Diffusion tensor imaging for Alzheimer's disease: A review of concepts and potential clinical applicability

Vasconcelos, Luciano de Gois; Brucki, Sonia Maria Dozzi; Jackowiski, Andrea Parolin; Bueno, Orlando Francisco Amodeo

doi:10.1590/S1980-57642009DN30400002

Abstract

In view of the urgent need to identify an early and specific biomarker for Alzheimer's disease (AD), a PubMed database search was performed using the terms "Alzheimer disease" and "Diffusion Magnetic Resonance Imaging" to enable review of Diffusion tensor imaging (DTI) concepts and its potential clinical role in AD evaluation. Detailed analysis of selected abstracts showed that the main DTI measures, fractional anisotropy and apparent diffusion coefficient, indicators of fiber tract integrity, provide a direct assessment of WM fibers and may be used as a new biomarker for AD. These findings were found to correlate with cognitive assessments, rates of AD progression and were also able to differentiate among groups including mild cognitive impairment, AD, and other dementias. Despite several consistent DTI findings in AD patients, there is still a lack of knowledge and studies on the DTI field. DTI is not yet ready for clinical use, and requires extensive further research in order to achieve this goal.

Key words:
Alzheimer's disease; magnetic resonance imaging; early diagnosis; review.

Resumo

Considerando a urgência em se determinar biomarcadores específicos e precoces da doença de Alzheimer (DA), realizou-se pesquisa bibliográfica no banco de dados Pubmed com os termos "Alzheimer disease" e "Diffusion Magnetic Resonance Imaging" objetivando-se revisar conceitos e utilidades clínicas da imagem do tensor de difusão (DTI) na avaliação da DA. A análise dos resumos selecionados mostrou que as principais medidas da DTI, anisotropia fracional e coeficiente de difusão aparente, indicadores de integridade dos feixes nervosos fornecem uma análise direta das fibras de substância branca e podem ser utilizadas como biomarcadores da DA. Estes achados correlacionaram-se com avaliações neuropsicológicas, taxa de progressão da DA e identificou grupos heterogêneos como declínio cognitivo leve, DA e outras demências. Apesar dos vários e consistentes achados da DTI na DA, ainda tem-se carência de conhecimento e pesquisas nesta área. DTI não está pronto para o uso clínico e muito trabalho deve ser realizado para obtenção deste objetivo.

Palavras-chave:
doença de Alzheimer; ressonância magnética; diagnóstico precoce; revisão.

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References

¹
Berr C,Wancata J, Ritchie K. Prevalence of dementia in the elderly in Europe. Eur Neuropsychopharmacology 2005;15:463-471.
²
Lopes MA, Hototian SR, Bustamante SE, et al. Prevalence of cognitive and functional impairment in a community sample in Ribeirão Preto, Brazil. Int J Geriatr Psychiatry 2007;22: 770-776.
³
Bottino CM, Azevedo D Jr, Tatsch M, et al. Estimate of dementia prevalence in a community sample from São Paulo, Brazil. Dement Geriatr Cogn Disord 2008;26:291-299.
⁴
Scazufca M, Menezes PR, Vallada HP, et al. High prevalence of dementia among older adults from poor socioeconomic backgrounds in São Paulo, Brazil. Int Psychogeriatr 2008;20:394-405.
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Teipel SJ, Meindl T, Grinberg L, Heinsen H, Hampel H. Novel MRI techniques in the assessment of dementia. Eur J Nucl Med Mol Imaging. 2008;35:S58-69.
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Hall AM, Moore RY, Lopez OL, Kuller L, Becker JT. Basal forebrain atrophy is a presymptomatic marker for Alzheimer's disease. Alzheimers Dement 2008;4:271-279.
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Rose SE, McMahon KL, Janke AL, et al. Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment. JNNP 2006; 77:1122-1128.
⁸
Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007;6:734-746.
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Zhou Y, Dougherty JH Jr, Hubner KF, Bai B, Cannon RL, Hutson RK. Abnormal connectivity in the posterior cingulate and hippocampus in early Alzheimer's disease and mild cognitive impairment. Alzheimers Dement 2008;4:265-270.
¹⁰
Duara R, Loewenstein D, Barker WW, Isaacson RS, Greig-Custo M. A Clinical Perspective of Mild Cognitive Impairment: What Radiologists Should Know. Neuroimag Clin N Am 2005;15:779-788.
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Foster NL. A new framework for the diagnosis of Alzheimer's disease. Lancet Neurol 2007;6:667-669.
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Petrella JR, Coleman ER, Doraiswamy PM. Neuroimaging and early diagnosis of Alzheimer Disease: a look to the future. Radiology 2003;226:315-336.
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Minati L, Grisoli M, Bruzzone MG. MR spectroscopy, functional MRI, and diffusion-tensor imaging in the aging brain: a conceptual review. J Geriatr Psychiatry Neurol 2007;20:3-21.
¹⁴
Krishnan S, Talley BD, Slavin MJ, Doraiswamy PM, Petrella JR. Current status of functional MR imaging, perfusion-weighted imaging, and diffusion-tensor imaging in Alzheimer's disease diagnosis and research. Neuroimaging Clin N Am 2005;15:853-868.
¹⁵
Cho H, Yang DW, Shon YM, et al. Abnormal integrity of corticocortical tracts in mild cognitive impairment: a diffusion tensor imaging study. J Korean Med Sci 2008;23:477-483.
¹⁶
Yasmin H, Nakata Y, Aoki S, et al. Diffusion abnormalities of the uncinate fasciculus in Alzheimer's disease: diffusion tensor tract-specific analysis using a new method to measure the core of the tract. Neuroradiology 2008;50:293-299.
¹⁷
Mueller SG, Schuff N, Weiner MW. Evaluation of treatment effects in Alzheimer's and other neurodegenerative diseases by MRI and MRS. NMR Biomed 2006;19:655-668.
¹⁸
Sunderland T, Hampel H, Takeda M, Putnam KT, Cohen RM. Biomarkers in the diagnosis of Alzheimer's disease: are we ready? J Geriatr Psychiatry Neurol 2006;19:172-179.
¹⁹
Consensus report of the Working Group on: "Molecular and Biochemical Markers of Alzheimer's Disease." The Ronald and Nancy Reagan Research Institute of the Alzheimer's Association and the National Institute on Aging Working Group. Neurobiol Aging 1998;19:109-116.
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Bozzali M, Cherubini A. Diffusion tensor MRI to investigate dementias: a brief review. Magn Reson Imaging 2007;25: 969-977.
²²
Mukherjee P, Berman JI, Chung SW, Hess CP, Henry RG. Diffusion tensor MR imaging and fiber tractography: theoretic underpinnings. AJNR 2008;29:632-641.
²³
Mori S, Barker PB. Diffusion magnetic resonance imaging: its principle and applications. Anat Rec 1999;257:102-9.
²⁴
Mori S, Zhang J. Principles of diffusion tensor imaging and its applications to basic neuroscience research. Neuron. 2006;51: 527-539.
²⁵
Hagmann P, Jonasson L, Maeder P, Thiran JP, Wedeen VJ, Meuli. Understanding diffusion MR imaging techniques: from scalar diffusion-weighted imaging to diffusion tensor imaging and beyond. Radiographics 2006;26:S205-23.
²⁶
Chua TC , Wen W , Slavin MJ , Sachdev PS . Diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease: a review. Curr Opin Neurol 2008;21:83-92.
²⁷
Ringman JM, O'Neill J, Geschwind D, et al. Diffusion tensor imaging in preclinical and presymptomatic carriers of familial Alzheimer's disease mutations. Brain 2007;130:1767-1776.
²⁸
Mukherjee P, Chung SW, Berman JI, Hess CP, Henry RG. Diffusion tensor MR imaging and fiber tractography: technical considerations. AJNR 2008;29:843-852.
²⁹
Chertkow H, Massoud F, Nasreddine Z, et al. Diagnosis and treatment of dementia:3. Mild cognitive impairment and cognitive impairment without dementia. CMAJ 2008;178: 1273-1285.
³⁰
Hampel H, Bürger K, Teipel SJ, Bokde AL, Zetterberg H, Blennow K. Core candidate neurochemical and imaging biomarkers of Alzheimer's disease. Alzheimers Dement 2008;4:38-48.
³¹
Hanyu H, Asano T, Sakurai H, et al. Diffusion-weighted and magnetization transfer imaging of the corpus callosum in Alzheimer's disease. J Neurol Sci 1999;167:37-44.
³²
Sandson TA, Felician O, Edelman RR, Warach S. Diffusion-weighted magnetic resonance imaging in Alzheimer's disease. Dement Geriatr Cogn Disord 1999;10:166-171.
³³
Kantarci K, Jack CR Jr, Xu YC, et al. Mild cognitive impairment and Alzheimer disease: regional diffusivity of water. Radiology 2001;219:101-7.
³⁴
Bozzali M, Falini A, Franceschi M, et al. White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging. J Neurol Neurosurg Psychiatry 2002;72:742-746.
³⁵
Fellgiebel A, Muller MJ, Wille P, et al. Color-coded diffusion-tensor-imaging of posterior cingulated fiber tracts in mild cognitive impairment. Neurobiol Aging 2005.26:1193-1198.
³⁶
Rose SE, Chen F, Chalk JB, et al. Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging. J Neurol Neurosurg Psychiatry 2000;69:528-530.
³⁷
Tabert MH, Manly JJ, Liu X, et al. Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment. Arch Gen Psychiatry 2006;63:916-924.
³⁸
Müller MJ, Greverus D, Dellani PR, et al. Functional implications of hippocampal volume and diffusivity in mild cognitive impairment. Neuroimage 2005;28:1033-1042.
³⁹
Kantarci K, Petersen RC, Boeve BF, et al. DWI predicts future progression to Alzheimer disease in amnestic mild cognitive impairment. Neurology. 2005;64:902-904.
⁴⁰
Gouw AA, Seewann A, Vrenken H, et al. Heterogeneity of white matter hyperintensities in Alzheimer's disease: post-mortem quantitative MRI and neuropathology. Brain 2008; 131:3286-3298.
⁴¹
Smith SM, Johansen-Berg H, Jenkinson M, et al. Acquisition and voxelwise analysis of multi-subject diffusion data with tract-based spatial statistics. Nat Protoc. 2007;2:499-503.
⁴²
Feldman HH, Jacova C, Robillard A, et al. Diagnosis and treatment of dementia: 2. Diagnosis. CMAJ 2008;178:825-836.

Publication Dates

Publication in this collection
Oct-Dec 2009

History

Received
05 Aug 2009
Accepted
11 Nov 2009

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] ¹
Berr C,Wancata J, Ritchie K. Prevalence of dementia in the elderly in Europe. Eur Neuropsychopharmacology 2005;15:463-471.

[2] ²
Lopes MA, Hototian SR, Bustamante SE, et al. Prevalence of cognitive and functional impairment in a community sample in Ribeirão Preto, Brazil. Int J Geriatr Psychiatry 2007;22: 770-776.

[3] ³
Bottino CM, Azevedo D Jr, Tatsch M, et al. Estimate of dementia prevalence in a community sample from São Paulo, Brazil. Dement Geriatr Cogn Disord 2008;26:291-299.

[4] ⁴
Scazufca M, Menezes PR, Vallada HP, et al. High prevalence of dementia among older adults from poor socioeconomic backgrounds in São Paulo, Brazil. Int Psychogeriatr 2008;20:394-405.

[5] ⁵
Teipel SJ, Meindl T, Grinberg L, Heinsen H, Hampel H. Novel MRI techniques in the assessment of dementia. Eur J Nucl Med Mol Imaging. 2008;35:S58-69.

[6] ⁶
Hall AM, Moore RY, Lopez OL, Kuller L, Becker JT. Basal forebrain atrophy is a presymptomatic marker for Alzheimer's disease. Alzheimers Dement 2008;4:271-279.

[7] ⁷
Rose SE, McMahon KL, Janke AL, et al. Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment. JNNP 2006; 77:1122-1128.

[8] ⁸
Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007;6:734-746.

[9] ⁹
Zhou Y, Dougherty JH Jr, Hubner KF, Bai B, Cannon RL, Hutson RK. Abnormal connectivity in the posterior cingulate and hippocampus in early Alzheimer's disease and mild cognitive impairment. Alzheimers Dement 2008;4:265-270.

[10] ¹⁰
Duara R, Loewenstein D, Barker WW, Isaacson RS, Greig-Custo M. A Clinical Perspective of Mild Cognitive Impairment: What Radiologists Should Know. Neuroimag Clin N Am 2005;15:779-788.

[11] ¹¹
Foster NL. A new framework for the diagnosis of Alzheimer's disease. Lancet Neurol 2007;6:667-669.

[12] ¹²
Petrella JR, Coleman ER, Doraiswamy PM. Neuroimaging and early diagnosis of Alzheimer Disease: a look to the future. Radiology 2003;226:315-336.

[13] ¹³
Minati L, Grisoli M, Bruzzone MG. MR spectroscopy, functional MRI, and diffusion-tensor imaging in the aging brain: a conceptual review. J Geriatr Psychiatry Neurol 2007;20:3-21.

[14] ¹⁴
Krishnan S, Talley BD, Slavin MJ, Doraiswamy PM, Petrella JR. Current status of functional MR imaging, perfusion-weighted imaging, and diffusion-tensor imaging in Alzheimer's disease diagnosis and research. Neuroimaging Clin N Am 2005;15:853-868.

[15] ¹⁵
Cho H, Yang DW, Shon YM, et al. Abnormal integrity of corticocortical tracts in mild cognitive impairment: a diffusion tensor imaging study. J Korean Med Sci 2008;23:477-483.

[16] ¹⁶
Yasmin H, Nakata Y, Aoki S, et al. Diffusion abnormalities of the uncinate fasciculus in Alzheimer's disease: diffusion tensor tract-specific analysis using a new method to measure the core of the tract. Neuroradiology 2008;50:293-299.

[17] ¹⁷
Mueller SG, Schuff N, Weiner MW. Evaluation of treatment effects in Alzheimer's and other neurodegenerative diseases by MRI and MRS. NMR Biomed 2006;19:655-668.

[18] ¹⁸
Sunderland T, Hampel H, Takeda M, Putnam KT, Cohen RM. Biomarkers in the diagnosis of Alzheimer's disease: are we ready? J Geriatr Psychiatry Neurol 2006;19:172-179.

[19] ¹⁹
Consensus report of the Working Group on: "Molecular and Biochemical Markers of Alzheimer's Disease." The Ronald and Nancy Reagan Research Institute of the Alzheimer's Association and the National Institute on Aging Working Group. Neurobiol Aging 1998;19:109-116.

[20] ²⁰
Filler, AG: The history, development, and impact of computed imaging in neurological diagnosis and neurosurgery: CT, MRI, DTI: Nature Precedings DOI:10.1038/npre.2009.3267.4.

[21] ²¹
Bozzali M, Cherubini A. Diffusion tensor MRI to investigate dementias: a brief review. Magn Reson Imaging 2007;25: 969-977.

[22] ²²
Mukherjee P, Berman JI, Chung SW, Hess CP, Henry RG. Diffusion tensor MR imaging and fiber tractography: theoretic underpinnings. AJNR 2008;29:632-641.

[23] ²³
Mori S, Barker PB. Diffusion magnetic resonance imaging: its principle and applications. Anat Rec 1999;257:102-9.

[24] ²⁴
Mori S, Zhang J. Principles of diffusion tensor imaging and its applications to basic neuroscience research. Neuron. 2006;51: 527-539.

[25] ²⁵
Hagmann P, Jonasson L, Maeder P, Thiran JP, Wedeen VJ, Meuli. Understanding diffusion MR imaging techniques: from scalar diffusion-weighted imaging to diffusion tensor imaging and beyond. Radiographics 2006;26:S205-23.

[26] ²⁶
Chua TC , Wen W , Slavin MJ , Sachdev PS . Diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease: a review. Curr Opin Neurol 2008;21:83-92.

[27] ²⁷
Ringman JM, O'Neill J, Geschwind D, et al. Diffusion tensor imaging in preclinical and presymptomatic carriers of familial Alzheimer's disease mutations. Brain 2007;130:1767-1776.

[28] ²⁸
Mukherjee P, Chung SW, Berman JI, Hess CP, Henry RG. Diffusion tensor MR imaging and fiber tractography: technical considerations. AJNR 2008;29:843-852.

[29] ²⁹
Chertkow H, Massoud F, Nasreddine Z, et al. Diagnosis and treatment of dementia:3. Mild cognitive impairment and cognitive impairment without dementia. CMAJ 2008;178: 1273-1285.

[30] ³⁰
Hampel H, Bürger K, Teipel SJ, Bokde AL, Zetterberg H, Blennow K. Core candidate neurochemical and imaging biomarkers of Alzheimer's disease. Alzheimers Dement 2008;4:38-48.

[31] ³¹
Hanyu H, Asano T, Sakurai H, et al. Diffusion-weighted and magnetization transfer imaging of the corpus callosum in Alzheimer's disease. J Neurol Sci 1999;167:37-44.

[32] ³²
Sandson TA, Felician O, Edelman RR, Warach S. Diffusion-weighted magnetic resonance imaging in Alzheimer's disease. Dement Geriatr Cogn Disord 1999;10:166-171.

[33] ³³
Kantarci K, Jack CR Jr, Xu YC, et al. Mild cognitive impairment and Alzheimer disease: regional diffusivity of water. Radiology 2001;219:101-7.

[34] ³⁴
Bozzali M, Falini A, Franceschi M, et al. White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging. J Neurol Neurosurg Psychiatry 2002;72:742-746.

[35] ³⁵
Fellgiebel A, Muller MJ, Wille P, et al. Color-coded diffusion-tensor-imaging of posterior cingulated fiber tracts in mild cognitive impairment. Neurobiol Aging 2005.26:1193-1198.

[36] ³⁶
Rose SE, Chen F, Chalk JB, et al. Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging. J Neurol Neurosurg Psychiatry 2000;69:528-530.

[37] ³⁷
Tabert MH, Manly JJ, Liu X, et al. Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment. Arch Gen Psychiatry 2006;63:916-924.

[38] ³⁸
Müller MJ, Greverus D, Dellani PR, et al. Functional implications of hippocampal volume and diffusivity in mild cognitive impairment. Neuroimage 2005;28:1033-1042.

[39] ³⁹
Kantarci K, Petersen RC, Boeve BF, et al. DWI predicts future progression to Alzheimer disease in amnestic mild cognitive impairment. Neurology. 2005;64:902-904.

[40] ⁴⁰
Gouw AA, Seewann A, Vrenken H, et al. Heterogeneity of white matter hyperintensities in Alzheimer's disease: post-mortem quantitative MRI and neuropathology. Brain 2008; 131:3286-3298.

[41] ⁴¹
Smith SM, Johansen-Berg H, Jenkinson M, et al. Acquisition and voxelwise analysis of multi-subject diffusion data with tract-based spatial statistics. Nat Protoc. 2007;2:499-503.

[42] ⁴²
Feldman HH, Jacova C, Robillard A, et al. Diagnosis and treatment of dementia: 2. Diagnosis. CMAJ 2008;178:825-836.

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