Usability of a Web-Based Registry for Preclinical Alzheimer's Disease: Implications from a Cross-Sectional Online Survey.

BACKGROUND: We have been conducting a Japanese trial-ready cohort web study since 2019 as a web-based online registry to enroll individuals with preclinical Alzheimer's disease to facilitate trials on Alzheimer's disease prevention. The usability of a website might be an important factor in determining user participation and retention. OBJECTIVES: We conducted a user questionnaire survey to analyze the usability of the Japanese trial-ready cohort website and user characteristics for future website improvement. DESIGN: This was a cross-sectional prospective observational study. SETTING: Online survey using Google Forms. PARTICIPANTS: Among the Japanese trial-ready cohort web study participants, we enrolled those who provided consent to participate in the study and had completed one or more Cognitive Function Instrument tests before May 2, 2023. We sent an invitation e-mail, including the questionnaire web address, to eligible participants on July 21 and 22, 2023. MEASUREMENTS: We analyzed the questionnaire answers, including the system usability scale score and time of response (in 24 h). We also compared the respondents' characteristics with that of all the Japanese trial-ready cohort web study participants to identify features associated with an increased/decreased response rate to the questionnaire. RESULTS: Among the 10,112 Japanese trial-ready cohort web study participants that we sent invitation e-mails, we received 1,574 eligible responses (15.6%) within three weeks of the response acceptance period. The mean system usability scale score was 67.6, and no difference in system usability scale scores was observed in terms of age or sex. Approximately half of the respondents of the Japanese trial-ready cohort web study heard about it online, whereas one-fourth heard about it via newspapers. Contribution to drug development for dementia treatment was the most frequent motivation for participating in the Japanese trial-ready cohort web study (51.5%), followed by participation in the latest research (48.1%), concerns about self-memory (43.4%), and a family history of dementia (34.6%). Female respondents responded approximately 1.5 h later than male respondents. Lastly, those who had participated in the Japanese trial-ready cohort onsite study, were in their 70's, or had a larger number of Cognitive Function Instrument or Cogstate tests completion history were more likely to respond to the current online survey (relative risk of response > 1). CONCLUSIONS: We conducted an online survey using Google Forms for participants in the Japanese trial-ready cohort web study to determine the usability. The results of this study might help to improve the user experience of the Japanese trial-ready cohort website itself, increase the web study registrants, maintain user retention, facilitate future online surveys, and serve as a reference for other web-based registries of presymptomatic disease status.

A Japanese Multicenter Study on PET and Other Biomarkers for Subjects with Potential Preclinical and Prodromal Alzheimer's Disease.

BACKGROUND: PET (positron emission tomography) and CSF (cerebrospinal fluid) provide the "ATN" (Amyloid, Tau, Neurodegeneration) classification and play an essential role in early and differential diagnosis of Alzheimer's disease (AD). OBJECTIVE: Biomarkers were evaluated in a Japanese multicenter study on cognitively unimpaired subjects (CU) and early (E) and late (L) mild cognitive impairment (MCI) patients. MEASUREMENTS: A total of 38 (26 CU, 7 EMCI, 5 LMCI) subjects with the age of 65-84 were enrolled. Amyloid-PET and FDG-PET as well as structural MRI were acquired on all of them, with an additional tau-PET with 18F-flortaucipir on 15 and CSF measurement of Aß1-42, P-tau, and T-tau on 18 subjects. Positivity of amyloid and tau was determined based on the positive result of either PET or CSF. RESULTS: The amyloid positivity was 13/38, with discordance between PET and CSF in 6/18. Cortical tau deposition quantified with PET was significantly correlated with CSF P-tau, in spite of discordance in the binary positivity between visual PET interpretation and CSF P-tau in 5/8 (PET-/CSF+). Tau was positive in 7/9 amyloid positive and 8/16 amyloid negative subjects who underwent tau measurement, respectively. Overall, a large number of subjects presented quantitative measures and/or visual read that are close to the borderline of binary positivity, which caused, at least partly, the discordance between PET and CSF in amyloid and/or tau. Nine subjects presented either tau or FDG-PET positive while amyloid was negative, suggesting the possibility of non-AD disorders. CONCLUSION: Positivity rate of amyloid and tau, together with their relationship, was consistent with previous reports. Multicenter study on subjects with very mild or no cognitive impairment may need refining the positivity criteria and cutoff level as well as strict quality control of the measurements.

Cohort-Specific Optimization of Models Predicting Preclinical Alzheimer's Disease, to Enhance Screening Performance in the Middle of Preclinical Alzheimer's Disease Clinical Studies.

BACKGROUND: Models that can predict brain amyloid beta (Aß) status more accurately have been desired to identify participants for clinical trials of preclinical Alzheimer's disease (AD). However, potential heterogeneity between different cohorts and the limited cohort size have been the reasons preventing the development of reliable models applicable to the Asian population, including Japan. OBJECTIVES: We aim to propose a novel approach to predict preclinical AD while overcoming these constraints, by building models specifically optimized for ADNI or for J-ADNI, based on the larger samples from A4 study data. DESIGN AND PARTICIPANTS: This is a retrospective study including cognitive normal participants (CDR-global = 0) from A4 study, Alzheimer Disease Neuroimaging Initiative (ADNI), and Japanese-ADNI (J-ADNI) cohorts. MEASUREMENTS: The model is made up of age, sex, education years, history of AD, Clinical Dementia Rating-Sum of Boxes, Preclinical Alzheimer Cognitive Composite score, and APOE genotype, to predict the degree of amyloid accumulation in amyloid PET as Standardized Uptake Value ratio (SUVr). The model was at first built based on A4 data, and we can choose at which SUVr threshold configuration the A4-based model may achieve the best performance area under the curve (AUC) when applied to the random-split half ADNI or J-ADNI subset. We then evaluated whether the selected model may also achieve better performance in the remaining ADNI or J-ADNI subsets. RESULT: When compared to the results without optimization, this procedure showed efficacy of AUC improvement of up to approximately 0.10 when applied to the models "without APOE;" the degree of AUC improvement was larger in the ADNI cohort than in the J-ADNI cohort. CONCLUSIONS: The obtained AUC had improved mildly when compared to the AUC in case of literature-based predetermined SUVr threshold configuration. This means our procedure allowed us to predict preclinical AD among ADNI or J-ADNI second-half samples with slightly better predictive performance. Our optimizing method may be practically useful in the middle of the ongoing clinical study of preclinical AD, as a screening to further increase the prior probability of preclinical AD before amyloid testing.

Cauda Equina and Filum Terminale Arteriovenous Fistulas: Anatomic and Radiographic Features.

Intradural AVF below the conus medullaris may develop either on the filum terminale or the cauda equina (lumbosacral and coccygeal radicular nerves). Although not a few filum terminale AVFs are found in the literature, only 3 detailed cauda equina AVFs have been reported. Here, we analyze the angiographic and MR imaging findings of our cauda equina and filum terminale AVF cases, supplemented with literature research to characterize the radiologic features of the 2 entities. On angiography, filum terminale AVFs were invariably supplied by the extension of the anterior spinal artery accompanied by a closely paralleling filum terminale vein. Cauda equina AVFs were fed by either a radicular or a spinal artery or both arteries, often with a characteristic wavy radicular-perimedullary draining vein. On thin-section axial MR imaging, the filum terminale AVF draining vein joined the spinal cord at the conus medullaris apex, but that of the cauda equina AVF joined above the conus medullaris apex.

Cavity resonator for circularly polarized microwave irradiation mounted on a cryostat.

We have constructed a cylindrical cavity resonator with a hybrid coupler where circularly polarized microwaves can be irradiated to a sample. The polarity of the microwave can be switched by changing the input ports of the hybrid coupler. The cavity resonator is small enough to be mounted on a cryostat which enables us to change the sample temperature in a wide range. To demonstrate the performance of the cavity resonator mounted on a cryostat, Yttrium Iron Garnet (YIG) was used as a test sample. We succeeded in selectively exciting left and right circularly polarized modes with high polarization (>80%). We also evaluated the susceptibility tensor of YIG in the cryostat. The technique presented here would offer a new direction in the fields of spintronics and quantum information.

Occlusion of Posterior Fossa Dural Sinuses in Vein of Galen Malformation.

BACKGROUND AND PURPOSE: Spontaneous or progressive occlusion of the posterior fossa dural sinuses is often observed in patients with vein of Galen malformation, which can affect the clinical course. The aim of this study was to examine the patency of the posterior fossa dural sinuses in patients with vein of Galen malformation and to analyze the clinical and angiographic course of this condition. MATERIALS AND METHODS: We retrospectively reviewed 61 consecutive children with vein of Galen malformations. Clinical presentation, management, outcome, and angiographic change were analyzed for the patients with attention paid to all dural sinus occlusions. RESULTS: Twenty patients (32.8%) demonstrated spontaneous sinus occlusion, mostly in the sigmoid sinus. This condition was not observed in neonates and was first discovered during infancy or childhood. Progression of sinus occlusion was seen in 10 patients, and the conditions of 6 of them deteriorated in accordance with the progression of sinus occlusion. After total or subtotal obliteration of the malformation by transarterial glue embolization, 13 patients recovered to healthy, 3 patients had only mild developmental delay, and 4 patients remained neurologically disabled. CONCLUSIONS: Spontaneous sinus occlusion is not a rare condition and can result in neurologic deterioration in the natural history of untreated vein of Galen malformation. If signs of progressive sinus occlusion are noticed, early arteriovenous shunt reduction or elimination by transarterial glue embolization is expected to prevent permanent brain damage.

Strong Suppression of the Spin Hall Effect in the Spin Glass State.

We have measured spin Hall effects in spin glass metals, CuMnBi alloys, with the spin absorption method in the lateral spin valve structure. Far above the spin glass temperature T(g) where the magnetic moments of Mn impurities are randomly frozen, the spin Hall angle of a CuMnBi ternary alloy is as large as that of a CuBi binary alloy. Surprisingly, however, it starts to decrease at about 4T(g) and becomes as little as 7 times smaller at 0.5T(g). A similar tendency was also observed in anomalous Hall effects in the ternary alloys. We propose an explanation in terms of a simple model considering the relative dynamics between the localized moment and the conduction electron spin.

The Preventive Effect of Endovascular Treatment for Recurrent Hemorrhage in Patients with Spinal Cord Arteriovenous Malformations.

BACKGROUND AND PURPOSE: Spinal cord AVMs represent rare and insufficiently studied pathologic entities. Embolization is thought to play an important role in the management of spinal cord AVMs. Factors for recurrent hemorrhage and the impact of endovascular treatment on prevention of recurrent hemorrhage remain to be confirmed. We aimed to assess recurrent hemorrhagic incidence of spinal cord AVMs and its prevention by endovascular treatment. MATERIALS AND METHODS: We reviewed 80 patients with spinal cord AVMs by spinal cord angiography who had hemorrhage before the first endovascular treatment at New York University Medical Center, Beth Israel Medical Center, or Roosevelt Hospital in New York. We compared the baseline and radiologic characteristics of patients with and without recurrent hemorrhage by the log-rank test and the Cox proportional hazards model. RESULTS: We observed recurrent hemorrhage in 35 (44%) patients (1/41 patients with endovascular treatment and 34/39 patients without endovascular treatment). The median length of total follow-up was 659 days (interquartile range, 129-2640 days), and the median length from first-to-recurrent hemorrhage was 369 days (interquartile range, 30-1596 days). The log-rank test revealed that endovascular treatment and venous thrombosis reduced recurrent hemorrhage, and associated aneurysm was related to recurrent hemorrhage. Even in multivariate analysis, the endovascular treatment reduced (hazard ratio, 0.027; P < .0001) and associated aneurysm increased (hazard ratio, 3.4; P = .044) the risk of recurrent hemorrhage. CONCLUSIONS: Endovascular embolization is the first choice of treatment for spinal cord AVMs and is effective in preventing recurrent hemorrhage.

Quasiparticle-mediated spin Hall effect in a superconductor.

In some materials the competition between superconductivity and magnetism brings about a variety of unique phenomena such as the coexistence of superconductivity and magnetism in heavy-fermion superconductors or spin-triplet supercurrent in ferromagnetic Josephson junctions. Recent observations of spin-charge separation in a lateral spin valve with a superconductor evidence that these remarkable properties are applicable to spintronics, although there are still few works exploring this possibility. Here, we report the experimental observation of the quasiparticle-mediated spin Hall effect in a superconductor, NbN. This compound exhibits the inverse spin Hall (ISH) effect even below the superconducting transition temperature. Surprisingly, the ISH signal increases by more than 2,000 times compared with that in the normal state with a decrease of the injected spin current. The effect disappears when the distance between the voltage probes becomes larger than the charge imbalance length, corroborating that the huge ISH signals measured are mediated by quasiparticles.

Pathology of embolic debris in carotid artery stenting.

BACKGROUND: The relationship between magnetic resonance (MR) plaque imaging and the pathology of distal embolic debris is unknown. We aimed to evaluate the relationship between the pathology of embolic debris in the embolic filter during carotid artery stenting (CAS), MR plaque imaging, and new ischemic lesions on diffusion-weighted imaging (DWI). METHOD: We prospectively reviewed the 36 patients who underwent CAS using a filter-type embolic protection device. Pathology of debris was categorized into thrombosis, inflammatory cells, elastic fiber, and calcification. We compared the clinical parameters, MR plaque imaging, and pathological characteristics of the embolic debris retained in the filter during CAS on univariate analysis. RESULTS: Eleven patients had and 25 patients did not have new lesion on DWI. All of DWI-high lesions were identified in affected side middle cerebral artery territory. Embolic debris was microscopically confirmed in 28 patients (78%); thrombosis in 11 (31%), inflammatory cells in 13 (36%), elastic fiber in 12 (33%), and calcification in 9 (25%). Proportion of asymptomatic carotid stenosis, intra-operative bradycardia/hypotension, and inflammatory cells of debris were significantly higher in patients with new DWI-high lesions. There was no significant relationship between the pathological characteristics and MR plaque imaging of distal embolic debris. CONCLUSIONS: Our study showed that new DWI-high lesions might be influenced by types of debris in the filter. The need for future studies specifically examine the association of pathology of debris and findings of MR plaque imaging with new DWI-high lesions during CAS is emphasized.

Arterial stiffness as a risk factor for cerebral aneurysm.

OBJECTIVES: A low ankle-brachial index (ABI) is associated with increased mortality and risk of myocardial infarction and stroke in the general population. Arterial stiffness can be assessed non-invasively by the measurement of brachial-ankle pulse wave velocity (PWV), a simple and reproducible method. Because the importance of ABI and baPWV in the pathogenesis of cerebral aneurysms remains uncertain, we aimed to measure ABI and baPWV in patients with intracranial saccular and dissecting aneurysms to clarify whether these aneurysms are associated with arterial stiffness and atherosclerosis. MATERIALS AND METHODS: We prospectively investigated 78 patients diagnosed with intracranial saccular (n = 66) and dissecting (n = 12) aneurysms. The control group consisted of an age- and gender-matched normal population. We compared the clinical characteristics in patients with intracranial saccular aneurysms and controls, those with intracranial dissecting aneurysms and controls, and those who had cerebral aneurysms with and without subarachnoid hemorrhage. We also compared ABI and baPWV among saccular aneurysm locations and evaluated the correlation between the number of saccular aneurysms and ABI and baPWV. RESULTS: Multivariate logistic regression analysis shows that hypertension and higher baPWV (>1400 cm/s) are significantly associated with saccular aneurysms. Simple regression analysis revealed no correlation between the number of saccular aneurysms and ABI (r = -0.064, P = 0.611), and baPWV (r = 0.007, P = 0.956). CONCLUSIONS: The baPWV was associated with intracranial saccular aneurysms even after adjustment of hypertension and smoking. Assessment of the baPWV may aid the evaluation of the intracranial saccular aneurysm and the development of strategies for screening patients with intracranial saccular aneurysms.

Spin injection into a superconductor with strong spin-orbit coupling.

We demonstrate spin injection into superconducting Nb by employing a spin absorption technique in lateral spin valve structures. Spin currents flowing in a nonmagnetic Cu channel are preferably absorbed into Nb due to its strong spin-orbit interaction, the amount of which dramatically changes below or above the superconducting critical temperature (TC). The charge imbalance effect observed in the Cu/Nb interface ensures that superconducting Nb absorbs pure spin currents even below TC. Our analyses based on the density of states calculated using the Usadel equation can well reproduce the experimental results, implying that the strong spin-orbit interaction of Nb is still effective for the spin absorption even below TC. Most importantly, our method allows us to determine the intrinsic spin relaxation time in the superconducting Nb, which reaches more than 4 times greater than that in the normal state.

Spinal arteriovenous metameric syndrome: clinical manifestations and endovascular management.

BACKGROUND AND PURPOSE: SAMS is a rare form of SCAVM. We discuss the clinical presentation, endovascular management, and outcome of this disease in our series. MATERIALS AND METHODS: Retrospective review was performed in patients with SCAVM and SAMS who underwent angiography with intent to treat at our institution from 1980 to 2010. RESULTS: One hundred forty-eight SCAVMs were identified, and 28 (19%) of these were SAMS. Of these 28 patients, 24 had nidus-type AVMs and 4 had fistulas. SAMS were more prevalent in females (71% versus 48%), and also presented earlier than non-SAMS SCAVMs. Intradural hemorrhage (SAH or hematomyelia) was the most common presentation and more common than in non-SAMS lesions. Twenty-six patients underwent embolization of the intradural lesion in 50 sessions. Thirteen patients underwent treatment of intradural aneurysms in 16 sessions. Six patients underwent embolization of extradural lesions in 16 sessions. Twenty-three patients had an average of 94 months of clinical follow-up (3-309 months) after the first treatment, during which 5 patients had hemorrhages. Angiographic follow-up was performed in 20 patients at an average of 85 months (range, 3-309 months), which showed new development or enlargement of an aneurysm in 5 patients. This type of angiographic progression was more common in patients with SAMS. CONCLUSIONS: SAMS most commonly presents with hemorrhage from the SCAVM. Endovascular embolization can be performed safely with good functional outcome, though most patients clinically deteriorate in the long term. Periodic angiographic follow-up with intent to perform preventive target embolization is important to control the disease.

Giant spin Hall effect induced by skew scattering from bismuth impurities inside thin film CuBi alloys.

We demonstrate that a giant spin Hall effect (SHE) can be induced by introducing a small amount of Bi impurities in Cu. Our analysis, based on a new three-dimensional finite element treatment of spin transport, shows that the sign of the SHE induced by the Bi impurities is negative and its spin Hall (SH) angle amounts to -0.24. Such a negative large SH angle in CuBi alloys can be explained by applying the resonant scattering model proposed by Fert and Levy [Phys. Rev. Lett. 106, 157208 (2011)] to 6p impurities.

The spin Hall effect as a probe of nonlinear spin fluctuations.

The spin Hall effect and its inverse have key roles in spintronic devices as they allow conversion of charge currents to and from spin currents. The conversion efficiency strongly depends on material details, such as the electronic band structure and the nature of impurities. Here we show an anomaly in the inverse spin Hall effect in weak ferromagnetic NiPd alloys near their Curie temperatures with a shape independent of material details, such as Ni concentrations. By extending Kondo's model for the anomalous Hall effect, we explain the observed anomaly as originating from the second-order nonlinear spin fluctuation of Ni moments. This brings to light an essential symmetry difference between the spin Hall effect and the anomalous Hall effect, which reflects the first-order nonlinear fluctuations of local moments. Our finding opens up a new application of the spin Hall effect, by which a minuscule magnetic moment can be detected.

Extrinsic spin Hall effect induced by iridium impurities in copper.

We study the extrinsic spin Hall effect induced by Ir impurities in Cu by injecting a pure spin current into a CuIr wire from a lateral spin valve structure. While no spin Hall effect is observed without Ir impurity, the spin Hall resistivity of CuIr increases linearly with the impurity concentration. The spin Hall angle of CuIr, (2.1±0.6)% throughout the concentration range between 1% and 12%, is practically independent of temperature. These results represent a clear example of predominant skew scattering extrinsic contribution to the spin Hall effect in a nonmagnetic alloy.

Effect of disorder on the quantum coherence in mesoscopic wires.

We present phase coherence time measurements in quasi-one-dimensional mesoscopic wires made from high mobility two-dimensional electron gas. By implanting gallium ions into a GaAs/AlGaAs heterojunction we are able to vary the diffusion coefficient over 2 orders of magnitude. We show that in the diffusive limit, the decoherence time follows a power law as a function of diffusion coefficient as expected by theory. When the disorder is low enough so that the samples are semiballistic, we observe a new and unexpected regime in which the phase coherence time is independent of disorder. In addition, for all samples the temperature dependence of the phase coherence time follows a power law down to the lowest temperatures without any sign of saturation and this strongly suggests that the frequently observed low temperature saturation is not intrinsic.

Localized distributions of quasi-two-dimensional electronic states near defects artificially created at graphite surfaces in magnetic fields.

We measured the local density of states of a quasi two-dimensional electron system (2DES) near defects, artificially created by Ar-ion sputtering, on surfaces of highly oriented pyrolytic graphite (HOPG) with scanning tunneling spectroscopy (STS) in high magnetic fields. At valley energies of the Landau level spectrum, we found two typical localized distributions of the 2DES depending on the defects. These are new types of distributions which are not observed in the previous STS work at the HOPG surface near a point defect [Y. Niimi, Phys. Rev. Lett. 97, 236804 (2006).10.1103/PhysRevLett.97.236804]. With increasing energy, we observed gradual transformation from the localized distributions to the extended ones as expected for the integer quantum Hall state. We show that the defect potential depth is responsible for the two localized distributions from comparison with theoretical calculations.