Yeonsil Moon

Patterns of Brain Iron Accumulation in Vascular Dementia and Alzheimer’s Dementia Using Quantitative Susceptibility Mapping Imaging

BACKGROUND Emerging evidence suggests that the excessive accumulation of iron in subcortical and deep gray matter has been related to dementia. However, the presence and pattern of iron accumulation in vascular dementia (VaD) and Alzheimers disease (AD) are rarely investigated. OBJECTIVE To examine and compare the pattern and presence of brain iron accumulation of VaD and AD using quantitative susceptibility mapping (QSM). MATERIALS AND METHODS Twelve patients with VaD, 27 patients with AD, and 18 control subjects were recruited in this institutional review-board approved study. Susceptibility maps were reconstructed from a three-dimensional multiecho spoiled gradient-echo sequence. Four regions of interest were drawn manually on QSM images, namely the globus pallidus, putamen, caudate nucleus, and pulvinar nucleus of the thalamus. Comparisons of patient demographics, and iron concentrations among the VaD, AD, and control subjects were assessed using analysis of variance and post-hoc analyses. The relationships of age and cognitive state with susceptibility values were assessed using partial correlation analysis. RESULTS In VaD and AD, overall susceptibility values were higher than those of control subjects. A significant difference in susceptibility values was found in the putamen and caudate nucleus (p <  0.001 and p = 0.002, respectively). However, susceptibility values did not differ between VaD and AD. Age and cognitive deficit severity were not related to susceptibility values in the VaD and AD groups. CONCLUSION Increased iron deposition in the putamen and caudate nucleus in VaD and AD patients was not associated with age or the severity of cognitive deficits. Further evaluations are needed to determine the temporal changes in iron load and their diagnostic role in dementia pathology.

Regional Atrophy of the Insular Cortex Is Associated with Neuropsychiatric Symptoms in Alzheimer's Disease Patients

Background: Alzheimers disease (AD) is a devastating illness that results in progressive cognitive decline and neuropsychiatric symptoms. The neuropsychiatric symptoms are associated with a rapid decline in cognition and activities of daily living and increased mortality, however the neuroanatomical localisation involved in the development of neuropsychiatric symptoms remains poorly understood. The aim of this study was to identify the association with the regional volume of the insular cortex and each neuropsychiatric symptom in patients with AD. Methods: Subjects diagnosed with AD (n = 40) were evaluated. Magnetic resonance images were obtained and the insular cortex was subdivided into four subregions through the central sulcus of the insula and bilaterally: right anterior insular cortex, right posterior insular cortex, left anterior insular cortex and left posterior insular cortex. The neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. A partial correlation analysis was performed. Results: A significant negative correlation existed between apathy, the irritability subscale score and the volume ratio of the bilateral anterior insular cortex and right posterior insular cortex (r = -0.457, -0.433 and -0.572, respectively, p = 0.032, 0.044 and 0.005, respectively). Conclusion: The findings suggest that the regional atrophy of the insular cortex is associated with neuropsychiatric symptoms in AD patients.

The Effect of Ischemic Cholinergic Damage on Cognition in Patients With Subcortical Vascular Cognitive Impairment

Prior research has shown that the total amount of white matter ischemia had no significant correlation with cognitive deficits. We compared the association of white matter hyperintensities (WMHs) of total as well as cholinergic pathways with clinical dementia severity and investigated whether cholinergic ischemic burden had an independent predictive value with respect to cognitive decline in subcortical vascular cognitive impairment (SVCI). Forty-eight patients underwent detailed neuropsychological tests and brain magnetic resonance imaging. Quantification of WMH in the total white matter and in cholinergic pathways was achieved using the visual Scheltens scale and Cholinergic Pathway HyperIntensity Scale (CHIPS), respectively. We explored the association between WMH scores and clinical dementia rating scale (CDR). To assess the relation between WMH and cognitive scores, multiple linear regression analysis was used. The CHIPS score was higher in subcortical vascular dementia compared to subcortical vascular MCI, while this difference was not found with the total TMHs (TWMH) score. The TWMH score had a positive correlation with CHIPS, however only CHIPS scores positively correlated with sum of box scores of CDR scale (CDR SB; ρ = .474, P = .001). Higher CHIPS scores were associated with lower performance on the semantic word fluency test (β = −.447, P = .036), whereas the TWMH scores had no independent predictive value with respect to cognitive impairment, after controlling for CHIPS score. Our data confirmed the association of ischemic damage within cholinergic pathways with dementia severity, independent of TWMH in SVCI. In addition, this cholinergic deficit is clinically relevant to cognitive deterioration, especially with frontal dysfunction.

Comprehensive evaluation of coronary artery disease and aortic atherosclerosis in acute ischemic stroke patients: usefulness based on Framingham risk score and stroke subtype.

Background: Evaluation of coronary artery disease (CAD) and aortic atherosclerosis has been performed in patients with acute ischemic stroke. We investigated the usefulness of a dual-source CT (DSCT) protocol enabling the comprehensive evaluation of CAD and aortic atherosclerosis. The clinical characteristics of those patients who would benefit more from this protocol were investigated based on vascular risk factors, Framingham Risk Score (FRS), and stroke subtype. Methods: Of 469 patients with acute ischemic stroke, the 274 who had no history of CAD and had undergone DSCT were analyzed. Predictors of CAD (≧50% stenosis) or complicated aortic plaque (CAP) were evaluated based on vascular risk factors, FRS and stroke subtype. Results: Of the 274 patients analyzed, asymptomatic CAD (≧50% stenosis) was found in 61 (22.3%) and CAP in 58 (21.2%). Furthermore, the severity of CAD or aortic atherosclerosis was correlated with FRS (CAD, r = 0.291, p < 0.001 and aortic atherosclerosis, r = 0.297, p < 0.001). Additionally, severe CAD and aortic atherosclerosis were independent predictors of each other: CAP for the presence of CAD (≧50% stenosis) [odds ratio (OR), 5.71; 95% confidence interval (CI), 1.94–16.87]; CAD (≧50% stenosis) for the presence of CAP (OR, 4.20; 95% CI, 1.82–9.72). Specific stroke subtypes as well as large-artery atherosclerosis (OR, 5.25; 95% CI, 2.24–12.31) and cardioembolism (OR, 5.22; 95% CI, 1.75–15.60) were associated with the presence of CAP. Conclusions: A comprehensive evaluation protocol for CAD and aortic atherosclerosis may be useful in acute ischemic stroke patients, especially in those with higher FRS or specific stroke subtypes.

Vascular factors are associated with the severity of the neuropsychiatric symptoms in Alzheimer's disease

Introduction: The purpose of this study is to determine whether vascular risk factors are associated with severity of neuropsychiatric symptoms (NPS) in patients of Alzheimers dementia. Methods: We reviewed medical records of 162 patients with Alzheimers dementia. The NPS were assessed using the Neuropsychiatric Inventory (NPI). Hypertension and cardiovascular events were detected through detailed history taking. Diabetes mellitus and hyperlipidemia were uncovered through laboratory test. The asymptomatic stroke and white matter hyperintensities (WMH) were defined by magnetic resonance imaging. Partial correlation analysis was used. Results: Hypertension was correlated with the severity of apathy (r = 0.231, p = 0.015). The asymptomatic stroke was related to the severity of depression (r = 0.255, p = 0.007). The remaining vascular factors were not significant. Conclusion: Presence of hypertension and asymptomatic stroke are related with the severity of apathy and depression in Alzheimers dementia.

Acute simultaneous multiple lacunar infarcts: a severe disease entity in small artery disease.

Background: We hypothesized that acute simultaneous multiple lacunar infarcts (sMLI) may have different clinico-radiological characteristics compared to acute single lacunar infarcts (SLI). Methods: We retrospectively reviewed stroke patients with sMLI or SLI in a consecutively collected stroke registry with a predefined long-term clinical follow-up. Clinical characteristics, including vascular risk factors, rheological profiles, premorbid functional status, and clinical outcome were evaluated. In addition, radiological characteristics, including white matter ischemic changes, previous lacunes, microbleeds, and concomitant intra- or extracranial arterial stenosis were evaluated. Results: Of the 548 acute ischemic stroke patients, sMLI was found in 23 (13.5%) and SLI in 148 (86.5%). There was no difference in vascular risk factors and rheological profiles between the two groups, except for advanced age and more frequent previous history of stroke in the sMLI group. The sMLI group also showed more previous lacunes (p < 0.001) and microbleeds (p < 0.001). A cardioembolic or atherothrombotic stroke mechanism was rare in both groups. Recurrent strokes were more frequent in the sMLI group. Conclusions: The main pathophysiology of sMLI may be small artery disease. However, clinico-radiological characteristics suggest that sMLI may be a more severe entity of small artery disease compared to SLI.

Vitamin D Deficiency Disrupts Neuronal Integrity in Cognitively Impaired Patients

BACKGROUND Emerging evidence suggests that low serum 25-hydroxyvitamin D (25OHD) may induce cognitive decline and dementia, however, the pathophysiological mechanisms are poorly understood. OBJECTIVE We sought to determine the relationship between vitamin D deficiency and neuronal integrity in cognitively impaired patients. METHODS One hundred nine patients with memory impairment were divided into quartiles according to serum concentrations of 25OHD concentration, from lowest (L-25OHD) to highest (H-25OHD). The diffusion tensor images from the L-25OHD group and the H-25OHD group were assessed. A mask of regional white matter hyperintensities was obtained in the T1-weighted image space. Data were analyzed using tract-based spatial statistics with a nonlinear registration algorithm. RESULTS Patients in the L-25OHD group had lower fractional anisotropy values compared with patients in the H-25OHD group in the frontal parts of the inferior and superior longitudinal fasciculi, cingulum bundle, corpus callosum (genu), anterior limb of the internal capsule, and anterior corona radiata (familywise error corrected, p < 0.05). CONCLUSIONS Vitamin D deficiency is associated with disruption of neuronal integrity, primarily in frontal regions. Vitamin D deficiency may lead to the loss of neuroprotective properties in cerebral ischemia and vascular lesions, contributing to memory impairment.

Validity of the Korean Version of the Fear of Alzheimer's Disease Scale for the Assessment of Anticipatory Dementia

Anticipatory dementia is related to anxiety, which is a clinical predictor of early conversion to Alzheimers disease. The Fear of Alzheimers Disease Scale (FADS) is a reliable and valid instrument to address anticipatory dementia. The aim of the present investigation was to develop the Korean version of the Fear of Alzheimers Disease Scale (K-FADS) and to verify its reliability and validity. We developed the K-FADS to consist of 30 items with total scores ranging from 0 to 120, as in the original FADS. One hundred eight healthy volunteer participants, drawn from 3 different university hospitals, were evaluated. The K-FADS revealed good reliability (Cronbach α=0.96) and good validity as compared to the Korean version of the State-Trait Anxiety Inventory Form (r=0.242, P=0.013). Test-retest reliability was excellent, as the intra-class correlation coefficient comparing the retest to test was 0.98 (95% confidence interval, 0.96-0.99). Our results show that the K-FADS is a suitable and valuable scale to assess anticipatory dementia in elderly Koreans. Graphical Abstract

Intravenous thrombolysis in a patient with acute ischemic stroke attributable to intracranial dissection.

Ischemic stroke attributable to intracranial dissection is a rare condition. We present a case of intravenous thrombolysis therapy in a patient with acute ischemic stroke after a dissection of the middle cerebral artery. Safety and outcome of intravenous thrombolysis therapy was favorable and the dissection regressed over 3 months with anticoagulation therapy.

Pathomechanisms of Atrophy in Insular Cortex in Alzheimer’s Disease

The insular cortex is associated with neuropsychiatric symptoms, changes in cardiovascular and autonomic control, and mortality in Alzheimer’s dementia. However, the insular cortex does not provide information on the contribution of the other cortices to cognitive decline. We hypothesized that the factors that affect to atrophy in insular cortex are different from other cortical regions. A total of 42 patients with probable Alzheimer’s dementia were included in the analyses. The manual drawing of regions of interest was used to detect insular cortex located in the deep gray matter and to avoid coatrophy. Covariates, which could affect to the atrophy of the cerebral cortex, were selected based on previous studies. Any of the demographic factors, vascular risk factors, and the severity scales of dementia was not associated with any insular volume ratio. We suggest that the pathomechanisms of atrophy in insular cortex are different from those of other cortex regions in Alzheimer’s disease.