Amyloid Imaging in Alzheimer's Disease: Relationships to Memory Deficits, Brain Atrophy, and Hypometabolism

Introduction

The development of radiotracers that bind to β -amyloid (Aβ) deposits allowing the in vivo detection of one of the main hallmarks of Alzheimer's disease (AD) has created a new powerful tool to better diagnose, monitor, and understand the physiopathology of this neurodegenerative disease. This review focuses on the relationships between amyloid deposition as assessed with molecular neuroimaging, memory deficits, atrophy, and hypometabolism in different stages of AD. Better insight into these relationships is crucial to further our understanding of the pathological mechanisms underlying AD as well as the sequence of pathological events resulting in this disease.

Abstract

Amyloid neuroimaging has made it possible to visualize in vivo one of the main hallmarks of Alzheimer's disease (AD), creating the opportunity to better diagnose, monitor, and understand this neurodegenerative condition. This review focuses on the relationships between amyloid deposition as assessed with [11C]Pittsburgh compound B (PiB) positron emission tomography (PET), and memory deficits, atrophy, and hypometabolism in different stages of AD. The presence of β -amyloid (Aβ) at a presymptomatic stage supports the hypothesis that the abnormal processing of Aβ, leading to β -amyloid deposition, is an upstream process. However, the link between global neocortical Aβ deposition and memory appears to be weak, early, and probably indirect though there may be a direct effect in specific brain regions. Studies assessing the relationships between PiB binding and atrophy or metabolism show that PiB (i) correlated to local atrophy only in the early stage and in regions of highest amyloid deposition (anterior and posterior cingulate and temporo-parietal areas), whereas hippocampal atrophy is related to distant deposition; (ii) shows only weak negative relationships with metabolism, essentially in the parietal cortex in AD; and (iii) can be observed in the non-expected direction (i.e., increased volume or metabolism with increased PiB), especially in the early stages. This suggests that atrophy and hypometabolism in AD-typical brain regions are not directly caused by the degree of local amyloid deposition. As a whole, neuroimaging studies suggest that, while Aβ dysregulation and deposition is necessary for the development of AD, the way this leads to neurodegeneration and dementia is complex, indirect, and not dose-dependant.

Keywords

Alzheimer's disease (AD), Mild Cognitive Impairment (MCI), amyloid PET imaging, hippocampus atrophy, glucose hypometabolism, memory