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From the Departments of Diagnostic Radiology (Drs. Jack and Xu), Neurology (Drs. Petersen, Boeve, and Kokmen), Health Sciences Research (P.C. O’Brien and S.C. Waring), Psychiatry and Psychology (G.E. Smith and R.J. Ivnik), and Internal Medicine (Dr. Tangalos), 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.
OBJECTIVE: To test the hypothesis that MRI-based measurements of hippocampal volume are related to the risk of future conversion to Alzheimer’s disease (AD) in older patients with a mild cognitive impairment (MCI).
BACKGROUND: Patients who develop AD pass through a transitional state, which can be characterized as MCI. In some patients, however, MCI is a more benign condition, which may not progress to AD or may do so slowly.Patients:— Eighty consecutive patients who met criteria for the diagnosis of MCI were recruited from the Mayo Clinic Alzheimer’s Disease Center/Alzheimer’s Disease Patient Registry.
METHODS: At entry into the study, each patient received an MRI examination of the head, from which the volumes of both hippocampi were measured. Patients were followed longitudinally with approximately annual clinical/cognitive assessments. The primary endpoint was the crossover of individual MCI patients to the clinical diagnosis of AD during longitudinal clinical follow-up.
RESULTS: During the period of longitudinal observation, which averaged 32.6 months, 27 of the 80 MCI patients became demented. Hippocampal atrophy at baseline was associated with crossover from MCI to AD (relative risk [RR], 0.69, p = 0.015). When hippocampal volume was entered into bivariate models—using age, postmenopausal estrogen replacement, standard neuropsychological tests, apolipoprotein E (APOE) genotype, history of ischemic heart disease, and hypertension—the RRs were not substantially different from that found univariately, and the associations between hippocampal volume and crossover remained significant.
CONCLUSION: In older patients with MCI, hippocampal atrophy determined by premorbid MRI-based volume measurements is predictive of subsequent conversion to AD.
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 T. den Heijer, S. E Vermeer, E. J van Dijk, N. D Prins, P. J Koudstaal, C. M van Duijn, A. Hofman, and M. M. Breteler Alcohol intake in relation to brain magnetic resonance imaging findings in older persons without dementia Am. J. Clinical Nutrition, October 1, 2004; 80(4): 992 - 997. [Abstract] [Full Text] [PDF]
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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]
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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]
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S. Adak, K. Illouz, W. Gorman, R. Tandon, E. A. Zimmerman, R. Guariglia, M. M. Moore, and J. A. Kaye Predicting the rate of cognitive decline in aging and early Alzheimer disease Neurology, July 13, 2004; 63(1): 108 - 114. [Abstract] [Full Text] [PDF]
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 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]
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C. R. Jack Jr., M. M. Shiung, J. L. Gunter, P. C. O'Brien, S. D. Weigand, D. S. Knopman, B. F. Boeve, R. J. Ivnik, G. E. Smith, R. H. Cha, et al. Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD Neurology, February 24, 2004; 62(4): 591 - 600. [Abstract] [Full Text] [PDF]
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T Jarvenpaa, M P Laakso, R Rossi, M Koskenvuo, J Kaprio, I Raiha, T Kurki, M Laine, G B Frisoni, and J O Rinne Hippocampal MRI volumetry in cognitively discordant monozygotic twin pairs J. Neurol. Neurosurg. Psychiatry, January 1, 2004; 75(1): 116 - 120. [Abstract] [Full Text] [PDF]
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M. Grundman, R. C. Petersen, S. H. Ferris, R. G. Thomas, P. S. Aisen, D. A. Bennett, N. L. Foster, C. R. Jack Jr, D. R. Galasko, R. Doody, et al. Mild Cognitive Impairment Can Be Distinguished From Alzheimer Disease and Normal Aging for Clinical Trials Arch Neurol, January 1, 2004; 61(1): 59 - 66. [Abstract] [Full Text] [PDF]
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J. F. Norfray and J. M. Provenzale Alzheimer's Disease: Neuropathologic Findings and Recent Advances in Imaging Am. J. Roentgenol., January 1, 2004; 182(1): 3 - 13. [Full Text] [PDF]
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M. A. Lambon Ralph, K. Patterson, N. Graham, K. Dawson, and J. R. Hodges Homogeneity and heterogeneity in mild cognitive impairment and Alzheimer's disease: a cross-sectional and longitudinal study of 55 cases Brain, November 1, 2003; 126(11): 2350 - 2362. [Abstract] [Full Text] [PDF]
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 S. T. DeKosky and K. Marek Looking Backward to Move Forward: Early Detection of Neurodegenerative Disorders Science, October 31, 2003; 302(5646): 830 - 834. [Abstract] [Full Text] [PDF]
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G B Frisoni, P h Scheltens, S Galluzzi, F M Nobili, N C Fox, P H Robert, H Soininen, L-O Wahlund, G Waldemar, and E Salmon Neuroimaging tools to rate regional atrophy, subcortical cerebrovascular disease, and regional cerebral blood flow and metabolism: consensus paper of the EADC J. Neurol. Neurosurg. Psychiatry, October 1, 2003; 74(10): 1371 - 1381. [Abstract] [Full Text] [PDF]
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 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]
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 T. C. Rosenthal and N. Khotianov Managing Alzheimer Dementia Tomorrow J Am Board Fam Med, September 1, 2003; 16(5): 423 - 434. [Abstract] [Full Text]
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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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J Tian, R S Bucks, J Haworth, and G Wilcock Neuropsychological prediction of conversion to dementia from questionable dementia: statistically significant but not yet clinically useful J. Neurol. Neurosurg. Psychiatry, April 1, 2003; 74(4): 433 - 438. [Abstract] [Full Text] [PDF]
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M.-A. Cordoliani-Mackowiak, H. Henon, J.-P. Pruvo, F. Pasquier, and D. Leys Poststroke Dementia: Influence of Hippocampal Atrophy Arch Neurol, April 1, 2003; 60(4): 585 - 590. [Abstract] [Full Text] [PDF]
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 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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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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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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J. Pantel, B. Kratz, M. Essig, and J. Schroder Parahippocampal Volume Deficits in Subjects With Aging-Associated Cognitive Decline Am J Psychiatry, February 1, 2003; 160(2): 379 - 382. [Abstract] [Full Text] [PDF]
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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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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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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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W. M. van der Flier, D.M. J. van den Heuvel, A.W. E. Weverling-Rijnsburger, A. Spilt, E.L.E. M. Bollen, R.G. J. Westendorp, H.A. M. Middelkoop, and M. A. van Buchem Cognitive decline in AD and mild cognitive impairment is associated with global brain damage Neurology, September 24, 2002; 59(6): 874 - 879. [Abstract] [Full Text] [PDF]
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