Abstract
OBJECTIVES—Hippocampal atrophy and hypometabolism in the posterior association neocortex are two well known features of Alzheimer's disease. A correlation between these two features was reported twice previously, suggesting intriguing relations. This question has been reassessed, this time controlling for severity of dementia as well as assessing each side of the brain separately and using a voxel based image analysis in addition to the previously employed regions of interest (ROIs). PATIENTS AND METHODS—Eleven patients were studied with probable Alzheimer's disease and mild to moderate dementia in whom both volume MRI and PET assessed cerebral glucose consumption (CMRGlc) were available. Hypothesis driven correlations between hippocampal width (an index of atrophy) and CMRGlc were performed for two posterior association regions, the superior temporal and the inferior parietal (angular gyrus) cortices, using ROIs set separately for each hemisphere. To confirm significant correlations from the ROIs approach, if any, and to assess their specificity for the posterior association neocortex, CMRGlc image voxel based analysis of correlations with hippocampal width was then carried out. RESULTS—There was a significant correlation, in the positive—neurobiologically expected—direction, between right hippocampal width and right angular gyrus metabolism (p< 0.01, Spearman), which remained significant with Kendall partial correlation controlling for dementia severity (estimated by mini mental state scores). Statistical non-parametric mapping (SnPM) confirmed this correlation (p< 0.025), and showed a single additional correlation in the right middle temporal gyrus (p< 0.005), which is also part of the posterior association cortex. CONCLUSION—The findings with both ROIs and voxel based mapping replicate earlier reports of a relation between hippocampal atrophy and ipsilateral association cortex hypometabolism in Alzheimer's disease, and for the first time document that this relation is both region specific and independent of the dementing process itself. Why the correlation was significant only for the right hemisphere is unclear but may be related to the limited sample. Hippocampal-neocortical disconnection due to early and severe medial temporal lobe pathology may at least partly explain the posterior association cortex hypometabolism found in Alzheimer's disease.
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- Baron J. C., Levasseur M., Mazoyer B., Legault-Demare F., Mauguière F., Pappata S., Jedynak P., Derome P., Cambier J., Tran-Dinh S. Thalamocortical diaschisis: positron emission tomography in humans. J Neurol Neurosurg Psychiatry. 1992 Oct;55(10):935–942. doi: 10.1136/jnnp.55.10.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Braak H., Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–259. doi: 10.1007/BF00308809. [DOI] [PubMed] [Google Scholar]
- Delacourte A., David J. P., Sergeant N., Buée L., Wattez A., Vermersch P., Ghozali F., Fallet-Bianco C., Pasquier F., Lebert F. The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer's disease. Neurology. 1999 Apr 12;52(6):1158–1165. doi: 10.1212/wnl.52.6.1158. [DOI] [PubMed] [Google Scholar]
- Desgranges B., Baron J. C., de la Sayette V., Petit-Taboué M. C., Benali K., Landeau B., Lechevalier B., Eustache F. The neural substrates of memory systems impairment in Alzheimer's disease. A PET study of resting brain glucose utilization. Brain. 1998 Apr;121(Pt 4):611–631. doi: 10.1093/brain/121.4.611. [DOI] [PubMed] [Google Scholar]
- Folstein M. F., Folstein S. E., McHugh P. R. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189–198. doi: 10.1016/0022-3956(75)90026-6. [DOI] [PubMed] [Google Scholar]
- Foster N. L., Chase T. N., Fedio P., Patronas N. J., Brooks R. A., Di Chiro G. Alzheimer's disease: focal cortical changes shown by positron emission tomography. Neurology. 1983 Aug;33(8):961–965. doi: 10.1212/wnl.33.8.961. [DOI] [PubMed] [Google Scholar]
- Friedland R. P., Brun A., Budinger T. F. Pathological and positron emission tomographic correlations in Alzheimer's disease. Lancet. 1985 Jan 26;1(8422):228–228. doi: 10.1016/s0140-6736(85)92074-4. [DOI] [PubMed] [Google Scholar]
- Friedland R. P., Budinger T. F., Ganz E., Yano Y., Mathis C. A., Koss B., Ober B. A., Huesman R. H., Derenzo S. E. Regional cerebral metabolic alterations in dementia of the Alzheimer type: positron emission tomography with [18F]fluorodeoxyglucose. J Comput Assist Tomogr. 1983 Aug;7(4):590–598. doi: 10.1097/00004728-198308000-00003. [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]
- Hasboun D., Chantôme M., Zouaoui A., Sahel M., Deladoeuille M., Sourour N., Duyme M., Baulac M., Marsault C., Dormont D. MR determination of hippocampal volume: comparison of three methods. AJNR Am J Neuroradiol. 1996 Jun-Jul;17(6):1091–1098. [PMC free article] [PubMed] [Google Scholar]
- Hayashi T., Fukuyama H., Katsumi Y., Hanakawa T., Nagahama Y., Yamauchi H., Tsukada H., Shibasaki H. Cerebral glucose metabolism in unilateral entorhinal cortex-lesioned rats: an animal PET study. Neuroreport. 1999 Jul 13;10(10):2113–2118. doi: 10.1097/00001756-199907130-00022. [DOI] [PubMed] [Google Scholar]
- Holmes A. P., Blair R. C., Watson J. D., Ford I. Nonparametric analysis of statistic images from functional mapping experiments. J Cereb Blood Flow Metab. 1996 Jan;16(1):7–22. doi: 10.1097/00004647-199601000-00002. [DOI] [PubMed] [Google Scholar]
- Ishii K., Imamura T., Sasaki M., Yamaji S., Sakamoto S., Kitagaki H., Hashimoto M., Hirono N., Shimomura T., Mori E. Regional cerebral glucose metabolism in dementia with Lewy bodies and Alzheimer's disease. Neurology. 1998 Jul;51(1):125–130. doi: 10.1212/wnl.51.1.125. [DOI] [PubMed] [Google Scholar]
- Jagust W. J., Eberling J. L., Richardson B. C., Reed B. R., Baker M. G., Nordahl T. E., Budinger T. F. The cortical topography of temporal lobe hypometabolism in early Alzheimer's disease. Brain Res. 1993 Dec 3;629(2):189–198. doi: 10.1016/0006-8993(93)91320-r. [DOI] [PubMed] [Google Scholar]
- Jobst K. A., Smith A. D., Barker C. S., Wear A., King E. M., Smith A., Anslow P. A., Molyneux A. J., Shepstone B. J., Soper N. Association of atrophy of the medial temporal lobe with reduced blood flow in the posterior parietotemporal cortex in patients with a clinical and pathological diagnosis of Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):190–194. doi: 10.1136/jnnp.55.3.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jobst K. A., Smith A. D., Szatmari M., Esiri M. M., Jaskowski A., Hindley N., McDonald B., Molyneux A. J. Rapidly progressing atrophy of medial temporal lobe in Alzheimer's disease. Lancet. 1994 Apr 2;343(8901):829–830. doi: 10.1016/s0140-6736(94)92028-1. [DOI] [PubMed] [Google Scholar]
- Jobst K. A., Smith A. D., Szatmari M., Molyneux A., Esiri M. E., King E., Smith A., Jaskowski A., McDonald B., Wald N. Detection in life of confirmed Alzheimer's disease using a simple measurement of medial temporal lobe atrophy by computed tomography. Lancet. 1992 Nov 14;340(8829):1179–1183. doi: 10.1016/0140-6736(92)92890-r. [DOI] [PubMed] [Google Scholar]
- Karbe H., Szelies B., Herholz K., Heiss W. D. Impairment of language is related to left parieto-temporal glucose metabolism in aphasic stroke patients. J Neurol. 1990 Feb;237(1):19–23. doi: 10.1007/BF00319662. [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]
- Kumar A., Schapiro M. B., Grady C., Haxby J. V., Wagner E., Salerno J. A., Friedland R. P., Rapoport S. I. High-resolution PET studies in Alzheimer's disease. Neuropsychopharmacology. 1991 Jan;4(1):35–46. [PubMed] [Google Scholar]
- Lavenex P., Amaral D. G. Hippocampal-neocortical interaction: a hierarchy of associativity. Hippocampus. 2000;10(4):420–430. doi: 10.1002/1098-1063(2000)10:4<420::AID-HIPO8>3.0.CO;2-5. [DOI] [PubMed] [Google Scholar]
- Loewenstein D. A., Barker W. W., Chang J. Y., Apicella A., Yoshii F., Kothari P., Levin B., Duara R. Predominant left hemisphere metabolic dysfunction in dementia. Arch Neurol. 1989 Feb;46(2):146–152. doi: 10.1001/archneur.1989.00520380046012. [DOI] [PubMed] [Google Scholar]
- McGeer P. L., Kamo H., Harrop R., McGeer E. G., Martin W. R., Pate B. D., Li D. K. Comparison of PET, MRI, and CT with pathology in a proven case of Alzheimer's disease. Neurology. 1986 Dec;36(12):1569–1574. doi: 10.1212/wnl.36.12.1569. [DOI] [PubMed] [Google Scholar]
- McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E. M. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul;34(7):939–944. doi: 10.1212/wnl.34.7.939. [DOI] [PubMed] [Google Scholar]
- Mega M. S., Chen S. S., Thompson P. M., Woods R. P., Karaca T. J., Tiwari A., Vinters H. V., Small G. W., Toga A. W. Mapping histology to metabolism: coregistration of stained whole-brain sections to premortem PET in Alzheimer's disease. Neuroimage. 1997 Feb;5(2):147–153. doi: 10.1006/nimg.1996.0255. [DOI] [PubMed] [Google Scholar]
- Mega M. S., Chu T., Mazziotta J. C., Trivedi K. H., Thompson P. M., Shah A., Cole G., Frautschy S. A., Toga A. W. Mapping biochemistry to metabolism: FDG-PET and amyloid burden in Alzheimer's disease. Neuroreport. 1999 Sep 29;10(14):2911–2917. doi: 10.1097/00001756-199909290-00007. [DOI] [PubMed] [Google Scholar]
- Meguro K., Blaizot X., Kondoh Y., Le Mestric C., Baron J. C., Chavoix C. Neocortical and hippocampal glucose hypometabolism following neurotoxic lesions of the entorhinal and perirhinal cortices in the non-human primate as shown by PET. Implications for Alzheimer's disease. Brain. 1999 Aug;122(Pt 8):1519–1531. doi: 10.1093/brain/122.8.1519. [DOI] [PubMed] [Google Scholar]
- Mielke R., Schröder R., Fink G. R., Kessler J., Herholz K., Heiss W. D. Regional cerebral glucose metabolism and postmortem pathology in Alzheimer's disease. Acta Neuropathol. 1996;91(2):174–179. doi: 10.1007/s004010050410. [DOI] [PubMed] [Google Scholar]
- Minoshima S., Giordani B., Berent S., Frey K. A., Foster N. L., Kuhl D. E. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann Neurol. 1997 Jul;42(1):85–94. doi: 10.1002/ana.410420114. [DOI] [PubMed] [Google Scholar]
- Penniello M. J., Lambert J., Eustache F., Petit-Taboué M. C., Barré L., Viader F., Morin P., Lechevalier B., Baron J. C. A PET study of the functional neuroanatomy of writing impairment in Alzheimer's disease. The role of the left supramarginal and left angular gyri. Brain. 1995 Jun;118(Pt 3):697–706. doi: 10.1093/brain/118.3.697. [DOI] [PubMed] [Google Scholar]
- Petit-Taboué M. C., Landeau B., Desson J. F., Desgranges B., Baron J. C. Effects of healthy aging on the regional cerebral metabolic rate of glucose assessed with statistical parametric mapping. Neuroimage. 1998 Apr;7(3):176–184. doi: 10.1006/nimg.1997.0318. [DOI] [PubMed] [Google Scholar]
- Phelps M. E., Huang S. C., Hoffman E. J., Selin C., Sokoloff L., Kuhl D. E. Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol. 1979 Nov;6(5):371–388. doi: 10.1002/ana.410060502. [DOI] [PubMed] [Google Scholar]
- Pruessner J. C., Li L. M., Serles W., Pruessner M., Collins D. L., Kabani N., Lupien S., Evans A. C. Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: minimizing the discrepancies between laboratories. Cereb Cortex. 2000 Apr;10(4):433–442. doi: 10.1093/cercor/10.4.433. [DOI] [PubMed] [Google Scholar]
- Smith A. D., Jobst K. A. Use of structural imaging to study the progression of Alzheimer's disease. Br Med Bull. 1996 Jul;52(3):575–586. doi: 10.1093/oxfordjournals.bmb.a011568. [DOI] [PubMed] [Google Scholar]
- Vander Borght T., Minoshima S., Giordani B., Foster N. L., Frey K. A., Berent S., Albin R. L., Koeppe R. A., Kuhl D. E. Cerebral metabolic differences in Parkinson's and Alzheimer's diseases matched for dementia severity. J Nucl Med. 1997 May;38(5):797–802. [PubMed] [Google Scholar]
- Vérard L., Allain P., Travère J. M., Baron J. C., Bloyet D. Fully automatic identification of AC and PC landmarks on brain MRI using scene analysis. IEEE Trans Med Imaging. 1997 Oct;16(5):610–616. doi: 10.1109/42.640751. [DOI] [PubMed] [Google Scholar]
- Yamaguchi S., Meguro K., Itoh M., Hayasaka C., Shimada M., Yamazaki H., Yamadori A. Decreased cortical glucose metabolism correlates with hippocampal atrophy in Alzheimer's disease as shown by MRI and PET. J Neurol Neurosurg Psychiatry. 1997 Jun;62(6):596–600. doi: 10.1136/jnnp.62.6.596. [DOI] [PMC free article] [PubMed] [Google Scholar]