The influence of white matter hyperintensity on cognitive impairment in Parkinson's disease

Abstract

The aim of this meta-analysis was to review systematically and to identify the relationship between the severity and location of white matter hyperintensities (WMHs) and the degree of cognitive decline in patients with Parkinson's disease (PD). We searched the PubMed, EMBASE, Web of Science, Ovid, and Cochrane Library databases for clinical trials of the severity and location of WMHs on the degree of cognitive impairment in PD through October 2020. We conducted the survey to compare the association of WMH burden in patients with PD with mild cognitive impairment (PD-MCI) versus those with normal cognition (PD-NC) and in patients with PD with dementia (PDD) versus those with PD without dementia (PD-ND). Nine studies with PD-MCI versus PD-NC and 10 studies with PDD versus PD-ND comparisons were included. The WMH burden in PD-MCI patients was significantly different compared to that in PD-NC patients (standard mean difference, SMD = 0.39, 95% CI: 0.12 to 0.66, p = 0.005), while there was no correlation shown in the age-matched subgroup of the comparison. In addition, PDD patients had a significantly higher burden of WMHs (SMD = 0.8, 95% CI: 0.44 to 1.71, p < 0.0001), especially deep white matter hyperintensities (SMD = 0.54, 95% CI: 0.36 to 0.73, p < 0.00001) and periventricular hyperintensities (SMD = 0.70, 95% CI: 0.36 to 1.04, p < 0.0001), than PD-NC patients, regardless of the adjustment of age. WMHs might be imaging markers for cognitive impairment in PDD but not in PD-MCI, regardless of age, vascular risk factors, or race. Further prospective studies are needed to validate the conclusions.

Figure 1

A flow diagram of the literature selection.

Figure 2

Forest plot showing the Std. mean difference and 95% confidence intervals of differences in WMHs between the PD‐MCI and PD‐NC patients. (A) WMH severity with the volumetric method in patients with PD‐MCI compared to PD‐NC; (B) Subgroup analysis of WMH according to whether age‐matched or not between comparisons; (C) Subgroup analysis of WMH in Asians and Caucasians; (D) WMHs in Caucasians with age‐matched group; (E) WMHs with visual methods in patients with PD‐MCI compared to PD‐NC.

Figure 3

Forest plot showing the Std. mean difference and 95% confidence intervals of differences in WMHs between the PDD and PD‐ND patients. (A) Total WMH with the visual measurement between the PDD and PD‐ND groups; (B) Subgroup analysis of total WMH according to whether age‐matched or not; (C) Subgroup analysis of total WMH in Asians and Caucasians; (D) Total WMH with volumetric method between the PDD and PD‐ND groups.

Figure 4

Forest plot showing the Std. mean difference and 95% confidence interval of differences in different locations of WMHs between PDD and PD‐ND patients. (A) DWMH between‐group comparisons; (B) PVH in PDD versus PD‐ND patients; (C) Basal ganglia hyperintensity (BGH) in PDD versus PD‐ND patients; (D) WMH in the infratentorial areas in PDD versus PD‐ND patients.

Figure 5

Begg's funnel plot and egger's test of publication bias in the selection of studies. (A) In the volumetric studies of PD‐MCI and PD‐NC comparison, the Begg's funnel plot is basically symmetrical; (B) Egger's method showed that the publication bias was small; (C) and (D) In the visual studies of PDD and PD‐ND comparison, Begg's funnel plot (C), and egger's method (D) did not reveal publication bias.