Neurology 2002;58:750-757
© 2002 American Academy of Neurology
Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia
C. R. Jack, Jr., MD,
D. W. Dickson, MD,
J. E. Parisi, MD,
Y. C. Xu, MD PhD,
R. H. Cha, MS,
P. C. OBrien, PhD,
S. D. Edland, PhD,
G. E. Smith, PhD,
B. F. Boeve, MD,
E. G. Tangalos, MD,
E. Kokmen, MD and
R. C. Petersen, MD PhD
Deceased.
Address correspondence and reprint requests to Dr. Clifford R. Jack, Jr., Mayo Clinic, Diagnostic Radiology, 200 First Street SW, Rochester, MN 55905; e-mail: jack.clifford{at}mayo.edu
Objectives: To assess the diagnostic specificity of MRI-defined hippocampal atrophy for AD among individuals with a variety of pathologically confirmed conditions associated with dementia as well as changes attributable to typical aging, and to measure correlations among premortem MRI measurements of hippocampal atrophy, mental status examination performance, and the pathologic stage of AD.
Methods: An unselected series of 67 individuals participating in the Mayo Alzheimers Disease Research Center/Alzheimers Disease Patient Registry who had undergone a standardized antemortem MRI study and also postmortem examination were identified. Hippocampal volumes were measured from antemortem MRI. Each postmortem specimen was assigned a pathologic diagnosis and in addition, the severity of AD pathology was staged using the method of Braak and Braak.
Results: Individuals with an isolated pathologic diagnosis of AD, hippocampal sclerosis, frontotemporal degeneration, and neurofibrillary tangleonly degeneration usually had substantial hippocampal atrophy, while those with changes of typical aging did not. Among all 67 subjects, correlations (all p < 0.001) were observed between hippocampal volume and Braak and Braak stage (r = -0.39), between hippocampal volume and Mini-Mental State Examination (MMSE) score (r = 0.60), and between MMSE score and Braak and Braak stage (r = -0.41).
Conclusions: Hippocampal atrophy, while not specific for AD, was a fairly sensitive marker of the pathologic AD stage (particularly among subjects with isolated AD pathology [r = -0.63, p = 0.001]) and consequent cognitive status.
This article has been cited by other articles:

|
 |

|
 |
 
J. Appel, E. Potter, N. Bhatia, Q. Shen, W. Zhao, M.T. Greig, A. Raj, W.W. Barker, H. Potter, E. Schofield, et al.
Association of White Matter Hyperintensity Measurements on Brain MR Imaging with Cognitive Status, Medial Temporal Atrophy, and Cardiovascular Risk Factors
AJNR Am. J. Neuroradiol.,
November 1, 2009;
30(10):
1870 - 1876.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. He, S. Farias, O. Martinez, B. Reed, D. Mungas, and C. DeCarli
Differences in Brain Volume, Hippocampal Volume, Cerebrovascular Risk Factors, and Apolipoprotein E4 Among Mild Cognitive Impairment Subtypes
Arch Neurol,
November 1, 2009;
66(11):
1393 - 1399.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W.J.P. Henneman, H. Vrenken, J. Barnes, I. C. Sluimer, N. A. Verwey, M. A. Blankenstein, M. Klein, N. C. Fox, P. Scheltens, F. Barkhof, et al.
Baseline CSF p-tau levels independently predict progression of hippocampal atrophy in Alzheimer disease
Neurology,
September 22, 2009;
73(12):
935 - 940.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Vemuri, H. J. Wiste, S. D. Weigand, L. M. Shaw, J. Q. Trojanowski, M. W. Weiner, D. S. Knopman, R. C. Petersen, C. R. Jack Jr, and On behalf of the Alzheimer's Disease Neuroimaging
MRI and CSF biomarkers in normal, MCI, and AD subjects: Diagnostic discrimination and cognitive correlations
Neurology,
July 28, 2009;
73(4):
287 - 293.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Vemuri, H. J. Wiste, S. D. Weigand, L. M. Shaw, J. Q. Trojanowski, M. W. Weiner, D. S. Knopman, R. C. Petersen, C. R. Jack Jr, and On behalf of the Alzheimer's Disease Neuroimaging
MRI and CSF biomarkers in normal, MCI, and AD subjects: Predicting future clinical change
Neurology,
July 28, 2009;
73(4):
294 - 301.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. C. Mormino, J. T. Kluth, C. M. Madison, G. D. Rabinovici, S. L. Baker, B. L. Miller, R. A. Koeppe, C. A. Mathis, M. W. Weiner, W. J. Jagust, et al.
Episodic memory loss is related to hippocampal-mediated {beta}-amyloid deposition in elderly subjects
Brain,
May 1, 2009;
132(5):
1310 - 1323.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. A. Ronald, Y. Chen, L. Bernas, H. H. Kitzler, K. A. Rogers, R. A. Hegele, and B. K. Rutt
Clinical field-strength MRI of amyloid plaques induced by low-level cholesterol feeding in rabbits
Brain,
May 1, 2009;
132(5):
1346 - 1354.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. R. Jack Jr, V. J. Lowe, S. D. Weigand, H. J. Wiste, M. L. Senjem, D. S. Knopman, M. M. Shiung, J. L. Gunter, B. F. Boeve, B. J. Kemp, et al.
Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease
Brain,
May 1, 2009;
132(5):
1355 - 1365.
[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,
March 1, 2009;
19(3):
497 - 510.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. SALLOWAY and S. CORREIA
Alzheimer disease: Time to improve its diagnosis and treatment
Cleveland Clinic Journal of Medicine,
January 1, 2009;
76(1):
49 - 58.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Duara, D. A. Loewenstein, E. Potter, J. Appel, M. T. Greig, R. Urs, Q. Shen, A. Raj, B. Small, W. Barker, et al.
Medial temporal lobe atrophy on MRI scans and the diagnosis of Alzheimer disease
Neurology,
December 9, 2008;
71(24):
1986 - 1992.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R Schmidt, S Ropele, B Pendl, P Ofner, C Enzinger, H Schmidt, A Berghold, M Windisch, H Kolassa, and F Fazekas
Longitudinal multimodal imaging in mild to moderate Alzheimer disease: a pilot study with memantine
J. Neurol. Neurosurg. Psychiatry,
December 1, 2008;
79(12):
1312 - 1317.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Kantarci, R. C. Petersen, S. A. Przybelski, S. D. Weigand, M. M. Shiung, J. L. Whitwell, S. Negash, R. J. Ivnik, B. F. Boeve, D. S. Knopman, et al.
Hippocampal Volumes, Proton Magnetic Resonance Spectroscopy Metabolites, and Cerebrovascular Disease in Mild Cognitive Impairment Subtypes
Arch Neurol,
December 1, 2008;
65(12):
1621 - 1628.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. T. Cuenco, K. L. Lunetta, C. T. Baldwin, A. C. McKee, J. Guo, L. A. Cupples, R. C. Green, P. H. St. George-Hyslop, H. Chui, C. DeCarli, et al.
Association of Distinct Variants in SORL1 With Cerebrovascular and Neurodegenerative Changes Related to Alzheimer Disease
Arch Neurol,
December 1, 2008;
65(12):
1640 - 1648.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. J. Jalbert, L. A. Daiello, and K. L. Lapane
Dementia of the Alzheimer Type
Epidemiol. Rev.,
November 1, 2008;
30(1):
15 - 34.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. L. Whitwell, K. A. Josephs, M. E. Murray, K. Kantarci, S. A. Przybelski, S. D. Weigand, P. Vemuri, M. L. Senjem, J. E. Parisi, D. S. Knopman, et al.
MRI correlates of neurofibrillary tangle pathology at autopsy: A voxel-based morphometry study
Neurology,
September 2, 2008;
71(10):
743 - 749.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. M. Brickman, N. Schupf, J. J. Manly, J. A. Luchsinger, H. Andrews, M. X. Tang, C. Reitz, S. A. Small, R. Mayeux, C. DeCarli, et al.
Brain Morphology in Older African Americans, Caribbean Hispanics, and Whites From Northern Manhattan
Arch Neurol,
August 1, 2008;
65(8):
1053 - 1061.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Kantarci, D. S. Knopman, D. W. Dickson, J. E. Parisi, J. L. Whitwell, S. D. Weigand, K. A. Josephs, B. F. Boeve, R. C. Petersen, and C. R. Jack Jr
Alzheimer Disease: Postmortem Neuropathologic Correlates of Antemortem 1H MR Spectroscopy Metabolite Measurements
Radiology,
July 1, 2008;
248(1):
210 - 220.
[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]
|
 |
|

|
 |

|
 |
 
S. Kloppel, C. M. Stonnington, C. Chu, B. Draganski, R. I. Scahill, J. D. Rohrer, N. C. Fox, C. R. Jack Jr, J. Ashburner, and R. S. J. Frackowiak
Automatic classification of MR scans in Alzheimer's disease
Brain,
March 1, 2008;
131(3):
681 - 689.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. R. Jack Jr, V. J. Lowe, M. L. Senjem, S. D. Weigand, B. J. Kemp, M. M. Shiung, D. S. Knopman, B. F. Boeve, W. E. Klunk, C. A. Mathis, et al.
11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment
Brain,
March 1, 2008;
131(3):
665 - 680.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J T O'BRIEN
Role of imaging techniques in the diagnosis of dementia
Br. J. Radiol.,
December 1, 2007;
80(Special_Issue_2):
S71 - S77.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Barkhof, T. M. Polvikoski, E.C.W. van Straaten, R. N. Kalaria, R. Sulkava, H. J. Aronen, L. Niinisto, S. Rastas, M. Oinas, P. Scheltens, et al.
The significance of medial temporal lobe atrophy: A postmortem MRI study in the very old
Neurology,
October 9, 2007;
69(15):
1521 - 1527.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. M. Burns, J. E. Donnelly, H. S. Anderson, M. S. Mayo, L. Spencer-Gardner, G. Thomas, B. B. Cronk, Z. Haddad, D. Klima, D. Hansen, et al.
Peripheral insulin and brain structure in early Alzheimer disease
Neurology,
September 11, 2007;
69(11):
1094 - 1104.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. L. Whitwell, C. R. Jack Jr, J. E. Parisi, D. S. Knopman, B. F. Boeve, R. C. Petersen, T. J. Ferman, D. W. Dickson, and K. A. Josephs
Rates of cerebral atrophy differ in different degenerative pathologies
Brain,
April 1, 2007;
130(4):
1148 - 1158.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Harper
The neurotoxicity of alcohol
Human and Experimental Toxicology,
March 1, 2007;
26(3):
251 - 257.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
L. G. Apostolova, I. D. Dinov, R. A. Dutton, K. M. Hayashi, A. W. Toga, J. L. Cummings, and P. M. Thompson
3D comparison of hippocampal atrophy in amnestic mild cognitive impairment and Alzheimer's disease
Brain,
November 1, 2006;
129(11):
2867 - 2873.
[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]
|
 |
|

|
 |

|
 |
 
T. Sunderland, H. Hampel, M. Takeda, K. T. Putnam, and R. M. Cohen
Biomarkers in the Diagnosis of Alzheimer's Disease: Are We Ready?
J Geriatr Psychiatry Neurol,
September 1, 2006;
19(3):
172 - 179.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
L. G. Apostolova, R. A. Dutton, I. D. Dinov, K. M. Hayashi, A. W. Toga, J. L. Cummings, and P. M. Thompson
Conversion of Mild Cognitive Impairment to Alzheimer Disease Predicted by Hippocampal Atrophy Maps
Arch Neurol,
May 1, 2006;
63(5):
693 - 699.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L A van de Pol, A Hensel, W M van der Flier, P-J Visser, Y A L Pijnenburg, F Barkhof, H J. Gertz, and P Scheltens
Hippocampal atrophy on MRI in frontotemporal lobar degeneration and Alzheimer's disease
J. Neurol. Neurosurg. Psychiatry,
April 1, 2006;
77(4):
439 - 442.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. A. van de Pol, A. Hensel, F. Barkhof, H. J. Gertz, P. Scheltens, and W. M. van der Flier
Hippocampal atrophy in Alzheimer disease: Age matters
Neurology,
January 24, 2006;
66(2):
236 - 238.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. A. Mortimer, A. R. Borenstein, K. M. Gosche, and D. A. Snowdon
Very Early Detection of Alzheimer Neuropathology and the Role of Brain Reserve in Modifying Its Clinical Expression
J Geriatr Psychiatry Neurol,
December 1, 2005;
18(4):
218 - 223.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
G. B. Frisoni and M. Filippi
Multiple Sclerosis and Alzheimer Disease through the Looking Glass of MR Imaging
AJNR Am. J. Neuroradiol.,
November 1, 2005;
26(10):
2488 - 2491.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Raz, U. Lindenberger, K. M. Rodrigue, K. M. Kennedy, D. Head, A. Williamson, C. Dahle, D. Gerstorf, and J. D. Acker
Regional Brain Changes in Aging Healthy Adults: General Trends, Individual Differences and Modifiers
Cereb Cortex,
November 1, 2005;
15(11):
1676 - 1689.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. Jagust, D. Harvey, D. Mungas, and M. Haan
Central Obesity and the Aging Brain
Arch Neurol,
October 1, 2005;
62(10):
1545 - 1548.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Likeman, V. M. Anderson, J. M. Stevens, A. D. Waldman, A. K. Godbolt, C. Frost, M. N. Rossor, and N. C. Fox
Visual Assessment of Atrophy on Magnetic Resonance Imaging in the Diagnosis of Pathologically Confirmed Young-Onset Dementias
Arch Neurol,
September 1, 2005;
62(9):
1410 - 1415.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Mungas, D. Harvey, B. R. Reed, W. J. Jagust, C. DeCarli, L. Beckett, W. J. Mack, J. H. Kramer, M. W. Weiner, N. Schuff, et al.
Longitudinal volumetric MRI change and rate of cognitive decline
Neurology,
August 23, 2005;
65(4):
565 - 571.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Head, A. Z. Snyder, L. E. Girton, J. C. Morris, and R. L. Buckner
Frontal-Hippocampal Double Dissociation Between Normal Aging and Alzheimer's Disease
Cereb Cortex,
June 1, 2005;
15(6):
732 - 739.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R Vandenberghe and J Tournoy
Cognitive aging and Alzheimer's disease
Postgrad. Med. J.,
June 1, 2005;
81(956):
343 - 352.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Jenssen
Electroencephalogram in the dementia workup
American Journal of Alzheimer's Disease and Other Dementias,
May 1, 2005;
20(3):
159 - 166.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
T. den Heijer, L. J. Launer, N. D. Prins, E. J. van Dijk, S. E. Vermeer, A. Hofman, P. J. Koudstaal, and M. M.B. Breteler
Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe
Neurology,
January 25, 2005;
64(2):
263 - 267.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. C. Steffens, K. A. Welsh-Bohmer, J. R. Burke, B. L. Plassman, J. L. Beyer, K. R. Gersing, and G. G. Potter
Methodology and Preliminary Results From the Neurocognitive Outcomes of Depression in the Elderly Study
J Geriatr Psychiatry Neurol,
December 1, 2004;
17(4):
202 - 211.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
R. M. Wiseman, B. K. Saxby, E. J. Burton, R. Barber, G. A. Ford, and J. T. O'Brien
Hippocampal atrophy, whole brain volume, and white matter lesions in older hypertensive subjects
Neurology,
November 23, 2004;
63(10):
1892 - 1897.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. R. Reed, J. L. Eberling, D. Mungas, M. Weiner, J. H. Kramer, and W. J. Jagust
Effects of White Matter Lesions and Lacunes on Cortical Function
Arch Neurol,
October 1, 2004;
61(10):
1545 - 1550.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. F. Lippa and D. W. Dickson
Hippocampal sclerosis dementia: Expanding the phenotypes of frontotemporal dementias?
Neurology,
August 10, 2004;
63(3):
414 - 415.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. J. Hatanpaa, D. M. Blass, O. Pletnikova, B. J. Crain, E. H. Bigio, J. C. Hedreen, C. L. White III, and J. C. Troncoso
Most cases of dementia with hippocampal sclerosis may represent frontotemporal dementia
Neurology,
August 10, 2004;
63(3):
538 - 542.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. DeCarli, D. Mungas, D. Harvey, B. Reed, M. Weiner, H. Chui, and W. Jagust
Memory impairment, but not cerebrovascular disease, predicts progression of MCI to dementia
Neurology,
July 27, 2004;
63(2):
220 - 227.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. S.C. Korf, L.-O. Wahlund, P. J. Visser, and P. Scheltens
Medial temporal lobe atrophy on MRI predicts dementia in patients with mild cognitive impairment
Neurology,
July 13, 2004;
63(1):
94 - 100.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. S.C. Korf, L. R. White, P. Scheltens, and L. J. Launer
Midlife Blood Pressure and the Risk of Hippocampal Atrophy: The Honolulu Asia Aging Study
Hypertension,
July 1, 2004;
44(1):
29 - 34.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Raz, K. M. Rodrigue, D. Head, K. M. Kennedy, and J. D. Acker
Differential aging of the medial temporal lobe: A study of a five-year change
Neurology,
February 10, 2004;
62(3):
433 - 438.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. V. Sullivan and L. Marsh
Hippocampal volume deficits in alcoholic Korsakoff's syndrome
Neurology,
December 23, 2003;
61(12):
1716 - 1719.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. R. R. Krishnan, H. C. Charles, P. M. Doraiswamy, J. Mintzer, R. Weisler, X. Yu, C. Perdomo, J. R. Ieni, and S. Rogers
Randomized, Placebo-Controlled Trial of the Effects of Donepezil on Neuronal Markers and Hippocampal Volumes in Alzheimer's Disease
Am J Psychiatry,
November 1, 2003;
160(11):
2003 - 2011.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. S. Knopman, B. F. Boeve, and R. C. Petersen
Essentials of the Proper Diagnoses of Mild Cognitive Impairment, Dementia, and Major Subtypes of Dementia
Mayo Clin. Proc.,
October 1, 2003;
78(10):
1290 - 1308.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
L.C. Silbert, J.F. Quinn, M.M. Moore, E. Corbridge, M.J. Ball, G. Murdoch, G. Sexton, and J.A. Kaye
Changes in premorbid brain volume predict Alzheimer's disease pathology
Neurology,
August 26, 2003;
61(4):
487 - 492.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|