Ya-Fang Chen

Executive dysfunction and periventricular diffusion tensor changes in amnesic mild cognitive impairment and early Alzheimer's disease

Our aim in this study was to explore the neural substrates of executive function in frontal and nonfrontal white matter using diffusion tensor imaging (DTI). We studied the relationship between executive dysfunction and DTI measurements on 13 subjects with amnesic mild cognitive impairment (aMCI), 11 subjects with early Alzheimers disease (AD), and 16 control subjects. All participants underwent an examination of their intelligence, memory, and executive function and were subjected to DTI. Both aMCI and early AD subjects showed executive function impairment with differential performance in frontal‐related behaviors. Both aMCI and early AD subjects showed increased mean diffusivity in the genu of the corpus callosum and left frontal periventricular white matter (PVWM), whereas subjects with early AD showed an additional decrease in the fractional anisotropy of bilateral frontal PVWM and in the genu of the corpus callosum. The frontal PVWM was associated with performance on the Verbal Fluency Test, the Wisconsin Card Sorting Test (WCST), and Part B of the Trail Making Test. The parietal PVWM was associated with perseverative errors on the WCST and Part A of the Trail Making Test. In summary, executive function was impaired in subjects with aMCI and early AD and was associated with frontal and parietal PVWM changes. These changes may be due to early AD degeneration of the lateral cholinergic projections or to early change of the superior longitudinal fasciculus. Hum Brain Mapp, 2009.

Diffusion tensor changes in patients with amnesic mild cognitive impairment and various dementias

White matter damage and its contribution to clinical manifestations in patients with dementia have been increasingly recognized. To explore white matter changes in different types of dementia, we examined brain water diffusivity with diffusion tensor imaging (DTI). We measured fractional anisotropy and mean diffusivity of multiple white matter regions in patients with amnesic mild cognitive impairment (MCI, n=10), Alzheimers disease (AD, n=30), subcortical ischemic vascular dementia (SIVD, n=18), frontotemporal dementia (FTD, n=7), and control subjects (n=20). We performed pairwise comparisons in each region of interest between patients and controls. MCI patients showed diffusion tensor change (DTC) in the left anterior periventricular (PV) area, possibly in the right posterior PV area, and the genu of the corpus callosum. AD patients showed DTC in the corpus callosum, and in frontal and parieto-occipital subcortical and anterior PV areas. In SIVD patients, DTC occurred in the genu of the corpus callosum, and in bilateral frontal subcortical and PV areas. FTD patients differed from controls in showing DTC in the temporal and frontal subcortical areas, the genu of the corpus callosum and PV areas. The degree of DTC correlated with the clinical severity of dementia as assessed by the clinical dementia rating (CDR). Mean diffusivity was diffusely and positively associated with the CDR scores. Fractional anisotropy of the PV areas was negatively associated with the CDR scores, suggesting a critical role of the lateral cholinergic pathways.

Cervicocranial arterial dissection: experience of 73 patients in a single center.

BACKGROUND Arterial dissection involving cervicocranial arteries usually results in ischemia or SAH. This study correlated the clinical manifestations, image characteristics, and outcome of arterial dissection and compared the differences between arterial dissection of anterior and posterior circulation at our institute. METHODS Clinical symptoms and neuroradiologic findings were retrospectively analyzed in 73 patients (6-75 years old) who had a spontaneous arterial dissection of cervicocranial vessels verified by angiography or MRI. Twenty-four cases of ACAD and 49 cases of PCAD were included in this study. RESULTS The leading presentation of arterial dissection of ACAD group was ischemic stroke (79.2%), and that of posterior circulation was SAH (44.9%), followed by ischemic stroke (42.8%). In the ACAD group, the extracranial ICA was more commonly involved (62.5%), with long segmental narrowing the most common angiographic finding. In the PCAD group, the intracranial VA was more commonly involved (81.6%), with alternating narrowing and dilatation the leading angiographic picture. All the cases presenting with ischemic stroke or headache were conservatively treated with anticoagulants or antiplatelets, except for one treated with intra-arterial thrombolysis for thromboembolism in basilar artery at an early stage. One of them died of progressed brainstem infarct in spite of anticoagulation therapy. All the others reached improved or stable clinical condition. Eighteen cases were treated by surgical or endovascular intervention. None of them had rebleeding. Of the 5 patients with SAH due to dissecting lumens without treatment, 2 died of rebleeding. CONCLUSIONS Ischemia is the predominant presentation of ACAD; and PCAD has similar occurrence of SAH and ischemia. Intracranial arterial dissection is not uncommon; and it should be kept in the list of differential diagnosis of young stroke. Aggressive treatment of arterial dissection presenting with SAH should be considered; otherwise, rebleeding may occur.

Plasma tau as a window to the brain—negative associations with brain volume and memory function in mild cognitive impairment and early alzheimer's disease

Neurofibrillary tangles are associated with cognitive dysfunction, and hippocampal atrophy with increased CSF tau markers. However, the plasma tau levels of Alzheimers disease (AD) have not been well studied. We investigated plasma tau by using an immunomagnetic reduction assay in 20 patients with mild cognitive impairment (MCI) due to AD, 10 early AD dementia, and 30 healthy elders (HE). All received a 3D‐brain MRI scan and a set of cognitive function test. We explored their relationships with both brain structure and cognitive functions. Images were analyzed to determine the brain volumes and gray matter densities. Patients with MCI or early AD had significantly increased plasma tau levels compared with HE. Plasma tau levels were negatively associated with the performance of logical memory, visual reproduction, and verbal fluency; also negatively associated with volume of total gray matter, hippocampus, amygdala; and gray matter densities of various regions. Regression analyses indicated that logical memory explained 0.394 and hippocampus volume predicted .608 of the variance of plasma tau levels, both P < 0.001. Education years were negatively associated with the gray matter densities of the supramarginal (r = −0.407), middle temporal gyrus (r = −0.40) and precuneus (r = −0.377; all P < 0.05) in HE; and negatively associated with plasma tau levels in patients (r = −0.626). We propose that plasma tau may serve as a window to both structure and function of the brain. Higher education is a protective factor against AD and is associated with lower plasma tau levels in patients. Hum Brain Mapp 35:3132–3142, 2014.

Multiphase CT Angiography versus Single-Phase CT Angiography: Comparison of Image Quality and Radiation Dose

BACKGROUND AND PURPOSE: Conventional CT angiography (CTA) is acquired during only a short interval in the arterial phase, which limits its ability to evaluate the cerebral circulation. Our aim was to compare the image quality and radiation dose of conventional single-phase CTA (SP-CTA) with a multiphase CTA (MP-CTA) algorithm reconstructed from a perfusion CT (PCT) dataset. MATERIALS AND METHODS: Fifty consecutive patients undergoing head CTA and PCT in 1 examination were enrolled. The PCT dataset was obtained with 40.0-mm-detector coverage, 5.0-mm axial thickness, 80 kilovolt peak (kVp), 180 mA, and 30 mL of contrast medium. MP-CTA was reconstructed from the same PCT dataset with an axial thickness of 0.625 mm by using a new axial reconstruction algorithm. A conventional SP-CTA dataset was obtained with 0.625-mm axial thickness, 120 kVp, 350 mA, and 60 mL of contrast medium. We compared image quality, vascular enhancement, and radiation dose. RESULTS: SP-CTA and MP-CTA of 50 patients (male/female ratio, 31/19; mean age, 59.25 years) were analyzed. MP-CTA was significantly better than SP-CTA in vascular enhancement (P = .002), in the absence of venous contamination (P = .006), and was significantly higher in image noise (P < .001). MP-CTA used less contrast medium than SP-CTA and could demonstrate hemodynamic information. The effective dose of MP-CTA was 5.73 mSv, which was equal to that in conventional PCT, and it was 3.57 mSv in SP-CTA. CONCLUSION: It is feasible that MP-CTA may provide both CTA and PCT results. Compared with SP-CTA, MP-CTA provides comparable image quality, better vascular enhancement, hemodynamic information, and more noise with less detail visibility with a lower tube voltage. The radiation dose of MP-CTA is higher than that of SP-CTA, but the dose can be reduced by altering the sampling interval.

Neurocognitive Improvement After Carotid Artery Stenting in Patients With Chronic Internal Carotid Artery Occlusion and Cerebral Ischemia

Background and Purpose— Chronic cerebral hypoperfusion may lead to impairment in neurocognitive performance in patients with chronic internal carotid artery occlusion, and the effects of carotid artery stenting on neurocognitive function have been unclear. Methods— We prospectively enrolled 20 chronic internal carotid artery occlusion patients with objective ipsilateral hemisphere ischemia, in whom carotid artery stenting was attempted. Functional assessments, including the National Institutes of Health Stroke Scale, Barthel Index, and a battery of neuropsychological tests, including the Mini-Mental State Examination, Alzheimer Disease Assessment Scale–Cognitive Subtest, verbal fluency, and Color Trail Making A and B, were administered before and 3 months after intervention. Results— Successful recanalization was achieved in 12 of 20 patients (60%). There was no procedural or new cerebral ischemic event, except for 1 intracranial hemorrhage, which occurred during the procedure and had neurologic sequelae; this case was excluded from analysis. The demographics and baseline cognitive performance were similar between the group with a successful outcome (group 1, n=12) and patients who did not (group 2, n=7). Ten of 12 patients in group 1 had improvement in ipsilateral brain perfusion after the procedure, but none in group 2 had improvement. Significant improvement in the scores on the Alzheimer Disease Assessment Scale–Cognitive Subtest (before, 7.7±8.9 versus after, 5.7±7.1; P=0.024), Mini-Mental State Examination (before, 25.8±3.8 versus after, 27.7±2.7; P=0.015), and Color Trail Making A (before, 123.2±68.6 versus after, 99.3±51.5; P=0.017) were found in group 1 but not in group 2. Conclusions— Successful carotid artery stenting improves global cognitive function as well as attention and psychomotor processing speed in patients with chronic internal carotid artery occlusion.

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Non-Small-Cell Lung Cancer Patients with Leptomeningeal Carcinomatosis

Background: Leptomeningeal carcinomatosis (LC) is a detrimental complication of patients with non–small-cell lung cancer (NSCLC). The effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) on the clinical outcome of these patients, particularly those with EGFR mutations, has not been studied yet. Methods: We searched the database for lung cancer patients diagnosed from 2003 to 2010 in one Asian medical center. NSCLC patients who also had LC diagnosed by either cytology or brain neuroimaging studies were identified. The treatments and clinical outcomes were reviewed. Results: Of 5526 lung cancer patients, we identified 212 (3.8%) NSCLC patients with LC. Most patients (88.7%) had adenocarcinoma histology, and 129 (60.9%) patients had been treated with at least one regimen of EGFR TKI before the diagnosis of LC. One hundred and twenty-four (58.5%) patients were treated with EGFR TKI, and 128 (60.4%) patients were treated with whole-brain radiation therapy (WBRT) after the diagnosis of LC. The median overall survival was 4.5 months (95% confidence interval, 3.5–7.3). Multivariate analysis suggested that EGFR TKI therapy, WBRT, and cytotoxic chemotherapy were independent predictors for longer survival. Mutational status of EGFR was evaluated in 101 patients, and 75 mutations (74.3%) were detected. Among the 75 patients with EGFR mutations, EGFR TKI therapy and cytotoxic chemotherapy after diagnosis of LC remained the independent factors predictive of extended survival in the multivariate analysis. Conclusions: Treatment of LC with EGFR TKI, cytotoxic chemotherapy, or WBRT in selected patients is associated with prolong survival period. These treatment options, especially EGFR TKIs, should be studied in patients with EGFR mutation-positive NSCLC and LC.

Regional Quantification of White Matter Hyperintensity in Normal Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

Background/Aims: A quantitative method was applied to measure the volume of white matter hyperintensity (WMH) in different brain regions of subjects with Alzheimer’s disease (AD), mild cognitive impairment (MCI) and normal healthy age-matched controls, and the relationship between regional WMH and age and cognitive function was investigated. Methods: Fifty-six subjects were included in this study, 27 AD, 15 MCI and 14 normal age-matched controls. A user-friendly software was developed for WMH quantification in frontal, temporal, and parieto-occipital lobes. Mini-Mental State Examination and cognitive scores in performing naming, language fluency, and memory tasks were obtained for correlation analysis. Results: AD patients had the greatest total WMH volume, followed by MCI, then controls. However, there was a large variation within each group, and the difference did not reach a significant level. There was a positive linear correlation between the total WMH (p = 0.031) and the frontal WMH (p = 0.006) vs. age. After age correction the Boston Naming Test scores were negatively correlated with the total WMH volume in the AD (p = 0.03) and the control (p = 0.03) groups, and with the frontal WMH in controls (p = 0.01). Conclusion: We demonstrated a quantitative analysis method to measure regional WMH. Although WMH was not strongly associated with disease severity or cognition, it may provide a characteristic neuroimaging parameter in the study of AD development.

New assay for old markers-plasma beta amyloid of mild cognitive impairment and Alzheimer's disease.

Although there is a consensus on the reduced levels of Aβ1-42 in the CSF of patients with AD, studies of plasma Aβ levels were inconsistent and have limited clinical value. We developed an immunomagnetic reduction assay (IMR) to determine the plasma levels of Aβ. We surveyed patients with varying AD severity (CDR = 0.5, n=16; CDR ≥ 1, n=18) and controls (n=26). Significant group differences were apparent in the levels of Aβ1-42 (F = 5.54, p = 0.002) and the Aβ1-42/Aβ1-40 ratio (F = 24.198, p < 0.001). Post-hoc analyses showed significant differences in the Aβ1-42 levels of controls and AD patients (p = 0.001) and in the Aβ1-42/Aβ1-40 ratio of control, MCI and AD subjects (all p ≤ 0.001). Regression analysis of Aβ1-42/Aβ1-40 ratios on dementia severity showed an adjusted R2 of 0.553 (p = 0.001). We identified a cut-off of 16.1 pg/ml for Aβ1-42 to differentiate control subjects from patients (both AD and MCI) with 85.3% sensitivity and 88.5% specificity. We also obtained a cut-off value of 0.303 for Aβ1-42/Aβ1-40 ratios with 85.3% sensitivity and 96.2% specificity. APOE 4 carriers had significantly higher Aβ1-42/Aβ1-40 ratios than the non-carriers (F = 4.839, p = 0.015). An independent group of case-control subjects validated both cut-off values for Aβ1-42/Aβ1-40 (100% sensitivity and 83.3% specificity) and for Aβ1-42 (100% sensitivity and 75.3% specificity). In a subgroup of longitudinal follow- up study, we found that the plasma Aβ was relatively stable with an interval of approximately 3 months. In conclusion, we found that the plasma Aβ1-42 is a useful biomarker for AD. The Aβ1-42/Aβ1-40 ratio improves the diagnostic power of the plasma Aβ biomarkers. The iron nanoparticles and IMR provides a novel method to measure plasma Aβ and could serve as an important clinical tool for the diagnosis of neurodegenerative diseases.

Intracranial Dural Arteriovenous Fistulas: Diagnosis and Evaluation with 64–Detector Row CT Angiography

PURPOSE To analyze the diagnostic effectiveness and application of computed tomographic (CT) angiography by using a new algorithm (hybrid CT angiography) in dural arteriovenous fistulas (AVFs). MATERIALS AND METHODS Institutional review board approval was obtained for retrospectively postprocessing the raw data from CT angiography by using hybrid CT, which is a mixture of a bone subtraction and masking method for bone removal. The study included 22 patients with 24 dural AVFs and 14 control subjects. The grades in patients with dural AVF determined with hybrid CT angiography and digital subtraction angiography (DSA) were compared, and hybrid CT angiography was applied as a tool for planning endovascular treatment. The adjusted Wald method was used to estimate confidence intervals (CIs), and the Cohen kappa statistic was used to assess interobserver agreement. RESULTS Hybrid CT angiography in the 24 dural AVFs revealed asymmetric sinus enhancement in 22 lesions (92%), engorged arteries in 19 (79%), transosseous enhanced vessels in 19 (79%), engorged extracranial veins in 13 (54%), engorged cortical veins in seven (29%), and sinus thrombosis in four (17%). In all 24 lesions, at least two of six imaging signs for diagnosis of dural AVFs were present. The kappa test analysis revealed a high level of interobserver agreement (kappa, 0.56-1.00) in reading the diagnostic imaging signs. The observed agreement between DSA and readers was 100% in the cavernous sinus region and in hypoglossal and clival lesions and 78%-89% in the transverse sigmoid sinus. The overall sensitivity, specificity, positive predictive value, and negative predictive value were 0.93 (95% CI: 0.85, 0.97), 0.98 (95% CI: 0.93, 1.00), 0.97 (95% CI: 0.90, 0.99), and 0.95 (95% CI: 0.90, 0.98), respectively. CONCLUSION Hybrid CT angiography is a promising tool for the diagnosis of dural AVF. It can provide key information necessary for treatment planning.