Differential Effects of Serum Lipoprotein-Associated Phospholipase A2 on Periventricular and Deep Subcortical White Matter Hyperintensity in Brain

Abstract

Background and Purpose: Serum level of lipoprotein-associated phospholipase A2 (Lp-PLA2) was associated with white matter hyperintensity (WMH). There were differences in the anatomical structure and pathophysiological mechanism between periventricular WMH (PVWMH) and deep subcortical WMH (DSWMH). In this study, we aimed to investigate the effects of serum Lp-PLA2 on the PVWMH and DSWMH.Methods: In total, 711 Chinese adults aged ≥45 years with cranial magnetic resonance imaging (MRI) were recruited in this cross-sectional study, who had received physical examinations in the Department of Neurology, the Affiliated Jiangning Hospital of Nanjing Medical University due to dizziness and headaches between January 2016 and July 2019. Enzyme linked immunosorbent assay (ELISA) was utilized to determine the serum Lp-PLA2. Fazekas scale was used to measure the severity of PVWMH (grade 0–3) and DSWMH (grade 0–3) on MRI scans. Ordinal regression analysis was carried out to investigate the relationship between serum Lp-PLA2 and PVWMH or DSWMH.Results: Finally, 567 cases were included in this study. The average level of serum Lp-PLA2 was 213.35±59.34 ng/ml. There were statistical differences in the age, hypertension, diabetes mellitus, atrial fibrillation, lacunar infarction, Lp-PLA2 grade, creatinine, Hcy, and H-CRP (P < 0.05) in PVWMH groups. Ordinal regression analysis indicated that there was a lower risk of PVWMH in the patients with normal and moderately elevated serum Lp-PLA2 compared with those with significantly elevated serum Lp-PLA2 after adjusting age, hypertension, diabetes mellitus, atrial fibrillation, lacunar infarction, Cr, Hcy, and H-CRP. In addition, PVWMH was correlated to advanced age, hypertension, diabetes mellitus, and lacunar infarction. After adjusting for confounding factors, DSWMH was correlated to advanced age and lacunar infarction. There was no correlation between serum Lp-PLA2 and DSWMH.Conclusions: Serum Lp-PLA2 was closely associated with the pathogenesis of PVWMH rather than DSWMH. There might be different pathological mechanisms between PVWMH and DSWMH.

Periventricular rather than deep white matter hyperintensities mediate effects of hypertension on cognitive performance in the population-based 1000BRAINS study

“…Also, in a cohort of 618 patients with ischemic stroke or transient ischemic attack, hypertension identified in medical records was significantly associated with higher PVH and DWMH in univariable but only with PVH in multivariable analyses adjusted for age and diabetes [7]. Similarly, self-reported hypertension showed a stronger association with PVH than DWMH in 567 patients from a Chinese neurology department examined because of dizziness and headaches [16]. Even in a cohort of 301 Tibetan patients residing at high altitudes with rather heterogeneous neurological diagnoses, patients with hypertension (BP !140/90 mmHg or antihypertensive medications) had significantly higher Fazekas scores than patients without hypertension, however, Fazekas scores were not evaluated separately as PVH and DWMH [36].…”

“…Fazekas score was not evaluated as separate outcome in this study [32]. Previous population-based studies mostly used automated volumetric WMH measurement or customized visual rating scales for the assessment of WMH load [3] instead of Fazekas scoring even though it is discussed that PVH and DWMH, which are quantified separately with Fazekas scoring, might have different pathomechanisms and cognitive consequences [4,16,33,34].…”

“…Fazekas scores are assigned separately for periventricular hyperintensities (PVH) and subcortical (also called deep white matter) hyperintensities (DWMH). There is an ongoing debate whether PVH and DWMH reflect different pathophysiological processes that have different cognitive consequences or just represent different stages of vascular disease, starting in the periventricular and progressing to the subcortical regions [4,16,17]. In the population-based 1000BRAINS study, we analysed the association of BP, its treatment, and BP/treatment category with WMH load using Fazekas score and also assessed the direct and indirect (via WMH) relationships of high BP with cognitive performance in the domains of verbal and nonverbal memory, executive function, language, and attention/speed of processing.…”

Cerebral Small Vessel Disease in Elderly Patients with Sudden Sensorineural Hearing Loss

“… Fazekas scale for MRI imaging. The figure displays hyperintensities in the deep white matter ( upper row ) and periventricular white matter ( lower row ) ( 24 ). …”

HDL-C/LDL-C and Risk of Cerebral White Matter Hyperintensities: A Cross-Sectional Study

“…Detailed parameters of the MRI scans were reported in our previous study. 9,10 Fazekas Scores for Assessment of the Severity of WMHs…”