White Matter Hyperintensities Fazekas Score Research Articles

Temporal Ordering of Biomarkers in Dutch-Type Hereditary Cerebral Amyloid Angiopathy.

The temporal ordering of biomarkers for cerebral amyloid angiopathy (CAA) is important for their use in trials and for the understanding of the pathological cascade of CAA. We investigated the presence and abnormality of the most common biomarkers in the largest (pre)symptomatic Dutch-type hereditary CAA (D-CAA) cohort to date. We included cross-sectional data from participants with (pre)symptomatic D-CAA and controls without CAA. We investigated CAA-related cerebral small vessel disease markers on 3T-MRI, cerebrovascular reactivity with functional 7T-MRI (fMRI) and amyloid-β40 and amyloid-β42 levels in cerebrospinal fluid. We calculated frequencies and plotted biomarker abnormality according to age to form scatterplots. We included 68 participants with D-CAA (59% presymptomatic, mean age, 50 [range, 26-75] years; 53% women), 53 controls (mean age, 51 years; 42% women) for cerebrospinal fluid analysis and 36 controls (mean age, 53 years; 100% women) for fMRI analysis. Decreased cerebrospinal fluid amyloid-β40 and amyloid-β42 levels were the earliest biomarkers present: all D-CAA participants had lower levels of amyloid-β40 and amyloid-β42 compared with controls (youngest participant 30 years). Markers of nonhemorrhagic injury (>20 enlarged perivascular spaces in the centrum semiovale and white matter hyperintensities Fazekas score, ≥2, present in 83% [n=54]) and markers of impaired cerebrovascular reactivity (abnormal BOLD amplitude, time to peak and time to baseline, present in 56% [n=38]) were present from the age of 30 years. Finally, markers of hemorrhagic injury were present in 64% (n=41) and only appeared after the age of 41 years (first microbleeds and macrobleeds followed by cortical superficial siderosis). Our results suggest that amyloid biomarkers in cerebrospinal fluid are the first to become abnormal in CAA, followed by MRI biomarkers for cerebrovascular reactivity and nonhemorrhagic injury and lastly hemorrhagic injury. This temporal ordering probably reflects the pathological stages of CAA and should be taken into account when future therapeutic trials targeting specific stages are designed.

White matter hyperintensities combined with serum NLRP3 in diagnosis of cognitive impairment in patients with cerebral small vessel disease

Background: White matter hyperintensities (WMH) are widely used for the diagnosis of cerebral small vessel disease (CSVD). However, whether NLRP3 is correlated with cognitive impairment after CSVD is still not clear. Objective: This study aimed to investigate the diagnostic value of WMHs combined with NLRP3 for cognitive impairment after CSVD. Methods: This prospective observational study enrolled a total of 188 CSVD patients from September 2019 to May 2022. All patients received brain MRI assessment and WMH Fazekas score, as well as WMH volume, was recorded. Serum NLRP3 level was measured by ELISA. Patients’ cognitive function was measured by MoCA after 6 months of diagnosis of CSVD. The serum levels of C reactive protein (CRP), interleukin (IL)-6, total cholesterol (TC), triglyceride (TG), high-density leptin cholesterol (HDL) and low-density leptin cholesterol (LDL) were recorded Results: CSVD patients with cognitive impairment had significantly higher Fazekas scores, WMH volumes, serum NLRP3 and IL-6 levels compared to patients without cognitive impairment. A positive correlation was found among Fazekas scores, WMH volumes and NLRP3 levels. The combination of WMH volume and NLRP3 could achieve a better specificity for the diagnosis of cognitive impairment. Coronary syndrome history, WMH volume and NLRP3 were found as independent risk factors for cognitive impairment after CSVD. Conclusion: Fazekas scores, WMH volume and serum NLRP3 levels are associated with cognitive impairment after CSVD and have the potential to be used as diagnostic biomarkers.

Cerebral Perfusion and the Burden of Small Vessel Disease in Patients Referred to a Memory Clinic

Background: Cerebral small vessel disease (SVD) lesions on MRI are common in patients with cognitive impairment. It has been suggested that cerebral hypoperfusion is involved in the etiology of these lesions. Objective: The aim of the study was to determine the relationship between cerebral blood flow (CBF) and SVD burden in patients referred to a memory clinic with SVD on MRI. Method: We included 132 memory clinic patients (mean age 73 ± 10, 56% male) with SVD on MRI. We excluded patients with large non-lacunar cortical infarcts. Global CBF (mL/min per 100 mL of brain tissue) was derived from 2-dimensional phase-contrast MRI focused on the internal carotid arteries and the basilar artery. SVD burden was defined as the sum of (each 1 point): white matter hyperintensities (WMHs) Fazekas 1 or more, lacunes, microbleeds (MBs), or enlarged perivascular spaces (PVS) presence, and each SVD feature separately. Linear regression analyses were performed to study the association between CBF and SVD burden, age- and sex-adjusted. Results: Median SVD burden score was 2, 36.4% of patients had MBs, 35.6% lacunar infarcts, 48.4% intermediate to severe enlarged PVS, and 57.6% a WMH Fazekas score 2 or more. Median WMH volume was 21.4 mL (25% quartile: 9.6 mL, 75% quartile: 32.5 mL). Mean CBF ± SD was 44.0 ± 11.9 mL/min per 100 mL brain. There was no relation between CBF and overall SVD burden (CBF difference per burden score point [95% CI]: −0.5 [−2.4; 1.4] mL/min/100 mL brain, p = 0.9). CBF did also not differ according to presence or absence or an high burden of any of the individual SVD features. Moreover, there was no significant relation between WMH volume and CBF (CBF difference per ml increase in WMH [95% CI] −0.6 [−1.5; 0.3] mL/min/100 mL brain p = 0.2). Conclusion: Global CBF was not related to overall SVD burden or with individual SVD features in this memory clinic cohort, indicating that in this setting these lesions were not primarily due to cerebral hypoperfusion.