Volume 31, Issue 1 p. 103-110
Research Article

Gray and white matter imaging: A biomarker for cognitive impairment in early Parkinson's disease?

Gordon W. Duncan PhD, MRCP

Corresponding Author

Gordon W. Duncan PhD, MRCP

Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom

Medicine of the Elderly, Western General Hospital, Edinburgh, United Kingdom

Correspondence to: Dr. Gordon W. Duncan, Medicine of the Elderly, Western General Hospital, Edinburgh, EH4 2XU, United Kingdom; [email protected]Search for more papers by this author
Michael J. Firbank PhD

Michael J. Firbank PhD

Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom

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Alison J. Yarnall PhD, MRCP

Alison J. Yarnall PhD, MRCP

Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom

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Tien K. Khoo PhD, MRCP

Tien K. Khoo PhD, MRCP

School of Medicine and Griffith Health Institute, Griffith University, Gold Coast, Australia

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David J. Brooks MD, FRCP

David J. Brooks MD, FRCP

Aarhus University, Aarhus, Denmark and Imperial College, London, United Kingdom

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Roger A. Barker PhD, MRCP

Roger A. Barker PhD, MRCP

John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom

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David J. Burn MD, FRCP

David J. Burn MD, FRCP

Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom

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John T. O'Brien DM, FRCPsych

John T. O'Brien DM, FRCPsych

Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom

Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom

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First published: 22 July 2015
Citations: 120

Funding agencies: This work was supported by a Parkinson's UK Program grant (grant no.: J-0802) and the Newcastle University Lockhart Parkinson's Disease Research Fund.

Relevant conflicts of interest/financial disclosures: Nothing to report.

Full financial disclosures and author roles may be found in the online version of this article.

ABSTRACT

Background

The aim of this work was to investigate the cortical and white matter changes that underlie cognitive impairment in patients with incident Parkinson's disease (PD) disease using voxel-based morphometry and diffusion tensor imaging.

Methods

Newly diagnosed nondemented PD (n = 125) and control subjects (n = 50) were recruited from the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in Parkinson's Disease Study and completed cognitive assessments and 3T structural and diffusion tensor MR imaging. Voxel-based morphometry was performed to investigate the relationship between gray matter volume and cognitive ability. Microstructural white matter changes were assessed with diffusion tensor imaging measures of fractional anisotropy and mean diffusivity using tract-based spatial statistics.

Results

Increased mean diffusivity was observed bilaterally in subjects with PD, relative to controls (P = 0.019). Increased mean diffusivity was associated with performance on the semantic fluency and Tower of London tasks in frontal and parietal white matter tracts, including the cingulum, superior longitudinal fasciculus, inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus. There was no difference in total gray matter volume between groups; however, bilateral reductions in frontal and parietal gray matter volume were associated with reduced performance on measures of executive function in PD subjects.

Conclusions

At the earliest stages of PD, regionally specific increases in central white matter mean diffusivity are present and suggest early axonal damage. Such changes are not accompanied by significant gray matter volume loss and are consistent with proposed models of pathological progression of the disease. Structural MRI, especially diffusion tensor imaging analysis, offers potential as a noninvasive biomarker reflecting cognitive impairment in PD. © 2015 International Parkinson and Movement Disorder Society