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Gepubliceerd in: Neuropraxis 5/2012

01-11-2012

De meerwaarde van diffusie gewogen beeldvorming bij de vroegdiagnostiek van de ziekte van Alzheimer

Auteurs: drs. Lies Clerx, dr. Pauline Aalten

Gepubliceerd in: Neuropraxis | Uitgave 5/2012

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Samenvatting

De ziekte van Alzheimer is de meest voorkomende vorm van dementie, die wereldwijd ongeveer 34 miljoen mensen treft. Onderzoekers voorspellen een tsunami van dementie, waarbij de prevalentie van de ziekte zal verdriedubbelen als gevolg van de vergrijzing van de bevolking. De toename in prevalentie en de ernst van deze ziekte leiden tot een dwingende noodzaak voor vroegdiagnostiek. Een behandeling met als doel genezing van de ziekte is tot dusver niet voor handen. Wanneer de ziekte echter in een vroege fase wordt gediagnosticeerd, kan het opstarten van bijvoorbeeld cholinesterase-inhibitoren verdere evolutie enigszins uitstellen en het gedrag van de patiënt positief beïnvloeden. Onderzoek naar de ziekte van Alzheimer heeft zich daarom veelal gefocust op het vroege stadium, de milde cognitieve stoornis, een overgangsfase tussen normale veroudering en beginnende alzheimerdementie (Jack et al., 2005 ; Petersen et al., 1999 ). Vijf tot 40 procent van de patiënten met een milde cognitieve stoornis converteert elk jaar naar de ziekte van Alzheimer (Bruscoli & Lovestone, 2004 ). Niet iedereen die lijdt aan een milde cognitieve stoornis zal uiteindelijk naar de ziekte van Alzheimer converteren. Een deel van deze patiënten blijft gedurende lange tijd stabiel, de meerderheid zal echter binnen de twee tot vier jaar duidelijke symptomen van dementie ontwikkelen.
Literatuur
go back to reference Acosta-Cabronero, J., Williams, G.B., Pengas, G. & Nestor, P.J. (2010). Absolute diffusivities define the landscape of white matter degeneration in Alzheimer’s disease. Brain, 133, 529–539.PubMedCrossRef Acosta-Cabronero, J., Williams, G.B., Pengas, G. & Nestor, P.J. (2010). Absolute diffusivities define the landscape of white matter degeneration in Alzheimer’s disease. Brain, 133, 529–539.PubMedCrossRef
go back to reference Basser, P.J., Mattiello, J. & Lebihan, D. (1994). Estimation of the Effective Self-Diffusion Tensor from the NMR Spin Echo. Journal of Magnetic Resonance, Series B, 103, 247–254CrossRef Basser, P.J., Mattiello, J. & Lebihan, D. (1994). Estimation of the Effective Self-Diffusion Tensor from the NMR Spin Echo. Journal of Magnetic Resonance, Series B, 103, 247–254CrossRef
go back to reference Bozzali, M., Falini, A., Cercignani, M., Baglio, F., Farina, E., Alberoni, M., Vezzulli, P., Olivotto, F., Mantovani, F., Shallice, T., Scotti, G., Canal, N. & Nemni, R. (2005). Brain tissue damage in dementia with Lewy bodies: an in vivo diffusion tensor MRI study. Brain, 128, 1595–1604.PubMedCrossRef Bozzali, M., Falini, A., Cercignani, M., Baglio, F., Farina, E., Alberoni, M., Vezzulli, P., Olivotto, F., Mantovani, F., Shallice, T., Scotti, G., Canal, N. & Nemni, R. (2005). Brain tissue damage in dementia with Lewy bodies: an in vivo diffusion tensor MRI study. Brain, 128, 1595–1604.PubMedCrossRef
go back to reference Braak, H. & Braak, E. (1990). Neurofibrillary changes confined to the entorhinal region and an abundance of cortical amyloid in cases of presenile and senile dementia. Acta Neuropathologica, 80, 479–486.PubMedCrossRef Braak, H. & Braak, E. (1990). Neurofibrillary changes confined to the entorhinal region and an abundance of cortical amyloid in cases of presenile and senile dementia. Acta Neuropathologica, 80, 479–486.PubMedCrossRef
go back to reference Bruscoli, M. & Lovestone, S. (2004). Is MCI really just early dementia? A systematic review of conversion studies. International Psychogeriatrics, 16, 129–140.PubMedCrossRef Bruscoli, M. & Lovestone, S. (2004). Is MCI really just early dementia? A systematic review of conversion studies. International Psychogeriatrics, 16, 129–140.PubMedCrossRef
go back to reference Choo, I.L.H., Lee, D.Y., Oh, J.S., Lee, J.S., Lee, D.S., Song, I.C., Youn, J.C., Kim, S.G., Kim, K.W., Jhoo, J.H. & Woo, J.I. (2010). Posterior cingulate cortex atrophy and regional cingulum disruption in mild cognitive impairment and Alzheimer’s disease. Neurobiology of Aging, 31, 772–779.PubMedCrossRef Choo, I.L.H., Lee, D.Y., Oh, J.S., Lee, J.S., Lee, D.S., Song, I.C., Youn, J.C., Kim, S.G., Kim, K.W., Jhoo, J.H. & Woo, J.I. (2010). Posterior cingulate cortex atrophy and regional cingulum disruption in mild cognitive impairment and Alzheimer’s disease. Neurobiology of Aging, 31, 772–779.PubMedCrossRef
go back to reference Clerx, L., Visser, P.J., Verhey, F. & Aalten, P. (2012). New MRI Markers for Alzheimer’s Disease: A Meta-Analysis of Diffusion Tensor Imaging and a Comparison with Medial Temporal Lobe Measurements. Journal of Alzheimer’s Disease, 29, 405–429.PubMed Clerx, L., Visser, P.J., Verhey, F. & Aalten, P. (2012). New MRI Markers for Alzheimer’s Disease: A Meta-Analysis of Diffusion Tensor Imaging and a Comparison with Medial Temporal Lobe Measurements. Journal of Alzheimer’s Disease, 29, 405–429.PubMed
go back to reference deToledo-Morrell, L., Stoub, T.R., Bulgakova, M., Wilson, R.S., Bennett, D.A., Leurgans, S., Wuu, J. & Turner, D.A. (2004). MRI-derived entorhinal volume is a good predictor of conversion from MCI to AD. Neurobiology of Aging, 25, 1197–1203.PubMedCrossRef deToledo-Morrell, L., Stoub, T.R., Bulgakova, M., Wilson, R.S., Bennett, D.A., Leurgans, S., Wuu, J. & Turner, D.A. (2004). MRI-derived entorhinal volume is a good predictor of conversion from MCI to AD. Neurobiology of Aging, 25, 1197–1203.PubMedCrossRef
go back to reference Dickerson, B.C., Goncharova, I., Sullivan, M.P., Forchetti, C., Wilson, R.S., Bennett, D.A., Beckett, L.A. & deToledo-Morrell, L. (2001). MRIderived entorhinal and hippocampal atrophy in incipient and very mild Alzheimer’s disease. Neurobiology of Aging, 22, 747–754.PubMedCrossRef Dickerson, B.C., Goncharova, I., Sullivan, M.P., Forchetti, C., Wilson, R.S., Bennett, D.A., Beckett, L.A. & deToledo-Morrell, L. (2001). MRIderived entorhinal and hippocampal atrophy in incipient and very mild Alzheimer’s disease. Neurobiology of Aging, 22, 747–754.PubMedCrossRef
go back to reference Dubois, B., Feldman, H.H., Jacova, C., DeKosky, S.T., Barberger-Gateau, P., Cummings, J., Delacourte, A., Galasko, D., Gauthier, S., Jicha, G., Meguro, K., O’Brien, J., Pasquier, F., Robert, P., Rossor, M., Salloway, S., Stern, Y., Visser, P.J. & Scheltens, P. (2007). Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. The Lancet Neurology, 6, 734–746.CrossRef Dubois, B., Feldman, H.H., Jacova, C., DeKosky, S.T., Barberger-Gateau, P., Cummings, J., Delacourte, A., Galasko, D., Gauthier, S., Jicha, G., Meguro, K., O’Brien, J., Pasquier, F., Robert, P., Rossor, M., Salloway, S., Stern, Y., Visser, P.J. & Scheltens, P. (2007). Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. The Lancet Neurology, 6, 734–746.CrossRef
go back to reference Hoesen, G.W. van (1982). The parahippocampal gyrus: New observations regarding its cortical connections in the monkey. Trends in Neurosciences, 5, 345–350CrossRef Hoesen, G.W. van (1982). The parahippocampal gyrus: New observations regarding its cortical connections in the monkey. Trends in Neurosciences, 5, 345–350CrossRef
go back to reference Jack, C.R., Shiung, M.M., Weigand, S.D., OBrien, P.C., Gunter, J.L., Boeve, B.F., Knopman, D.S., Smith, G.E., Ivnik, R.J., Tangalos, E.G. & Petersen, R.C. (2005). Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI. Neurology, 65,1227–1231.PubMedCrossRef Jack, C.R., Shiung, M.M., Weigand, S.D., OBrien, P.C., Gunter, J.L., Boeve, B.F., Knopman, D.S., Smith, G.E., Ivnik, R.J., Tangalos, E.G. & Petersen, R.C. (2005). Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI. Neurology, 65,1227–1231.PubMedCrossRef
go back to reference Medina, D., deToledo-Morrell, L., Urresta, F., Gabrieli, J.D.E., Moseley, M., Fleischman, D., Bennett, D.A., Leurgans, S., Turner, D.A. & Stebbins, G.T. (2006). White matter changes in mild cognitive impairment and AD: A diffusion tensor imaging study. Neurobiology of Aging, 27, 663–672.CrossRef Medina, D., deToledo-Morrell, L., Urresta, F., Gabrieli, J.D.E., Moseley, M., Fleischman, D., Bennett, D.A., Leurgans, S., Turner, D.A. & Stebbins, G.T. (2006). White matter changes in mild cognitive impairment and AD: A diffusion tensor imaging study. Neurobiology of Aging, 27, 663–672.CrossRef
go back to reference Müller, M.J., Greverus, D., Dellani, P.R., Weibrich, C., Wille, P.R., Scheurich, A., Stoeter, P. & Fellgiebel, A. (2005). Functional implications of hippocampal volume and diffusivity in mild cognitive impairment. Neuroimage, 28, 1033–1042.PubMedCrossRef Müller, M.J., Greverus, D., Dellani, P.R., Weibrich, C., Wille, P.R., Scheurich, A., Stoeter, P. & Fellgiebel, A. (2005). Functional implications of hippocampal volume and diffusivity in mild cognitive impairment. Neuroimage, 28, 1033–1042.PubMedCrossRef
go back to reference Müller, M.J., Greverus, D., Weibrich, C., Dellani, P.R., Scheurich, A., Stoeter, P. & Fellgiebel, A. (2007). Diagnostic utility of hippocampal size and mean diffusivity in amnestic MCI. Neurobiology of Aging, 28, 398–403.PubMedCrossRef Müller, M.J., Greverus, D., Weibrich, C., Dellani, P.R., Scheurich, A., Stoeter, P. & Fellgiebel, A. (2007). Diagnostic utility of hippocampal size and mean diffusivity in amnestic MCI. Neurobiology of Aging, 28, 398–403.PubMedCrossRef
go back to reference Nakata, Y., Sato, N., Abe, O., Shikakura, S., Arima, K., Furuta, N., Uno, M., Hirai, S., Masutani, Y., Ohtomo, K. & Aoki, S. (2008). Diffusion abnormality in posterior cingulate fiber tracts in Alzheimer’s disease: tract-specific analysis. Radiation Medicine, 26, 466–473.PubMedCrossRef Nakata, Y., Sato, N., Abe, O., Shikakura, S., Arima, K., Furuta, N., Uno, M., Hirai, S., Masutani, Y., Ohtomo, K. & Aoki, S. (2008). Diffusion abnormality in posterior cingulate fiber tracts in Alzheimer’s disease: tract-specific analysis. Radiation Medicine, 26, 466–473.PubMedCrossRef
go back to reference Pennanen, C., Kivipelto, M., Tuomainen, S., Hartikainen, P., Hänninen, T., Laakso, M.P., Hallikainen, M., Vanhanen, M., Nissinen, A., Helkala, E.-L., Vainio, P., Vanninen, R., Partanen, K. & Soininen, H. (2004). Hippocampus and entorhinal cortex in mild cognitive impairment and early AD. Neurobiology of Aging, 25, 303–310.CrossRef Pennanen, C., Kivipelto, M., Tuomainen, S., Hartikainen, P., Hänninen, T., Laakso, M.P., Hallikainen, M., Vanhanen, M., Nissinen, A., Helkala, E.-L., Vainio, P., Vanninen, R., Partanen, K. & Soininen, H. (2004). Hippocampus and entorhinal cortex in mild cognitive impairment and early AD. Neurobiology of Aging, 25, 303–310.CrossRef
go back to reference Petersen, R.C., Smith, G.E., Waring, S.C., Ivnik, R.J., Tangalos, E.G. & Kokmen, E. (1999). Mild Cognitive Impairment: Clinical Characterization and Outcome. Archives of Neurology, 56, 303–308.CrossRef Petersen, R.C., Smith, G.E., Waring, S.C., Ivnik, R.J., Tangalos, E.G. & Kokmen, E. (1999). Mild Cognitive Impairment: Clinical Characterization and Outcome. Archives of Neurology, 56, 303–308.CrossRef
go back to reference Pierpaoli, C., Jezzard, P., Basser, P.J., Barnett, A. & Di Chiro, G. (1996). Diffusion tensor MR imaging of the human brain. Radiology, 201, 637–648.PubMed Pierpaoli, C., Jezzard, P., Basser, P.J., Barnett, A. & Di Chiro, G. (1996). Diffusion tensor MR imaging of the human brain. Radiology, 201, 637–648.PubMed
go back to reference Ridha, B.H., Barnes, J., Pol, L.A. van de, Schott, J.M., Boyes, R.G., Siddique, M.M., Rossor, M.N., Scheltens, P. & Fox, N.C. (2007). Application of Automated Medial Temporal Lobe Atrophy Scale to Alzheimer Disease. Archives of Neurology 64, 849–854.PubMedCrossRef Ridha, B.H., Barnes, J., Pol, L.A. van de, Schott, J.M., Boyes, R.G., Siddique, M.M., Rossor, M.N., Scheltens, P. & Fox, N.C. (2007). Application of Automated Medial Temporal Lobe Atrophy Scale to Alzheimer Disease. Archives of Neurology 64, 849–854.PubMedCrossRef
go back to reference Rusinek, H.P., Endo, Y.M., De Santi, S.P., Frid, D.B., Tsui, W.H.M., Segal, S.M., Convit, A.M. & Leon, M.J.E. de (2004). Atrophy rate in medial temporal lobe during progression of Alzheimer disease. Neurology, 63, 2354–2359.PubMedCrossRef Rusinek, H.P., Endo, Y.M., De Santi, S.P., Frid, D.B., Tsui, W.H.M., Segal, S.M., Convit, A.M. & Leon, M.J.E. de (2004). Atrophy rate in medial temporal lobe during progression of Alzheimer disease. Neurology, 63, 2354–2359.PubMedCrossRef
go back to reference Scheltens, P., Leys, D., Barkhof, F., Huglo, D., Weinstein, H.C., Vermersch, P., Kuiper, M., Steinling, M., Wolters, E.C. & Valk, J. (1992). Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. Journal of Neurology, Neurosurgery, and Psychiatry, 55, 967–972.CrossRef Scheltens, P., Leys, D., Barkhof, F., Huglo, D., Weinstein, H.C., Vermersch, P., Kuiper, M., Steinling, M., Wolters, E.C. & Valk, J. (1992). Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. Journal of Neurology, Neurosurgery, and Psychiatry, 55, 967–972.CrossRef
go back to reference Schmand, B., Huizenga, H.M. & Gool, W.A. van (2010). Meta-analysis of CSF and MRI biomarkers for detecting preclinical Alzheimer’s disease. Psychological Medicine, 40, 135–145.PubMedCrossRef Schmand, B., Huizenga, H.M. & Gool, W.A. van (2010). Meta-analysis of CSF and MRI biomarkers for detecting preclinical Alzheimer’s disease. Psychological Medicine, 40, 135–145.PubMedCrossRef
go back to reference Schoonenboom, N.S.M., Flier, W.M. van der, Blankenstein, M.A., Bouwman, F.H., Kamp, G.J. van, Barkhof, F. & Scheltens, P. (2008). CSF and MRI markers independently contribute to the diagnosis of Alzheimer’s disease. Neurobiology of Aging, 29, 669–675.PubMedCrossRef Schoonenboom, N.S.M., Flier, W.M. van der, Blankenstein, M.A., Bouwman, F.H., Kamp, G.J. van, Barkhof, F. & Scheltens, P. (2008). CSF and MRI markers independently contribute to the diagnosis of Alzheimer’s disease. Neurobiology of Aging, 29, 669–675.PubMedCrossRef
go back to reference Sexton, C.E., Kalu, U.G., Filippini, N., Mackay, C.E. & Ebmeier, K.P. (2010a). A meta-analysis of diffusion tensor imaging in mild cognitive impairment and Alzheimer’s disease. Neurobiology of Aging, 32. Sexton, C.E., Kalu, U.G., Filippini, N., Mackay, C.E. & Ebmeier, K.P. (2010a). A meta-analysis of diffusion tensor imaging in mild cognitive impairment and Alzheimer’s disease. Neurobiology of Aging, 32.
go back to reference Sexton, C.E., Mackay, C.E., Lonie, J.A., Bastin, M.E., TerriËre, E., O’Carroll, R.E. & Ebmeier, K.P. (2010b). MRI correlates of episodic memory in Alzheimer’s disease, mild cognitive impairment, and healthy aging. Psychiatry Research: Neuroimaging, 184, 57–62.CrossRef Sexton, C.E., Mackay, C.E., Lonie, J.A., Bastin, M.E., TerriËre, E., O’Carroll, R.E. & Ebmeier, K.P. (2010b). MRI correlates of episodic memory in Alzheimer’s disease, mild cognitive impairment, and healthy aging. Psychiatry Research: Neuroimaging, 184, 57–62.CrossRef
go back to reference Smith, S.M., Johansen-Berg, H., Jenkinson, M., Rueckert, D., Nichols, T.E., Miller, K.L., Robson, M.D., Jones, D.K., Klein, J.C., Bartsch, A.J. & Behrens, T.E.J. (2007). Acquisition and voxelwise analysis of multisubject diffusion data with Tract-Based Spatial Statistics. Nature Protocols, 2, 499–503.CrossRef Smith, S.M., Johansen-Berg, H., Jenkinson, M., Rueckert, D., Nichols, T.E., Miller, K.L., Robson, M.D., Jones, D.K., Klein, J.C., Bartsch, A.J. & Behrens, T.E.J. (2007). Acquisition and voxelwise analysis of multisubject diffusion data with Tract-Based Spatial Statistics. Nature Protocols, 2, 499–503.CrossRef
go back to reference Stebbins, G., Smith, C., Bartt, R., Kessler, H., Adeyemi, O., Martin, E., Cox, J., Bammer, R. & Moseley, M. (2007). HIV-Associated Alterations in Normal-Appearing White Matter: A Voxel-Wise Diffusion Tensor Imaging Study. Journal of Acquired Immune Deficiency Syndromes, 46, 564–573.CrossRef Stebbins, G., Smith, C., Bartt, R., Kessler, H., Adeyemi, O., Martin, E., Cox, J., Bammer, R. & Moseley, M. (2007). HIV-Associated Alterations in Normal-Appearing White Matter: A Voxel-Wise Diffusion Tensor Imaging Study. Journal of Acquired Immune Deficiency Syndromes, 46, 564–573.CrossRef
go back to reference Stebbins, G.T. & Murphy, C.M. (2009). Diffusion tensor imaging in Alzheimer’s disease and mild cognitive impairment. Stebbins, G.T. & Murphy, C.M. (2009). Diffusion tensor imaging in Alzheimer’s disease and mild cognitive impairment.
go back to reference Sugihara, S., Kinoshita, T., Matsusue, E., Fujii, S. & Ogawa, T. (2004). Usefulness of Diffusion Tensor Imaging of White Matter in Alzheimer Disease and Vascular Dementia. Acta Radiologica, 45, 658–663.PubMedCrossRef Sugihara, S., Kinoshita, T., Matsusue, E., Fujii, S. & Ogawa, T. (2004). Usefulness of Diffusion Tensor Imaging of White Matter in Alzheimer Disease and Vascular Dementia. Acta Radiologica, 45, 658–663.PubMedCrossRef
go back to reference Urs, R., Potter, E., Barker, W., Appel, J., Loewenstein, D.A., Zhao, W. & Duara, R. (2009). Visual Rating System for Assessing Magnetic Resonance Images: A Tool in the Diagnosis of Mild Cognitive Impairment and Alzheimer Disease. Journal of Computer Assisted Tomography, 33.CrossRef Urs, R., Potter, E., Barker, W., Appel, J., Loewenstein, D.A., Zhao, W. & Duara, R. (2009). Visual Rating System for Assessing Magnetic Resonance Images: A Tool in the Diagnosis of Mild Cognitive Impairment and Alzheimer Disease. Journal of Computer Assisted Tomography, 33.CrossRef
go back to reference Visser, P.J., Scheltens, P., Verhey, F.R.J., Schmand, B., Launer, L., Jolles, J. & Jonker, C. (1999). Medial temporal lobe atrophy and memory dysfunction as predictors for dementia in subjects with mild cognitive impairment. Journal of Neurology, 246, 477–485.PubMedCrossRef Visser, P.J., Scheltens, P., Verhey, F.R.J., Schmand, B., Launer, L., Jolles, J. & Jonker, C. (1999). Medial temporal lobe atrophy and memory dysfunction as predictors for dementia in subjects with mild cognitive impairment. Journal of Neurology, 246, 477–485.PubMedCrossRef
go back to reference Wang, L., Goldstein, F.C., Veledar, E., Levey, A.I., Lah, J.J., Meltzer, C.C., Holder, C.A. & Mao, H. (2009). Alterations in Cortical Thickness and White Matter Integrity in Mild Cognitive Impairment Measured by Whole-Brain Cortical Thickness Mapping and Diffusion Tensor Imaging. AJNR. American Journal of Neuroradiology, 30, 893–899.CrossRef Wang, L., Goldstein, F.C., Veledar, E., Levey, A.I., Lah, J.J., Meltzer, C.C., Holder, C.A. & Mao, H. (2009). Alterations in Cortical Thickness and White Matter Integrity in Mild Cognitive Impairment Measured by Whole-Brain Cortical Thickness Mapping and Diffusion Tensor Imaging. AJNR. American Journal of Neuroradiology, 30, 893–899.CrossRef
go back to reference Zhang, Y., Schuff, N., Du, A.-T., Rosen, H.J., Kramer, J.H., Gorno- Tempini, M.L., Miller, B.L. & Weiner, M.W. (2009). White matter damage in frontotemporal dementia and Alzheimer’s disease measured by diffusion MRI. Brain, 132, 2579–2592.PubMedCrossRef Zhang, Y., Schuff, N., Du, A.-T., Rosen, H.J., Kramer, J.H., Gorno- Tempini, M.L., Miller, B.L. & Weiner, M.W. (2009). White matter damage in frontotemporal dementia and Alzheimer’s disease measured by diffusion MRI. Brain, 132, 2579–2592.PubMedCrossRef
Metagegevens
Titel
De meerwaarde van diffusie gewogen beeldvorming bij de vroegdiagnostiek van de ziekte van Alzheimer
Auteurs
drs. Lies Clerx
dr. Pauline Aalten
Publicatiedatum
01-11-2012
Uitgeverij
Bohn Stafleu van Loghum
Gepubliceerd in
Neuropraxis / Uitgave 5/2012
Print ISSN: 1387-5817
Elektronisch ISSN: 1876-5785
DOI
https://doi.org/10.1007/s12474-012-0025-1

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