Dataset Information

Differential Influence of Location-Specific White-Matter Hyperintensities on Attention Subdomains Measured Using the Attention Network Test.

ABSTRACT: BACKGROUND Elderly people with white-matter hyperintensities (WMHs) typically show cognitive impairment. Attention, consisting of 3 independent component processes (alerting, orienting, and executive control), is crucial for cognitive functioning. Little is known about how WMHs interfere with these attention subdomains. In the present study, we sought to describe characteristics of attention deficits in patients with age-related WMHs and to assess whether the severity and location of lesions differentially affect specific attention subdomains using the attention network test (ANT), which is a computer-based paradigm tailored to accurately provide behavioral measures of the aforementioned subdomains. MATERIAL AND METHODS A total of 39 WMH patients and 39 age-, sex-, and education-matched controls underwent comprehensive neuropsychological and ANT evaluation. Brain magnetic resonance imaging (MRI) was performed to visualize severity of total and location-specific WMH lesions. Multiple linear regression analyses adjusted for possible confounders were performed. RESULTS Compared with controls, WMH patients showed pronounced deficits in orienting and executive control efficiencies (P<0.050), but not alerting efficiency (P=0.642). As total WMH severity increased, efficiencies in the impaired subdomains significantly declined (P<0.050). In terms of lesion location, fronto-parietal type of periventricular WMH (PWMH) and deep WMH (DWMH) in the parietal lobe affected orienting efficiency, while all PWMH types and DWMH in the frontal, parietal, and temporal lobes affected executive control efficiency (P<0.050). Additional adjustment for other MRI lesions significantly changed the impact on orienting, but not on executive control efficiency. CONCLUSIONS Our results reveal specific attention deficits in patients with age-related WMH and may help clarify how the location of lesions influences their effects on attention subdomains.

SUBMITTER: Wang B

PROVIDER: S-EPMC6983326 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Differential Influence of Location-Specific White-Matter Hyperintensities on Attention Subdomains Measured Using the Attention Network Test.

Wang Bing B Zhang Jun J Pan Wen W Cao Shanshan S Li Bin B Bai Lu L Hu Panpan P Tian Yanghua Y Jiang Dan D Wang Kai K

Medical science monitor : international medical journal of experimental and clinical research 20200115

BACKGROUND Elderly people with white-matter hyperintensities (WMHs) typically show cognitive impairment. Attention, consisting of 3 independent component processes (alerting, orienting, and executive control), is crucial for cognitive functioning. Little is known about how WMHs interfere with these attention subdomains. In the present study, we sought to describe characteristics of attention deficits in patients with age-related WMHs and to assess whether the severity and location of lesions dif ...[more]

PMID: 31940305

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Project description:White matter hyperintensities of presumed vascular origin are frequently observed on magnetic resonance imaging in normal aging. They are typically found in cerebral small vessel disease and suspected culprits in the etiology of complex age- and small vessel disease-related conditions, such as late-onset depression. White matter hyperintensities may interfere with surrounding white matter metabolic demands by disrupting fiber tract integrity. Meanwhile, risk factors for small vessel disease are thought to reduce tissue oxygenation, not only by reducing regional blood supply, but also by impairing capillary function. To address white matter oxygen supply-demand balance, we estimated voxel-wise capillary density as an index of resting white matter metabolism, and combined estimates of blood supply and capillary function to calculate white matter oxygen availability. We conducted a cross-sectional study with structural, perfusion- and diffusion-weighted magnetic resonance imaging in 21 patients with late-onset depression and 21 controls. We outlined white matter hyperintensities and used tractography to identify the tracts they intersect. Perfusion data comprised cerebral blood flow, blood volume, mean transit time and relative transit time heterogeneity-the latter a marker of capillary dysfunction. Based on these, white matter oxygenation was calculated as the steady state cerebral metabolic rate of oxygen under the assumption of normal tissue oxygen tension and vice versa. The number, volume and perfusion characteristics of white matter hyperintensities did not differ significantly between groups. Hemodynamic data showed white matter hyperintensities to have lower blood flow and blood volume, but higher relative transit time heterogeneity, than normal-appearing white matter, resulting in either reduced capillary metabolic rate of oxygen or oxygen tension. Intersected tracts showed significantly lower blood flow, blood volume and capillary metabolic rate of oxygen than normal-appearing white matter. Across groups, lower lesion oxygen tension was associated with higher lesion number and volume. Compared with normal-appearing white matter, tissue oxygenation is significantly reduced in white matter hyperintensities as well as the fiber tracts they intersect, independent of parallel late-onset depression. In white matter hyperintensities, reduced microvascular blood volume and concomitant capillary dysfunction indicate a severe oxygen supply-demand imbalance with hypoxic tissue injury. In intersected fiber tracts, parallel reductions in oxygenation and microvascular blood volume are consistent with adaptations to reduced metabolic demands. We speculate, that aging and vascular risk factors impair white matter hyperintensity perfusion and capillary function to create hypoxic tissue injury, which in turn affect the function and metabolic demands of the white matter tracts they disrupt.

Project description:Objective: In CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), white matter hyperintensities (WMH) are considered to result from hypoperfusion. We hypothesized that in fact the burden of WMH results from the combination of several regional populations of WMH with different mechanisms and clinical consequences. Methods: To identify regional WMH populations, we used a 4-step approach. First, we used an unsupervised principal component algorithm to determine, without a priori knowledge, the main sources of variation of the global spatial pattern of WMH. Thereafter, to determine whether these sources are likely to include relevant information regarding regional populations of WMH, we tested their relationships with: (1) MRI markers of the disease; (2) the clinical severity assessed by the Mattis Dementia Rating scale (MDRS) (cognitive outcome) and the modified Rankin's score (disability outcome). Finally, through careful interpretation of all the results, we tried to identify different regional populations of WMH. Results: The unsupervised principal component algorithm identified 3 main sources of variation of the global spatial pattern of WMH, which showed significant and sometime inverse relationships with MRI markers and clinical scores. The models predicting clinical severity based on these sources outperformed those evaluating WMH by their volume (MDRS, coefficient of determination of 39.0 vs. 35.3%, p = 0.01; modified Rankin's score, 43.7 vs. 38.1%, p = 0.001). By carefully interpreting the visual aspect of these sources as well as their relationships with MRI markers and clinical severity, we found strong arguments supporting the existence of different regional populations of WMH. For instance, in multivariate analyses, larger extents of WMH in anterior temporal poles and superior frontal gyri were associated with better outcomes, while larger extents of WMH in pyramidal tracts were associated with worse outcomes, which could not be explained if WMH in these different areas shared the same mechanisms. Conclusion: The results of the present study support the hypothesis that the whole extent of WMH results from a combination of different regional populations of WMH, some of which are associated, for yet undetermined reasons, with milder forms of the disease.

Dataset Information

Differential Influence of Location-Specific White-Matter Hyperintensities on Attention Subdomains Measured Using the Attention Network Test.

Publications

Differential Influence of Location-Specific White-Matter Hyperintensities on Attention Subdomains Measured Using the Attention Network Test.

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