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Severity of white matter hyperintensities: Lesion patterns, cognition, and microstructural changes.

ABSTRACT: White matter hyperintensity (WMH) is a common finding in aging population and considered to be a contributor to cognitive decline. Our study aimed to characterize the spatial patterns of WMH in different severities and explore its impact on cognition and brain microstructure in non-demented elderly. Lesions were both qualitatively (Fazekas scale) and quantitatively assessed among 321 community-dwelled individuals with MRI scanning. Voxel- and atlas-based analyses of the whole-brain white matter microstructure were performed. The WMH of the same severities was found to occur uniformly with a specific pattern of lesions. The severity of WMH had a significant negative association with the performance of working and episodic memory, beginning to appear in Fazekas 3 and 4. The white matter tracts presented significant impairments in Fazekas 3, which showed brain-wide changes above Fazekas 4. Lower FA in the superior cerebellar peduncle and left posterior thalamic radiation was mainly associated with episodic memory, and the middle cerebellar peduncle was significantly associated with working memory. These results support that memory is the primary domain to be affected by WMH, and the effect may potentially be influenced by tract-specific WM abnormalities. Fazekas scale 3 might be the critical stage predicting a future decline in cognition.

SUBMITTER: Zeng W

PROVIDER: S-EPMC7820685 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Severity of white matter hyperintensities: Lesion patterns, cognition, and microstructural changes.

Zeng Weiyi W Chen Yaojing Y Zhu Zhibao Z Gao Shudan S Xia Jianan J Chen Xiaochun X Jia Jianjun J Zhang Zhanjun Z

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20191222 12

White matter hyperintensity (WMH) is a common finding in aging population and considered to be a contributor to cognitive decline. Our study aimed to characterize the spatial patterns of WMH in different severities and explore its impact on cognition and brain microstructure in non-demented elderly. Lesions were both qualitatively (Fazekas scale) and quantitatively assessed among 321 community-dwelled individuals with MRI scanning. Voxel- and atlas-based analyses of the whole-brain white matter ...[more]

PMID: 31865841

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Project description:White matter microstructure undergoes progressive changes during the lifespan, but the neurobiological underpinnings related to ageing and disease remains unclear. We used an advanced diffusion MRI, Neurite Orientation Dispersion and Density Imaging, to investigate the microstructural alterations due to demographics, common age-related pathological processes (amyloid, tau and white matter hyperintensities) and cognition. We also compared Neurite Orientation Dispersion and Density Imaging findings to the older Diffusion Tensor Imaging model-based findings. Three hundred and twenty-eight participants (264 cognitively unimpaired, 57 mild cognitive impairment and 7 dementia with a mean age of 68.3 ± 13.1 years) from the Mayo Clinic Study of Aging with multi-shell diffusion imaging, fluid attenuated inversion recovery MRI as well as amyloid and tau PET scans were included in this study. White matter tract level diffusion measures were calculated from Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging. Pearson correlation and multiple linear regression analyses were performed with diffusion measures as the outcome and age, sex, education/occupation, white matter hyperintensities, amyloid and tau as predictors. Analyses were also performed with each diffusion MRI measure as a predictor of cognitive outcomes. Age and white matter hyperintensities were the strongest predictors of all white matter diffusion measures with low associations with amyloid and tau. However, neurite density decrease from Neurite Orientation Dispersion and Density Imaging was observed with amyloidosis specifically in the temporal lobes. White matter integrity (mean diffusivity and free water) in the corpus callosum showed the greatest associations with cognitive measures. All diffusion measures provided information about white matter ageing and white matter changes due to age-related pathological processes and were associated with cognition. Neurite orientation dispersion and density imaging and diffusion tensor imaging are two different diffusion models that provide distinct information about variation in white matter microstructural integrity. Neurite Orientation Dispersion and Density Imaging provides additional information about synaptic density, organization and free water content which may aid in providing mechanistic insights into disease progression.

Project description:Background and Purpose: White matter hyperintensities (WMH) are commonly seen on structural MRI of older adults and are a manifestation of underlying and adjacent tissue damage. WMH may contribute to cortical disconnection and cognitive dysfunction, but it is unclear how WMH affect intersecting or nearby white matter tract integrity. This study investigated the effects of WMH on tract microstructure by determining the spatial distribution of water diffusion characteristics in white matter tract areas adjacent to both intersecting and nearby WMH. Methods: We used diffusion and structural MRI data from 52 representative participants from the Lothian Birth Cohort 1936 (72.2 ± 0.7 years) including a range of WMH burden. We segmented WMH, reconstructed 18 main white mater tracts using automated quantitative tractography and identified intersections between tracts and WMH. We measured mean diffusivity (MD) and fractional anisotropy (FA) in tract tissue at 2 mm incremental distances from tract-intersecting and non-intersecting (nearby) WMH. Results: We observed a spatial gradient of FA and MD abnormalities for most white matter tracts which diminished with a similar distance pattern for tract-intersecting and nearby WMH. Overall, FA was higher, while MD was lower around nearby WMH compared with tract-intersecting WMH. However, for some tracts, FA was lower in areas immediately surrounding nearby WMH, although with faster normalization than in FA values surrounding tract-intersecting WMH. Conclusion: WMH have similar effects on tract infrastructure, whether they be intersecting or nearby. However, the observed differences in tract water diffusion properties around WMH suggest that degenerative processes in small vessel disease may propagate further along the tract for intersecting WMH, while in some areas of the brain there is a larger and more localized accumulation of axonal damage in tract tissue nearby a non-connected WMH. Longitudinal studies should address differential effects of intersecting vs. nearby WMH progression and how they contribute to cognitive aging.

Project description:ObjectivesWhite matter hyperintensities (WMH) are highly prevalent in older adults and considered to be a contributor to cognition impairment. However, the strategic WMH lesion distribution related to cognitive impairment is still debated. The aim of this study was to characterize the spatial patterns of WMH associated with cognitive impairment and explore its risk factors.MethodsWe retrospectively analyzed patients who underwent T2 fluid attenuated inversion recovery (FLAIR) and mini-mental state examination (MMSE) in two centers. WHM was classified into four patterns based on T2 FLAIR as follows: (1) multiple subcortical spots (multi-spots); (2) peri-basal ganglia (peri-BG); (3) anterior subcortical patches (anterior SC patches); and (4) posterior subcortical patches (posterior SC patches). We cross-sectionally and longitudinally estimated associations between different WMH patterns and all-cause dementia and cognitive decline. Multivariable logistic regression analysis was followed to identify risk factors of WMH patterns related to cognitive impairment.ResultsA total of 442 patients with WMH were enrolled, with average age of 71.6 ± 11.3 years, and MMSE score of 24.1 ± 5.4. Among them, 281 (63.6%), 66 (14.9%), 163 (36.9%) and 197 (44.6%) patients presented multi-spots, peri-BG, anterior SC patches and posterior SC patches, respectively. Patients with anterior SC patches were more likely to have all-cause dementia in cross-sectional study (OR 2.002; 95% CI 1.098-3.649; p = 0.024), and have cognitive decline in longitudinal analysis (OR 3.029; 95% CI 1.270-7.223; p = 0.012). Four patterns of WMH referred to different cognitive domains, and anterior SC patches had the most significant and extensive impact on cognition after Bonferroni multiple comparison correction (all p < 0.0125). In addition, older age (OR 1.054; 95% CI 1.027-1.082; p < 0.001), hypertension (OR 1.956; 95% CI 1.145-3.341; p = 0.014), higher percentage of neutrophils (OR 1.046; 95% CI 1.014-1.080; p = 0.005) and lower concentration of hemoglobin (OR 0.983; 95% CI 0.967-1.000; p = 0.044) were risk factors for the presence of anterior SC patches.ConclusionsDifferent patterns of subcortical leukoaraiosis visually identified on MRI might have different impacts on cognitive impairment. Further studies should be undertaken to validate this simple visual classification of WMH in different population.

Project description:BackgroundWhite matter hyperintensities are an important marker of cerebral small vessel disease. This disease burden is commonly described as hyperintense areas in the cerebral white matter, as seen on T2-weighted fluid attenuated inversion recovery magnetic resonance imaging data. Studies have demonstrated associations with various cognitive impairments, neurological diseases, and neuropathologies, as well as clinical and risk factors, such as age, sex, and hypertension. Due to their heterogeneous appearance in location and size, studies have started to investigate spatial distributions and patterns, beyond summarizing this cerebrovascular disease burden in a single metric-its volume. Here, we review the evidence of association of white matter hyperintensity spatial patterns with its risk factors and clinical diagnoses.Design/methodsWe performed a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. We used the standards for reporting vascular changes on neuroimaging criteria to construct a search string for literature search on PubMed. Studies written in English from the earliest records available until January 31st, 2023, were eligible for inclusion if they reported on spatial patterns of white matter hyperintensities of presumed vascular origin.ResultsA total of 380 studies were identified by the initial literature search, of which 41 studies satisfied the inclusion criteria. These studies included cohorts based on mild cognitive impairment (15/41), Alzheimer's disease (14/41), Dementia (5/41), Parkinson's disease (3/41), and subjective cognitive decline (2/41). Additionally, 6 of 41 studies investigated cognitively normal, older cohorts, two of which were population-based, or other clinical findings such as acute ischemic stroke or reduced cardiac output. Cohorts ranged from 32 to 882 patients/participants [median cohort size 191.5 and 51.6% female (range: 17.9-81.3%)]. The studies included in this review have identified spatial heterogeneity of WMHs with various impairments, diseases, and pathologies as well as with sex and (cerebro)vascular risk factors.ConclusionThe results show that studying white matter hyperintensities on a more granular level might give a deeper understanding of the underlying neuropathology and their effects. This motivates further studies examining the spatial patterns of white matter hyperintensities.

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Severity of white matter hyperintensities: Lesion patterns, cognition, and microstructural changes.

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Severity of white matter hyperintensities: Lesion patterns, cognition, and microstructural changes.

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