Location Of Hyperintensities Research Articles

Cerebral amyloid burden is associated with white matter hyperintensity location in specific posterior white matter regions

White matter hyperintensities (WMHs) are a common manifestation of cerebral small vessel disease. WMHs are also frequently observed in patients with familial and sporadic Alzheimer's disease, often with a particular posterior predominance. Whether amyloid and tau pathologies are linked to WMH occurrence is still debated. We examined whether cerebral amyloid and tau burden, reflected in cerebrospinal fluid amyloid-beta 1-42 (Aβ-42) and phosphorylated tau (p-tau), are related to WMH location in a cohort of 517 memory clinic patients. Two lesion mapping techniques were performed: voxel-based analyses and region of interest-based linear regression. Voxelwise associations were found between lower Aβ-42 and parieto-occipital periventricular WMHs. Regression analyses demonstrated that lower Aβ-42 correlated with larger WMH volumes in the splenium of the corpus callosum and posterior thalamic radiation, also after controlling for markers of vascular disease. P-tau was not consistently related to WMH occurrence. Our findings indicate that cerebral amyloid burden is associated with WMHs located in specific posterior white matter regions, possibly reflecting region-specific effects of amyloid pathology on the white matter.

Impact of white matter hyperintensity location on depressive symptoms in memory-clinic patients: a lesion–symptom mapping study

We investigated the association between white matter hyperintensity location and depressive symptoms in a memoryclinic population using lesion–symptom mapping. We included 680 patients with vascular brain injury from the TRACE-VCI cohort (mean age ± standard deviation: 67 ± 8 years; 52% female): 168 patients with subjective cognitive decline, 164 with mild cognitive impairment and 348 with dementia. We assessed depressive symptoms using the Geriatric Depression Scale. We applied assumptionfree voxel-based lesion–symptom mapping, adjusted for age, sex, total white matter hyperintensity volume and multiple testing. Next, we applied exploratory region-of-interest linear regression analyses of major white matter tracts, with additional adjustment for diagnosis. Voxel-based lesion–symptom mapping identified voxel clusters related to the Geriatric Depression Scale in the left corticospinal tract. Region-of-interest analyses showed no relation between white matter hyperintensity volume and the Geriatric Depression Scale, but revealed an interaction with diagnosis in the forceps minor, where larger regional white matter hyperintensity volume was associated with more depressive symptoms in subjective cognitive decline (β = 0.26, p < 0.05), but not in mild cognitive impairment or dementia. We observed a lack of convergence of findings between voxel-based lesion–symptom mapping and region-of-interest analyses, which may have been due to small effect sizes and limited lesion coverage despite the large sample size. This warrants replication of our findings and further investigation in other cohorts. This lesion–symptom mapping study in depressive symptoms indicates the corticospinal tract and forceps minor as strategic tracts in which white matter hyperintensity is associated with depressive symptoms in memory-clinic patients with vascular brain injury. The impact of white matter hyperintensity on depressive symptoms is modest, but it appears to depend on the location of white matter hyperintensity and disease severity.

The Additional Contribution of White Matter Hyperintensity Location to Post-stroke Cognitive Impairment: Insights From a Multiple-Lesion Symptom Mapping Study.

White matter hyperintensities (WMH) are common in acute ischemic stroke patients. Although WMH volume has been reported to influence post-stroke cognition, it is still not clear whether WMH location, independent of acute ischemic lesion (AIL) volume and location, contributes to cognitive impairment after stroke. Here, we proposed a multiple-lesion symptom mapping model that considers both the presence of WMH and AIL to measure the additional contribution of WMH locations to post-stroke cognitive impairment. Seventy-six first-ever stroke patients with AILs in the left hemisphere were examined by Montreal Cognitive Assessment (MoCA) at baseline and 1 year after stroke. The association between the location of AIL and WMH and global cognition was investigated by a multiple-lesion symptom mapping (MLSM) model based on support vector regression (SVR). To explore the relative merits of MLSM over the existing lesion-symptom mapping approaches with only AIL considered (mass-univariate VLSM and SVR-LSM), we measured the contribution of the significant AIL and/or WMH clusters from these models to post-stroke cognitive impairment. In addition, we compared the significant WMH locations identified by the optimal SVR-MLSM model for cognitive impairment at baseline and 1 year post stroke. The identified strategic locations of WMH significantly contributed to the prediction of MoCA at baseline (short-term) and 1 year (long-term) after stroke independent of the strategic locations of AIL. The significant clusters of WMH for short-term and long-term post-stroke cognitive impairment were mainly in the corpus callosum, corona radiata, and posterior thalamic radiation. We noted that in some regions, the AIL clusters that were significant for short-term outcome were no longer significant for long-term outcome, and interestingly more WMH clusters in these regions became significant for long-term outcome compared to short-term outcome. This indicated that there are some regions where local WMH burden has larger impact than AIL burden on the long-term post-stroke cognitive impairment. In consequence, SVR-MLSM was effective in identifying the WMH locations that have additional impact on post-stroke cognition on top of AIL locations. Such a method can also be applied to other lesion-behavior studies where multiple types of lesions may have potential contributions to a specific behavior.

Lower Magnetization Transfer Ratio in the Forceps Minor Is Associated with Poorer Gait Velocity in Older Adults.

Gait disturbances in the elderly are disabling and a major public health issue but are poorly understood. In this multimodal MR imaging study, we used 2 voxel-based analysis methods to assess the voxelwise relationship of magnetization transfer ratio and white matter hyperintensity location with gait velocity in older adults. We assessed 230 community-dwelling participants of the Austrian Stroke Prevention Family Study. Every participant underwent 3T MR imaging, including magnetization transfer imaging. Voxel-based magnetization transfer ratio-symptom mapping correlated the white matter magnetization transfer ratio of each voxel with gait velocity. To assess a possible relationship between white matter hyperintensity location and gait velocity, we applied voxel-based lesion-symptom mapping. We found a significant association between the magnetization transfer ratio within the forceps minor and gait velocity (β = 0.134; 95% CI, 0.011-0.258; P = .033), independent of demographics, general physical performance, vascular risk factors, and brain volume. White matter hyperintensities did not significantly change this association. Our study provides new evidence for the importance of magnetization transfer ratio changes in gait disturbances at an older age, particularly in the forceps minor. The histopathologic basis of these findings is yet to be determined.

Brain hyperintensity location determines outcome in the triad of impaired cognition, physical health and depressive symptoms: A cohort study in late life

Purpose of the studyBrain hyperintensities, detectable with MRI, increase with age. They are associated with a triad of impairment in cognitive ability, depression and physical health. Here we test the hypothesis that the association between hyperintensities and cognitive ability, physical health and depressive symptoms depends on lesion location. Design and methods244 members of the Aberdeen 1936 Birth Cohort were recruited to this study. 227 participants completed brain MRI and their hyperintensities were scored using Scheltens’s scale. 205 had complete imaging, cognitive, physical health and depressive symptom score data. The relationships between hyperintensity location and depressive symptoms, cognitive ability and physical health were examined by correlation and structural equation analysis. ResultsWe found that depressive symptoms correlated with hyperintensity burden in the grey matter (r=0.14, p=0.04) and infratentorial regions (r=0.17, p=0.01). Infratentorial hyperintensities correlated with reduced peak expiratory flow rate (r=−0.26, p<0.001) and impaired gait (r=0.13, p=0.05). No relationship was found between white matter and periventricular (supratentoral) hyperintensities and depressive symptoms. Hyperintensities in the supratentorial and infratentorial regions were associated with reduced cognitive performance. Using structural equation modelling we found that the association between hyperintensities and depressive symptoms was mediated by negative effects on physical health and cognitive ability. ConclusionsHyperintensities in deep brain structures are associated with depressive symptoms, mediated via impaired physical health and cognitive ability. Participants with higher cognitive ability and better physical health are at lower risk of depressive symptoms.

Hyperintense MRI lesions in bipolar disorder: A meta-analysis and review

Background: Cortical and subcortical hyperintensities in magnetic resonance imaging (MRI) scans are thought to represent areas of ischemic damage to brain tissue. Researchers have focused on the possible role these lesions may have in psychiatric disorders, including bipolar disorder. In 1997, the proposed ‘vascular mania’ diagnosis suggested utilizing not only the presence of strokes, but also confluent hyperintensities in its diagnostic criteria. This study was conducted to use meta-analytic techniques to investigate the association of hyperintensities and bipolar illness and to evaluate the current state of the literature.Methods: Using the PubMed and MEDLINE databases, we conducted a systematic literature search of studies investigating hyperintensities in subjects with bipolar disorder and controls or other psychiatric illnesses. We identified 44 publications from which 35 studies were included for review and 27 were selected for meta-analysis. Summary statistics of the prevalence were estimated through odds-ratios and confidence interval. Heterogeneity of the results across studies was tested using Q-statistics.Results: Meta-analysis identified an odds ratio of 2.5 (95% CI 1.9, 3.3) for hyperintensities in bipolar subjects compared to controls; however, there was significant heterogeneity among the studies (Q-statistics = 32; p = 0.04). This finding was most prominent for adolescents and children where the odds ratio was 5.7 (95% CI 2.3, 13.7). Deep white matter hyperintensities (odd ratio 3.2; 95% CI 2.2, 4.5) and subcortical grey matter hyperintensities (odds ratio 2.7; 95% CI 1.3, 2.9) were more strongly associated with bipolar subjects. There were no differences between bipolar subjects and controls for perivascular hyperintensities (odds ratio 1.3; 95% CI 0.8, 1.9). Though hyperintensities were numerically greater in bipolar subjects, meta-analysis did not demonstrate any significant differences between bipolar subjects and unipolar depression subjects (OR 1.6; 95% CI 0.9, 2.7) nor subjects with schizophrenia (OR 1.5; 95% CI 0.9, 2.7).Conclusions: This meta-analysis continues to support the association of bipolar disorder and hyperintensities, especially in the deep white matter and subcortical grey matter. It also highlights the increased incidence in children and adolescence with bipolar disorder. However, hyperintensities are not specific to bipolar disorder, but appear at similar rates in unipolar depression and schizophrenia. Thus, the role of hyperintensities in the pathogenesis, pathophysiology, and treatment of bipolar disorder remains unclear. Further studies are required that are large enough to decrease the heterogeneity of the samples and MRI techniques, assess size and location of hyperintensities, and the impact on treatment response. Coordination with newer imaging techniques, such as diffusion tensor imaging (DTI) may be especially helpful in understanding the pathology of these lesions.

Neuropsychological significance of areas of high signal intensity on brain MRIs of children with neurofibromatosis.

Of children with neurofibromatosis (NF), 40% have a cognitive or learning impairment. Approximately 60% also have anomalous areas of high signal intensity on T2-weighted brain MRIs. The association of these hyperintensities and neuropsychological status is not fully understood. We administered a battery of neuropsychological tests and a standard clinical MRI to determine the impact of hyperintensity presence, number, and location on cognitive status in 84 children (8 to 16 years) with NF type 1. These children underwent standard clinical MRI using a GE 1.5-tesla scanner (except one child who was examined with a 1.0-tesla scanner). We conducted three types of analyses: Hyperintensity presence or absence.-Scores of children with (55%) and without hyperintensities (45%) were compared using t tests. No statistically significant differences between groups in intellectual functioning or any neuropsychological variable were found. Number of hyperintensities-The number of hyperintensity locations per child ranged from one to five (mean = 2.22). Pearson correlations revealed no significant association between the number of hyperintensities and neuropsychological performance. Location of hyperintensities-In four of the five locations studied, no statistically significant differences were found between scores of children with a hyperintensity in an area and those with one elsewhere. However, mean scores for IQ, Memory, Motor, Distractibility, and Attention domains for children with hyperintensities in the thalamus were significantly lower than scores for those with hyperintensities elsewhere. These results suggest that the simple presence or absence of hyperintensities, or their total number, is not as important as their anatomic location for detecting their relationship with neuropsychological status. Taking location into account, hyperintensities in the cerebral hemispheres, basal ganglia, brainstem, or cerebellum seem to have no impact on neuropsychological functioning, whereas hyperintensities in the thalamus do.

Basal ganglia volumes and white matter hyperintensities in patients with bipolar disorder.

Accumulating evidence suggests an association between abnormalities of the basal ganglia and affective disorders. The authors hypothesized that patients with bipolar disorder would demonstrate smaller basal ganglia volumes and a greater number of hyperintensities on magnetic resonance imaging than comparison subjects who were matched on age, race, sex, and education. Volumes of the caudate, putamen, and globus pallidus were measured in 30 patients with bipolar disorder and 30 matched normal comparison subjects. The presence, number, and location of hyperintensities were also assessed. Male patients with bipolar disorder demonstrated larger caudate volumes than male comparison subjects. Older, but not younger, patients with bipolar disorder demonstrated more hyperintensities than comparison subjects, primarily in frontal lobe white matter. These results are not consistent with those of previous studies showing reduced basal ganglia volume in subjects with affective disorders, but they are consistent with previous findings of increased white matter hyperintensities, especially in older patients with bipolar disorder. Considered together with results from other studies, the findings suggest that the nature of basal ganglia/subcortical white matter involvement may differ according to the type of depression (unipolar versus bipolar) and the age and sex of the patient.