The burden of white matter hyperintensities is a predictor of progressive mild cognitive impairment in patients with Parkinson's disease

Background and purpose: To evaluate whether white matter hyperintensities (WMHs) may act as an independent predictor for progression of cognitive status, the authors analyzed the longitudinal effects of WMHs on cognitive dysfunction in non-demented patients with Parkinson's disease (PD). Methods: A total of 111 patients with PD were enrolled, including subjects with mild cognitive impairment (MCI, n = 65) and cognitively normal subjects (CN, n = 46). These individuals were classified as MCI converters (n = 22) or MCI non-converters (n = 43) and CN converters (n = 18) or CN non-converters (n = 28) based on whether they were subsequently diagnosed with PD dementia or PD-MCI during a minimum 24-month follow-up. The WMH burden and the Cholinergic Pathway Hyperintensities Scale (CHIPS) and their relationships to longitudinal changes in cognitive performance were examined. Results: PD-MCI converters had larger WMH volume (14421.0 vs. 5180.4, P < 0.001) and higher CHIPS score (22.6 vs. 11.2, P = 0.001) compared with PD-MCI non-converters. Logistic regression analysis revealed in patients with PD-MCI that WMH volume (odds ratio 1.616, P = 0.009) and CHIPS score (odds ratio 1.084, P = 0.007) were independently associated with PD dementia conversion. However, WMH volume and CHIPS score did not differ between PD-CN converters and PD-CN non-converters. In patients with PD-MCI, both WMH volume and CHIPS score were closely associated with longitudinal decline in general cognition, semantic fluency and Stroop test scores. Conclusions: The present study demonstrates that WMH burden is a significant predictor of conversion from PD-MCI to PD dementia and is related to ongoing decline in frontal-lobe-based cognitive performance.