| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Departments of Neurology (Drs. Dickerson, Bertram, Tanzi, Albert, and Sperling, and E. Rand-Giovannetti and K. Mullin), Psychiatry (Drs. Blacker and Albert), Radiology (Drs. Salat and Greve), and the Athinoula A. Martinos Center for Biomedical Imaging (Drs. Dickerson, Salat, Greve, Blacker, Albert, and Sperling, and E.F. Chua and E. Rand-Giovannetti), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (Drs. Dickerson, Rentz, and Sperling, and E.F. Chua), Brigham & Women's Hospital, Boston, MA; and Department of Neurology (Dr. Albert), Johns Hopkins University School of Medicine, Baltimore, MD.
Address correspondence and reprint requests to Dr. Reisa A. Sperling, Memory Disorders Unit, Brigham & Women's Hospital, 221 Longwood Ave., Boston, MA 02115; e-mail: reisa{at}rics.bwh.harvard.edu
Objective: To use fMRI to investigate whether hippocampal and entorhinal activation during learning is altered in the earliest phase of mild cognitive impairment (MCI).
Methods: Three groups of older individuals were studied: 10 cognitively intact controls, 9 individuals at the mild end of the spectrum of MCI, and 10 patients with probable Alzheimer disease (AD). Subjects performed a face-name associative encoding task during fMRI scanning, and were tested for recognition of stimuli afterward. Data were analyzed using a functional-anatomic method in which medial temporal lobe (MTL) regions of interest were identified from each individual's structural MRI, and fMRI activation was quantified within each region.
Results: Significantly greater hippocampal activation was present in the MCI group compared to controls; there were no differences between these two groups in hippocampal or entorhinal volumes. In contrast, the AD group showed hippocampal and entorhinal hypoactivation and atrophy in comparison to controls. The subjects with MCI performed similarly to controls on the fMRI recognition memory task; patients with AD exhibited poorer performance. Across all 29 subjects, greater mean entorhinal activation was found in the subgroup of 13 carriers of the APOE 
4 allele than in the 16 noncarriers.
Conclusions: The authors hypothesize that there is a phase of increased medial temporal lobe activation early in the course of prodromal Alzheimer disease followed by a subsequent decrease as the disease progresses.
Supported by the National Institute on Aging (PO1-AG04953; K23-AG22509), National Institute of Neurologic Disorders and Stroke (K23-NS02189), Beeson Scholars in Aging Program (American Federation for Aging Research), Clinical Investigator Training Program (Harvard/MIT Health Sciences and Technology–Beth Israel Deaconess Medical Center, in collaboration with Pfizer Inc.), Mental Illness and Neuroscience Discovery (MIND) Institute, Eli Lilly Pharmaceuticals, MA ADRC (P50-AG05134), NCRR (P41-RR14075), and NCRR BIRN Morphometry Project (BIRN004).
Disclosure: The authors report no conflicts of interest.
Received October 21, 2004. Accepted in final form April 27, 2005.
This article has been cited by other articles:
|
|
 |
|
  S. Duverne, S. Motamedinia, and M. D. Rugg The Relationship between Aging, Performance, and the Neural Correlates of Successful Memory Encoding Cereb Cortex, July 24, 2008; (2008) bhn122v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Dickerson, A. Bakkour, D. H. Salat, E. Feczko, J. Pacheco, D. N. Greve, F. Grodstein, C. I. Wright, D. Blacker, H. D. Rosas, et al. The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals Cereb Cortex, July 16, 2008; (2008) bhn113v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S L Miller, E Fenstermacher, J Bates, D Blacker, R A Sperling, and B C Dickerson Hippocampal activation in adults with mild cognitive impairment predicts subsequent cognitive decline J. Neurol. Neurosurg. Psychiatry, June 1, 2008; 79(6): 630 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Yassa, G. Verduzco, C. Cristinzio, and S. S. Bassett Altered fMRI activation during mental rotation in those at genetic risk for Alzheimer disease Neurology, May 13, 2008; 70(20): 1898 - 1904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Miller, K. Celone, K. DePeau, E. Diamond, B. C. Dickerson, D. Rentz, M. Pihlajamaki, and R. A. Sperling Age-related memory impairment associated with loss of parietal deactivation but preserved hippocampal activation PNAS, February 12, 2008; 105(6): 2181 - 2186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Chetelat, B. Desgranges, B. Landeau, F. Mezenge, J. B. Poline, V. de la Sayette, F. Viader, F. Eustache, and J.-C. Baron Direct voxel-based comparison between grey matter hypometabolism and atrophy in Alzheimer's disease Brain, January 1, 2008; 131(1): 60 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sorg, V. Riedl, M. Muhlau, V. D. Calhoun, T. Eichele, L. Laer, A. Drzezga, H. Forstl, A. Kurz, C. Zimmer, et al. Selective changes of resting-state networks in individuals at risk for Alzheimer's disease PNAS, November 20, 2007; 104(47): 18760 - 18765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. F. S. Bell, D. A. Bennett, and A. C. Cuello Paradoxical Upregulation of Glutamatergic Presynaptic Boutons during Mild Cognitive Impairment J. Neurosci., October 3, 2007; 27(40): 10810 - 10817. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Johnson, M. L. Ries, T. M. Hess, C. M. Carlsson, C. E. Gleason, A. L. Alexander, H. A. Rowley, S. Asthana, and M. A. Sager Effect of Alzheimer Disease Risk on Brain Function During Self-appraisal in Healthy Middle-aged Adults Arch Gen Psychiatry, October 1, 2007; 64(10): 1163 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Petrella, L. Wang, S. Krishnan, M. J. Slavin, S. E. Prince, T.-T. T. Tran, and P. M. Doraiswamy Cortical Deactivation in Mild Cognitive Impairment: High-Field-Strength Functional MR Imaging Radiology, October 1, 2007; 245(1): 224 - 235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Diamond, S. Miller, B. C. Dickerson, A. Atri, K. DePeau, E. Fenstermacher, M. Pihlajamaki, K. Celone, S. Salisbury, M. Gregas, et al. Relationship of fMRI activation to clinical trial memory measures in Alzheimer disease Neurology, September 25, 2007; 69(13): 1331 - 1341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Truchot, S. N. Costes, L. Zimmer, B. Laurent, D. Le Bars, C. Thomas-Anterion, B. Croisile, B. Mercier, M. Hermier, A. Vighetto, et al. Up-regulation of hippocampal serotonin metabolism in mild cognitive impairment Neurology, September 4, 2007; 69(10): 1012 - 1017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. T Kircher, S. Weis, K. Freymann, M. Erb, F. Jessen, W. Grodd, R. Heun, and D. T Leube Hippocampal activation in patients with mild cognitive impairment is necessary for successful memory encoding J. Neurol. Neurosurg. Psychiatry, August 1, 2007; 78(8): 812 - 818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Smith, V. S. Pankratz, S. Negash, M. M. Machulda, R. C. Petersen, B. F. Boeve, D. S. Knopman, J. A. Lucas, T. J. Ferman, N. Graff-Radford, et al. A plateau in pre-Alzheimer memory decline: Evidence for compensatory mechanisms? Neurology, July 10, 2007; 69(2): 133 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Minati, M. Grisoli, and M. G. Bruzzone MR Spectroscopy, Functional MRI, and Diffusion-Tensor Imaging in the Aging Brain: A Conceptual Review J Geriatr Psychiatry Neurol, March 1, 2007; 20(1): 3 - 21. [Abstract] [PDF]
|
|
|
|
|
|
M. Vandenbulcke, R. Peeters, P. Dupont, P. Van Hecke, and R. Vandenberghe Word Reading and Posterior Temporal Dysfunction in Amnestic Mild Cognitive Impairment Cereb Cortex, March 1, 2007; 17(3): 542 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Gleason, T. W. Schmitz, T. Hess, R. L. Koscik, M. A. Trivedi, M. L. Ries, C. M. Carlsson, M. A. Sager, S. Asthana, and S. C. Johnson Hormone effects on fMRI and cognitive measures of encoding: Importance of hormone preparation Neurology, December 12, 2006; 67(11): 2039 - 2041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Celone, V. D. Calhoun, B. C. Dickerson, A. Atri, E. F. Chua, S. L. Miller, K. DePeau, D. M. Rentz, D. J. Selkoe, D. Blacker, et al. Alterations in Memory Networks in Mild Cognitive Impairment and Alzheimer's Disease: An Independent Component Analysis J. Neurosci., October 4, 2006; 26(40): 10222 - 10231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.K. Sandstrom, S. Krishnan, M.J. Slavin, T.-T.T. Tran, P.M. Doraiswamy, and J.R. Petrella Hippocampal Atrophy Confounds Template-Based Functional MR Imaging Measures of Hippocampal Activation in Patients with Mild Cognitive Impairment. AJNR Am. J. Neuroradiol., September 1, 2006; 27(8): 1622 - 1627. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. M. L. Chuah, V. Venkatraman, D. F. Dinges, and M. W. L. Chee The neural basis of interindividual variability in inhibitory efficiency after sleep deprivation. J. Neurosci., July 5, 2006; 26(27): 7156 - 7162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Johnson, T. W. Schmitz, M. A. Trivedi, M. L. Ries, B. M. Torgerson, C. M. Carlsson, S. Asthana, B. P. Hermann, and M. A. Sager The influence of Alzheimer disease family history and apolipoprotein E epsilon4 on mesial temporal lobe activation. J. Neurosci., May 31, 2006; 26(22): 6069 - 6076. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
