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White matter hyperintensities and changes in white matter integrity in patients with Alzheimer’s disease

  • Functional Neuroradiology
  • Published:
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Abstract

Introduction

White matter hyperintensities (WMHs) are a risk factor for Alzheimer’s disease (AD). This study investigated the relationship between WMHs and white matter changes in AD using diffusion tensor imaging (DTI) and the sensitivity of each DTI index in distinguishing AD with WMHs.

Methods

Forty-four subjects with WMHs were included. Subjects were classified into three groups based on the Scheltens rating scale: 15 AD patients with mild WMHs, 12 AD patients with severe WMHs, and 17 controls with mild WMHs. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (DR), and axial diffusivity (DA) were analyzed using the region of interest and tract-based spatial statistics methods. Sensitivity and specificity of DTI indices in distinguishing AD groups from the controls were evaluated.

Results

AD patients with mild WMHs exhibited differences from control subjects in most DTI indices in the medial temporal and frontal areas; however, differences in DTI indices from AD patients with mild WMHs and AD patients with severe WMHs were found in the parietal and occipital areas. FA and DR were more sensitive measurements than MD and DA in differentiating AD patients from controls, while MD was a more sensitive measurement in distinguishing AD patients with severe WMHs from those with mild WMHs.

Conclusions

WMHs may contribute to the white matter changes in AD brains, specifically in temporal and frontal areas. Changes in parietal and occipital lobes may be related to the severity of WMHs. DR may serve as an imaging marker of myelin deficits associated with AD.

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Abbreviations

MRI:

Magnetic resonance imaging

DTI:

Diffusion tensor imaging

WMHs:

White matter hyperintensities

AD:

Alzheimer’s disease

TBSS:

Tract-based spatial statistics

FA:

Fractional anisotropy

MD:

Mean diffusivity

DR :

Radial diffusivity

DA :

Axial diffusivity

ROC:

Receiver operator characteristics

AUC:

Area under curve

AIC:

Anterior internal capsule

PIC:

Posterior internal capsule

References

  1. Schmidt R, Schmidt H, Kapeller P, Enzinger C, Ropele S et al (2002) The natural course of MRI white matter hyperintensities. J Neurol Sci 203–204:253–257

    Article  PubMed  Google Scholar 

  2. Gunning-Dixon FM, Brickman AM, Cheng JC, Alexopoulos GS (2009) Aging of cerebral white matter: a review of MRI findings. Int J Geriatr Psychiatry 24:109–117

    Article  PubMed  Google Scholar 

  3. Madden DJ, Bennett IJ, Song AW (2009) Cerebral white matter integrity and cognitive aging: contributions from diffusion tensor imaging. Neuropsychol Rev 19:415–435

    Article  PubMed  Google Scholar 

  4. Appel J, Potter E, Bhatia N, Shen Q, Zhao W et al (2009) Association of white matter hyperintensity measurements on brain MR imaging with cognitive status, medial temporal atrophy, and cardiovascular risk factors. AJNR Am J Neuroradiol 30:1870–1876

    Article  PubMed  CAS  Google Scholar 

  5. Lee DY, Fletcher E, Martinez O, Ortega M, Zozulya N et al (2009) Regional pattern of white matter microstructural changes in normal aging, MCI, and AD. Neurology 73:1722–1728

    Article  PubMed  CAS  Google Scholar 

  6. Riekse RG, Leverenz JB, McCormick W, Bowen JD, Teri L et al (2004) Effect of vascular lesions on cognition in Alzheimer’s disease: a community-based study. J Am Geriatr Soc 52:1442–1448

    Article  PubMed  Google Scholar 

  7. Hirono N, Kitagaki H, Kazui H, Hashimoto M, Mori E (2000) Impact of white matter changes on clinical manifestation of Alzheimer’s disease: a quantitative study. Stroke 31:2182–2188

    PubMed  CAS  Google Scholar 

  8. Cheong JL, Thompson DK, Wang HX, Hunt RW, Anderson PJ et al (2009) Abnormal white matter signal on MR imaging is related to abnormal tissue microstructure. AJNR Am J Neuroradiol 30:623–628

    Article  PubMed  CAS  Google Scholar 

  9. Huang J, Friedland RP, Auchus AP (2007) Diffusion tensor imaging of normal-appearing white matter in mild cognitive impairment and early Alzheimer disease: preliminary evidence of axonal degeneration in the temporal lobe. AJNR Am J Neuroradiol 28:1943–1948

    Article  PubMed  CAS  Google Scholar 

  10. Zhang Y, Schuff N, Du AT, Rosen HJ, Kramer JH et al (2009) White matter damage in frontotemporal dementia and Alzheimer’s disease measured by diffusion MRI. Brain 132:2579–2592

    Article  PubMed  Google Scholar 

  11. Rose SE, Janke AL, Chalk JB (2008) Gray and white matter changes in Alzheimer’s disease: a diffusion tensor imaging study. J Magn Reson Imaging 27:20–26

    Article  PubMed  Google Scholar 

  12. Xie S, Xiao JX, Gong GL, Zang YF, Wang YH et al (2006) Voxel-based detection of white matter abnormalities in mild Alzheimer disease. Neurology 66:1845–1849

    Article  PubMed  CAS  Google Scholar 

  13. Klingberg T, Vaidya CJ, Gabrieli JD, Moseley ME, Hedehus M (1999) Myelination and organization of the frontal white matter in children: a diffusion tensor MRI study. Neuroreport 10:2817–2821

    Article  PubMed  CAS  Google Scholar 

  14. Song SK, Sun SW, Ramsbottom MJ, Chang C, Russell J et al (2002) Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage 17:1429–1436

    Article  PubMed  Google Scholar 

  15. Budde MD, Xie M, Cross AH, Song SK (2009) Axial diffusivity is the primary correlate of axonal injury in the experimental autoimmune encephalomyelitis spinal cord: a quantitative pixelwise analysis. J Neurosci 29:2805–2813

    Article  PubMed  CAS  Google Scholar 

  16. Wheeler-Kingshott CA, Cercignani M (2009) About “axial” and “radial” diffusivities. Magn Reson Med 61:1255–1260

    Article  PubMed  Google Scholar 

  17. Gouw AA, Seewann A, Vrenken H, van der Flier WM, Rozemuller JM et al (2008) Heterogeneity of white matter hyperintensities in Alzheimer’s disease: post-mortem quantitative MRI and neuropathology. Brain 131:3286–3298

    Article  PubMed  CAS  Google Scholar 

  18. Mckhann G, Drachman D, Folstein M, Katzman R, Price D et al (1984) Clinical-diagnosis of Alzheimers-disease—report of the Nincds-Adrda work group under the Auspices of Department-of-health-and-human-services task-force on Alzheimers-disease. Neurology 34:939–944

    PubMed  CAS  Google Scholar 

  19. Scheltens P, Barkhof F, Leys D, Pruvo JP, Nauta JJ et al (1993) A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging. J Neurol Sci 114:7–12

    Article  PubMed  CAS  Google Scholar 

  20. Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M et al (2001) A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 32:1318–1322

    PubMed  CAS  Google Scholar 

  21. Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE et al (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31:1487–1505

    Article  PubMed  Google Scholar 

  22. Capizzano AA, Acion L, Bekinschtein T, Furman M, Gomila H et al (2004) White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 75:822–827

    Article  PubMed  CAS  Google Scholar 

  23. Lee PH, Oh SH, Bang OY, Joo IS, Huh K (2005) Pathogenesis of deep white matter medullary infarcts: a diffusion weighted magnetic resonance imaging study. J Neurol Neurosurg Psychiatry 76:1659–1663

    Article  PubMed  CAS  Google Scholar 

  24. Chen SQ, Kang Z, Hu XQ, Hu B, Zou Y (2007) Diffusion tensor imaging of the brain in patients with Alzheimer’s disease and cerebrovascular lesions. J Zhejiang Univ Sci B 8:242–247

    Article  PubMed  Google Scholar 

  25. DeCarli C, Grady CL, Clark CM, Katz DA, Brady DR et al (1996) Comparison of positron emission tomography, cognition, and brain volume in Alzheimer’s disease with and without severe abnormalities of white matter. J Neurol Neurosurg Psychiatry 60:158–167

    Article  PubMed  CAS  Google Scholar 

  26. O’Brien JT, Wiseman R, Burton EJ, Barber B, Wesnes K et al (2002) Cognitive associations of subcortical white matter lesions in older people. Ann N Y Acad Sci 977:436–444

    Article  PubMed  Google Scholar 

  27. Schmidt R, Ropele S, Enzinger C, Petrovic K, Smith S et al (2005) White matter lesion progression, brain atrophy, and cognitive decline: the Austrian stroke prevention study. Ann Neurol 58:610–616

    Article  PubMed  Google Scholar 

  28. Damoiseaux JS, Smith SM, Witter MP, Sanz-Arigita EJ, Barkhof F et al (2009) White matter tract integrity in aging and Alzheimer’s disease. Hum Brain Mapp 30:1051–1059

    Article  PubMed  Google Scholar 

  29. Zarei M, Damoiseaux JS, Morgese C, Beckmann CF, Smith SM et al (2009) Regional white matter integrity differentiates between vascular dementia and Alzheimer disease. Stroke 40:773–779

    Article  PubMed  Google Scholar 

  30. Lee JH, Olichney JM, Hansen LA, Hofstetter CR, Thal LJ (2000) Small concomitant vascular lesions do not influence rates of cognitive decline in patients with Alzheimer disease. Arch Neurol 57:1474–1479

    Article  PubMed  CAS  Google Scholar 

  31. Wang L, Goldstein FC, Veledar E, Levey AI, Lah JJ et al (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 Am J Neuroradiol 30:893–899

    Article  PubMed  CAS  Google Scholar 

  32. Seo SW, Im K, Lee JM, Kim YH, Kim ST et al (2007) Cortical thickness in single- versus multiple-domain amnestic mild cognitive impairment. Neuroimage 36:289–297

    Article  PubMed  Google Scholar 

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Acknowledgements

This study was supported in part by a grant from NIH (R21AG027335 to HM) and a pilot project grant from The Emory Alzheimer’s Disease Research Center (NIH-NIA P50 AG025688 to HM).

The authors thank Dr. Longchuan Li (Department of Biomedical Engineering, Emory University) and Dr. Xiaodong Zhong (MR R&D Collaborations, Siemens Medical Solutions) for their assistances and helpful discussions.

Conflict of interest

We declare we have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Radiology, Emory University School of Medicine, 1364 Clifton Road, Atlanta, GA, 30329, USA

    Liya Wang, Carolyn C. Meltzer, Chad A. Holder & Hui Mao

  2. Center for Systems Imaging, Emory University School of Medicine, Atlanta, GA, 30329, USA

    Liya Wang, Carolyn C. Meltzer & Hui Mao

  3. Department of Neurology, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Felicia C. Goldstein, Allan I. Levey, James J. Lah & Carolyn C. Meltzer

  4. Department of Psychiatry and Behavior Sciences, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Carolyn C. Meltzer

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  1. Liya Wang
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Correspondence to Hui Mao.

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Wang, L., Goldstein, F.C., Levey, A.I. et al. White matter hyperintensities and changes in white matter integrity in patients with Alzheimer’s disease. Neuroradiology 53, 373–381 (2011). https://doi.org/10.1007/s00234-010-0806-2

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  • DOI: https://doi.org/10.1007/s00234-010-0806-2

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