Abstract
OBJECTIVES—To explore volume changes of the entorhinal cortex (ERC) and hippocampus in mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared with normal cognition (NC); to determine the powers of the ERC and the hippocampus for discrimination between these groups. METHODS—This study included 40 subjects with NC, 36 patients with MCI, and 29 patients with AD. Volumes of the ERC and hippocampus were manually measured based on coronal T1 weighted MR images. Global cerebral changes were assessed using semiautomatic image segmentation. RESULTS—Both ERC and hippocampal volumes were reduced in MCI (ERC 13%, hippocampus 11%, p<0.05) and AD (ERC 39%, hippocampus 27%, p<0.01) compared with NC. Furthermore, AD showed greater volume losses in the ERC than in the hippocampus (p<0.01). In addition, AD and MCI also had cortical grey matter loss (p< 0.01) and ventricular enlargement (p<0.01) when compared with NC. There was a significant correlation between ERC and hippocampal volumes in MCI and AD (both p<0.001), but not in NC. Using ERC and hippocampus together improved discrimination between AD and CN but did not improve discrimination between MCI and NC. The ERC was better than the hippocampus for distinguishing MCI from AD. In addition, loss of cortical grey matter significantly contributed to the hippocampus for discriminating MCI and AD from NC. CONCLUSIONS—Volume reductions in the ERC and hippocampus may be early signs of AD pathology that can be measured using MRI.
Full Text
The Full Text of this article is available as a PDF (191.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barber R., Scheltens P., Gholkar A., Ballard C., McKeith I., Ince P., Perry R., O'Brien J. White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer's disease, vascular dementia, and normal aging. J Neurol Neurosurg Psychiatry. 1999 Jul;67(1):66–72. doi: 10.1136/jnnp.67.1.66. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bobinski M., de Leon M. J., Convit A., De Santi S., Wegiel J., Tarshish C. Y., Saint Louis L. A., Wisniewski H. M. MRI of entorhinal cortex in mild Alzheimer's disease. Lancet. 1999 Jan 2;353(9146):38–40. doi: 10.1016/s0140-6736(05)74869-8. [DOI] [PubMed] [Google Scholar]
- Braak H., Braak E., Bohl J. Staging of Alzheimer-related cortical destruction. Eur Neurol. 1993;33(6):403–408. doi: 10.1159/000116984. [DOI] [PubMed] [Google Scholar]
- Convit A., De Leon M. J., Tarshish C., De Santi S., Tsui W., Rusinek H., George A. Specific hippocampal volume reductions in individuals at risk for Alzheimer's disease. Neurobiol Aging. 1997 Mar-Apr;18(2):131–138. doi: 10.1016/s0197-4580(97)00001-8. [DOI] [PubMed] [Google Scholar]
- Convit A., de Leon M. J., Tarshish C., De Santi S., Kluger A., Rusinek H., George A. E. Hippocampal volume losses in minimally impaired elderly. Lancet. 1995 Jan 28;345(8944):266–266. doi: 10.1016/s0140-6736(95)90265-1. [DOI] [PubMed] [Google Scholar]
- Fox N. C., Warrington E. K., Stevens J. M., Rossor M. N. Atrophy of the hippocampal formation in early familial Alzheimer's disease. A longitudinal MRI study of at-risk members of a family with an amyloid precursor protein 717Val-Gly mutation. Ann N Y Acad Sci. 1996 Jan 17;777:226–232. doi: 10.1111/j.1749-6632.1996.tb34423.x. [DOI] [PubMed] [Google Scholar]
- Frisoni G. B., Laakso M. P., Beltramello A., Geroldi C., Bianchetti A., Soininen H., Trabucchi M. Hippocampal and entorhinal cortex atrophy in frontotemporal dementia and Alzheimer's disease. Neurology. 1999 Jan 1;52(1):91–100. doi: 10.1212/wnl.52.1.91. [DOI] [PubMed] [Google Scholar]
- Geroldi C., Pihlajamäki M., Laakso M. P., DeCarli C., Beltramello A., Bianchetti A., Soininen H., Trabucchi M., Frisoni G. B. APOE-epsilon4 is associated with less frontal and more medial temporal lobe atrophy in AD. Neurology. 1999 Nov 10;53(8):1825–1832. doi: 10.1212/wnl.53.8.1825. [DOI] [PubMed] [Google Scholar]
- Hanyu H., Sakurai H., Iwamoto T., Takasaki M., Shindo H., Abe K. Diffusion-weighted MR imaging of the hippocampus and temporal white matter in Alzheimer's disease. J Neurol Sci. 1998 Apr 1;156(2):195–200. doi: 10.1016/s0022-510x(98)00043-4. [DOI] [PubMed] [Google Scholar]
- Haroutunian V., Perl D. P., Purohit D. P., Marin D., Khan K., Lantz M., Davis K. L., Mohs R. C. Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease. Arch Neurol. 1998 Sep;55(9):1185–1191. doi: 10.1001/archneur.55.9.1185. [DOI] [PubMed] [Google Scholar]
- Haroutunian V., Purohit D. P., Perl D. P., Marin D., Khan K., Lantz M., Davis K. L., Mohs R. C. Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimer disease. Arch Neurol. 1999 Jun;56(6):713–718. doi: 10.1001/archneur.56.6.713. [DOI] [PubMed] [Google Scholar]
- Insausti R., Juottonen K., Soininen H., Insausti A. M., Partanen K., Vainio P., Laakso M. P., Pitkänen A. MR volumetric analysis of the human entorhinal, perirhinal, and temporopolar cortices. AJNR Am J Neuroradiol. 1998 Apr;19(4):659–671. [PMC free article] [PubMed] [Google Scholar]
- Jack C. R., Jr, Petersen R. C., O'Brien P. C., Tangalos E. G. MR-based hippocampal volumetry in the diagnosis of Alzheimer's disease. Neurology. 1992 Jan;42(1):183–188. doi: 10.1212/wnl.42.1.183. [DOI] [PubMed] [Google Scholar]
- Jack C. R., Jr, Petersen R. C., Xu Y. C., O'Brien P. C., Smith G. E., Ivnik R. J., Boeve B. F., Waring S. C., Tangalos E. G., Kokmen E. Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology. 1999 Apr 22;52(7):1397–1403. doi: 10.1212/wnl.52.7.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jack C. R., Jr, Petersen R. C., Xu Y. C., Waring S. C., O'Brien P. C., Tangalos E. G., Smith G. E., Ivnik R. J., Kokmen E. Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease. Neurology. 1997 Sep;49(3):786–794. doi: 10.1212/wnl.49.3.786. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jack C. R., Jr, Petersen R. C., Xu Y., O'Brien P. C., Smith G. E., Ivnik R. J., Tangalos E. G., Kokmen E. Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease. Neurology. 1998 Oct;51(4):993–999. doi: 10.1212/wnl.51.4.993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Juottonen K., Laakso M. P., Insausti R., Lehtovirta M., Pitkänen A., Partanen K., Soininen H. Volumes of the entorhinal and perirhinal cortices in Alzheimer's disease. Neurobiol Aging. 1998 Jan-Feb;19(1):15–22. doi: 10.1016/s0197-4580(98)00007-4. [DOI] [PubMed] [Google Scholar]
- Juottonen K., Laakso M. P., Partanen K., Soininen H. Comparative MR analysis of the entorhinal cortex and hippocampus in diagnosing Alzheimer disease. AJNR Am J Neuroradiol. 1999 Jan;20(1):139–144. [PubMed] [Google Scholar]
- Kaye J. A., Swihart T., Howieson D., Dame A., Moore M. M., Karnos T., Camicioli R., Ball M., Oken B., Sexton G. Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia. Neurology. 1997 May;48(5):1297–1304. doi: 10.1212/wnl.48.5.1297. [DOI] [PubMed] [Google Scholar]
- Kesslak J. P., Nalcioglu O., Cotman C. W. Quantification of magnetic resonance scans for hippocampal and parahippocampal atrophy in Alzheimer's disease. Neurology. 1991 Jan;41(1):51–54. doi: 10.1212/wnl.41.1.51. [DOI] [PubMed] [Google Scholar]
- Kidron D., Black S. E., Stanchev P., Buck B., Szalai J. P., Parker J., Szekely C., Bronskill M. J. Quantitative MR volumetry in Alzheimer's disease. Topographic markers and the effects of sex and education. Neurology. 1997 Dec;49(6):1504–1512. doi: 10.1212/wnl.49.6.1504. [DOI] [PubMed] [Google Scholar]
- Killiany R. J., Gomez-Isla T., Moss M., Kikinis R., Sandor T., Jolesz F., Tanzi R., Jones K., Hyman B. T., Albert M. S. Use of structural magnetic resonance imaging to predict who will get Alzheimer's disease. Ann Neurol. 2000 Apr;47(4):430–439. [PubMed] [Google Scholar]
- Kitagaki H., Mori E., Yamaji S., Ishii K., Hirono N., Kobashi S., Hata Y. Frontotemporal dementia and Alzheimer disease: evaluation of cortical atrophy with automated hemispheric surface display generated with MR images. Radiology. 1998 Aug;208(2):431–439. doi: 10.1148/radiology.208.2.9680572. [DOI] [PubMed] [Google Scholar]
- Krasuski J. S., Alexander G. E., Horwitz B., Daly E. M., Murphy D. G., Rapoport S. I., Schapiro M. B. Volumes of medial temporal lobe structures in patients with Alzheimer's disease and mild cognitive impairment (and in healthy controls). Biol Psychiatry. 1998 Jan 1;43(1):60–68. doi: 10.1016/s0006-3223(97)00013-9. [DOI] [PubMed] [Google Scholar]
- Laakso M. P., Soininen H., Partanen K., Helkala E. L., Hartikainen P., Vainio P., Hallikainen M., Hänninen T., Riekkinen P. J., Sr Volumes of hippocampus, amygdala and frontal lobes in the MRI-based diagnosis of early Alzheimer's disease: correlation with memory functions. J Neural Transm Park Dis Dement Sect. 1995;9(1):73–86. doi: 10.1007/BF02252964. [DOI] [PubMed] [Google Scholar]
- MacKay S., Ezekiel F., Di Sclafani V., Meyerhoff D. J., Gerson J., Norman D., Fein G., Weiner M. W. Alzheimer disease and subcortical ischemic vascular dementia: evaluation by combining MR imaging segmentation and H-1 MR spectroscopic imaging. Radiology. 1996 Feb;198(2):537–545. doi: 10.1148/radiology.198.2.8596863. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacKay S., Meyerhoff D. J., Constans J. M., Norman D., Fein G., Weiner M. W. Regional gray and white matter metabolite differences in subjects with AD, with subcortical ischemic vascular dementia, and elderly controls with 1H magnetic resonance spectroscopic imaging. Arch Neurol. 1996 Feb;53(2):167–174. doi: 10.1001/archneur.1996.00550020079018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pantel J., Schröder J., Schad L. R., Friedlinger M., Knopp M. V., Schmitt R., Geissler M., Blüml S., Essig M., Sauer H. Quantitative magnetic resonance imaging and neuropsychological functions in dementia of the Alzheimer type. Psychol Med. 1997 Jan;27(1):221–229. doi: 10.1017/s003329179600431x. [DOI] [PubMed] [Google Scholar]
- Pearlson G. D., Harris G. J., Powers R. E., Barta P. E., Camargo E. E., Chase G. A., Noga J. T., Tune L. E. Quantitative changes in mesial temporal volume, regional cerebral blood flow, and cognition in Alzheimer's disease. Arch Gen Psychiatry. 1992 May;49(5):402–408. doi: 10.1001/archpsyc.1992.01820050066012. [DOI] [PubMed] [Google Scholar]
- Petersen R. C., Smith G. E., Waring S. C., Ivnik R. J., Tangalos E. G., Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999 Mar;56(3):303–308. doi: 10.1001/archneur.56.3.303. [DOI] [PubMed] [Google Scholar]
- Reiman E. M., Uecker A., Caselli R. J., Lewis S., Bandy D., de Leon M. J., De Santi S., Convit A., Osborne D., Weaver A. Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease. Ann Neurol. 1998 Aug;44(2):288–291. doi: 10.1002/ana.410440226. [DOI] [PubMed] [Google Scholar]
- Sandson T. A., Felician O., Edelman R. R., Warach S. Diffusion-weighted magnetic resonance imaging in Alzheimer's disease. Dement Geriatr Cogn Disord. 1999 Mar-Apr;10(2):166–171. doi: 10.1159/000017099. [DOI] [PubMed] [Google Scholar]
- Sandson T. A., O'Connor M., Sperling R. A., Edelman R. R., Warach S. Noninvasive perfusion MRI in Alzheimer's disease: a preliminary report. Neurology. 1996 Nov;47(5):1339–1342. doi: 10.1212/wnl.47.5.1339. [DOI] [PubMed] [Google Scholar]
- Schuff N., Amend D. L., Meyerhoff D. J., Tanabe J. L., Norman D., Fein G., Weiner M. W. Alzheimer disease: quantitative H-1 MR spectroscopic imaging of frontoparietal brain. Radiology. 1998 Apr;207(1):91–102. doi: 10.1148/radiology.207.1.9530304. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schuff N., Amend D., Ezekiel F., Steinman S. K., Tanabe J., Norman D., Jagust W., Kramer J. H., Mastrianni J. A., Fein G. Changes of hippocampal N-acetyl aspartate and volume in Alzheimer's disease. A proton MR spectroscopic imaging and MRI study. Neurology. 1997 Dec;49(6):1513–1521. doi: 10.1212/wnl.49.6.1513. [DOI] [PubMed] [Google Scholar]
- Tanabe J. L., Amend D., Schuff N., DiSclafani V., Ezekiel F., Norman D., Fein G., Weiner M. W. Tissue segmentation of the brain in Alzheimer disease. AJNR Am J Neuroradiol. 1997 Jan;18(1):115–123. [PMC free article] [PubMed] [Google Scholar]
- Visser P. J., Scheltens P., Verhey F. R., Schmand B., Launer L. J., Jolles J., Jonker C. Medial temporal lobe atrophy and memory dysfunction as predictors for dementia in subjects with mild cognitive impairment. J Neurol. 1999 Jun;246(6):477–485. doi: 10.1007/s004150050387. [DOI] [PubMed] [Google Scholar]
- Watson C., Andermann F., Gloor P., Jones-Gotman M., Peters T., Evans A., Olivier A., Melanson D., Leroux G. Anatomic basis of amygdaloid and hippocampal volume measurement by magnetic resonance imaging. Neurology. 1992 Sep;42(9):1743–1750. doi: 10.1212/wnl.42.9.1743. [DOI] [PubMed] [Google Scholar]
- Wolf H., Grunwald M., Ecke G. M., Zedlick D., Bettin S., Dannenberg C., Dietrich J., Eschrich K., Arendt T., Gertz H. J. The prognosis of mild cognitive impairment in the elderly. J Neural Transm Suppl. 1998;54:31–50. doi: 10.1007/978-3-7091-7508-8_4. [DOI] [PubMed] [Google Scholar]
- Xu Y., Jack C. R., Jr, O'Brien P. C., Kokmen E., Smith G. E., Ivnik R. J., Boeve B. F., Tangalos R. G., Petersen R. C. Usefulness of MRI measures of entorhinal cortex versus hippocampus in AD. Neurology. 2000 May 9;54(9):1760–1767. doi: 10.1212/wnl.54.9.1760. [DOI] [PubMed] [Google Scholar]
- de Leon M. J., Convit A., DeSanti S., Bobinski M., George A. E., Wisniewski H. M., Rusinek H., Carroll R., Saint Louis L. A. Contribution of structural neuroimaging to the early diagnosis of Alzheimer's disease. Int Psychogeriatr. 1997;9 (Suppl 1):183–252. doi: 10.1017/s1041610297004900. [DOI] [PubMed] [Google Scholar]