Affiliations: Department of Neurology, Harvard Medical School,
Boston, MA, USA | Massachusetts Alzheimer's Disease Research Center,
Harvard Medical School, Boston, MA, USA | Frontotemporal Dementia Unit, Harvard Medical School,
Boston, MA, USA | Athinoula A. Martinos Center for Biomedical Imaging,
Massachusetts General Hospital and Harvard Medical School, Boston, MA,
USA | Division of Cognitive and Behavioral Neurology,
Department of Neurology, Brigham & Women's Hospital, Boston, MA,
USA
Note: [] Corresponding author: Bradford C. Dickerson, M.D., Gerontology
Research Unit, Massachusetts General Hospital, 149 13th St., Suite 2691,
Charlestown, MA 02129, USA. Tel.: +1 617 726 5571; Fax: +1 617 726 5760;
E-mail: bradd@nmr.mgh.harvard.edu
Abstract: 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.
