Abstract
White Matter Lesions (WML) are a radiological finding common in aged subjects. We explored the impact of WML on underlying neurodegenerative processes. We focused on the impact of WML on two neurodegenerative diseases with different pathology. In this cross-sectional study of 137 subjects (78 female, 59 men, mean age 67.2; 43–87 years), we compared WML in healthy controls (HC; n = 55), patients with Alzheimer’s disease and amnestic Mild Cognitive Impairment (aMCI), and Parkinson’s disease patients with normal cognition and with MCI. Subjects with AD and aMCI were treated as one group (n = 40), subjects with PD and PDMCI were another group (n = 42). MRI T2_FLAIR sequences were analyzed. WML were divided into periventricular (pWML) or subcortical (sWML) depending on their distance from the ventricles. Subjects from the AD + aMCI group, had a significantly greater volume of WML than both HC and the PD + PDMCI group. The volume of WML was greater in the PD + PDMCI than in HC but the difference was not significant. In AD + aMCI subjects, sWML and not pWML were related to a decrease in global cognitive functioning despite greater volume of pWML. In PD + PDMCI, pWML correlate with decline in executive functions and working memory. In HC, pWML correlated with the multidomain decrease corresponding with the aging. This points to a difference between normal aging and pathological aging due to AD and PD brain pathology. The WML location together with underlying disease related neurodegeneration may play a role in determining the effect of WML on cognition. Our results suggest that the impact of WML is not uniform in all patients; rather, their volume, location and cognitive effect may be disease-specific.
This is a preview of subscription content, access via your institution.


Data availability
The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
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 (2011) 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 J Alzheimers Assoc 7:270–279. https://doi.org/10.1016/j.jalz.2011.03.008
Anderkova L, Barton M, Rektorova I (2017) Striato-cortical connections in Parkinson’s and Alzheimer’s diseases: relation to cognition. Mov Disord 32:917–922. https://doi.org/10.1002/mds.26956
Bolandzadeh N, Davis JC, Tam R, Handy TC, Liu-Ambrose T (2012) The association between cognitive function and white matter lesion location in older adults: a systematic review. BMC Neurol 12:126. https://doi.org/10.1186/1471-2377-12-126
De Groot JC, De Leeuw F-E, Oudkerk M, Van Gijn J, Hofman A, Jolles J, Breteler MMB (2002) Periventricular cerebral white matter lesions predict rate of cognitive decline. Ann Neurol 52:335–341. https://doi.org/10.1002/ana.10294
Grey MT, Veselý B, Gajdoš M, Klobušiaková P, Rektor I (2019) Contribution of white matter lesions to cognitive decline in Parkinson’s disease. Parkinsonism Relat Disord 61:248–249. https://doi.org/10.1016/j.parkreldis.2018.10.015
Griffanti L, Jenkinson M, Suri S, Zsoldos E, Mahmood A, Filippini N, Sexton CE, Topiwala A, Allan C, Kivimäki M, Singh-Manoux A, Ebmeier KP, Mackay CE, Zamboni G (2018) Classification and characterization of periventricular and deep white matter hyperintensities on MRI: a study in older adults. Neuroimage 170:174–181. https://doi.org/10.1016/j.neuroimage.2017.03.024
Joki H, Higashiyama Y, Nakae Y, Kugimoto C, Doi H, Kimura K, Kishida H, Ueda N, Nakano T, Takahashi T, Koyano S, Takeuchi H, Tanaka F (2018) White matter hyperintensities on MRI in dementia with Lewy bodies, Parkinson’s disease with dementia, and Alzheimer’s disease. J Neurol Sci 385:99–104. https://doi.org/10.1016/j.jns.2017.12.018
Kempton MJ, Underwood TSA, Brunton S, Stylios F, Schmechtig A, Ettinger U, Smith MS, Lovestone S, Crum WR, Frangou S, Williams SCR, Simmons A (2011) A comprehensive testing protocol for MRI neuroanatomical segmentation techniques: evaluation of a novel lateral ventricle segmentation method. Neuroimage 58:1051–1059. https://doi.org/10.1016/j.neuroimage.2011.06.080
Litvan I, Goldman JG, Tröster AI, Schmand BA, Weintraub D, Petersen RC, Mollenhauer B, Adler CH, Marder K, Williams-Gray CH, Aarsland D, Kulisevsky J, Rodriguez-Oroz MC, Burn DJ, Barker RA, Emre M (2012) Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: movement Disorder Society Task Force guidelines. Mov Disord off J Mov Disord Soc 27:349–356. https://doi.org/10.1002/mds.24893
Minsterova AS, Klobusiakova P, Pies A, Galaz Z, Mekyska J, Novakova L, Elfmarkova NN, Rektorova I (2020) Patterns of diffusion kurtosis changes in Parkinson’s disease subtypes. Parkinsonism Relat Disord 81:96–102. https://doi.org/10.1016/j.parkreldis.2020.10.032
Pozorski V, Oh JM, Okonkwo O, Krislov S, Barzgari A, Theisen F, Sojkova J, Bendlin BB, Johnson SC, Gallagher CL (2019) Cross-sectional and longitudinal associations between total and regional white matter hyperintensity volume and cognitive and motor function in Parkinson’s disease. NeuroImage Clin 23:101870. https://doi.org/10.1016/j.nicl.2019.101870
Veselý B, Rektor I (2016) The contribution of white matter lesions (WML) to Parkinson’s disease cognitive impairment symptoms: a critical review of the literature. Parkinsonism Relat Disord 22(Suppl 1):S166-170. https://doi.org/10.1016/j.parkreldis.2015.09.019
Acknowledgements
This research has been financially supported by Grants: Ministerstvo Zdravotnictví České Republiky NU20-04-00294, Czech science foundation GAČR 21-25953S and Czech health research council AZV NU21-04-00445. We also acknowledge the core facility MAFIL of CEITEC supported by the MEYS CR (LM2018129 Czech-BioImaging).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
None.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Grey, M.T., Mitterová, K., Gajdoš, M. et al. Differential spatial distribution of white matter lesions in Parkinson’s and Alzheimer’s diseases and cognitive sequelae. J Neural Transm 129, 1023–1030 (2022). https://doi.org/10.1007/s00702-022-02519-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-022-02519-z