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Microstructural White Matter Alterations in Mild Cognitive Impairment and Alzheimer’s Disease

Study Based on Neurite Orientation Dispersion and Density Imaging (NODDI)

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Abstract

Purpose

To investigate microstructural alterations in white matter in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) using neurite orientation dispersion and density imaging (NODDI) and to assess the potential diagnostic performance of NODDI-derived parameters.

Methods

In this study 14 MCI patients, 14 AD patients, and 14 healthy controls (HC) were recruited. The diffusion tensor imaging(DTI)-derived fractional anisotropy (FA) and NODDI-derived neurite density index (NDI), orientation dispersion index (ODI), and volume fraction of isotropic water molecules (Viso) were calculated from the diffusion data. The tract-based spatial statistics (TBSS) method was used for statistical analysis with one-way ANOVA. The correlations between the parameter values and mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) scores were examined. A receiver operating characteristic (ROC) curve was conducted to assess the diagnostic performance of different parameters.

Results

Compared with the HC group, the NDI and ODI values decreased significantly and the Viso values were significantly increased in the MCI and AD groups (p < 0.01, threshold-free cluster enhancement (TFCE)-corrected); however, there were no significant differences in FA values in the MCI group. The NDI, ODI, and Viso values of multiple fibers were significantly correlated with MMSE and MoCA scores. For the diagnosis of AD, the area under the ROC curve (AUC) for the NDI value of the splenium of corpus callosum was larger than the FA value (AUC = 0.885, 0.714, p = 0.042). The AUC of the Viso value of the right cerebral peduncle was larger than FA value (AUC = 0.934, 0.531, p = 0.004).

Conclusion

The NDI is more sensitive to white matter microstructural changes than FA and NODDI could be superior to DTI in the diagnosis of AD.

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References

  1. Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Thies B, Trojanowski JQ, Vinters HV, Montine TJ. National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement. 2012;8:1–13.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Radanovic M, Pereira FR, Stella F, Aprahamian I, Ferreira LK, Forlenza OV, Busatto GF. White matter abnormalities associated with Alzheimer’s disease and mild cognitive impairment: a critical review of MRI studies. Expert Rev Neurother. 2013;13:483–93.

    Article  CAS  PubMed  Google Scholar 

  3. Amlien IK, Fjell AM. Diffusion tensor imaging of white matter degeneration in Alzheimer’s disease and mild cognitive impairment. Neuroscience. 2014;276:206–15.

    Article  CAS  PubMed  Google Scholar 

  4. Mitchell AJ, Shiri-Feshki M. Rate of progression of mild cognitive impairment to dementia—meta-analysis of 41 robust inception cohort studies. Acta Psychiatr Scand. 2009;119:252–65.

    Article  CAS  PubMed  Google Scholar 

  5. Jones DK, Knösche TR, Turner R. White matter integrity, fiber count, and other fallacies: the do’s and don’ts of diffusion MRI. Neuroimage. 2013;73:239–54.

    Article  PubMed  Google Scholar 

  6. Zhang H, Schneider T, Wheeler-Kingshott CA, Alexander DC. NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain. Neuroimage. 2012;61:1000–16.

    Article  PubMed  Google Scholar 

  7. Merluzzi AP, Dean DC, Adluru N, Suryawanshi GS, Okonkwo OC, Oh JM, Hermann BP, Sager MA, Asthana S, Zhang H, Johnson SC, Alexander AL, Bendlin BB. Age-dependent differences in brain tissue microstructure assessed with neurite orientation dispersion and density imaging. Neurobiol Aging. 2016;43:79–88.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Sepehrband F, Clark KA, Ullmann JF, Kurniawan ND, Leanage G, Reutens DC, Yang Z. Brain tissue compartment density estimated using diffusion-weighted MRI yields tissue parameters consistent with histology. Hum Brain Mapp. 2015;36:3687–702.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Grussu F, Schneider T, Tur C, Yates RL, Tachrount M, Ianuş A, Yiannakas MC, Newcombe J, Zhang H, Alexander DC, DeLuca GC, Gandini Wheeler-Kingshott CAM. Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology? Ann Clin Transl Neurol. 2017;4:663–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jespersen SN, Bjarkam CR, Nyengaard JR, Chakravarty MM, Hansen B, Vosegaard T, Ostergaard L, Yablonskiy D, Nielsen NC, Vestergaard-Poulsen P. Neurite density from magnetic resonance diffusion measurements at ultrahigh field: comparison with light microscopy and electron microscopy. Neuroimage. 2010;49:205–16.

    Article  PubMed  Google Scholar 

  11. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256:183–94.

    Article  CAS  PubMed  Google Scholar 

  12. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:270–9.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Liu Y, Spulber G, Lehtimäki KK, Könönen M, Hallikainen I, Gröhn H, Kivipelto M, Hallikainen M, Vanninen R, Soininen H. Diffusion tensor imaging and tract-based spatial statistics in Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging. 2011;32:1558–71.

    Article  PubMed  Google Scholar 

  14. Sexton CE, Kalu UG, Filippini N, Mackay CE, Ebmeier KP. A meta-analysis of diffusion tensor imaging in mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging. 2011;32:2322.e5–e18.

    Article  Google Scholar 

  15. Wang PN, Chou KH, Chang NJ, Lin KN, Chen WT, Lan GY, Lin CP, Lirng JF. Callosal degeneration topographically correlated with cognitive function in amnestic mild cognitive impairment and Alzheimer’s disease dementia. Hum Brain Mapp. 2014;35:1529–43.

    Article  CAS  PubMed  Google Scholar 

  16. Liu J, Liang P, Yin L, Shu N, Zhao T, Xing Y, Li F, Zhao Z, Li K, Han Y. White matter abnormalities in two different subtypes of amnestic mild cognitive impairment. PLoS ONE. 2017;12:e170185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bellucci A, Luccarini I, Scali C, Prosperi C, Giovannini MG, Pepeu G, Casamenti F. Cholinergic dysfunction, neuronal damage and axonal loss in TgCRND8 mice. Neurobiol Dis. 2006;23:260–72.

    Article  CAS  PubMed  Google Scholar 

  18. Sun SW, Liang HF, Mei J, Xu D, Shi WX. In vivo diffusion tensor imaging of amyloid-beta-induced white matter damage in mice. J Alzheimers Dis. 2014;38:93–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Slattery CF, Zhang J, Paterson RW, Foulkes AJM, Carton A, Macpherson K, Mancini L, Thomas DL, Modat M, Toussaint N, Cash DM, Thornton JS, Henley SMD, Crutch SJ, Alexander DC, Ourselin S, Fox NC, Zhang H, Schott JM. ApoE influences regional white-matter axonal density loss in Alzheimer’s disease. Neurobiol Aging. 2017;57:8–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Thal DR, Attems J, Ewers M. Spreading of amyloid, tau, and microvascular pathology in Alzheimer’s disease: findings from neuropathological and neuroimaging studies. J Alzheimers Dis. 2014;42 Suppl 4:S421-9.

    Article  PubMed  Google Scholar 

  21. Calderon-Garcidueñas AL, Duyckaerts C. Alzheimer disease. Handb Clin Neurol. 2017;145:325–37.

    Article  PubMed  Google Scholar 

  22. Colgan N, Siow B, O’Callaghan JM, Harrison IF, Wells JA, Holmes HE, Ismail O, Richardson S, Alexander DC, Collins EC, Fisher EM, Johnson R, Schwarz AJ, Ahmed Z, O’Neill MJ, Murray TK, Zhang H, Lythgoe MF. Application of neurite orientation dispersion and density imaging (NODDI) to a tau pathology model of Alzheimer’s disease. Neuroimage. 2016;125:739–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Merluzzi AP, Dean DC 3rd, Adluru N, Suryawanshi GS, Okonkwo OC, Oh JM, Hermann BP, Sager MA, Asthana S, Zhang H, Johnson SC, Alexander AL, Bendlin BB. Age-dependent differences in brain tissue microstructure assessed with neurite orientation dispersion and density imaging. Neurobiol Aging. 2016;43:79–88.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Li J, Pan P, Huang R, Shang H. A meta-analysis of voxel-based morphometry studies of white matter volume alterations in Alzheimer’s disease. Neurosci Biobehav Rev. 2012;36:757–63.

    Article  PubMed  Google Scholar 

  25. Pettigrew C, Soldan A, Sloane K, Cai Q, Wang J, Wang MC, Moghekar A, Miller MI, Albert M; BIOCARD Research Team. Progressive medial temporal lobe atrophy during preclinical Alzheimer’s disease. Neuroimage Clin. 2017;16:439–46.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Mormino EC, Papp KV. Amyloid accumulation and cognitive decline in clinically normal older individuals: implications for aging and early alzheimer’s disease. J Alzheimers Dis. 2018;64(s1):S633–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mito R, Raffelt D, Dhollander T, Vaughan DN, Tournier JD, Salvado O, Brodtmann A, Rowe CC, Villemagne VL, Connelly A. Reply: Cortical tau pathology: a major player in fibre-specific white matter reductions in Alzheimer’s disease? Brain. 2018;141:e45.

    Article  PubMed  Google Scholar 

  28. Scheff SW, Price DA, Schmitt FA, Scheff MA, Mufson EJ. Synaptic loss in the inferior temporal gyrus in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis. 2011;24:547–57.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Scheff SW, Price DA, Schmitt FA, Mufson EJ. Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging. 2006;27:1372–84.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the Natural Scientific Foundation of China (Grant number 30870713, PI: Hongyan Ni) and the Tianjin Natural Science Foundation Project (Grant number 16JCYBJC25900, PI: Hongyan Ni). The authors would like to thank Yuanyuan Chen from the Tianjin International Joint Research Center for Neural Engineering, the Academy of Medical Engineering and Translational Medicine, Tianjin University for assistance in data processing and thank Chunchao Ma from the Department of Neurology, Tianjin First Central Hospital for assistance in providing patients.

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Authors and Affiliations

  1. Department of Radiology, First Central Clinical College, Tianjin Medical University, Tianjin, China

    Xiuwei Fu, Susan Shrestha & Yuan Luo

  2. Department of Radiology, Tianjin Hospital of Tianjin, Tianjin, China

    Man Sun

  3. Tianjin University of Traditional Chinese Medicine, Tianjin, China

    Qiaoling Wu

  4. MR Collaboration, Siemens Healthcare Ltd., Beijing, China

    Xianchang Zhang

  5. Department of Radiology, Tianjin First Central Hospital, 24 Fukang Road, Nankai District, 300192, Tianjin, China

    Jianzhong Yin & Hongyan Ni

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  1. Xiuwei Fu
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  2. Susan Shrestha
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  3. Man Sun
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  4. Qiaoling Wu
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  5. Yuan Luo
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  7. Jianzhong Yin
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  8. Hongyan Ni
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Corresponding author

Correspondence to Hongyan Ni.

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Conflict of interest

X. Fu, S. Shrestha, M. Sun, Q. Wu, Y. Luo, X. Zhang, J. Yin and H. Ni declare that they have no competing interests.

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Fu, X., Shrestha, S., Sun, M. et al. Microstructural White Matter Alterations in Mild Cognitive Impairment and Alzheimer’s Disease. Clin Neuroradiol 30, 569–579 (2020). https://doi.org/10.1007/s00062-019-00805-0

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  • DOI: https://doi.org/10.1007/s00062-019-00805-0

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