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Behavioural Neurology
Volume 21 (2009), Issue 1-2, Pages 63-75

Large-Scale Functional Brain Network Abnormalities in Alzheimer’s Disease: Insights from Functional Neuroimaging

Bradford C. Dickerson1,2,3,4,5 and Reisa A. Sperling1,2,4,5

1Department of Neurology, Harvard Medical School, Boston, MA, USA
2Massachusetts Alzheimer’s Disease Research Center, Harvard Medical School, Boston, MA, USA
3Frontotemporal Dementia Unit, Harvard Medical School, Boston, MA, USA
4Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
5Division of Cognitive and Behavioral Neurology, Department of Neurology, Brigham & Women’s Hospital, Boston, MA, USA

Received 16 October 2009; Accepted 16 October 2009

Copyright © 2009 Hindawi Publishing Corporation and the authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Functional MRI (fMRI) studies of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) have begun to reveal abnormalities in large-scale memory and cognitive brain networks. Since the medial temporal lobe (MTL) memory system is a site of very early pathology in AD, a number of studies have focused on this region of the brain. Yet it is clear that other regions of the large-scale episodic memory network are affected early in the disease as well, and fMRI has begun to illuminate functional abnormalities in frontal, temporal, and parietal cortices as well in MCI and AD. Besides predictable hypoactivation of brain regions as they accrue pathology and undergo atrophy, there are also areas of hyperactivation in brain memory and cognitive circuits, possibly representing attempted compensatory activity. Recent fMRI data in MCI and AD are beginning to reveal relationships between abnormalities of functional activity in the MTL memory system and in functionally connected brain regions, such as the precuneus. Additional work with “resting state” fMRI data is illuminating functional-anatomic brain circuits and their disruption by disease. As this work continues to mature, it will likely contribute to our understanding of fundamental memory processes in the human brain and how these are perturbed in memory disorders. We hope these insights will translate into the incorporation of measures of task-related brain function into diagnostic assessment or therapeutic monitoring, which will hopefully one day be useful for demonstrating beneficial effects of treatments being tested in clinical trials.