Brain imaging in Alzheimer disease

Abstract

Imaging has played a variety of roles in the study of Alzheimer disease (AD) over the past four decades. Initially, computed tomography (CT) and then magnetic resonance imaging (MRI) were used diagnostically to rule out other causes of dementia. More recently, a variety of imaging modalities including structural and functional MRI and positron emission tomography (PET) studies of cerebral metabolism with fluoro-deoxy-d-glucose (FDG) and amyloid tracers such as Pittsburgh Compound-B (PiB) have shown characteristic changes in the brains of patients with AD, and in prodromal and even presymptomatic states that can help rule-in the AD pathophysiological process. No one imaging modality can serve all purposes as each have unique strengths and weaknesses. These modalities and their particular utilities are discussed in this article. The challenge for the future will be to combine imaging biomarkers to most efficiently facilitate diagnosis, disease staging, and, most importantly, development of effective disease-modifying therapies.

Figure 1.

This series of three coronal T1-weighted studies, from an individual with autopsy-proven Alzheimer disease (AD), were each acquired ∼1 yr apart and show progressive hippocampal (H) atrophy as the individual progressed from memory complaints (left column, t = 0) to MCI (center, t = 1y) and on to fulfill criteria for AD.

Figure 2.

(Left) Group map of fMRI activity showing regions that increase activity (yellow/red) or decrease (blue) activity during successful encoding. (Right) Group map of 11C-PiB retention in a group of non-demented older individuals. Note the anatomic overlap of PiB retention to default network (regions in blue on left).

Figure 3.

Transaxial FDG-PET images of a normal control subject and a patient with mild AD. Note severe hypometabolism (yellow and blue cortical regions) in association and limbic cortex. These are the typically involved brain regions that define the FDG endophenotype of AD. They include posteriomedial parietal (precuneus), lateral parietal, lateral temporal, and medial temporal lobes. This pattern slowly worsens in parallel with symptoms and is well correlated at autopsy with AD pathologic diagnosis.

Figure 4.

PiB PET Images of normal control, MCI, and AD subjects showing a range of amyloid-β deposition. Most controls show no evidence of amyloid-β deposition (NC−), but a substantial portion (∼25%) do (NC+). Most patients with MCI show moderate (MCI+) or severe amyloid-β deposition (MCI++), but as many as 40%–50% show no evidence of amyloid-β pathology (MCI−). The vast majority of clinically diagnosed AD patients show heavy amyloid-β deposition (AD).