Hyemin Jang

Head to head comparison of [18F] AV-1451 and [18F] THK5351 for tau imaging in Alzheimer’s disease and frontotemporal dementia

PurposeTau accumulation is a core pathologic change in various neurodegenerative diseases including Alzheimer’s disease and frontotemporal lobar degeneration-tau. Recently, tau positron emission tomography tracers such as [18F] AV-1451 and [18F] THK5351 have been developed to detect tau deposition in vivo. In the present study, we performed a head to head comparison of these two tracers in Alzheimer’s disease and frontotemporal dementia cases and aimed to investigate which tracers are better suited to image tau in these disorders.MethodsA cross-sectional study was conducted using a hospital-based sample at a tertiary referral center. We recruited eight participants (two Alzheimer’s disease, four frontotemporal dementia and two normal controls) who underwent magnetic resonance image, amyloid positron emission tomography with [18F]-Florbetaben and tau positron emission tomography with both THK5351 and AV-1451. To measure regional AV1451 and THK5351 uptakes, we used the standardized uptake value ratios by dividing mean activity in target volume of interest by mean activity in the cerebellar hemispheric gray matter.ResultsAlthough THK5351 and AV-1451 uptakes were highly correlated, cortical uptake of AV-1451 was more striking in Alzheimer’s disease, while cortical uptake of THK5351 was more prominent in frontotemporal dementia. THK5351 showed higher off-target binding than AV-1451 in the white matter, midbrain, thalamus, and basal ganglia.ConclusionsAV-1451 is more sensitive and specific to Alzheimer’s disease type tau and shows lower off-target binding, while THK5351 may mirror non-specific neurodegeneration.

Rabbit Antithymocyte Globulin Compared with Basiliximab in Kidney Transplantation: A Single-Center Study

BACKGROUND Induction therapy is used to reduce the incidence of acute rejection and to prevent or treat delayed graft function. We compared basiliximab with rabbit antithymocyte globulin (ATG) as induction therapies for kidney transplant recipients. METHODS We retrospectively analyzed the clinical data from 514 patients who received ATG or basiliximab. The patients in the ATG group (n = 152) received ATG (1.5 mg/kg/d) for 5-7 days and those in the basiliximab group (n = 362) were given 2 doses of basiliximab (20 mg) on posttransplantation days 0 and 4. All patients received standard triple immunosuppressive therapy with calcineurin inhibitors, mycophenolate mofetil, and steroids. RESULTS There were statistically significant differences in the incidences of delayed graft function, 1-year acute rejection rate, death-censored graft survival, and patient survival between the 2 groups, even though the ATG group had more kidney transplants from deceased donors, higher levels of panel reactive antibodies, and more retransplantations. The incidences of cytomegalovirus (CMV) infection and parvovirus infection in the ATG group were higher than those in the basiliximab group. However, there was no statistically significant difference in the incidence of CMV disease between the 2 groups. CONCLUSIONS ATG is safe and efficacious for use in kidney transplant recipients. Our results suggest that ATG should be considered for induction therapy in high-risk patients, such as those who have a kidney allograft from a deceased donor, high levels of panel reactive antibodies, and are undergoing retransplantation.

Hormonal Differences Between Female Kidney Transplant Recipients and Healthy Women With the Same Gynecologic Conditions

BACKGROUND End-stage renal disease is associated with severe abnormalities in reproductive function. However, the abnormalities are reversed by successful kidney transplantation. The aim of the present study was to compare hormonal levels between recipients with successful kidney transplantations and healthy women with the same gynecologic conditions. METHODS The study group consisted of 31 women of reproductive age with end-stage renal disease who underwent successful kidney transplantation. The ratio of the control group, composed of healthy woman, to the study group was 3:1 matched for age and symptoms. RESULTS Abnormal bleeding (n = 14) and infertility were the most common gynecologic conditions in kidney transplant recipients. The levels of estrogen (E2) and follicle-stimulating hormone (FSH) in the study group were higher than in the control group, but the levels of progesterone (P4) and luteinizing hormone (LH) were lower in the study group than in the control group. There were no significant differences in prolactin and thyroid-stimulating hormone between the two groups. The incidence of infertility in patients who receive steroid was higher than those with no steroid use (P = .007). CONCLUSIONS Compared with healthy age- and symptom-matched women, female kidney transplant recipients have increased levels of E2 and FSH and decreased levels of P4 and LH. These differences in hormone profiles may predispose kidney transplant recipients to increased risk of gynecologic pathologies.

Prevalence of antineuronal antibodies in patients with encephalopathy of unknown etiology: Data from a nationwide registry in Korea

We aimed to evaluate the prevalence of antineuronal antibodies in a nationwide cohort of patients with encephalopathy of unknown etiology. We screened 1699 patients with idiopathic encephalopathy who were referred from 70 hospitals across Korea for autoimmune synaptic and classic paraneoplastic antibodies. Those with cerebellar degeneration, sensory polyneuropathy or other paraneoplastic syndromes without encephalopathy were not included in this study. One-hundred and four patients (6.12%) had antibody-associated autoimmune encephalopathy. Autoimmune synaptic antibodies were identified in 89 patients (5.24%) and classic paraneoplastic antibodies were identified in 16 patients (0.94%). The patients with antibody-associated autoimmune encephalopathy comprised a small but significant portion of the total number of patients with encephalopathy of unknown cause.

Comparison Between Thymoglobulin and ATGAM as an Induction Agent in Adult Kidney Transplantation: A Single-Center Experience

OBJECTIVE The best antithymocyte globulin (ATG) preparation for induction suppression in kidney transplant recipients is still not clear. The aim of this study was to identify short- and long-term outcomes in kidney transplant recipients who received thymoglobulin or ATGAM as an induction agent. METHODS We retrospectively reviewed patients who underwent kidney transplantation from 1996 to 2010. Recipients were classified according to the ATG preparation. RESULTS One hundred fifty-two patients (64.4%) received thymoglobulin and 84 (35.6%) received ATGAM. The occurrence of delayed graft function in patients receiving thymoglobulin was higher than in patients receiving ATGAM (P = .005), but serum creatinine levels and acute rejection after kidney transplantation were not different between the two groups. The death-censored graft survival curve in thymoglobulin recipients was higher than in ATGAM recipients (P = .027). Bacterial infection was a predisposing factor for graft survival (P = .008). CONCLUSION The efficacy of thymoglobulin induction is generally better than that of ATGAM induction, and prevention of bacterial infections was just as important as the use of ATG because bacterial infection was an important risk factor for graft failure.

Assessment of Extent and Role of Tau in Subcortical Vascular Cognitive Impairment Using 18F-AV1451 Positron Emission Tomography Imaging

Importance Amyloid-&bgr; (A&bgr;), tau, and cerebral small vessel disease (CSVD), which occasionally coexist, are the most common causes of cognitive impairments in older people. However, whether tau is observed in patients with subcortical vascular cognitive impairment (SVCI), as well as its associations with A&bgr; and CSVD, are not yet established. More importantly, the role of tau underlying cognitive impairments in SVCI is unknown. Objective To investigate the extent and the role of tau in patients with SVCI using 18F-AV1451, which is a new ligand to detect neurofibrillary tangles in vivo. Design, Setting, and Participants This cross-sectional study recruited 64 patients with SVCI from June 2015 to December 2016 at Samsung Medical Center, Seoul, Korea. The patients had significant ischemia on brain magnetic resonance imaging, defined as periventricular white matter hyperintensity at least 10 mm and deep white matter hyperintensity at least 25 mm. We excluded 3 patients with SVCI owing to segmentation error during AV1451 positron emission tomography analysis. Main Outcomes and Measures We calculated CSVD scores based on the volumes of white matter hyperintensities, numbers of lacunes, and microbleeds using magnetic resonance imaging data. The presence of A&bgr; was assessed using fluorine 18–labeled (18F) florbetaben positron emission tomography. Tau was measured using 18F-AV1451 positron emission tomography. We determined the spreading order of tau by sorting the regional frequencies of cortical involvement. We evaluated the complex associations between A&bgr;, CSVD, AV1451 uptake, and cognition in patients with SVCI. Results Of the 61 patients with SVCI, 44 (72.1%) were women and the mean (SD) age was 78.7 (6.3) years. Patients with SVCI, especially patients with A&bgr;-negative SVCI, showed higher AV1451 uptake in the inferior temporal areas compared with normal control individuals. In patients with SVCI, A&bgr; positivity and CSVD score were each independently associated with increased AV1451 uptake in the medial temporal and inferior temporal regions, respectively. Involvement frequency of AV1451 uptake in the fusiform gyrus, inferior temporal, and precuneus regions were higher than that in the parahippocampal region. In patients with SVCI, higher AV1451 uptake in the inferior temporal and medial temporal regions correlated with worse language and general cognitive function. In patients with SVCI, A&bgr; positivity and CSVD score each correlated with worse general cognitive function, which was completely mediated by AV1451 uptake in the entorhinal cortex and inferior temporal gyrus, respectively. Conclusions and Relevance Our findings suggest that in SVCI, both A&bgr; and CSVD were independently associated with increased tau accumulation. Furthermore, tau burden played a pivotal role because it was the final common pathway for the cognitive impairment in patients with SVCI.

Correlations between Gray Matter and White Matter Degeneration in Pure Alzheimer’s Disease, Pure Subcortical Vascular Dementia, and Mixed Dementia

Alzheimer’s disease dementia (ADD) and subcortical vascular dementia (SVaD) both show cortical thinning and white matter (WM) microstructural changes. We evaluated different patterns of correlation between gray matter (GM) and WM microstructural changes in pure ADD, pure SVaD, and mixed dementia. We enrolled 40 Pittsburgh compound B (PiB) positive ADD patients without WM hyperintensities (pure ADD), 32 PiB negative SVaD patients (pure SVaD), 23 PiB positive SVaD patients (mixed dementia), and 56 normal controls. WM microstructural integrity was quantified using fractional anisotropy (FA), axial diffusivity (DA), and radial diffusivity (DR) values. We used sparse canonical correlation analysis to show correlated regions of cortical thinning and WM microstructural changes. In pure ADD patients, lower FA in the frontoparietal area correlated with cortical thinning in the left inferior parietal lobule and bilateral paracentral lobules. In pure SVaD patients, lower FA and higher DR across extensive WM regions correlated with cortical thinning in bilateral fronto-temporo-parietal regions. In mixed dementia patients, DR and DA changes across extensive WM regions correlated with cortical thinning in the bilateral fronto-temporo-parietal regions. Our findings showed that the relationships between GM and WM degeneration are distinct in pure ADD, pure SVaD, and mixed dementia, suggesting that different pathomechanisms underlie their correlations.

Association between pre‐donation serum uric acid concentration and change in renal function after living kidney donation in women

Reduction in renal mass after unilateral nephrectomy causes functional and structural changes in the remaining kidney.

Distinctive Clinical Effects of Haemorrhagic Markers in Cerebral Amyloid Angiopathy

Restricted lobar cerebral microbleeds (CMBs) and cortical superficial siderosis (CSS) are the characteristic markers of cerebral amyloid angiopathy (CAA). However, their effects on clinical features has not been evaluated well. The purpose of this study is to investigate the clinical implication of these markers in clinical-radiologically diagnosed CAA. A total of 372 patients with possible or probable CAA who met the modified Boston criteria were recruited in a memory clinic setting. Cortical thickness was measured using surface based methods. Presence of restricted multiple lobar CMBs were independently associated with cortical thinning across the entire cortical regions while presence of CSS was independently associated with cortical thinning primarily in the bilateral frontal region. Presence of restricted multiple lobar CMBs was associated with impairment in all cognitive domains such as attention, language, visuospatial, memory and frontal executive functions while presence of CSS was associated with attention and frontal dysfunction. The relationships of restricted multiple lobar CMBs or CSS with cognitive impairment were partially mediated by thinning in the corresponding cortical regions. Our findings suggested that restricted multiple lobar CMBs and CSS affect distinctive clinical features, providing new insights into potential mechanisms in CAA.

Prediction Model of Conversion to Dementia Risk in Subjects with Amnestic Mild Cognitive Impairment: A Longitudinal, Multi-Center Clinic-Based Study

BACKGROUND Patients with amnestic mild cognitive impairment (aMCI) have an increased risk of dementia. However, conversion rate varies. Therefore, predicting the dementia conversion in these patients is important. OBJECTIVE We aimed to develop a nomogram to predict dementia conversion in aMCI subjects using neuropsychological profiles. METHODS A total of 338 aMCI patients from two hospital-based cohorts were used in analysis. All patients were classified into 1) verbal, visual, or both, 2) early or late, and 3) single or multiple-domain aMCI according to the modality, severity of memory dysfunction, and multiplicity of involved cognitive domains, respectively. Patients were followed up, and conversion to dementia within 3 years was defined as the primary outcome. Our patients were divided into a training data set and a validation data set. The associations of potential covariates with outcome were tested, and nomogram was constructed by logistic regression model. We also developed another model with APOE data, which included 242 patients. RESULTS In logistic regression models, both modalities compared with visual only (OR 4.44, 95% CI 1.83-10.75, p = 0.001), late compared to early (OR 2.59, 95% CI 1.17-5.72, p = 0.019), and multiple compared to single domain (OR 3.51, 95% CI 1.62-7.60, p = 0.002) aMCI were significantly associated with dementia conversion within 3 years. A nomogram incorporating these clinical variables was constructed on the training data set and validated on the validation data set. Both nomograms with and without APOE data showed good prediction performance (c-statistics ≥ 0.75). CONCLUSIONS This study showed that several neuropsychological profiles of aMCI are significantly associated with imminent dementia conversion, and a nomogram incorporating these clinical subtypes is simple and useful to help to predict disease progression.