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From the Departments of Diagnostic Radiology (Drs. Jack and Xu), Neurology(Drs. Petersen and Kokmen), Health Sciences Research (Drs. Waring, O'Brien, and Petersen), Internal Medicine (Dr. Tangalos), Department of Psychiatry and Psychology (Drs. Smith and Ivnik), Mayo Clinic and Foundation, Rochester, MN.
Address correspondence and reprint requests to Dr. Clifford R. Jack, Jr., Mayo Clinic, Diagnostic Radiology, 200 First Street SW, Rochester, MN 55905.
Magnetic resonance imaging (MRI)-based volumetric measurements of medial temporal lobe (MTL) structures can discriminate between normal elderly control subjects and patients with Alzheimer's disease (AD) of moderate to advanced severity. In terms of clinical utility, however, a more important issue concerns the ability of the technique to differentiate between normal elderly control subjects and AD patients with the very mildest form of the disease. We performed MRI-based volumetric measurements of the hippocampus, parahippocampal gyrus, and amygdala in 126 cognitively normal elderly control subjects and 94 patients with probable AD. The diagnosis of AD was made according to NINDS/ADRDA criteria, and disease severity was categorized by Clinical Dementia Rating (CDR) scores. Patients with CDR 0.5 were classified as very mild, CDR 1 as mild, and CDR 2 as moderate disease severity. Volumes of each structure declined with increasing age in control subjects and did so in parallel for men and women. The volume of each measured MTL structure also declined with age in patients with AD. The volume of each MTL structure was significantly smaller in AD patients than control subjects (p < 0.001). Of the several MTL measures, the total hippocampal volumetric measurements were best at discriminating control subjects from AD patients. The mean hippocampal volumes for AD patients relative to control subjects by severity of disease were as follows: very mild AD (CDR 0.5) -1.75 SD below the control mean, mild AD (CDR 1) -1.99 SD, and moderate AD (CDR 2) -2.22 SD. Age- and gender-adjusted, normalized MRI-based hippocampal volumetric measurements provide a sensitive marker of the MTL neuroanatomic degeneration in AD early in the disease process.
Supported by NIH-NIA-AG11378, AG-08031, AG-06786, NINDS-NS29059, The DANA Foundation, and the Alzheimer's Association.
Received December 2, 1996. Accepted in final form April 10, 1997.
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J. R. Petrella, R. E. Coleman, and P. M. Doraiswamy Neuroimaging and Early Diagnosis of Alzheimer Disease: A Look to the Future Radiology, February 1, 2003; 226(2): 315 - 336. [Abstract] [Full Text] [PDF] |
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C. R. Jack Jr., M. Slomkowski, S. Gracon, T. M. Hoover, J. P. Felmlee, K. Stewart, Y. Xu, M. Shiung, P. C. O'Brien, R. Cha, et al. MRI as a biomarker of disease progression in a therapeutic trial of milameline for AD Neurology, January 28, 2003; 60(2): 253 - 260. [Abstract] [Full Text] [PDF] |
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R A Sperling, J F Bates, E F Chua, A J Cocchiarella, D M Rentz, B R Rosen, D L Schacter, and M S Albert fMRI studies of associative encoding in young and elderly controls and mild Alzheimer's disease J. Neurol. Neurosurg. Psychiatry, January 1, 2003; 74(1): 44 - 50. [Abstract] [Full Text] [PDF] |
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G B Frisoni, C Testa, A Zorzan, F Sabattoli, A Beltramello, H Soininen, and M P Laakso Detection of grey matter loss in mild Alzheimer's disease with voxel based morphometry J. Neurol. Neurosurg. Psychiatry, December 1, 2002; 73(6): 657 - 664. [Abstract] [Full Text] [PDF] |
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S A R B Rombouts, F Barkhof, C S van Meel, and P Scheltens Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer's disease J. Neurol. Neurosurg. Psychiatry, December 1, 2002; 73(6): 665 - 671. [Abstract] [Full Text] [PDF] |
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G E J Garrido, S S Furuie, C A Buchpiguel, C M C Bottino, O P Almeida, C G Cid, C H P Camargo, C C Castro, M F Glabus, and G F Busatto Relation between medial temporal atrophy and functional brain activity during memory processing in Alzheimer's disease: a combined MRI and SPECT study J. Neurol. Neurosurg. Psychiatry, November 1, 2002; 73(5): 508 - 516. [Abstract] [Full Text] [PDF] |
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R. M. Dixon, K. M. Bradley, M. M. Budge, P. Styles, and A. D. Smith Longitudinal quantitative proton magnetic resonance spectroscopy of the hippocampus in Alzheimer's disease Brain, October 1, 2002; 125(10): 2332 - 2341. [Abstract] [Full Text] [PDF] |
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S.-J. Li, Z. Li, G. Wu, M.-J. Zhang, M. Franczak, and P. G. Antuono Alzheimer Disease: Evaluation of a Functional MR Imaging Index as a Marker Radiology, October 1, 2002; 225(1): 253 - 259. [Abstract] [Full Text] [PDF] |
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D. Mungas, B. R. Reed, W. J. Jagust, C. DeCarli, W. J. Mack, J. H. Kramer, M. W. Weiner, N. Schuff, and H. C. Chui Volumetric MRI predicts rate of cognitive decline related to AD and cerebrovascular disease Neurology, September 24, 2002; 59(6): 867 - 873. [Abstract] [Full Text] [PDF] |
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C. C. Wu, D. Mungas, C. I. Petkov, J. L. Eberling, P. A. Zrelak, M. H. Buonocore, J. A. Brunberg, M. N. Haan, and W. J. Jagust Brain structure and cognition in a community sample of elderly Latinos Neurology, August 13, 2002; 59(3): 383 - 391. [Abstract] [Full Text] [PDF] |
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K. M. Bradley, V. T. O'Sullivan, N. D. W. Soper, Z. Nagy, E. M.-F. King, A. D. Smith, and B. J. Shepstone Cerebral perfusion SPET correlated with Braak pathological stage in Alzheimer's disease Brain, August 1, 2002; 125(8): 1772 - 1781. [Abstract] [Full Text] [PDF] |
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A. M.J. MacLullich, K. J. Ferguson, I. J. Deary, J. R. Seckl, J. M. Starr, and J. M. Wardlaw Intracranial capacity and brain volumes are associated with cognition in healthy elderly men Neurology, July 23, 2002; 59(2): 169 - 174. [Abstract] [Full Text] [PDF] |
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S. D. Edland, Y. Xu, M. Plevak, P. O'Brien, E. G. Tangalos, R. C. Petersen, and C. R. Jack Jr. Total intracranial volume: Normative values and lack of association with Alzheimer's disease Neurology, July 23, 2002; 59(2): 272 - 274. [Abstract] [Full Text] [PDF] |
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N. A. Thacker, A. R. Varma, D. Bathgate, S. Stivaros, J. S. Snowden, D. Neary, and A. Jackson Dementing Disorders: Volumetric Measurement of Cerebrospinal Fluid to Distinguish Normal from Pathologic Findings—Feasibility Study Radiology, July 1, 2002; 224(1): 278 - 285. [Abstract] [Full Text] |
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S. Chantal, M. Labelle, R. W. Bouchard, C. M. J. Braun, and Y. Boulanger Correlation of Regional Proton Magnetic Resonance Spectroscopic Metabolic Changes With Cognitive Deficits in Mild Alzheimer Disease Arch Neurol, June 1, 2002; 59(6): 955 - 962. [Abstract] [Full Text] [PDF] |
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K M Bradley, G M Bydder, M M Budge, J V Hajnal, S J White, B D Ripley, and A D Smith Serial brain MRI at 3-6 month intervals as a surrogate marker for Alzheimer's disease Br. J. Radiol., June 1, 2002; 75(894): 506 - 513. [Abstract] [Full Text] [PDF] |
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