Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

White matter lesions in Parkinson disease

Nature Reviews Neurology volume 7, pages 229–236 (2011)Cite this article

Subjects

Abstract

Pure vascular parkinsonism without evidence of nigral Lewy body pathology may occur as a distinct clinicopathological entity, but a much more frequent occurrence is the comorbid presence of age-associated white matter lesions (WMLs) in idiopathic Parkinson disease (PD). WMLs are associated with motor and cognitive symptoms in otherwise normal elderly individuals. Comorbid WMLs are, therefore, expected to contribute to clinical symptoms in PD. Studies of WMLs in PD differ with regard to methods of assessment of WML burden and the patient populations selected for analysis, but converging evidence suggests that postural stability and gait motor functions are predominantly affected. WMLs are described to contribute to dementia in Alzheimer disease, and emerging but inconclusive evidence indicates similar effects in PD. In this article, we review the literature addressing the occurrence and impact of WMLs in PD, and suggest that WMLs may exacerbate or contribute to some motor and cognitive deficits associated with PD. We review existing and emerging methods for studying white matter pathology in vivo, and propose future research directions.

Key Points

  • White matter lesions (WMLs) correlate with motor and cognitive abnormalities in otherwise normal elderly individuals, and some of these abnormalities overlap with features of Parkinson disease (PD)

  • Comorbid WMLs in PD may contribute to motor symptoms—in particular, balance disturbances—possibly by disrupting subcortical–cortical tracts involved in gait and balance

  • Most pathobiological emphasis in PD has been on proximal neural systems, but clinical symptom augmentation by comorbid WMLs illustrates the importance of integrity of afferent and efferent subcortical–cortical projections

  • Diffusion tensor MRI is a novel imaging modality to study microstructural white matter changes; findings of such changes in early PD are consistent with other evidence of widespread neurodegeneration

  • Early prevention or mitigation of comorbid WMLs, perhaps by reducing cerebrovascular or metabolic risk factors, could result in reduced motor and cognitive disability in PD

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Venn diagram showing overlap between idiopathic PD and WMLs of normal aging.
Figure 2: Imaging WMLs.
Figure 3: Monoaminergic and cholinergic pathways that can be disrupted by white matter lesions.

Similar content being viewed by others

References

  1. Murray, M. E. et al. Functional impact of white matter hyperintensities in cognitively normal elderly subjects. Arch. Neurol. 67, 1379–1385 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Baloh, R. W., Yue, Q., Socotch, T. M. & Jacobson, K. M. White matter lesions and disequilibrium in older people. I. Case–control comparison. Arch. Neurol. 52, 970–974 (1995).

    Article  CAS  PubMed  Google Scholar 

  3. Gunning-Dixon, F. M. & Raz, N. The cognitive correlates of white matter abnormalities in normal aging: a quantitative review. Neuropsychology 14, 224–232 (2000).

    Article  CAS  PubMed  Google Scholar 

  4. Baezner, H. et al. Association of gait and balance disorders with age-related white matter changes: the LADIS study. Neurology 70, 935–942 (2008).

    Article  CAS  PubMed  Google Scholar 

  5. Novak, V. et al. White matter hyperintensities and dynamics of postural control. Magn. Reson. Imaging 27, 752–759 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Tullberg, M. et al. White matter lesions impair frontal lobe function regardless of their location. Neurology 63, 246–253 (2004).

    Article  CAS  PubMed  Google Scholar 

  7. Prins, N. D. et al. Cerebral small-vessel disease and decline in information processing speed, executive function and memory. Brain 128, 2034–2041 (2005).

    Article  PubMed  Google Scholar 

  8. de Laat, K. F. et al. Loss of white matter integrity is associated with gait disorders in cerebral small vessel disease. Brain 134, 73–83 (2011).

    Article  PubMed  Google Scholar 

  9. Pantoni, L. & Garcia, J. H. Pathogenesis of leukoaraiosis. Stroke 28, 652–659 (1997).

    Article  CAS  PubMed  Google Scholar 

  10. Young, V. G., Halliday, G. M. & Kril, J. J. Neuropathologic correlates of white matter hyperintensities. Neurology 71, 804–811 (2008).

    Article  PubMed  Google Scholar 

  11. Black, S., Gao, F. & Bilbao, J. Understanding white matter disease: imaging–pathological correlations in vascular cognitive impairment. Stroke 40 (3 Suppl.), S48–S52 (2009).

    PubMed  Google Scholar 

  12. van Swieten, J. C. et al. Periventricular lesions in the white matter on magnetic resonance imaging in the elderly. A morphometric correlation with arteriolosclerosis and dilated perivascular spaces. Brain 114, 761–774 (1991).

    Article  PubMed  Google Scholar 

  13. Fazekas, F. et al. Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology 43, 1683–1689 (1993).

    Article  CAS  PubMed  Google Scholar 

  14. Leys, D. et al. Could Wallerian degeneration contribute to “leuko-araiosis” in subjects free of any vascular disorder? J. Neurol. Neurosurg. Psychiatry 54, 46–50 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ballard, C. et al. Neurocardiovascular instability, hypotensive episodes, and MRI lesions in neurodegenerative dementia. Ann. N. Y. Acad. Sci. 903, 442–445 (2000).

    Article  CAS  PubMed  Google Scholar 

  16. Wersching, H. et al. Serum C-reactive protein is linked to cerebral microstructural integrity and cognitive function. Neurology 74, 1022–1029 (2010).

    Article  CAS  PubMed  Google Scholar 

  17. Pieters, B. et al. Periventricular white matter lucencies relate to low vitamin B12 levels in patients with small vessel stroke. Stroke 40, 1623–1626 (2009).

    Article  CAS  PubMed  Google Scholar 

  18. Demirkiran, M., Bozdemir, H. & Sarica, Y. Vascular parkinsonism: a distinct, heterogeneous clinical entity. Acta Neurol. Scand. 104, 63–67 (2001).

    Article  CAS  PubMed  Google Scholar 

  19. Thanvi, B., Lo, N. & Robinson, T. Vascular parkinsonism—an important cause of parkinsonism in older people. Age Ageing 34, 114–119 (2005).

    Article  PubMed  Google Scholar 

  20. Zijlmans, J. C., Daniel, S. E., Hughes, A. J., Revesz, T. & Lees, A. J. Clinicopathological investigation of vascular parkinsonism, including clinical criteria for diagnosis. Mov. Disord. 19, 630–640 (2004).

    Article  PubMed  Google Scholar 

  21. Jellinger, K. A. The pathology of Parkinson's disease. Adv. Neurol. 86, 55–72 (2001).

    CAS  PubMed  Google Scholar 

  22. Hughes, A. J., Daniel, S. E., Kilford, L. & Lees, A. J. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinicopathologic study of 100 cases. J. Neurol. Neurosurg. Psychiatry 55, 181–184 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jellinger, K. A. Prevalence of cerebrovascular lesions in Parkinson's disease. A postmortem study. Acta Neuropathol. 105, 415–419 (2003).

    Article  PubMed  Google Scholar 

  24. Choi, S. A. et al. Are there differences in cerebral white matter lesion burdens between Parkinson's disease patients with or without dementia? Acta Neuropathol. 119, 147–149 (2010).

    Article  PubMed  Google Scholar 

  25. Sohn, Y. H. & Kim, J. S. The influence of white matter hyperintensities on the clinical features of Parkinson's disease. Yonsei Med. J. 39, 50–55 (1998).

    Article  CAS  PubMed  Google Scholar 

  26. Slawek, J. et al. The influence of vascular risk factors and white matter hyperintensities on the degree of cognitive impairment in Parkinson's disease. Neurol. Neurochir. Pol. 42, 505–512 (2008).

    PubMed  Google Scholar 

  27. Lee, S. J. et al. The severity of leukoaraiosis correlates with the clinical phenotype of Parkinson's disease. Arch. Gerontol. Geriatr. 49, 255–259 (2009).

    Article  PubMed  Google Scholar 

  28. Stern, M. B., Braffman, B. H., Skolnick, B. E., Hurtig, H. I. & Grossman, R. I. Magnetic resonance imaging in Parkinson's disease and parkinsonian syndromes. Neurology 39, 1524–1526 (1989).

    Article  CAS  PubMed  Google Scholar 

  29. Piccini, P. et al. White matter hyperintensities in Parkinson's disease. Clinical correlations. Arch. Neurol. 52, 191–194 (1995).

    Article  CAS  PubMed  Google Scholar 

  30. Van Rossum, E. et al. The level of physical activity in patients with Parkinson's disease [abstract P2.096]. Parkinsonism Relat. Disord. 14 (Suppl. 1), S67–S68 (2008).

    Article  Google Scholar 

  31. Acharya, H. J., Bouchard, T. P., Emery, D. J. & Camicioli, R. M. Axial signs and magnetic resonance imaging correlates in Parkinson's disease. Can. J. Neurol. Sci. 34, 56–61 (2007).

    Article  PubMed  Google Scholar 

  32. Dalaker, T. O. et al. Brain atrophy and white matter hyperintensities in early Parkinson's disease. Mov. Disord. 24, 2233–2241 (2009).

    Article  PubMed  Google Scholar 

  33. Joseph, J. A., Roth, G. S. & Strong, R. The striatum, a microcosm for the examination of age-related alterations in the CNS: a selected review. Rev. Biol. Res. Aging 4, 181–199 (1990).

    Google Scholar 

  34. Volkow, N. D. et al. Dopamine transporters decrease with age in healthy subjects. J. Nucl. Med. 37, 554–558 (1996).

    CAS  PubMed  Google Scholar 

  35. Bernheimer, H., Birkmayer, W., Hornykiewicz, O., Jellinger, K. & Seitelberger, F. Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J. Neurol. Sci. 20, 415–455 (1973).

    Article  CAS  PubMed  Google Scholar 

  36. Fearnley, J. M. & Lees, A. J. Ageing and Parkinson's disease: Substantia nigra regional selectivity. Brain 114, 2283–2301 (1991).

    Article  PubMed  Google Scholar 

  37. Bohnen, N. I. et al. Positron emission tomography of monoaminergic vesicular binding in aging and Parkinson disease. J. Cereb. Blood Flow Metab. 26, 1198–1212 (2006).

    Article  CAS  PubMed  Google Scholar 

  38. Louis, E. D. et al. Quantitative brain measurements in community-dwelling elderly persons with mild parkinsonian signs. Arch. Neurol. 65, 1649–1654 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Brant-Zawadzki, M. et al. MR imaging of the aging brain: patchy white-matter lesions and dementia. Am. J. Neuroradiol. 6, 675–682 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Fazekas, F., Chawluk, J. B., Alavi, A., Hurtig, H. I. & Zimmerman, R. A. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am. J. Roentgenol. 149, 351–356 (1987).

    Article  CAS  PubMed  Google Scholar 

  41. Longstreth, W. T. Jr et al. Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people: the cardiovascular health study. Stroke 27, 1274–1282 (1996).

    Article  PubMed  Google Scholar 

  42. Scheltens, P. et al. A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging. J. Neurol. Sci. 114, 7–12 (1993).

    Article  CAS  PubMed  Google Scholar 

  43. DeCarli, C., Fletcher, E., Ramey, V., Harvey, D. & Jagust, W. J. Anatomical mapping of white matter hyperintensities (WMH): exploring the relationships between periventricular WMH, deep WMH, and total WMH burden. Stroke 36, 50–55 (2005).

    Article  PubMed  Google Scholar 

  44. Barkhof, F. & Scheltens, P. Is the whole brain periventricular? J. Neurol. Neurosurg. Psychiatry 77, 143–144 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bohnen, N. I., Muller, M. L., Kuwabara, H., Constantine, G. M. & Studenski, S. A. Age-associated leukoaraiosis and cortical cholinergic deafferentation. Neurology 72, 1411–1416 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. de Boer, R. et al. White matter lesion extension to automatic brain tissue segmentation on MRI. Neuroimage 45, 1151–1161 (2009).

    Article  PubMed  Google Scholar 

  47. Bohnen, N. I., Bogan, C. W. & Müller, M. L. Frontal and periventricular brain white matter lesions and cortical deafferentation of cholinergic and other neuromodulatory axonal projections. Eur. Neurol. J. I, 33–40 (2009).

    Google Scholar 

  48. Sugihara, S., Kinoshita, T., Matsusue, E., Fujii, S. & Ogawa, T. Usefulness of diffusion tensor imaging of white matter in Alzheimer disease and vascular dementia. Acta Radiol. 45, 658–663 (2004).

    Article  CAS  PubMed  Google Scholar 

  49. Gattellaro, G. et al. White matter involvement in idiopathic Parkinson disease: a diffusion tensor imaging study. AJNR Am. J. Neuroradiol. 30, 1222–1226 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Karagulle Kendi, A. T., Lehericy, S., Luciana, M., Ugurbil, K. & Tuite, P. Altered diffusion in the frontal lobe in Parkinson disease. AJNR Am. J. Neuroradiol. 29, 501–505 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lee, D. Y. et al. Vascular and degenerative processes differentially affect regional interhemispheric connections in normal aging, mild cognitive impairment, and Alzheimer disease. Stroke 41, 1791–1797 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Slawek, J. et al. Vascular risk factors do not contribute to motor and cognitive impairment in Parkinson's disease. Parkinsonism Relat. Disord. 16, 73–74 (2010).

    Article  CAS  PubMed  Google Scholar 

  53. Albin, R. L. et al. White matter lesions augment motor impairments of nigrostriatal dopaminergic denervation in Parkinson disease [abstract S53.004]. Neurology 74 (Suppl. 2), A500 (2010).

    Google Scholar 

  54. Mayeux, R. et al. An estimate of the incidence of dementia in idiopathic Parkinson's disease. Neurology 40, 1513–1517 (1990).

    Article  CAS  PubMed  Google Scholar 

  55. Marder, K., Tang, M.-X., Côté, L., Stern, Y. & Mayeux, R. The frequency and associated risk factors for dementia in patients with Parkinson's disease. Arch. Neurol. 52, 695–701 (1995).

    Article  CAS  PubMed  Google Scholar 

  56. Aarsland, D. & Kurz, M. W. The epidemiology of dementia associated with Parkinson disease. J. Neurol. Sci. 289, 18–22 (2010).

    Article  PubMed  Google Scholar 

  57. Kuczynski, B. et al. Cognitive and anatomic contributions of metabolic decline in Alzheimer disease and cerebrovascular disease. Arch. Neurol. 65, 650–655 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Chui, H. C. et al. Cognitive impact of subcortical vascular and Alzheimer's disease pathology. Ann. Neurol. 60, 677–687 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Marshall, G. A., Shchelchkov, E., Kaufer, D. I., Ivanco, L. S. & Bohnen, N. I. White matter hyperintensities and cortical acetylcholinesterase activity in parkinsonian dementia. Acta Neurol. Scand. 113, 87–91 (2006).

    Article  CAS  PubMed  Google Scholar 

  60. Burton, E. J., McKeith, I. G., Burn, D. J., Firbank, M. J. & O'Brien, J. T. Progression of white matter hyperintensities in Alzheimer disease, dementia with lewy bodies, and Parkinson disease dementia: a comparison with normal aging. Am. J. Geriatr. Psychiatry 14, 842–849 (2006).

    Article  PubMed  Google Scholar 

  61. Beyer, M. K., Aarsland, D., Greve, O. J. & Larsen, J. P. Visual rating of white matter hyperintensities in Parkinson's disease. Mov. Disord. 21, 223–229 (2006).

    Article  PubMed  Google Scholar 

  62. Lee, S. J. et al. Influence of white matter hyperintensities on the cognition of patients with Parkinson disease. Alzheimer Dis. Assoc. Disord. 24, 227–233 (2010).

    Article  PubMed  Google Scholar 

  63. Dalaker, T. O. et al. White matter hyperintensities do not impact cognitive function in patients with newly diagnosed Parkinson's disease. Neuroimage 47, 2083–2089 (2009).

    Article  PubMed  Google Scholar 

  64. Meyer, J. S., Huang, J. & Chowdhury, M. H. MRI confirms mild cognitive impairments prodromal for Alzheimer's, vascular and Parkinson–Lewy body dementias. J. Neurol. Sci. 257, 97–104 (2007).

    Article  PubMed  Google Scholar 

  65. Santangelo, G. et al. Differential neuropsychological profiles in Parkinsonian patients with or without vascular lesions. Mov. Disord. 25, 50–56 (2010).

    Article  PubMed  Google Scholar 

  66. Zarzhevsky, N. et al. White matter lesions augment cognitive impairments of dopaminergic denervation of the caudate nucleus in Parkinson disease [abstract OP294]. Eur. J. Nucl. Med. Mol. Imaging 37 (Suppl. 2), S249 (2010).

    Google Scholar 

  67. Murrow, R. W., Schweiger, G. D., Kepes, J. J. & Koller, W. C. Parkinsonism due to a basal ganglia lacunar state: clinicopathologic correlation. Neurology 40, 897–900 (1990).

    Article  CAS  PubMed  Google Scholar 

  68. Alexander, G. E., DeLong, M. R. & Strick, P. L. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu. Rev. Neurosci. 9, 357–381 (1986).

    Article  CAS  PubMed  Google Scholar 

  69. Herrmann, L. L., Le Masurier, M. & Ebmeier, K. P. White matter hyperintensities in late life depression: a systematic review. J. Neurol. Neurosurg. Psychiatry 79, 619–624 (2008).

    Article  CAS  PubMed  Google Scholar 

  70. Kerr, B., Condon, S. M. & McDonald, L. A. Cognitive spatial processing and the regulation of posture. J. Exp. Psychol. Hum. Percept. Perform. 11, 617–622 (1985).

    Article  CAS  PubMed  Google Scholar 

  71. Takakusaki, K., Tomita, N. & Yano, M. Substrates for normal gait and pathophysiology of gait disturbances with respect to the basal ganglia dysfunction. J. Neurol. 255 (Suppl. 4), 19–29 (2008).

    Article  PubMed  Google Scholar 

  72. Critchley, M. Arteriosclerotic parkinsonism. Brain 52, 23–83 (1929).

    Article  Google Scholar 

  73. Kalra, S., Grosset, D. G. & Benamer, H. T. Differentiating vascular parkinsonism from idiopathic Parkinson's disease: a systematic review. Mov. Disord. 25, 149–156 (2010).

    Article  PubMed  Google Scholar 

  74. Thompson, P. D. & Marsden, C. D. Gait disorder of subcortical arteriosclerotic encephalopathy: Binswanger's disease. Mov. Disord. 2, 1–8 (1987).

    Article  CAS  PubMed  Google Scholar 

  75. Grimbergen, Y. A., Langston, J. W., Roos, R. A. & Bloem, B. R. Postural instability in Parkinson's disease: the adrenergic hypothesis and the locus coeruleus. Expert Rev. Neurother. 9, 279–290 (2009).

    Article  CAS  PubMed  Google Scholar 

  76. Bloem, B. R., Steijns, J. A. & Smits-Engelsman, B. C. An update on falls. Curr. Opin. Neurol. 16, 15–26 (2003).

    Article  PubMed  Google Scholar 

  77. Bohnen, N. I. et al. History of falls in Parkinson disease is associated with reduced cholinergic activity. Neurology 73, 1670–1676 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Horak, F. B. Postural orientation and equilibrium: what do we need to know about neural control of balance to prevent falls? Age Ageing 35 (Suppl. 2), ii7–ii11 (2006).

    Article  PubMed  Google Scholar 

  79. Papapetropoulos, S. et al. The effect of vascular disease on late onset Parkinson's disease. Eur. J. Neurol. 11, 231–235 (2004).

    Article  CAS  PubMed  Google Scholar 

  80. Park, K. et al. Significant association between leukoaraiosis and metabolic syndrome in healthy subjects. Neurology 69, 974–978 (2007).

    Article  CAS  PubMed  Google Scholar 

  81. Nakaso, K. et al. Hypertrophy of IMC of carotid artery in Parkinson's disease is associated with L-DOPA, homocysteine, and MTHFR genotype. J. Neurol. Sci. 207, 19–23 (2003).

    Article  CAS  PubMed  Google Scholar 

  82. Aisen, P. S. et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA 300, 1774–1783 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. VITATOPS Trial Study Group. B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial. Lancet Neurol. 9, 855–865 (2010).

  84. Wright, C. B. et al. White matter hyperintensities and subclinical infarction: associations with psychomotor speed and cognitive flexibility. Stroke 39, 800–805 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Alves, G., Larsen, J. P., Emre, M., Wentzel-Larsen, T. & Aarsland, D. Changes in motor subtype and risk for incident dementia in Parkinson's disease. Mov. Disord. 21, 1123–1130 (2006).

    Article  PubMed  Google Scholar 

  86. Brickman, A. M. et al. Reduction in cerebral blood flow in areas appearing as white matter hyperintensities on magnetic resonance imaging. Psychiatry Res. 172, 117–120 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Bastos-Leite, A. J. et al. Cerebral blood flow by using pulsed arterial spin-labeling in elderly subjects with white matter hyperintensities. AJNR Am. J. Neuroradiol. 29, 1296–1301 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Kuczynski, B. et al. White matter integrity and cortical metabolic associations in aging and dementia. Alzheimers Dement. 6, 54–62 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Jagust, W. J. et al. Neuropathological basis of magnetic resonance images in aging and dementia. Ann. Neurol. 63, 72–80 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Schuur, M. et al. Genetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population. J. Neurol. Neurosurg. Psychiatry 82, 41–44 (2011).

    Article  CAS  PubMed  Google Scholar 

  91. Lieberman, A. et al. Dementia in Parkinson's disease. Ann. Neurol. 6, 355–359 (1979).

    Article  CAS  PubMed  Google Scholar 

  92. Utter, S. et al. Cerebral small vessel disease-induced apolipoprotein E leakage is associated with Alzheimer disease and the accumulation of amyloid beta-protein in perivascular astrocytes. J. Neuropathol. Exp. Neurol. 67, 842–856 (2008).

    Article  CAS  PubMed  Google Scholar 

  93. Schneider, J. A., Arvanitakis, Z., Leurgans, S. E. & Bennett, D. A. The neuropathology of probable Alzheimer disease and mild cognitive impairment. Ann. Neurol. 66, 200–208 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank Bryan Benson for his assistance with the MRI figures. The authors gratefully acknowledge research support from the NIH–National Institute of Neurological Disorders and Stroke, the Department of Veterans Affairs and the Michael J. Fox Foundation.

Author information

Authors and Affiliations

  1. Departments of Radiology and Neurology, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, 48109, MI, USA

    Nicolaas I. Bohnen & Roger L. Albin

  2. VA Ann Arbor Healthcare System, 2215 Fuller Road, Ann Arbor, 48105, MI, USA

    Nicolaas I. Bohnen & Roger L. Albin

Authors
  1. Nicolaas I. Bohnen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roger L. Albin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors researched data for the article, discussed the content, wrote the text, and reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Roger L. Albin.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bohnen, N., Albin, R. White matter lesions in Parkinson disease. Nat Rev Neurol 7, 229–236 (2011). https://doi.org/10.1038/nrneurol.2011.21

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2011.21

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing