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NEUROLOGY 1997;49:786-794
© 1997 American Academy of Neurology

Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease

Clifford R. Jack, Jr, MD, Ronald C. Petersen, PhD, MD, Yue Cheng Xu, MD, PhD, Stephen C. Waring, DVM, PhD, Peter C. O'Brien, PhD, Eric G. Tangalos, MD, Glenn E. Smith, PhD, Robert J. Ivnik, PhD and Emre Kokmen, MD

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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Mild cognitive impairment: Directions for future research
Neurology, August 26, 2003; 61(4): 438 - 444.
[Abstract] [Full Text] [PDF]

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 NeurologyHome page
M. M. Machulda, H. A. Ward, B. Borowski, J. L. Gunter, R. H. Cha, P. C. O'Brien, R. C. Petersen, B. F. Boeve, D. Knopman, D. F. Tang-Wai, et al.
Comparison of memory fMRI response among normal, MCI, and Alzheimer's patients
Neurology, August 26, 2003; 61(4): 500 - 506.
[Abstract] [Full Text] [PDF]

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 BrainHome page
M. Sailer, B. Fischl, D. Salat, C. Tempelmann, M. A. Schonfeld, E. Busa, N. Bodammer, H.-J. Heinze, and A. Dale
Focal thinning of the cerebral cortex in multiple sclerosis
Brain, August 1, 2003; 126(8): 1734 - 1744.
[Abstract] [Full Text] [PDF]

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 Arch NeurolHome page
A. L. Boxer, K. P. Rankin, B. L. Miller, N. Schuff, M. Weiner, M.-L. Gorno-Tempini, and H. J. Rosen
Cinguloparietal Atrophy Distinguishes Alzheimer Disease From Semantic Dementia
Arch Neurol, July 1, 2003; 60(7): 949 - 956.
[Abstract] [Full Text] [PDF]

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 Arch NeurolHome page
R. I. Scahill, C. Frost, R. Jenkins, J. L. Whitwell, M. N. Rossor, and N. C. Fox
A Longitudinal Study of Brain Volume Changes in Normal Aging Using Serial Registered Magnetic Resonance Imaging
Arch Neurol, July 1, 2003; 60(7): 989 - 994.
[Abstract] [Full Text] [PDF]

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 Arch NeurolHome page
A. L. Guillozet, S. Weintraub, D. C. Mash, and M. M. Mesulam
Neurofibrillary Tangles, Amyloid, and Memory in Aging and Mild Cognitive Impairment
Arch Neurol, May 1, 2003; 60(5): 729 - 736.
[Abstract] [Full Text] [PDF]

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 ANN INTERN MEDHome page
C. M. Clark and J. H.T. Karlawish
Alzheimer Disease: Current Concepts and Emerging Diagnostic and Therapeutic Strategies
Ann Intern Med, March 4, 2003; 138(5): 400 - 410.
[Abstract] [Full Text] [PDF]

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 Am. J. Neuroradiol.Home page
A. Fernandez, J. Arrazola, F. Maestu, C. Amo, P. Gil-Gregorio, C. Wienbruch, and T. Ortiz
Correlations of Hippocampal Atrophy and Focal Low-Frequency Magnetic Activity in Alzheimer Disease: Volumetric MR Imaging-Magnetoencephalographic Study
AJNR Am. J. Neuroradiol., March 1, 2003; 24(3): 481 - 487.
[Abstract] [Full Text] [PDF]

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 NeurologyHome page
B. Boeve, J. McCormick, G. Smith, T. Ferman, T. Rummans, T. Carpenter, R. Ivnik, E. Kokmen, E. Tangalos, S. Edland, et al.
Mild cognitive impairment in the oldest old
Neurology, February 11, 2003; 60(3): 477 - 480.
[Abstract] [Full Text] [PDF]

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 NeurologyHome page
A. T. Du, N. Schuff, X. P. Zhu, W. J. Jagust, B. L. Miller, B. R. Reed, J. H. Kramer, D. Mungas, K. Yaffe, H. C. Chui, et al.
Atrophy rates of entorhinal cortex in AD and normal aging
Neurology, February 11, 2003; 60(3): 481 - 486.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
J. M. Redwine, B. Kosofsky, R. E. Jacobs, D. Games, J. F. Reilly, J. H. Morrison, W. G. Young, and F. E. Bloom
Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: A magnetic resonance microscopy and stereologic analysis
PNAS, February 4, 2003; 100(3): 1381 - 1386.
[Abstract] [Full Text] [PDF]

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 RadiologyHome page
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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 NeurologyHome page
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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 J. Neurol. Neurosurg. PsychiatryHome page
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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 J. Neurol. Neurosurg. PsychiatryHome page
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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 J. Neurol. Neurosurg. PsychiatryHome page
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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 J. Neurol. Neurosurg. PsychiatryHome page
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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 BrainHome page
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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 RadiologyHome page
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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 NeurologyHome page
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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 NeurologyHome page
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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 BrainHome page
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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 NeurologyHome page
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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 NeurologyHome page
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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 RadiologyHome page
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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 Arch NeurolHome page
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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 Br. J. Radiol.Home page
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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