Clinical Significance of the Plasma Biomarker Panels in Amyloid-Negative and Tau PET-Positive Amnestic Patients: Comparisons with Alzheimer's Disease and Unimpaired Cognitive Controls.

The purpose of this study was to investigate whether plasma biomarkers can help to diagnose, differentiate from Alzheimer disease (AD), and stage cognitive performance in patients with positron emission tomography (PET)-confirmed primary age-related tauopathy, termed tau-first cognitive proteinopathy (TCP) in this study. In this multi-center study, we enrolled 285 subjects with young-onset AD (YOAD; n = 55), late-onset AD (LOAD; n = 96), TCP (n = 44), and cognitively unimpaired controls (CTL; n = 90) and analyzed plasma Aß42/Aß40, pTau181, neurofilament light (NFL), and total-tau using single-molecule assays. Amyloid and tau centiloids reflected pathological burden, and hippocampal volume reflected structural integrity. Receiver operating characteristic curves and areas under the curves (AUCs) were used to determine the diagnostic accuracy of plasma biomarkers compared to hippocampal volume and amyloid and tau centiloids. The Mini-Mental State Examination score (MMSE) served as the major cognitive outcome. Logistic stepwise regression was used to assess the overall diagnostic accuracy, combining fluid and structural biomarkers and a stepwise linear regression model for the significant variables for MMSE. For TCP, tau centiloid reached the highest AUC for diagnosis (0.79), while pTau181 could differentiate TCP from YOAD (accuracy 0.775) and LOAD (accuracy 0.806). NFL reflected the clinical dementia rating in TCP, while pTau181 (rho = 0.3487, p = 0.03) and Aß42/Aß40 (rho = -0.36, p = 0.02) were significantly correlated with tau centiloid. Hippocampal volume (unstandardized ß = 4.99, p = 0.01) outperformed all of the fluid biomarkers in predicting MMSE scores in the TCP group. Our results support the superiority of tau PET to diagnose TCP, pTau181 to differentiate TCP from YOAD or LOAD, and NFL for functional staging.

Assessment for Tactile Perception in Children With Cerebral Palsy.

IMPORTANCE: Impaired tactile perception frequently accompanies motor deficits in children with cerebral palsy (CP). Assessing tactile perception precisely for children with CP remains challenging because of a lack of assessments with robust psychometric evidence or standard procedures. OBJECTIVE: To develop a standardized assessment tool, the Tactile Perceptual Test (TPT), for measuring tactile perception in children with CP and to examine its psychometric properties. DESIGN: Observational study design. SETTING: University research laboratory and medical center. PARTICIPANTS: Children with CP (n = 100) and typical development (TD; n = 50). OUTCOMES AND MEASURES: The TPT includes four subtests measuring stereognosis, roughness, hardness, and heaviness. Three comparator instruments, Semmes-Weinstein monofilaments, Two-Point Discrimination, and the stereognosis subtest of the Revised Nottingham Sensory Assessment, were used for convergent validity. RESULTS: Good test-retest reliability was confirmed for all of the TPT subtests. The values of minimal detectable change were acceptable. Moderate correlations between the TPT and comparator instruments were found, as expected. For known-groups validity, the significant difference was confirmed between children with CP and those with TD. CONCLUSIONS AND RELEVANCE: The TPT is a reliable and valid measure for multiple subdomains of tactile perception in children with CP. This tactile assessment may help clarify tactile performance to provide appropriate, precise interventions. What This Article Adds: The TPT measures tactile perception in children with CP. It has four subdomains of tactile perception that could facilitate prioritization of tactile treatment of specific subdomains and thereby aid in the provision of appropriate interventions.

Hypothyroidism and risks of cerebrovascular complications among patients with head and neck cancer after radiotherapy.

BACKGROUND: Hypothyroidism (HT) and carotid artery stenosis (CAS) are complications of radiotherapy (RT) in patients with head and neck cancer (HNC). The impact of post-RT HT on CAS progression remains unclear. METHODS: Between 2013 and 2014, HNC patients who had ever received RT and were under regular follow-up in our hospital were initially screened. Patients were categorized into euthyroid (EU) and HT groups. Details of RT and HNC were recorded. Total plaque scores and degrees of CAS were measured during annual extracranial duplex follow-up. Patients were monitored for CAS progression to > 50 % stenosis or ischemic stroke (IS). Cumulative time to CAS progression and IS between the 2 groups were compared. Data were further analyzed based on the use or nonuse of thyroxine of the HT group. RESULTS: 333 HNC patients with RT history were screened. Finally, 216 patients were recruited (94 and 122 patients in the EU and HT groups). Patients of the HT group received higher mean RT doses (HT vs. EU; 7021.55 ± 401.67 vs. 6869.69 ± 425.32 centi-grays, p = 0.02). Multivariate Cox models showed comparable CAS progression (p = 0.24) and IS occurrence (p = 0.51) between the 2 groups. Moreover, no significant difference was observed in time to CAS progression (p = 0.49) or IS (p = 0.31) among patients with EU and HT using and not using thyroxine supplement. CONCLUSIONS: Our results did not demonstrate significant effects of HT and thyroxine supplementation on CAS progression and IS incidence in patients with HNC after RT.

Investigation of reactive astrogliosis effect on post-stroke cognitive impairment.

BACKGROUND: The aim of this study is to investigate the associations between post-stroke cognitive impairment (PSCI) severity and reactive astrogliosis (RA) extent on normalized 18F-THK-5351 positron-emission tomography (PET) imaging in amyloid-negative patients with first-ever stroke. METHODS: We prospectively enrolled 63 amyloid-negative patients with first-ever stroke. Neurocognitive evaluation, MRI, 18F-THK-5351, and 18F-florbetapir PET were performed around 3 months after stroke. The 18F-THK-5351 uptake intensity was normalized using a signal distribution template to obtain the Z-SUM scores as the RA extent in the whole brain and cerebral hemisphere ipsilateral to stroke lesion. We evaluated stroke volume, leukoaraiosis, and brain atrophy on MRI. We used a comprehensive neurocognitive battery to obtain composite cognitive scores, and defined PSCI as a general cognitive function score < - 1. We analyzed the influence of Z-SUM scores on PSCI severity after adjusting for demographic, vascular, and neurodegenerative variables. RESULTS: Twenty-five of 63 stroke patients had PSCI. Patients with PSCI had older age, lower education, and more severe cortical atrophy and total Z-SUM scores. Total Z-SUM scores were significantly associated with general cognitive and executive functions at multiple regression models. Path analyses showed that stroke can exert cognitive influence directly by stroke itself as well as indirectly through RA, including total and ipsilateral Z-SUM scores, in patients with either right or left hemisphere stroke. CONCLUSION: The patterns and intensity of 18F-THK-5351 uptake in amyloid-negative patients with first-ever stroke were associated with PSCI manifestations, which suggests that RA presents a modulating effect in PSCI development.

Computed Tomography Angiography in Acute Stroke Patients Receiving Recombinant Tissue Plasminogen Activator: Outcome and Safety Evaluations in an Asian Population.

INTRODUCTION: The multiphase computed tomography angiography (mCTA) is superior to the noncontrast computed tomography (NCCT) in selecting patients that would benefit from mechanical thrombectomy following an acute ischemic stroke (AIS). It remains unclear whether the longer examination time of mCTA worsens outcomes of intravenous recombinant tissue plasminogen activator (IV r-tPA) or increases the risk of hemorrhagic transformation (HT) compared to NCCT in Asian stroke patients. METHODS: Between January 2011 and December 2017, 199 AIS patients receiving IV r-tPA with initial National Institute of Health Stroke Scale (NIHSS) scores between 6 and 25 were enrolled in a single medical center. Onset-to-needle time (ONT), door-to-needle time (DNT), and creatinine levels before and after thrombolysis were recorded. We evaluated NIHSS scores 2, 24 h after treatment, and at discharge, the modified Rankin Scale (mRS) at discharge, and mortality rate. The presence of HT was reviewed within 7 days after thrombolysis. RESULTS: DNT, perithrombolysis creatinine levels, NIHSS, and mRS scores at the emergency room were similar between the NCCT and mCTA groups. ONT was shorter in the mCTA group. AIS patients got more significant neurologic improvement (NIHSS decrease ≥4) after thrombolysis and physically independent (mRS ≤2) at discharge in the mCTA group. Mortality rates, symptomatic, and total HT rates were similar between the NCCT and mCTA groups. CONCLUSION: Comparing to NCCT, mCTA-based IV r-tPA would not delay DNT nor worsen the outcome. Furthermore, mCTA provides more information for early identification of candidates for mechanical thrombectomy in Asian AIS patients.

Correlation between visual association memory test and structural changes in patients with Alzheimer's disease and amnestic mild cognitive impairment.

BACKGROUND: Visual association memory test (VAMT) is a brief 6-point cognition test that has been shown to be effective in differentiating Alzheimer's disease (AD) from other types of dementia. This study aimed to investigate the correlation of the VAMT performance with amyloid plaque burden and hippocampal atrophy. METHODS: Fourteen patients with AD, 29 with amnestic mild cognitive impairment (aMCI), and 11 normal cognition (NC) subjects were recruited. Brain magnetic resonance imaging (MRI) and [18F]AV-45 positron emission tomography (PET) were performed to evaluate hippocampal atrophy and amyloid plaque burden. RESULTS: The VAMT median score and interquartile range of the NC, aMCI and AD groups were 6 (6-6), 2 (0-4), and 0 (0-1), respectively (p < 0.001). The hippocampal atrophy was correlated with VAMT results across each group. The VAMT score was correlated with the occipital and parietal cortical [18F]AV-45 uptake in the NC group, and with the frontal, parietal and precuneus uptake in the aMCI group. However, no correlation between VAMT score and [18F]AV-45 uptake was found in the AD group. CONCLUSION: The VAMT can be an adjunctive cognitive test to identify patients with AD, and the early amyloid plaque accumulation is correlated with VAMT scores in patients with aMCI and even NC subjects.

Dual-phase 18F-florbetapir positron emission tomography in patients with primary progressive aphasia, Alzheimer's disease, and healthy controls: A preliminary study.

BACKGROUND/PURPOSE: To determine whether dual-phase 18F-florbetapir positron emission tomography imaging with perfusion-like and amyloid deposition information can distinguish among primary progressive aphasia (PPA), Alzheimer's disease (AD), and healthy controls (HCs). METHODS: Patients diagnosed with PPA, including four semantic dementia (SD) and two progressive nonfluent aphasia (PNFA), as well as one logopenic variant (LV) of PPA, were studied. All PPA patients, and age-/sex-matched patients with probable AD (n=8) and HCs (n=8) were subjected to dual-phase 18F-florbetapir imaging. Atlas-based quantitative volumes of interest (VOIs) analysis for six cortical areas and whole cerebellum was performed. The standardized uptake value ratios were calculated by normalizing the dual-phase-integrated activities of the six VOIs to whole cerebellum counts. RESULTS: Early phase 18F-florbetapir image showed significantly lower global perfusion index in six PPA patients as compared with HCs. According to VOI analysis, the hypoperfusion lesions were identified in the frontal, anterior cingulate, parietal, precuneus, and temporal regions. Similar findings were confirmed by voxel-base image comparison. 18F-florbetapir late-phase image showed significantly increased amyloid burden in the global cortex index and all six brain regions of eight AD and LV patients when compared with the other six PPA patients and eight HCs. There was no apparent uptake of amyloid tracer in both six PPA patients and eight HCs. CONCLUSION: Dual-phase 18F-florbetapir images of six PPA (SD and PNFA) patients showed hypoperfusion in the frontotemporal cortex, and little global amyloid uptake, which may be a distinct image pattern for differentiation among HC, AD, and PPA patients.

Imaging characteristic of dual-phase (18)F-florbetapir (AV-45/Amyvid) PET for the concomitant detection of perfusion deficits and beta-amyloid deposition in Alzheimer's disease and mild cognitive impairment.

PURPOSE: We investigated dual-phase (18)F-florbetapir (AV-45/Amyvid) PET imaging for the concomitant detection of brain perfusion deficits and beta-amyloid deposition in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI), and in cognitively healthy controls (HCs). METHODS: A total of 82 subjects (24 AD patients, 44 MCI patients and 14 HCs) underwent both dual-phase (18)F-AV-45 PET and MRI imaging. Dual-phase dynamic PET imaging consisted of (1) five 1-min scans obtained 1 - 6 min after tracer injection (perfusion (18)F-AV-45 imaging, pAV-45), and (2) ten 1-min scans obtained 50 - 60 min after tracer injection (amyloid (18)F-AV-45 imaging). Amyloid-negative MCI/AD patients were excluded. Volume of interest analysis and statistical parametric mapping of pAV-45 and (18)F-AV-45 images were performed to investigate the perfusion deficits and the beta-amyloid burden in the three study groups. The associations between Mini-Mental State Examination (MMSE) scores and global perfusion deficits and amyloid deposition were investigated with linear and segmental linear correlation analyses. RESULTS: HCs generally had normal pAV-45 findings, whereas perfusion deficits were evident in the hippocampus, and temporal, parietal and middle frontal cortices in both MCI and AD patients. The motor-sensory cortex was relatively preserved. MMSE scores in the entire study cohort were significantly associated with the degree of perfusion impairment as assessed by pAV-45 imaging (r = 0.5156, P < 0.0001). (18)F-AV-45 uptake was significantly higher in AD patients than in the two other study groups. However, the correlation between MMSE scores and (18)F-AV-45 uptake in MCI patients was more of a binary phenomenon and began in MCI patients with MMSE score 23.14 when (18)F-AV-45 uptake was higher and MMSE score lower than in patients with early MCI. Amyloid deposition started in the precuneus and the frontal and temporal regions in early MCI, ultimately reaching the maximum burden in advanced MCI. CONCLUSION: Our results indicate that brain perfusion deficits and beta-amyloid deposition in AD follow different trajectories that can be successfully traced using dual-phase (18)F-AV-45 PET imaging.

Initial blood pressure is associated with stroke severity and is predictive of admission cost and one-year outcome in different stroke subtypes: a SRICHS registry study.

BACKGROUND: To investigate if initial blood pressure (BP) on admission is associated with stroke severity and predictive of admission costs and one-year-outcome in acute ischemic (IS) and hemorrhagic stroke (HS). METHODS: This is a single-center retrospective cohort study. Stroke patients admitted within 3 days after onset between January 1st and December 31st in 2009 were recruited. The initial BP on admission was subdivided into high (systolic BP ≥ 211 mmHg or diastolic BP ≥ 111 mmHg), medium (systolic BP 111-210 mmHg or diastolic BP 71-110 mmHg), and low (systolic BP ≤ 110 mmHg or diastolic BP ≤ 70 mmHg) groups and further subgrouped with 25 mmHg difference in systole and 10 mmHg difference in diastole for the correlation analysis with demographics, admission cost and one-year modified Rankin scale (mRS). RESULTS: In 1173 IS patients (mean age: 67.8 ± 12.8 years old, 61.4% male), low diastolic BP group had higher frequency of heart disease (p =0.001), dehydration (p =0.03) and lower hemoglobin level (p <0.001). The extremely high and low systolic BP subgroups had worse National Institutes of Health Stroke Scale (NIHSS) score (p =0.03), higher admission cost (p <0.001), and worse one-year mRS (p =0.03), while extremely high and low diastolic BP subgroups had higher admission cost (p <0.01). In 282 HS patients (mean age: 62.4 ± 15.4 years old, 60.6% male), both low systolic and diastolic BP groups had lower hemoglobin level (systole: p =0.05; diastole: p <0.001). The extremely high and low BP subgroups had worse NIHSS score (p =0.01 and p <0.001, respectively), worse one-year mRS (p =0.002 and p =0.001, respectively), and higher admission cost (diastole: p <0.002). CONCLUSIONS: Stroke patients with extremely high and low BP on admission have not only worse stroke severity but also higher admission cost and/or worse one-year outcome. In those patients with low BP, low admission hemoglobin might be a contributing factor.

Presence of Gyriform Air Predicts Unfavorable Outcome in Venous Catheter-Related Cerebral Air Embolism.

BACKGROUND: This study aimed to investigate the clinical predictors of unfavorable prognosis in patients with venous catheter-related cerebral air embolism. METHODS: An extensive review of English literature was performed to obtain reports on cerebral air embolism published between January 1982 and July 2014 through PubMed, Journal at Ovid, and Web of Science using the Mesh terms and keywords "cerebral air embolism" and "cerebral gas embolism." Reports not fulfilling the diagnosis of cerebral air embolism and iterant articles were excluded. Demographics, clinical manifestations, and imaging findings were recorded. The air distribution on initial brain computed tomography (CT) was recorded as gyriform air (GF), cavernous sinus bubble, venous sinus bubble, and parenchymal and subarachnoid bubble. The enrolled subjects were further divided into favorable and unfavorable outcome groups for analyses. RESULTS: Of the 33 cases enrolled, 31 had documented follow-up outcomes, including 14 with favorable and 17 with unfavorable prognoses. Patients with unfavorable outcome had older onset age (67.5 ± 15.8 versus 46.7 ± 17.0 years, P < .001), higher frequency of GF on brain CT (58.8% versus 0%, P < .01), initial consciousness disturbance (100% versus 42.9%, P < .001), and hemiparesis (100% versus 42.9%, P < .001), but lower frequency of cardiopulmonary symptoms (5.9% versus 64.3%, P < .01). In patients with central venous catheter-related cerebral air embolism, the retrograde mechanism had a tendency for worse outcomes (43.8% versus 0%, P = .023). CONCLUSIONS: In patients with venous catheter-related cerebral air embolism, the presence of GF on brain CT imaging, old age, initial conscious disturbance, and hemiparesis may predict unfavorable outcomes.

Coexisting diseases of moyamoya vasculopathy.

BACKGROUND: Several coexisting diseases have been reported in patients with moyamoya vasculopathy (MMV), but studies of quasi-moyamoya disease (quasi-MMD) are rare. This study aims to investigate the frequency of known coexisting diseases in patients with quasi-MMD and to compare quasi-MMD with moyamoya disease (MMD). METHODS: Between 2000 and 2011, we retrospectively screened patients with International Classification of Diseases, Ninth Revision, code of 4375 (MMD) in the Health Information System of our hospital. The vascular images of each patient were confirmed by 2 neurologists and 1 neuroradiologist based on the diagnostic criteria of Japan Ministry of Health and Welfare. We excluded the patients with missing images and erroneous diagnosis. Demographics, coexisting diseases, laboratory data, treatment, and recurrent strokes were recorded. The eligible patients were divided into quasi-MMD and MMD groups according to the presence or absence of coexisting diseases. RESULTS: MMV was found in 90 patients including 37 (41.1%) quasi-MMD and 53 (58.9%) MMD. Atherosclerosis (32.4%) and thyroid disease (29.7%) were the leading coexisting diseases in quasi-MMD. Patients with MMD became symptomatic in a bimodal age distribution, whereas patients with quasi-MMD became symptomatic in a single-peak distribution. The prognosis of recurrent strokes was similar between quasi-MMD and MMD based on Kaplan-Meier analysis. CONCLUSIONS: A bimodal distribution of onset age was noted in MMD, whereas a single-peak distribution was found in quasi-MMD. Coexisting diseases were usually underevaluated but were more common than expected in patients with MMV. Atherosclerosis and thyroid diseases were the leading coexisting diseases in different preferential age.

Human biodistribution and radiation dosimetry for the tau tracer [18F]Florzolotau in healthy subjects.

BACKGROUND: Tau pathology plays a crucial role in neurodegeneration diseases including Alzheimer's disease (AD) and non-AD diseases such as progressive supranuclear palsy. Tau positron emission tomography (PET) is an in-vivo and non-invasive medical imaging technique for detecting and visualizing tau deposition within a human brain. In this work, we aim to investigate the biodistribution of the dosimetry in the whole body and various organs for the [18F]Florzolotau tau-PET tracer. A total of 12 healthy controls (HCs) were enrolled at Chang Gung Memorial Hospital. All subjects were injected with approximately 379.03 ± 7.03 MBq of [18F]Florzolotau intravenously, and a whole-body PET/CT scan was performed for each subject. For image processing, the VOI for each organ was delineated manually by using the PMOD 3.7 software. Then, the time-activity curve of each organ was acquired by optimally fitting an exponential uptake and clearance model using the least squares method implemented in OLINDA/EXM 2.1 software. The absorbed dose for each target organ and the effective dose were finally calculated. RESULTS: From the biodistribution results, the elimination of [18F]Florzolotau is observed mainly from the liver to the intestine and partially through the kidneys. The highest organ-absorbed dose occurred in the right colon wall (255.83 µSv/MBq), and then in the small intestine (218.67 µSv/MBq), gallbladder wall (151.42 µSv/MBq), left colon wall (93.31 µSv/MBq), and liver (84.15 µSv/MBq). Based on the ICRP103, the final computed effective dose was 34.9 µSv/MBq with CV of 10.07%. CONCLUSIONS: The biodistribution study of [18F]Florzolotau demonstrated that the excretion of [18F]Florzolotau are mainly through the hepatobiliary and gastrointestinal pathways. Therefore, a routine injection of 370 MBq or 185 MBq of [18F]Florzolotau leads to an estimated effective dose of 12.92 or 6.46 mSv, and as a result, the radiation exposure to the whole-body and each organ remains within acceptable limits and adheres to established constraints. TRIAL REGISTRATION: Retrospectively Registered at Clinicaltrials.gov (NCT03625128) on 12 July, 2018, https://clinicaltrials.gov/study/NCT03625128 .

Dominance of Tau Burden in Cortical Over Subcortical Regions Mediates Glymphatic Activity and Clinical Severity in PSP.

BACKGROUND: Progressive supranuclear palsy (PSP) is a tauopathy that involves subcortical regions but also extends to cortical areas. The clinical impact of different tau protein sites and their influence on glymphatic dysfunction have not been investigated. PATIENTS AND METHODS: Participants (n = 55; 65.6 ± 7.1 years; 29 women) with PSP (n = 32) and age-matched normal controls (NCs; n = 23) underwent 18 F-Florzolotau tau PET, MRI, PSP Rating Scale (PSPRS), and Mini-Mental State Examination. Cerebellar gray matter (GM) and parametric estimation of reference signal intensity were used as references for tau burden measured by SUV ratios. Glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS). RESULTS: Parametric estimation of reference signal intensity is a better reference than cerebellar GM to distinguish tau burden between PSP and NCs. PSP patients showed higher cortical and subcortical tau SUV ratios than NCs ( P < 0.001 and <0.001). Cortical and subcortical tau deposition correlated with PSPRS, UPDRS, and Mini-Mental State Examination scores (all P 's < 0.05). Cortical tau deposition was further associated with the DTI-ALPS index and frontal-temporal-parietal GM atrophy. The DTI-ALPS indexes showed a significantly negative correlation with the PSPRS total scores ( P < 0.01). Finally, parietal and occipital lobe tau depositions showed mediating effects between the DTI-ALPS index and PSPRS score. CONCLUSIONS: Cortical tau deposition is associated with glymphatic dysfunction and plays a role in mediating glymphatic dysfunction and clinical severity. Our results provide a possible explanation for the worsening of clinical severity in patients with PSP.

Visual reading for [18F]Florzolotau ([18F]APN-1607) tau PET imaging in clinical assessment of Alzheimer's disease.

Introduction: Tau-targeted positron emission tomography (tau-PET) is a potential tool for the differential diagnosis of Alzheimer's disease (AD) and to clarify the distribution of tau deposition. In addition to the quantitative analysis of tau-PET scans, visual reading supports the assessment of tau loading for clinical diagnosis. This study aimed to propose a method for visually interpreting tau-PET using the [18F] Florzolotau tracer and investigate the performance and utility of the visual reading. Materials and methods: A total number of 46 individuals with 12 cognitively unimpaired subjects (CU), 20 AD patients with mild cognitive impairment (AD-MCI), and 14 AD with dementia (AD-D) patients with both [18F]Florbetapir amyloid PET and [18F]Florzolotau tau PET scans were included. Clinical information, cognitive assessment, and amyloid PET scan results were recorded. For visual interpretation, a modified rainbow colormap was created and a regional tau uptake scoring system was proposed to evaluate the degree of tracer uptake and its spatial distribution within five cortical regions. Each region was scored on a scale of [0, 2] as compared to the background, and that resulted in a global scale range of [0, 10]. Four readers interpreted [18F]Florzolotau PET using the visual scale. The global and regional standardized uptake value ratios (SUVr) were also calculated for analysis. Results: The result indicates the average global visual scores were 0 ± 0 in the CU group, 3.43 ± 3.35 in the AD-MCI group, and 6.31 ± 2.97 in the AD-D group (p < 0.001). The consensus among the four observers on image scores was high with an intraclass correlation coefficient of 0.880 (95% CI: 0.767-0.936). The average global visual score was significantly associated with global SUVr (r = 0.884, p < 0.0001) and with the CDR-sum of box (r = 0.677, p < 0.0001). Conclusion: The visual reading method generated a visual score of [18F]Florzolotau tau-PET with good sensitivity and specificity to identify AD-D or CU individuals from the other patients. The preliminary result also showed that the global visual scores are significantly and reliably correlated with global cortical SUVr, and associated well with the clinical diagnosis and cognitive performance.

Identification of Metabolomics Biomarkers in Extracranial Carotid Artery Stenosis.

The biochemical identification of carotid artery stenosis (CAS) is still a challenge. Hence, 349 male subjects (176 normal controls and 173 stroke patients with extracranial CAS ≥ 50% diameter stenosis) were recruited. Blood samples were collected 14 days after stroke onset with no acute illness. Carotid plaque score (≥2, ≥5 and ≥8) was used to define CAS severity. Serum metabolites were analyzed using a targeted Absolute IDQ®p180 kit. Results showed hypertension, diabetes, smoking, and alcohol consumption were more common, but levels of diastolic blood pressure, HDL-C, LDL-C, and cholesterol were lower in CAS patients than controls (p < 0.05), suggesting intensive medical treatment for CAS. PCA and PLS-DA did not demonstrate clear separation between controls and CAS patients. Decision tree and random forest showed that acylcarnitine species (C4, C14:1, C18), amino acids and biogenic amines (SDMA), and glycerophospholipids (PC aa C36:6, PC ae C34:3) contributed to the prediction of CAS. Metabolite panel analysis showed high specificity (0.923 ± 0.081, 0.906 ± 0.086 and 0.881 ± 0.109) but low sensitivity (0.230 ± 0.166, 0.240 ± 0.176 and 0.271 ± 0.169) in the detection of CAS (≥2, ≥5 and ≥8, respectively). The present study suggests that metabolomics profiles could help in differentiating between controls and CAS patients and in monitoring the progression of CAS.

Automatic identification of early ischemic lesions on non-contrast CT with deep learning approach.

Early ischemic lesion on non-contrast computed tomogram (NCCT) in acute stroke can be subtle and need confirmation with magnetic resonance (MR) image for treatment decision-making. We retrospectively included the NCCT slices of 129 normal subjects and 546 ischemic stroke patients (onset < 12 h) with corresponding MR slices as reference standard from a prospective registry of Chang Gung Research Databank. In model selection, NCCT slices were preprocessed and fed into five different pre-trained convolutional neural network (CNN) models including Visual Geometry Group 16 (VGG16), Residual Networks 50, Inception-ResNet-v2, Inception-v3, and Inception-v4. In model derivation, the customized-VGG16 model could achieve an accuracy of 0.83, sensitivity 0.85, F-score 0.80, specificity 0.82, and AP 0.82 after using a tenfold cross-validation method, outperforming the pre-trained VGG16 model. In model evaluation, the customized-VGG16 model could correctly identify 53 in 58 subjects (91.37%) including 29 ischemic stroke patients and 24 normal subjects and reached the sensitivity of 86.95% in identifying ischemic NCCT slices (200/230), irrespective of supratentorial or infratentorial lesions. The customized-VGG16 CNN model can successfully identify the presence of early ischemic lesions on NCCT slices using the concept of automatic feature learning. Further study will be proceeded to detect the location of ischemic lesion.

Mediating roles of leukoaraiosis and infarcts in the effects of unilateral carotid artery stenosis on cognition.

Background and objectives: Leukoaraiosis and infarcts are common in patients with carotid artery stenosis (CAS), and CAS severity, leukoaraiosis and infarcts all have been implicated in cognitive impairments. CAS severity was not only hypothesized to directly impede specific cognitive domains, but also transmit its effects indirectly to cognitive function through ipsilateral infarcts as well as periventricular leukoaraiosis (PVL) and deep white matter leukoaraiosis (DWML). We aimed to delineate the contributions of leukoaraiosis, infarcts and CAS to different specific cognitive domains. Materials and methods: One hundred and sixty one participants with unilateral CAS (>50%) on the left (n = 85) or right (n = 76) side and 65 volunteers without significant CAS (<50%) were recruited. The PVL, DWML, and infarct severity were visually rated on MRI. A comprehensive cognitive battery was administered and standardized based on age norms. Correlation and mediation analyses were adopted to examine the direct and indirect influence of CAS, leukoaraiosis, and infarct on specific cognitive domains with adjustment for education, hypertension, diabetes mellitus, and hyperlipidemia. Results: Carotid artery stenosis severity was associated with ipsilateral leukoaraiosis and infarct. Left CAS had direct effects on most cognitive domains, except for visual memory and constructional ability, and transmitted its indirect effects on all cognitive domains through ipsilateral PVL, and on constructional ability and psychomotor through infarcts. Right CAS only had negative direct effects on visual memory, psychomotor, design fluency and color processing speed, and transmitted its indirect effects on visual memory, word and color processing speed through ipsilateral infarcts. The trends of direct and indirect cognitive effects remained similar after covariate adjustment. Conclusion: Left and right CAS would predominantly lead to verbal and non-verbal cognitive impairment respectively, and such effects could be mediated through CAS-related leukoaraiosis and infarct. Given that cognition is subject to heterogeneous pathologies, the exact relationships between markers of large and small vessel diseases and their composite prognostic effects on cognition requires further investigation.

Head and Neck Cancer Types and Risks of Cervical-Cranial Vascular Complications within 5 Years after Radiation Therapy.

Background and purpose: to investigate the frequency of cervical−cranial vascular complications soon after radiation therapy (RT) and identify differences among patients with various types of head and neck cancer (HNC). Methods: We enrolled 496 patients with HNC who had received their final RT dose in our hospital. These patients underwent carotid duplex ultrasound (CDU) for monitoring significant carotid artery stenosis (CAS). Brain imaging were reviewed to detect vertebral, intracranial artery stenosis, or preexisted CAS before RT. Primary outcome was significant CAS at the internal or common carotid artery within first 5 years after RT. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of significant CAS between the groups using Kaplan−Meier and Cox-regression analyses. Results: Compared to the NPC group, the non-NPC group had a higher frequency of significant CAS (12.7% vs. 2.0%) and were more commonly associated with significant CAS after adjusting the covariates (Adjusted hazard ratio: 0.17, 95% confident interval: 0.05−0.57) during the follow-up period. All the non-NPC subtypes (oral cancer/oropharyngeal, hypopharyngeal, and laryngeal cancers) were associated with higher risks of significant CAS than the NPC group (p < 0.001 respectively). Conclusion: Significant CAS was more frequently noted within 5 years of RT among the patients with non-NPC HNC than among the patients with NPC. Scheduled carotid artery surveillance and vascular risk monitoring should be commenced earlier for patients with non-NPC HNC. By contrast, vascular surveillance could be deferred to 5 years after RT completion in NPC patients.

Immediate regression of leukoaraiosis after carotid artery revascularization.

BACKGROUND: Leukoaraiosis (LA) affects cognition after stroke and reversal of LA may improve cognitive performance. We aimed to determine the impact of cerebral perfusion and circle of Willis (CoW) flow patterns on the extent of LA after carotid artery revascularization. METHODS: LA was scored on fluid-attenuated inversion recovery magnetic resonance (MR) images at the levels of the centrum semiovale and frontal horns in both cerebral hemispheres of 62 contiguous patients (men/women = 38/24, mean age = 63.2 ± 8.4 years, range 44-82) before and after unilateral carotid artery revascularization. The pre- and poststenting differences in LA scores, CoW flow pattern on MR angiography, and MR perfusion parameters were analyzed. RESULTS: The total LA score decreased from 9.87 ± 0.65 to 8.33 ± 0.72 after stenting (p = 0.03). The CoW was complete in 21 subjects and incomplete in 41 subjects. The incomplete CoW group had a higher preoperative LA load and higher cerebral interhemispheric asymmetry index, both of which decreased significantly postoperatively. CONCLUSIONS: CoW anomalies may contribute to LA in patients with carotid artery stenosis, and restoration of cerebral perfusion by carotid artery revascularization can reduce LA severity.

Associations between Circle of Willis morphology and white matter lesion load in subjects with carotid artery stenosis.

BACKGROUND: Various cerebral pathological changes have been reported to cause leukoaraiosis (LA). We hypothesized that circle of Willis (CoW) anomalies may contribute to LA in severe carotid artery stenosis victims through impaired cerebral autoregulation. We conducted a retrospective review on cerebral magnetic resonance (MR) patterns in patients with severe symptomatic carotid artery stenosis and compared white matter lesion (WML) load between subjects with and without complete CoW. METHODS: LA on fluid attenuation inversion recovery (FLAIR) MR images at the levels of the centrum semiovale and frontal horns in both cerebral hemispheres were scored in 106 patients with unilateral carotid artery stenosis (64 men and 42 women; mean age 68.7 ± 9.2 years, range 44-82). Subjects were divided into groups of complete and incomplete CoW according to cerebral MR angiography. Differences in the LA scores between the groups of complete and incomplete CoW were further analyzed. RESULTS: Compared with those with incomplete configuration of the CoW, subjects with a complete CoW demonstrated a decreased WML load at the level of the centrum semiovale (2.78 ± 1.17 vs. 5.62 ± 2.12, p = 0.02) and frontal horns (2.21 ± 0.79 vs. 4.22 ± 1.83, p = 0.01). CONCLUSION: Our results support the importance of a complete CoW since it may protect from WML in case of carotid stenosis.