J Stroke.  2024 May;26(2):131-163. 10.5853/jos.2023.02719.

Leukoaraiosis: Epidemiology, Imaging, Risk Factors, and Management of Age-Related Cerebral White Matter Hyperintensities

• Huang WQ
• Lin Q
• Tzeng CM

• KMID: 2556038
• DOI: http://doi.org/10.5853/jos.2023.02719

Abstract

Leukoaraiosis (LA) manifests as cerebral white matter hyperintensities on T2-weighted magnetic resonance imaging scans and corresponds to white matter lesions or abnormalities in brain tissue. Clinically, it is generally detected in the early 40s and is highly prevalent globally in individuals aged >60 years. From the imaging perspective, LA can present as several heterogeneous forms, including punctate and patchy lesions in deep or subcortical white matter; lesions with periventricular caps, a pencil-thin lining, and smooth halo; as well as irregular lesions, which are not always benign. Given its potential of having deleterious effects on normal brain function and the resulting increase in public health burden, considerable effort has been focused on investigating the associations between various risk factors and LA risk, and developing its associated clinical interventions. However, study results have been inconsistent, most likely due to potential differences in study designs, neuroimaging methods, and sample sizes as well as the inherent neuroimaging heterogeneity and multi-factorial nature of LA. In this article, we provided an overview of LA and summarized the current knowledge regarding its epidemiology, neuroimaging classification, pathological characteristics, risk factors, and potential intervention strategies.

Keyword

Leukoaraiosis; White matter hyperintensities; White matter lesions; Imaging; Risk factors; Genetic variants

Figure

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  Figure 1. Global leukoaraiosis epidemiology.

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  Figure 2. LA definition and heterogeneous forms on FLAIR-MRI. WMH, white matter hyperintensity; LA, leukoaraiosis; FLAIR-MRI, fluid-attenuated inversionrecovery magnetic resonance imaging.

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  Figure 3. Potential risk factors for leukoaraiosis. BP, blood pressure; tHcy, total plasma homocysteine.

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  Figure 4. LA susceptibility genes. (A) Risk genes of LA revealed by the previous genetic studies. (B) Venn diagram of risk genes identified by the 7 previous GWAS studies on LA. (C) Venn diagram of risk genes identified by the 18 CGAS, 7 GWAS, and 2 WES studies of LA. (D) Venn diagram of LA subtype-associated risk genes revealed by a genome-wide association meta-analysis of PVWMH, and DWMH. (E) Shared risk genes between PVWMH and DWMH, and its specific susceptibility genes. (F) Venn diagram of dysregulated genes identified by 4 previous gene expression studies of LA [292-295]. (G) Venn diagram of dysregulated and variant genes identified in the blood or lesional tissue of PVWMH, DWMH, and WMH patients, respectively. CGAS, candidate gene association study; GWAS, genome-wide association study; WES, whole-exome sequencing study; DWMHs, deep/subcortical white matter hyperintensity; PVWMH, periventricular white matter hyperintensity; WMH, white matter hyperintensity; LA, leukoaraiosis.

Reference

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