Affiliations: Memory Disorders Unit, Department of Neurology,
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA | Unit of Neurology, Institute of Clinical Medicine,
University of Kuopio, Kuopio, Finland | Department of Psychiatry, Massachusetts General
Hospital, Boston, MA, USA
Note: [] Corresponding author: Maija Pihlajamäki, MD, PhD, Unit of
Neurology, Institute of Clinical Medicine, University of Kuopio, POB 1627,
FIN-70211 Kuopio, Finland. Tel.: +358 17 173 311; Fax: +358 17 173 019; E-mail:
[email protected]
Abstract: Alzheimer's disease (AD) is the most common form of dementia in old
age, and is characterized by prominent impairment of episodic memory. Recent
functional imaging studies in AD have demonstrated alterations in a distributed
network of brain regions supporting memory function, including regions of the
default mode network. Previous positron emission tomography studies of older
individuals at risk for AD have revealed hypometabolism of association cortical
regions similar to the metabolic abnormalities seen in AD patients. In recent
functional magnetic resonance imaging (fMRI) studies of AD, corresponding brain
default mode regions have also been found to demonstrate an abnormal fMRI
task-induced deactivation response pattern. That is, the relative decreases in
fMRI signal normally observed in the default mode regions in healthy subjects
performing a cognitive task are not seen in AD patients, or may even be
reversed to a paradoxical activation response. Our recent studies have revealed
alterations in the pattern of deactivation also in elderly individuals at risk
for AD by virtue of their APOE e4 genotype, or evidence of mild cognitive
impairment (MCI). In agreement with recent reports from other groups, these
studies demonstrate that the pattern of fMRI task-induced deactivation is
progressively disrupted along the continuum from normal aging to MCI and to
clinical AD and more impaired in e4 carriers compared to non-carriers. These
findings will be discussed in the context of current literature regarding
functional imaging of the default network in AD and at-risk populations.
