The impact of white matter lesions on the cognitive outcome of subthalamic nucleus deep brain stimulation in Parkinson's disease

Objectives: White Matter lesions (WML) are a risk factor for cognitive impairment in Parkinson's disease. There is no clear evidence of reduced general cognitive function after DBS. However, a subgroup of patients develops dementia rapidly after DBS despite careful patient selection processes. The aim of this study was to evaluate the load of WML as a possible risk factor for cognitive decline following STN DBS. Patients and methods: 40 PD-patients receiving bilateral STN-DBS were followed at least three years after surgery to detect dementia. All patients underwent comprehensive neuropsychological assessment and MRI before surgery. The extent of WML was assessed using an automated approach. WML volume was correlated to the onset of dementia and the decline of a cognitive composite score retrospectively. Results: Patients with a rapid onset of dementia within one, respective three following DBS showed significant higher WML volumes compared to cognitive normal and MCI patients (55.8 cm(3) +/- 18.836 vs. 9.3 cm(3) +/- 12.2; p = 0.002). The same significant association was found in a multivariable model, including the covariables age, gender and PD disease duration (p = 0.01). WML volume was associated to the rate of decline in cognitive composite score within three years after DBS surgery (p = 0.006; R-2 = 0.40) after correction for age. Conclusions: Damaged white matter may lead to a reduced compensation of disconnections in cognitive circuits caused by the implantation of the DBS electrodes or by chronic stimulation. The role of WML as a prognostic factor for the cognitive outcome after DBS may be underestimated. The WML burden should be taken seriously in preoperative risk stratification.