REGIONAL WHITE MATTER HYPERINTENSITY CHANGES PREDICT COGNITIVE DECLINE IN MILD COGNITIVE IMPAIRMENT OF SUBCORTICAL VASCULAR TYPE: A THREE-YEAR FOLLOW-UP STUDY

Abstract

White matter hyperintensities (WMH) is a typical marker of small vessel disease and known to be related to cognitive impairment. A previous cross-sectional study also suggested that WMH were associated with frontal dysfunction, regardless of their locations. However, a previous study from our group suggested that WMH location as well as WMH volume might be important in predicting cognitive impairments, especially in the specific domains. In this study, we investigated the effects of longitudinal WMH changes on cognitive decline in patients with subcortical vascular mild cognitive impairment (svMCI), globally and regionally. We hypothesized that regional changes of WMH, especially in the frontal region, may predict cognitive decline than global or other regional changes of WMH. We prospectively recruited 92 patients from a single referral center. All patients underwent neuropsychological tests, 3T brain magnetic resonance image (MRI), and [11C] Pittsburgh compound B (PiB) PET. Neuropsychological tests and brain MRI were performed annually. Mean follow up length was 3.7 ± 1.5 years. Linear mixed effect regression models were used to evaluate the relationship between WMH change and cognitive change. Time, age, sex, years of education, PiB standardized uptake value ratio, and time varying WMH volume were used as fixed effects and subjects were used as random effects. Total WMH change linked to cognitive decline in attention (beta coefficiency = -0.0001; P value = 0.003) and visuospatial domains (beta coefficiency = -0.0001; P value = 0.033). Periventricular WMH (PWMH) change did not show any significant effect on cognitive decline. However, deep WMH (DWMH) changes predicted the alteration of attention and frontal executive function. WMH change in the frontal, and occipital regions had impact on deterioration of attention, visuospatial and frontal executive functions. The temporal WMH change was associated with decreased score of attention, and frontal executive function. The parietal WMH change related with only attention domain. Our findings suggested that WMH change were associated with decline in the frontal related function, regardless of their location. Furthermore, DWHM changes, but not PWMH changes, were more likely to affect cognitive changes.