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The Journal of Neuroscience, October 4, 2006, 26(40):10222-10231; doi:10.1523/JNEUROSCI.2250-06.2006
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Neurobiology of Disease
Alterations in Memory Networks in Mild Cognitive Impairment and Alzheimer's Disease: An Independent Component Analysis
Kim A. Celone,1,2 Vince D. Calhoun,3,4 Bradford C. Dickerson,1,2 Alireza Atri,2 Elizabeth F. Chua,1 Saul L. Miller,1,2 Kristina DePeau,1,2 Doreen M. Rentz,1 Dennis J. Selkoe,1 Deborah Blacker,1,2 Marilyn S. Albert,2,5 andReisa A. Sperling1,2 1Memory Disorders Unit, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, 2Departments of Neurology, Psychiatry, and Radiology, and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Massachusetts 02114, 3Olin Neuropsychiatry Research Center, The Institute of Living/Hartford Hospital, Hartford, Connecticut 06106, 4Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06511, and 5Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
Correspondence should be addressed to Dr. Reisa A. Sperling, Memory Disorders Unit, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115. Email: reisa{at}rics.bwh.harvard.edu
Memory function is likely subserved by multiple distributed neural networks, which are disrupted by the pathophysiological process of Alzheimer's disease (AD). In this study, we used multivariate analytic techniques to investigate memory-related functional magnetic resonance imaging (fMRI) activity in 52 individuals across the continuum of normal aging, mild cognitive impairment (MCI), and mild AD. Independent component analyses revealed specific memory-related networks that activated or deactivated during an associative memory paradigm. Across all subjects, hippocampal activation and parietal deactivation demonstrated a strong reciprocal relationship. Furthermore, we found evidence of a nonlinear trajectory of fMRI activation across the continuum of impairment. Less impaired MCI subjects showed paradoxical hyperactivation in the hippocampus compared with controls, whereas more impaired MCI subjects demonstrated significant hypoactivation, similar to the levels observed in the mild AD subjects. We found a remarkably parallel curve in the pattern of memory-related deactivation in medial and lateral parietal regions with greater deactivation in less-impaired MCI and loss of deactivation in more impaired MCI and mild AD subjects. Interestingly, the failure of deactivation in these regions was also associated with increased positive activity in a neocortical attentional network in MCI and AD. Our findings suggest that loss of functional integrity of the hippocampal-based memory systems is directly related to alterations of neural activity in parietal regions seen over the course of MCI and AD. These data may also provide functional evidence of the interaction between neocortical and medial temporal lobe pathology in early AD.
Key words: Alzheimer's disease; mild cognitive impairment; fMRI; hippocampus; default mode network; independent component analyses
Received Jan. 12, 2006; revised Aug. 4, 2006; accepted Aug. 27, 2006.
Correspondence should be addressed to Dr. Reisa A. Sperling, Memory Disorders Unit, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115. Email: reisa{at}rics.bwh.harvard.edu
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