Abstract
Older patients with confluent white matter hyperintensities (WMHs) on magnetic resonance imaging have an increased risk for the onset of vascular cognitive impairment (VCI). This study investigates the predictive effects of the white matter (WM) fractional anisotropy (FA) and brain volumes on cognitive impairment for those with confluent WMHs. This study enrolled 77 participants with confluent WMHs (Fazekas grade 2 or 3), including 44 with VCI-no dementia (VCIND) and 33 with normal cognition (NC). The mean FA of 20 WM tracts was calculated to evaluate the global WM microstructural integrity, and major WM tracts were reconstructed using probabilistic tractography. Voxel-based morphometry was used to calculate brain volumes for the total gray matter (GM), the hippocampus, and the nucleus basalis of Meynert (NbM). All volumetric assays were corrected for total intracranial volume. All regression analyses were adjusted for age, gender, education, and apolipoprotein E (ApoE) gene ε4 status. Logistic regression analysis revealed that the mean FA value for global WM was the only independent risk factor for VCI (z score of FA: OR = 4.649, 95%CI 1.576–13.712, p = 0.005). The tract-specific FAs were not associated with the risk of cognitive impairment after controlling the mean FA for global WM. The mean FA value was significantly associated with scores of Mini-Mental State Examination (MMSE) and Auditory Verbal Learning Test. A lower FA was also associated with smaller volumes of total GM, hippocampus, and NbM. However, brain volumes were not found to be directly related to cognitive performances, except for an association between the hippocampal volume and MMSE. In conclusion, the mean FA for global WM microstructural integrity is a superior predictor for cognitive impairment than tract-specific FA and brain volumes in people with confluent WMHs.
Highlights
Vascular cognitive impairment (VCI) is the second most common cause of acquired cognitive impairment, behind only Alzheimer’s disease (AD), with subcortical ischemic VCI (SIVCI) caused by cerebral small vessel disease (SVD) as its most common subtype [1]
Our results indicated that the mean fractional anisotropy (FA) value for global white matter (WM) was the only independent risk factor for the onset of VCI
A lower global mean FA was associated with smaller total volumes of gray matter (GM), hippocampus and nucleus basalis of Meynert (NbM)
Summary
Vascular cognitive impairment (VCI) is the second most common cause of acquired cognitive impairment, behind only Alzheimer’s disease (AD), with subcortical ischemic VCI (SIVCI) caused by cerebral small vessel disease (SVD) as its most common subtype [1]. The appearance of WMHs varies from small punctures, to diffuse and confluent lesions. It has been demonstrated that WMHs and VCI are associated in a severity-dependent manner. Compared to patients with mild WMHs, those with severe WMHs experienced a three-fold increase in the risk of vascular dementia in a 3year follow-up study [2]. This association sparked the suggestion that preventive trials for VCI should focus on patients with confluent WMHs [3]. Within the same severity of WMHs, some patients rapidly develop cognitive impairment while others maintain normal cognition for an extensive period. Identifying the predictors of cognitive impairment, especially in those who already have confluent WMHs, would provide a crucial tool for early detection and prevention
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