Jee Hoon Roh

Cardiovascular risk factors cause cortical thinning in cognitively impaired patients: relationships among cardiovascular risk factors, white matter hyperintensities, and cortical atrophy.

Cardiovascular risk factors are associated with cognitive impairments. However, the effects of cardiovascular risk factors on the topography of cortical thinning have not yet been studied in patients with mild cognitive impairment (MCI) or dementia. Thus, we aimed to evaluate the topography of cortical thinning related to cardiovascular risk factors and the relationships among cardiovascular risk factors, white matter hyperintensities (WMH), and cortical atrophy. Participants included 226 patients with Alzheimer disease or subcortical vascular dementia and 135 patients with amnestic MCI or subcortical vascular MCI. We automatically measured the volume of WMH and cortical thickness. Hypertension was associated with cortical thinning in the frontal and perisylvian regions, and cortical thinning related to diabetes mellitus (DM) occurred in the frontal region. In path analyses, hypertension accounted for 0.04 of the frontal thinning with the mediation of WMH and 0.16 without the mediation of WMH. In case of DM, it accounted for 0.02 of the frontal thinning with the mediation of WMH and 0.13 without the mediation of WMH. Hypertension and DM predominantly affected frontal thinning both with and without the mediation of WMH, where the effects without the mediation of WMH were greater than those with the mediation of WMH.

Cortical asymmetries in normal, mild cognitive impairment, and Alzheimer's disease

There are functional and structural neocortical hemispheric asymmetries in people with normal cognition. These asymmetries may be altered in patients with Alzheimers disease (AD) because there is a loss of neuronal connectivity in the heteromodal cortex. The purpose of this study is to test the hypothesis that individuals with amnestic mild cognitive impairment (aMCI), mild AD, and moderate to severe AD have progressive reductions in thickness asymmetries of the heteromodal neocortex. Right-handed elderly volunteers including normal cognition (NC), aMCI, and AD underwent 3-D volume imaging for cortical thickness. Although the cortical asymmetry pattern observed in normal cognition brains was generally maintained in aMCI and AD, there was a progressive decrease in the degree of asymmetry, especially in the inferior parietal lobule. A reduction of neocortical asymmetries may be a characteristic sign that occurs in patients with AD. Future studies are needed to evaluate whether this loss is specific to AD and if measurements of asymmetry can be used as diagnostic markers and for monitoring disease progression.

Spectral-based automatic labeling and refining of human cortical sulcal curves using expert-provided examples

We present a spectral-based method for automatically labeling and refining major sulcal curves of a human cerebral cortex. Given a set of input (unlabeled) sulcal curves automatically extracted from a cortical surface and a collection of expert-provided examples (labeled sulcal curves), our objective is to identify the input major sulcal curves and assign their neuroanatomical labels, and then refines these curves based on the expert-provided example data, without employing any atlas-based registration scheme as preprocessing. In order to construct the example data, neuroanatomists manually labeled a set of 24 major sulcal curves (12 each for the left and right hemispheres) for each individual subject according to a precise protocol. We collected 30 sets of such curves from 30 subjects. Given the raw input sulcal curve set of a subject, we choose the most similar example curve to each input curve in the set to label and refine the latter according to the former. We adapt a spectral matching algorithm to choose the example curve by exploiting the sulcal curve features and their relationship. The high dimensionality of sulcal curve data in spectral matching is addressed by using their multi-resolution representations, which greatly reduces time and space complexities. Our method provides consistent labeling and refining results even under high variability of cortical sulci across the subjects. Through experiments we show that the results are comparable in accuracy to those done manually. Most output curves exhibited accuracy values higher than 80%, and the mean accuracy values of the curves in the left and the right hemispheres were 84.69% and 84.58%, respectively.

Prediction of Alzheimer's disease pathophysiology based on cortical thickness patterns

Recent studies have shown that pathologically defined subtypes of Alzheimers disease (AD) represent distinctive atrophy patterns and clinical characteristics. We investigated whether a cortical thickness–based clustering method can reflect such findings.

Cerebellar atrophy in patients with subcortical-type vascular cognitive impairment.

Recent studies suggest that the role of the cerebellum extends into cognitive regulation and that subcortical vascular dementia (SVaD) can result in cerebellar atrophy. However, there has been no evaluation of the cerebellar volume in the preclinical stage of SVaD. We aimed to compare cerebellar volume among patients with amnestic mild cognitive impairment (aMCI) and subcortical vascular mild cognitive impairment (svMCI) and evaluate which factors could have contributed to the cerebellar volume. Participants were composed of 355 patients with aMCI, svMCI, Alzheimers disease (AD), and SVaD. Cerebellar volumes were measured using automated methods. A direct comparison of the cerebellar volume in SVaD and AD groups showed that the SVaD group had a statistically smaller cerebellar volume than the AD group. Additionally, the svMCI group had a smaller cerebellar volume than the aMCI group, with the number of lacunes (especially in the supratentorial regions) being associated with cerebellar volume. Cerebellar volumes were associated with some neuropsychological tests, digit span backward and ideomotor apraxia. These findings suggest that cerebellar atrophy may be useful in differentiating subtypes of dementia and the cerebellum plays a potential role in cognition.

Neurochemical alterations of the entorhinal cortex in amnestic mild cognitive impairment (aMCI): A three-year follow-up study

The neurochemical alterations in the entorhinal cortex have not yet been measured, even though the entorhinal cortex is the earliest involved brain region in aMCI. In this study, we investigated whether brain regions including the entorhinal cortex would show early involvement of neurochemical abnormalities in aMCI, and whether magnetic resonance spectroscopy (MRS) abnormalities might be a predictive marker of conversion of aMCI to Alzheimers disease (AD). MRS was performed on 13 aMCI patients and 11 patients with no cognitive impairment (NCI). Localizing voxels were placed within the entorhinal cortex, hippocampus, posterior cingulate gyrus, and occipital white matter in the dominant hemisphere. N-acetyl aspartate/creatinine (NAA/Cr) ratios in the entorhinal cortex were significantly lower in aMCI patients than in NCI subjects. After a three-year follow-up, seven aMCI patients converted to AD and six remained stable. Baseline NAA/Cr ratios of entorhinal cortex were decreased in converters, compared to NCI. Our study suggested the entorhinal cortex is the earliest site that is subject to neurochemical alteration in aMCI patients, and baseline MRS metabolite ratios in the entorhinal cortex can be a marker for predicting conversion of aMCI to AD.

Cortical thinning in verbal, visual, and both memory-predominant mild cognitive impairment.

The amnestic form of mild cognitive impairment (aMCI) is likely a precursor of Alzheimer disease (AD). Both verbal and visual memory tests are used in the diagnosis of aMCI; however, it is unknown which type of test is superior at predicting the underlying pathologic changes associated with AD. In this study, we compared the topography of cortical thinning among 3 subtypes of patients with aMCI: 33 patients with predominant verbal memory impairment (verbal-aMCI), 35 with predominant visual memory impairment (visual-aMCI), and 56 with both verbal and visual memory-predominant impairment (both-aMCI), and 143 patients with normal cognition. As a result, patients with verbal-aMCI showed cortical thinning in the left anterior and medial temporal regions compared with individuals with normal cognition, while those with visual-aMCI did not show significant cortical thinning. The cortical thinning areas of both-aMCI group overlapped those of verbal-aMCI but were more widespread involving the bilateral temporal regions. These findings suggest that the verbal-aMCI and both-aMCI are more likely to be a precursor of AD than visual-aMCI, and that both-aMCI may be more advanced subtype than verbal-aMCI on the spectrum from MCI to AD.

Effect of midazolam on memory during fiberoptic gastroscopy under conscious sedation.

ObjectiveAs the fiberoptic gastroscopy using midazolam is being in widespread use, the exact nature of midazolam on memory should be clarified. We intended to examine whether midazolam causes selective anterograde amnesia and what impact it has on other aspects of memory and general cognitive function. MethodsWe recruited healthy subjects undergoing fiberoptic gastroscopy under conscious sedation. At baseline, history taking for retrograde amnesia and the Korean version of the Montreal Cognitive Assessment were performed. A man’s name and address were given immediately after intravenous midazolam administration. After gastroscopy, the subjects were asked to recall those items. By the time they had fully recovered consciousness, the same test was repeated along with the Korean version of the Montreal Cognitive Assessment and a test for retrograde amnesia. ResultsA total of 30 subjects were enrolled in this study. Subjects with high-dose midazolam showed lower scores in the immediate and delayed recall of “a man’s name and address” compared with those with low-dose midazolam. The midazolam dose was inversely correlated with the delayed recall scores of “a man’s name and address.” On full recovery of consciousness, the subjects did not exhibit any of anterograde or retrograde amnesia. ConclusionsThese findings suggest that midazolam causes transient selective anterograde amnesia in a dose-dependent manner.

GLUCOSE METABOLISM IN PROGRESSIVE NONFLUENT APHASIA WITH AND WITHOUT PARKINSONISM

Progressive nonfluent aphasia (PNFA) is one of the language variants of frontotemporal dementia.1 Previously, PNFA, corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP) were regarded as separate disease entities because of their distinctive clinical features and different anatomic involvement: left perisylvian area in PNFA,2 basal ganglia and dorsal midbrain in PSP, and perirolandic area in CBD.3 However, recent studies show that the 3 disorders share tauopathy and clinical features such as language disturbance and parkinsonism in common.4 Furthermore, one disorder even evolves into others along the course of disease progression.5 One of the typical examples of this evolution is that PNFA can develop into CBD or PSP.6 Therefore, we hypothesized that the topography of glucose hypometabolism in patients with PNFA with parkinsonism (PNFA+P) would differ from those without parkinsonism (PNFA-P), even before evolving into PSP or CBD. That is, PNFA+P would have more glucose hypometabolism in the basal ganglia, midbrain, or perirolandic areas that are known to be affected in PSP or CBD. ### Methods. #### Subjects. We retrospectively found a total of 21 patients with PNFA who underwent clinical evaluations, including neuropsychological tests and [18F]fluoro-2-deoxy-d-glucose PET (FDG-PET) within a 3-month interval at a university-affiliated hospital. All patients fulfilled the diagnostic criteria for PNFA proposed …

Improved Diagnostic Accuracy of Alzheimer’s Disease by Combining Regional Cortical Thickness and Default Mode Network Functional Connectivity: Validated in the Alzheimer’s Disease Neuroimaging Initiative Set

Objective To identify potential imaging biomarkers of Alzheimers disease by combining brain cortical thickness (CThk) and functional connectivity and to validate this models diagnostic accuracy in a validation set. Materials and Methods Data from 98 subjects was retrospectively reviewed, including a study set (n = 63) and a validation set from the Alzheimers Disease Neuroimaging Initiative (n = 35). From each subject, data for CThk and functional connectivity of the default mode network was extracted from structural T1-weighted and resting-state functional magnetic resonance imaging. Cortical regions with significant differences between patients and healthy controls in the correlation of CThk and functional connectivity were identified in the study set. The diagnostic accuracy of functional connectivity measures combined with CThk in the identified regions was evaluated against that in the medial temporal lobes using the validation set and application of a support vector machine. Results Group-wise differences in the correlation of CThk and default mode network functional connectivity were identified in the superior temporal (p < 0.001) and supramarginal gyrus (p = 0.007) of the left cerebral hemisphere. Default mode network functional connectivity combined with the CThk of those two regions were more accurate than that combined with the CThk of both medial temporal lobes (91.7% vs. 75%). Conclusion Combining functional information with CThk of the superior temporal and supramarginal gyri in the left cerebral hemisphere improves diagnostic accuracy, making it a potential imaging biomarker for Alzheimers disease.