Prospective study of major depressive disorder with white matter hyperintensity

Objective To investigate clinical characteristics, outcome, and risk factor for cerebrovascular disease in patients who had major depressive disorder and white matter hyperintensity (WMHI). Method A total of 123 new patients diagnosed with major depressive disorder by semi-structured interview underwent magnetic resonance imaging (MRI) and were placed into one of three groups based on results. Patients with no abnormal findings (NF), patients with WMHI and no lacunar infarction (WMHI), and patients with lacunar infarction (LI). Results In the WMHI group, age at initial onset of depression and age at time of interview were both higher than in the NF group, as was severity of depression. Hamilton Rating Scale for Depression (HRSD) scores were significantly higher in the WMHI group than in the NF group. Total WMHI was significantly correlated only with age at initial onset of depression and age at time of interview. In the WMHI group, age at interview was lower than in the LI group and systolic and diastolic blood pressures were lower. Survival analysis regarding the clinical outcome of remission was conducted, but no significant differences were discovered among the three groups, WMHI, LI, and NF. However, the suicide rate was significantly higher in the LI group than in the other two groups. Conclusions The origin and clinical characteristics of depression accompanied by WMHI may be specific; additional stringent study in comparison with individuals with LI is needed.     

Visual evoked potentials in cerebral white matter hyperintensity on MRI

OBJECTIVES: To investigate the correlation of the cerebral white matter hyperintensities (WMH) on MRI, and latency and amplitude of visual evoked potentials (VEPs) in elderly subjects. PATIENTS AND METHODS: Pattern VEP (PVEP) and flash VEP (FVEP) were recorded in 25 patients with WMH consisting of 12 patients with frontal dominant WMH (FMH) and 13 patients with occipital dominant WMH (OMH) and 25 patients with basal ganglionic hyperintensities (BGH). RESULTS: In WMHs, there were significantly larger P100 and P2 amplitudes than in BGHs and controls. Regarding the distribution of WMH, OMH showed significantly larger P100 amplitudes than FMH. In OMH in males, there was significantly prolonged P100 latency compared with females, and in females, there were significantly larger P100 and P2 amplitudes compared with males. CONCLUSION: Appropriate clinical values in VEP should take into consideration WMH in addition to gender and age-related changes.     

Deep Bayesian networks for uncertainty estimation and adversarial resistance of white matter hyperintensity segmentation

White matter hyperintensities (WMHs) are frequently observed on structural neuroimaging of elderly populations and are associated with cognitive decline and increased risk of dementia. Many existing WMH segmentation algorithms produce suboptimal results in populations with vascular lesions or brain atrophy, or require parameter tuning and are computationally expensive. Additionally, most algorithms do not generate a confidence estimate of segmentation quality, limiting their interpretation. MRI‐based segmentation methods are often sensitive to acquisition protocols, scanners, noise‐level, and image contrast, failing to generalize to other populations and out‐of‐distribution datasets. Given these concerns, we propose a novel Bayesian 3D convolutional neural network with a U‐Net architecture that automatically segments WMH, provides uncertainty estimates of the segmentation output for quality control, and is robust to changes in acquisition protocols. We also provide a second model to differentiate deep and periventricular WMH. Four hundred thirty‐two subjects were recruited to train the CNNs from four multisite imaging studies. A separate test set of 158 subjects was used for evaluation, including an unseen multisite study. We compared our model to two established state‐of‐the‐art techniques (BIANCA and DeepMedic), highlighting its accuracy and efficiency. Our Bayesian 3D U‐Net achieved the highest Dice similarity coefficient of 0.89 ± 0.08 and the lowest modified Hausdorff distance of 2.98 ± 4.40 mm. We further validated our models highlighting their robustness on “clinical adversarial cases” simulating data with low signal‐to‐noise ratio, low resolution, and different contrast (stemming from MRI sequences with different parameters). Our pipeline and models are available at: https://hypermapp3r.readthedocs.io.     

White matter hyperintensities in the forties: their prevalence and topography in an epidemiological sample aged 44-48

White matter hyperintensities (WMHs) are a frequent finding on T2-weighted MRI of the brain in elderly individuals, but their prevalence and severity in younger asymptomatic populations is less well studied. We report the topography of WMHs on T2-weighted fluid inversion recovery (FLAIR) MRI in 428 individuals aged 44-48 years recruited randomly from a healthy community sample. WMHs were delineated from FLAIR and T1-weighted scans by using a computer algorithm, further verified and then classified using k-nearest neighbor (kNN) algorithm into deep WMH (DWMH), and periventricular WMH (PVWMH), which included extended periventricular "rims" and frontal and occipital "caps". Small caps and pencil-thin rims were not taken as WMHs for this analysis. The new computer algorithm was validated and compared with the scores of visual rating, and the correspondence between the two methods was high. We found that 218 (50.9%) subjects had WMHs. 146 of the 218 (34.1% of whole sample population of 428) subjects had deep white matter hyperintensities (DWMHs). The average number of WMH clusters (occurrences) per brain was 1.37 (0.94 for DWMH and 0.43 for pathological PVWMH) and the mean WMH tissue volume was 0.278 ml. There was no significant sex difference in the severity and distribution of WMHs. The study suggests that small punctate or focal WMHs are common in the brains of individuals in their 40s, and may represent an early stage of development of these lesions.     

White matter lesions - age-adjusted values for cognitively healthy and demented subjects

OBJECTIVES: To develop age-adjusted norms for white matter lesions (WML) and to differentiate dementia from mild cognitive impairment and normal aging. MATERIALS AND METHODS: 240 patients underwent a comprehensive clinical, neuropsychological and MRI examination. A scale was developed quantify WML in anatomically defined regions by rating size and frequency. FLAIR sequences were used to determine a global and a frontal score. The scores were correlated with the psychometric test results and the final clinical diagnosis: cognitively normal (CN), mild cognitive impairment (MCI), Alzheimer's Disease (AD), vascular dementia (VD). Age-adjusted curves for WML scores were calculated by means of a non-parametic smoothing method. RESULTS: WML scores of the whole cerebrum and the frontal lobe were significantly increased in vascular dementia as compared to CN, MCI and AD. Individual WML scores correlated significantly with age and neuropsychological test results. For the age range 55-72, the WML scores of VD were significantly different from those of CN, MCI and AD. CONCLUSIONS: Age-corrected WML load was significantly higher in vascular dementia as compared to MCI, AD and cognitively normals over a wide age range.     

White matter hyperintensities in subjects with bipolar disorder

There have been divergent reports on the prevalence and severity of white matter hyperintensities (WMH) on brain magnetic resonance (MR) images in subjects with bipolar disorder. In the present study, evaluations were made on the prevalence and severity of WMH in subjects with bipolar disorder using contiguous 3-mm thick MR slices as well as fluid attenuated inversion recovery (FLAIR) images. A detailed WMH rating system was employed to assess these WMH. A total of 43 bipolar patients, as diagnosed by the Structured Clinical Interview from the Diagnostic and Statistical Manual-IV (SCID-IV), and 39 healthy comparison subjects were scanned using a 1.5-T whole body GE magnetic resonance scanner. WMH were assessed with a modified composite version of the Fazekas' and Coffey's rating scales to detect less severe WMH. Periventricular and subcortical WMH were coded separately. Subjects with bipolar disorder had greater prevalence of WMH abnormalities than comparison subjects (Bipolar, grade 1 = 11.6%, grade 2 = 9.3%, grade 3 = 7.0%; Comparison, grade 1 = 5.1%, grade 2 = 2.6%, grade 3 = 0%). This difference is mainly due to the differences in deep WMH (Bipolar, grade 1 = 14.0%, grade 2 = 14.0%; Comparison, grade 1 = 7.7%, grade 2 = 0%). The current study confirms the higher prevalence of WMH in subjects with bipolar disorder. Differences of small-sized WMH abnormalities between groups were successfully detected using a large number of bipolar subjects and thinner sliced MR images with FLAIR.     

Sex disparity of cerebral white matter hyperintensity in the hypertensive elderly: The Shanghai Changfeng study

White matter hyperintensity (WMH) is associated with vascular hemodynamic alterations and reflects white matter injury. To date, the sex difference of tract‐specific WMH and the relationship between high blood pressure (BP) and tract‐specific WMH remain unclear. We recruited 515 subjects from the Shanghai Changfeng study (range 53–89 years, mean age 67.33 years). Systolic and diastolic blood pressure (SBP and DBP) were collected and used to calculate pulse pressure (PP). Magnetic resonance T1 and T2 FLAIR images were acquired to measure WMH and calculate WMH index. The ANCOVA test was performed to test the difference between sexes, and the linear regression model was used to examine the associations between BP and WMH index. Men showed higher WMH index than women in all white matter tracts (p < .001, respectively) except for the bilateral superior longitudinal fasciculus (SLF) and its left temporal part (tSLF). High SBP and PP was associated with a lower WMH index on the left corticospinal tract (CST), SLF, tSLF and right cingulum in hippocampus (p ≤ .001, respectively) in women, while high DBP was associated with a higher WMH index on the bilateral CST (left p < .001; right p = .001), left inferior longitudinal fasciculus (p < .001) and inferior fronto‐occipital fasciculus (p = .002) in men. Men tend to have more WMH compared to women. A high SBP/PP relates to a lower WMH burden in women. This suggests that women could benefit from higher blood pressure in older age.     

Clonal hematopoiesis with DNMT3A mutation is associated with lower white matter hyperintensity volume

Background

Clonal hematopoiesis of indeterminate potential (CHIP) increases the risk of cerebrovascular events, while its association with cerebral white matter hyperintensity (WMH) is undemonstrated. We evaluated the effect of CHIP and its major driving mutations on cerebral WMH severity.

Methods

From an institutional cohort of a routine health check-up program with a DNA repository database, subjects who were ≥50 years of age, with one or more cardiovascular risk factors but no central nervous system disorder, and performed brain MRI were included. Along with the presence of CHIP and its major driving mutations, clinical and laboratory data were obtained. WMH volume was measured in total, periventricular, and subcortical regions.

Results

Among the total 964 subjects, 160 subjects were classified as CHIP positive group. CHIP was most frequently associated with DNMT3A mutation (48.8%), followed by TET2 (11.9%) and ASXL1 (8.1%) mutations. Linear regression analysis adjusting for age, sex, and conventional cerebrovascular risk factors suggested that CHIP with DNMT3A mutation was associated with the lower log-transformed total WMH volume, unlike other CHIP mutations. When classified according to variant allele fraction (VAF) value of DNMT3A mutation, higher VAF classes were associated with the lower log-transformed total WMH and the lower log-transformed periventricular WMH volume, but not with the log-transformed subcortical WMH volumes.

Conclusions

Clonal hematopoiesis with DNMT3A mutation is quantitatively associated with a lower volume of cerebral WMH, especially in the periventricular region. CHIP with DNMT3A mutation might have a protective role in the endothelial pathomechanism of WMH.     

White matter hyperintensities mediate gray matter volume and processing speed relationship in cognitively unimpaired participants

White matter hyperintensities (WMH) have been extensively associated with cognitive impairment and reductions in gray matter volume (GMv) independently. This study explored whether WMH lesion volume mediates the relationship between cerebral patterns of GMv and cognition in 521 (mean age 57.7 years) cognitively unimpaired middle‐aged individuals. Episodic memory (EM) was measured with the Memory Binding Test and executive functions (EF) using five WAIS‐IV subtests. WMH were automatically determined from T2 and FLAIR sequences and characterized using diffusion‐weighted imaging (DWI) parameters. WMH volume was entered as a mediator in a voxel‐wise mediation analysis relating GMv and cognitive performance (with both EM and EF composites and the individual tests independently). The mediation model was corrected by age, sex, education, number of Apolipoprotein E (APOE)‐ε4 alleles and total intracranial volume. We found that even at very low levels of WMH burden in the cohort (median volume of 3.2 mL), higher WMH lesion volume was significantly associated with a widespread pattern of lower GMv in temporal, frontal, and cerebellar areas. WMH mediated the relationship between GMv and EF, mainly driven by processing speed, but not EM. DWI parameters in these lesions were compatible with incipient demyelination and axonal loss. These findings lead to the reflection on the relevance of the control of cardiovascular risk factors in middle‐aged individuals as a valuable preventive strategy to reduce or delay cognitive decline.     

偏头痛患者脑白质损害的MRI特征

目的探讨偏头痛患者脑白质损害的MRI特征。方法对80例偏头痛患者(偏头痛组)及80例健康体检者(对照组)进行MRI检查。对结果进行比较分析。结果 MRI检查显示偏头痛组中有42例脑白质损害,表现为皮质下脑白质内等T1、长T2信号影,T2Flair高信号;对照组中有9例脑白质损害。偏头痛组脑白质损害的比例(52.5%)明显高于对照组(11.3%)(χ2=31.34,P0.01)。偏头痛组中有先兆偏头痛患者脑白质损害的比例(68.6%,24/35)明显高于无先兆偏头痛患者(40.0%,18/45)(χ2=15.58,P0.01)。结论偏头痛患者脑白质损害的MRI表现与其它原因引起的脑白质病变类似。偏头痛患者脑白质损害的发生率较高,且有先兆偏头痛者较无先兆偏头痛者更高。     

White matter magnetic resonance imaging hyperintensity in Alzheimer's disease: correlations with corpus callosum atrophy

We have previously demonstrated with MRI that as well as marked white matter involvement in late-onset Alzheimer's disease (AD), atrophy of the corpus callosum may also be present. This finding prompted us to study possible correlations between atrophy of the corpus callosum and white matter hyperintensity (WMH) and between white matter lesions and the severity of the disease. We compared the corpus callosum and white matter lesions on MRI from 15 AD patients and 15 controls. The white matter lesions were scored according to the Scheltens' rating scale. We found a significant reduction of the area of the corpus callosum and more severe white matter lesions in AD patients than in controls. Both atrophy of the corpus callosum and the severity of lesions depended mainly on the diagnosis of senile dementia of the Alzheimer type and on age but not on the diagnosis of presenile AD. We demonstrated a negative correlation between white matter lesions scores and areas of corpus callosum in AD patients and no correlation between the white matter lesions and the severity of the disease. We demonstrated that white matter lesions including WMH and atrophy of the corpus callosum are more frequent in AD than in controls. The predominance of white matter lesions in senile AD may be explained by the combination of aging and disease processes.     

Relationship Between Cerebral Vasomotor Reactivity and White Matter Lesions in Elderly Subjects Without Large Artery Occlusive Disease

BACKGROUND AND PURPOSE: The relationships between cerebral vasomotor reactivity (CVR) and white matter lesions (WMLs) were investigated mainly in patients with carotid stenosis. We aimed to study the relationship in asymptomatic elderly subjects without large artery occlusive disease. METHODS: A total of 33 elderly individuals (mean age was 76.2 years) who were free from neurological deficit or cognitive impairment were studied. Bilateral mean blood flow velocity was measured in the middle cerebral artery using a 2-MHz pulsed transcranial Doppler (TCD) system together with intravenous administration of acetazolamide as vasodilatory stimuli. WMLs on a fluid-attenuated inversion recovery (FLAIR) sequence of MRI were classified into two categories: subcortical deep white matter hyperintensity (SDWMH) and periventricular hyperintensity (PVH). The lesions in each category were then divided into three grades (grade 0-I, grade II, grade III) according to the Fazekas scale. RESULTS: CVR was inversely associated with the extent of SDWMH and PVH. The differences in CVR were statistically significant among different severity of WMLs: for SDWMH (70%+/- 10% in grade 0-I, 60%+/- 10% in grade II, and 40%+/- 10% in grade III, P < .001); for PVH (80%+/- 10% in grade 0-I, 60%+/- 10% in grade II, and 40%+/- 10% in grade III, P < .001). CONCLUSIONS: Impaired CVR is related to the extent of WMLs in asymptomatic elderly individuals without large artery stenosis. The findings in our study suggest that dysfunction of cerebral vascular autoregulation might be an important factor in the development of WMLs in the asymptomatic elderly without large artery occlusive disease.