Longitudinal diffusion tensor imaging changes in early Parkinson’s disease: ICICLE-PD study

ObjectiveTo investigate whether white matter microstructural changes can be used as a predictor of worsening of motor features or cognitive decline in patients with Parkinson’s disease and verify whether white matter microstructural longitudinal changes differ between patients with Parkinson’s disease with normal cognition and those with mild cognitive impairment.MethodsWe enrolled 120 newly diagnosed patients with early stage Parkinson’s disease (27 with mild cognitive impairment and 93 with normal cognition) along with 48 controls. Participants were part of the incidence of cognitive impairment in cohorts with longitudinal evaluation in Parkinson’s disease study and were assessed at baseline and 18 months later with cognitive, motor tests and diffusion tensor imaging. The relationships between fractional anisotropy and mean diffusivity with disease status, cognitive and motor function were investigated.ResultsAt baseline, patients with early stage Parkinson’s disease had significantly higher widespread mean diffusivity relative to controls, regardless of cognitive status. In patients with Parkinson’s disease/mild cognitive impairment, higher mean diffusivity was significantly correlated with lower attention and executive function scores. At follow-up frontal mean diffusivity increased significantly when comparing patients with Parkinson’s disease/mild cognitive impairment with those with normal cognition. Baseline mean diffusivity was a significant predictor of worsening of motor features in Parkinson’s disease.ConclusionsMean diffusivity represents an important correlate of cognitive function and predictor of motor impairment in Parkinson’s disease: DTI is potentially a useful tool in stratification of patients into clinical trials and to monitor the impact of treatment on motor function.

[1]  M. Hoehn,et al.  Parkinsonism , 1998, Neurology.

[2]  R. Barker,et al.  Stability of mild cognitive impairment in newly diagnosed Parkinson's disease , 2017, Journal of Neurology, Neurosurgery & Psychiatry.

[3]  R. Barker,et al.  Gray and white matter imaging: A biomarker for cognitive impairment in early Parkinson's disease? , 2016, Movement disorders : official journal of the Movement Disorder Society.

[4]  T. Anderson,et al.  White matter microstructure deteriorates across cognitive stages in Parkinson disease , 2013, Neurology.

[5]  O. Coulon,et al.  Diffusion tensor imaging in Parkinson's disease: Review and meta-analysis , 2017, NeuroImage: Clinical.

[6]  J. Jankovic,et al.  Functional decline in Parkinson disease. , 2001, Archives of neurology.

[7]  P. Hobson,et al.  Risk and incidence of dementia in a cohort of older subjects with Parkinson's disease in the United Kingdom , 2004, Movement disorders : official journal of the Movement Disorder Society.

[8]  J. Jankovic,et al.  Movement Disorder Society‐sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS): Scale presentation and clinimetric testing results , 2008, Movement disorders : official journal of the Movement Disorder Society.

[9]  Roger A. Barker,et al.  White matter pathology in Parkinson's disease: The effect of imaging protocol differences and relevance to executive function , 2012, NeuroImage.

[10]  Paul G. Ince,et al.  Vascular pathologies and cognition in a population-based cohort of elderly people , 2004, Journal of the Neurological Sciences.

[11]  Roger A. Barker,et al.  Severity of mild cognitive impairment in early Parkinson's disease contributes to poorer quality of life , 2014, Parkinsonism & related disorders.

[12]  A. Alexander,et al.  Diffusion tensor imaging of the brain , 2007, Neurotherapeutics.

[13]  J. O'Brien,et al.  Comparison of the pathology of cerebral white matter with post‐mortem magnetic resonance imaging (MRI) in the elderly brain , 2004, Neuropathology and applied neurobiology.

[14]  M. Firbank,et al.  Structural Brain Alterations in Motor Subtypes of Parkinson’s Disease: Evidence from Probabilistic Tractography and Shape Analysis , 2016, PloS one.

[15]  N. Kumar,et al.  The Sydney Multicenter Study of Parkinson's Disease: The Inevitability of Dementia at 20 years , 2009 .

[16]  C. Clarke,et al.  Systematic review of levodopa dose equivalency reporting in Parkinson's disease , 2010, Movement disorders : official journal of the Movement Disorder Society.

[17]  W. Gibb,et al.  The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[18]  E. Tolosa,et al.  Clinical diagnostic criteria for dementia associated with Parkinson's disease , 2007, Movement disorders : official journal of the Movement Disorder Society.

[19]  D. Eckstein,et al.  Parkinson's disease and dopaminergic therapy—differential effects on movement, reward and cognition , 2008, Brain : a journal of neurology.

[20]  T. Robbins,et al.  The cognitive ability of an incident cohort of Parkinson's patients in the UK. The CamPaIGN study. , 2004, Brain : a journal of neurology.

[21]  H. Spiers,et al.  Prefrontal and medial temporal lobe interactions in long-term memory , 2003, Nature Reviews Neuroscience.

[22]  L. Passamonti,et al.  Characterizing structural neural networks in de novo Parkinson disease patients using diffusion tensor imaging , 2016, Human brain mapping.

[23]  Guy B. Williams,et al.  Baseline and longitudinal grey matter changes in newly diagnosed Parkinson’s disease: ICICLE-PD study , 2015, Brain : a journal of neurology.

[24]  K. Hugdahl,et al.  Subtypes of mild cognitive impairment in parkinson's disease: Progression to dementia , 2006, Movement disorders : official journal of the Movement Disorder Society.

[25]  P. Svenningsson,et al.  Initial cognitive decline is associated with cortical thinning in early Parkinson disease , 2014, Neurology.

[26]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[27]  Wang Zhan,et al.  Regional alterations of brain microstructure in Parkinson's disease using diffusion tensor imaging , 2012, Movement disorders : official journal of the Movement Disorder Society.

[28]  Daniel Rueckert,et al.  Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data , 2006, NeuroImage.

[29]  J. O'Brien,et al.  Changes in DWI and MRS associated with white matter hyperintensities in elderly subjects , 2003, Neurology.

[30]  G. Stebbins,et al.  Defining optimal cutoff scores for cognitive impairment using Movement Disorder Society Task Force criteria for mild cognitive impairment in Parkinson's disease , 2013, Movement disorders : official journal of the Movement Disorder Society.

[31]  T. Robbins,et al.  Characterizing mild cognitive impairment in incident Parkinson disease , 2014, Neurology.

[32]  T. Melzer.  The evolution of diffusion tensor imaging in Parkinson's disease research , 2013, Movement disorders : official journal of the Movement Disorder Society.

[33]  M. Hoehn,et al.  Parkinsonism , 1967, Neurology.

[34]  Stephen M. Smith,et al.  Permutation inference for the general linear model , 2014, NeuroImage.

[35]  S. Olmos,et al.  Correlation of findings in advanced MRI techniques with global severity scales in patients with Parkinson disease. , 2011, Academic radiology.

[36]  R. Barker,et al.  Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines , 2012, Movement disorders : official journal of the Movement Disorder Society.

[37]  C. Adler,et al.  The neurobiological basis of cognitive impairment in Parkinson's disease , 2014, Movement disorders : official journal of the Movement Disorder Society.

[38]  J. Cummings,et al.  Frontal-subcortical circuitry and behavior , 2007, Dialogues in clinical neuroscience.

[39]  T. Anderson,et al.  Tracking Parkinson’s Disease over One Year with Multimodal Magnetic Resonance Imaging in a Group of Older Patients with Moderate Disease , 2015, PloS one.

[40]  G. E. Alexander,et al.  Functional architecture of basal ganglia circuits: neural substrates of parallel processing , 1990, Trends in Neurosciences.

[41]  D. Vaillancourt,et al.  Longitudinal changes in free-water within the substantia nigra of Parkinson's disease. , 2015, Brain : a journal of neurology.

[42]  Roger A. Barker,et al.  Improving Response Inhibition in Parkinson’s Disease with Atomoxetine , 2015, Biological Psychiatry.

[43]  Peter E Keller,et al.  Diffusion alterations associated with Parkinson's disease symptomatology: A review of the literature. , 2016, Parkinsonism & related disorders.

[44]  C. Tanner,et al.  Clinical features in early Parkinson disease and survival. , 2009, Archives of neurology.

[45]  Paul M. Thompson,et al.  Improved DTI registration allows voxel-based analysis that outperforms Tract-Based Spatial Statistics , 2014, NeuroImage.

[46]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[47]  Maija E. Rossi,et al.  Imaging brain iron and diffusion patterns: a follow-up study of Parkinson's disease in the initial stages. , 2014, Academic radiology.

[48]  Nicolaas I. Bohnen,et al.  White matter lesions in Parkinson disease , 2011, Nature Reviews Neurology.

[49]  D. Yang,et al.  Influence of White Matter Hyperintensities on the Cognition of Patients With Parkinson Disease , 2010, Alzheimer disease and associated disorders.

[50]  J. Jankovic,et al.  How to identify tremor dominant and postural instability/gait difficulty groups with the movement disorder society unified Parkinson's disease rating scale: Comparison with the unified Parkinson's disease rating scale , 2013, Movement disorders : official journal of the Movement Disorder Society.