some of which have been less extensively applied or more recently developed. We then consider the how these imaging techniques have contributed to the scientific understanding of AD, their growing roles in the clinical setting, and their emerging roles in the evaluation of treatments to slow down the progression or prevent the onset of AD symptoms. Finally, we consider future research directions and offer a few recommendations. We are indebted to many investigators who have played pioneering roles in the development of brain imaging research, and we apologize in advance for our inability to cite all of the researchers and studies that have had a major impact on the field.