Dual Antiplatelet Therapy With Cilostazol for Secondary Prevention in Lacunar Stroke: Subanalysis of the CSPS.com Trial.

BACKGROUND: The effectiveness of long-term dual antiplatelet therapy (DAPT) to prevent recurrent strokes in patients with lacunar stroke remains unclarified. Therefore, this study aimed to compare and to elucidate the safety and effectiveness of DAPT and single antiplatelet therapy (SAPT) in preventing recurrence in chronic lacunar stroke. METHODS: CSPS.com (Cilostazol Stroke Prevention Study for Antiplatelet Combination) was a prospective, multicenter, randomized controlled trial. In this prespecified subanalysis, 925 patients (mean age, 69.5 years; 69.4% men) with lacunar stroke were selected from 1884 patients with high-risk noncardioembolic stroke, enrolled in the CSPS.com trial after 8 to 180 days following stroke. Patients were randomly assigned to receive either SAPT or DAPT using cilostazol and were followed for 0.5 to 3.5 years. The primary efficacy outcome was the first recurrence of ischemic stroke. The safety outcomes were severe or life-threatening bleeding. RESULTS: The DAPT group receiving cilostazol and either aspirin or clopidogrel and SAPT group receiving aspirin or clopidogrel alone comprised 464 (50.2%) and 461 (49.8%) patients, respectively. Ischemic stroke occurred in 12 of 464 patients (1.84 per 100 patient-years) in the DAPT group and 31 of 461 patients (4.42 per 100 patient-years) in the SAPT group, during follow-up. After adjusting for multiple potential confounding factors, ischemic stroke risk was significantly lower in the DAPT group than in the SAPT group (hazard ratio, 0.43 [95% CI, 0.22-0.84]). The rate of severe or life-threatening hemorrhage did not differ significantly between the groups (2 patients [0.31 per 100 patient-years] versus 6 patients [0.86 per 100 patient-years] in the DAPT and SAPT groups, respectively; hazard ratio, 0.36 [95% CI, 0.07-1.81]). CONCLUSIONS: In patients with lacunar stroke, DAPT using cilostazol had significant benefits in reducing recurrent ischemic stroke incidence compared with SAPT without increasing the risk of severe or life-threatening bleeding. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000012180.

[The questionnaire survey regarding the impact of COVID-19 pandemic on Parkinson's disease patients].

We conducted the multicenter questionnaire survey targeting patients with Parkinson's disease (PD) in order to investigate the impacts on their daily lives and their requests to hospitals in the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Mainly using open-ended questionnaire, we asked their anxiety, troubles they are facing, and requests toward hospitals in the pandemic of SARS-CoV-2. Two hundred fifth-eight PD patients answered the questionnaire. There were various opinions about anxiety such as "PD patients are susceptible and vulnerable to SARS-CoV-2" (36.8%). Concerning the troubles in the pandemic, the most frequent answer was that they couldn't participate in the rehabilitation and elderly day care (38.4%). Relatively many PD patients requested telemedicine (29.5%), whereas some people hoped face-to-face medical care (8.1%). There were demands about the delivery of medications (50.0%), the establishment of telephone consultations (43.8%), resources for rehabilitation at home (43.8%). The medical care adapted to the anxiety, trouble and requests of PD patients will be required in the era when we have to live with SARS-CoV-2.

Dual Antiplatelet Therapy Using Cilostazol in Patients With Stroke and Intracranial Arterial Stenosis.

Background Long-term benefit of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) for the prevention of recurrent stroke has not been established in patients with intracranial arterial stenosis. We compared the efficacy and safety of DAPT with cilostazol and clopidogrel or aspirin to those of SAPT with clopidogrel or aspirin in patients with intracranial arterial stenosis, who were recruited to the Cilostazol Stroke Prevention Study for Antiplatelet Combination trial, a randomized controlled trial in high-risk Japanese patients with ischemic stroke. Methods and Results We compared the vascular and hemorrhagic events between DAPT and SAPT in patients with ischemic stroke and symptomatic or asymptomatic intracranial arterial stenosis of at least 50% in a major intracranial artery. Patients were placed in two groups: 275 were assigned to receive DAPT and 272 patients SAPT. The risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.23-0.95); and composite of stroke, myocardial infarction, and vascular death (HR, 0.48; 95% CI, 0.26-0.91) were lower in DAPT than SAPT, whereas the risk of severe or life-threatening bleeding (HR, 0.72; 95% CI, 0.12-4.30) did not differ between the 2 treatment groups. Conclusions DAPT using cilostazol was superior to SAPT with clopidogrel or aspirin for the prevention of recurrent stroke and vascular events without increasing bleeding risk among patients with intracranial arterial stenosis after stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370.

Dual Antiplatelet Therapy Using Cilostazol With Aspirin or Clopidogrel: Subanalysis of the CSPS.com Trial.

Background and Purpose: Although dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the recurrence of ischemic stroke while significantly increasing the bleeding events compared with monotherapy, the CSPS.com trial (Cilostazol Stroke Prevention Study combination) showed that DAPT using cilostazol was more effective without the bleeding risk. In the CSPS.com trial, aspirin or clopidogrel was used as the underlying antiplatelet drug. The effectiveness and safety of each combination were examined and clarified. Methods: In the CSPS.com trial, a multicenter, open-label, randomized controlled study, patients with high-risk, noncardioembolic ischemic stroke 8 to 180 days after onset treated with aspirin or clopidogrel alone at the discretion of the physician in charge were recruited. Patients were randomly assigned to receive either monotherapy or DAPT using cilostazol and followed for 0.5 to 3.5 years. The primary efficacy outcome was first recurrence of ischemic stroke. The safety outcome was severe or life-threatening bleeding. The analysis was based on the underlying antiplatelet agents. Results: A total of 763 patients taking aspirin and 1116 taking clopidogrel were included in the intention-to-treat analysis. Although the clopidogrel group had more risk factors than the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the 2 groups. In the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the DAPT group and the aspirin-monotherapy group. In the clopidogrel group, the primary end point occurred at a rate of 2.31 per 100 patient-years in the DAPT group and 5.19 per 100 patient-years in the clopidogrel-monotherapy group (hazard ratio, 0.447 [95% CI, 0.258­0.774]). Safety outcome did not differ significantly between groups (0.51 per 100 patient-years versus 0.71 per 100 patient-years, respectively; hazard ratio, 0.730 [95% CI, 0.206­2.588]). Conclusions: The combination of cilostazol and clopidogrel significantly reduced the recurrence of ischemic stroke without increasing the bleeding risk in noncardioembolic, high-risk patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000012180.

Influence of PAR-1 in patients with non-valvular atrial fibrillation: The antiplatelet effect of dabigatran.

INTRODUCTION: Dabigatran, a direct thrombin inhibitor, has been widely used in patients with non-valvular atrial fibrillation (NVAF) and is considered to have an antiplatelet effect. However, the mechanisms remain unclear. We evaluated protease-activated receptor-1 (PAR-1) expression and activation by thrombin on platelets from NVAF patients, before and after dabigatran treatment, in addition to the expression of platelet activation marker CD62P. MATERIALS AND METHODS: The study included 18 NVAF patients. We used flow cytometry to measure the binding of PAR-1 monoclonal antibodies (SPAN12 and WEDE15) and the expression of CD62P with and without thrombin stimulation, before, 14 days after, and 28 days after treatment with dabigatran. Coagulation fibrinolysis markers were also measured. RESULTS: PAR-1 expression was significantly lower in NVAF patients than in healthy controls (HC); it was further reduced by thrombin stimulation. CD62P expression was almost absent on the platelets in NVAF patients, but was significantly increased by thrombin stimulation. PAR-1 expression was not significantly different before and after treatment; CD62P expression was inhibited by dabigatran. The levels of coagulation markers were significantly higher in NVAF patients than in HC, and decreased after treatment. CONCLUSIONS: Lower expression of PAR-1 in NVAF patients resulted from the cleavage of PAR-1 on some platelets, by exposure to small amounts of thrombin in vivo. The therapeutic effect of dabigatran in NVAF patients was demonstrated by inhibition of CD62P expression on the platelet upon thrombin stimulation in vitro. Our results indicate that dabigatran may reveal antithrombotic activity with antiplatelet and anticoagulant effects.

Evaluating recanalization of relevant lenticulostriate arteries in acute ischemic stroke using high-resolution MRA at 7T.

BACKGROUND: Occluded major intracranial arteries can spontaneously recanalize in patients with acute ischemic stroke mainly due to embolic mechanisms. However, it remains unknown whether recanalization can occur in perforating arteries, such as lenticulostriate arteries. Therefore, in the present study, we assessed changes suggesting recanalization of the lenticulostriate arteries in patients with acute ischemic stroke of the lenticulostriate artery territory using high-resolution magnetic resonance angiography (HR-MRA) at 7T. METHODS: We prospectively examined 39 consecutive patients with acute infarcts confined within the lenticulostriate artery territory. Using a 7T scanner during the acute period and one month thereafter, we evaluated imaging findings indicating the recanalization of the relevant lenticulostriate arteries, following which we examined differences in other imaging findings and clinical characteristics between patients with/without recanalization. RESULTS: HR-MRA findings suggestive of recanalization (i.e. patent lenticulostriate arteries within acute infarct lesions with/without hemorrhagic changes) were observed in 8 (25%) of 32 patients who were eligible for analyses. These findings were detected in three and five patients on the baseline and follow-up images, respectively. The lengths of relevant lenticulostriate arteries on the follow-up MRA were significantly larger in patients with recanalization than in those without (P = 0.01). However, there were no significant differences in the infarct volume or clinical outcomes between the recanalization and non-recanalization groups. CONCLUSION: HR-MRA at 7T revealed that recanalization of the relevant lenticulostriate arteries can occur in patients with acute ischemic stroke confined to the lenticulostriate artery territory.

Inhibitory Effects of P2Y12 Receptor Antagonist on PAR1- and PAR4-AP-Induced Platelet Aggregation in Patients with Stroke or TIA.

OBJECTIVES: The inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-activating peptide (AP)-induced platelet aggregation have not been fully elucidated. The present study aimed to investigate the inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-AP-induced platelet aggregation using platelet-rich plasma (PRP) from individuals including patients with stroke or transient ischemic attack (TIA). MATERIALS AND METHODS: PRP was given to 10 healthy individuals pretreated in vitro with cangrelor, then stimulated with adenosine diphosphate (ADP), PAR4-AP, or PAR1-AP. Moreover, 20 patients were enrolled from 148 consecutive patients with acute ischemic stroke or TIA admitted to our institute between December 2017 and April 2019. PRP obtained from each patient before and >7 days after initiation of clopidogrel was similarly stimulated with these agonists. Platelet aggregation was measured using an automatic coagulation analyzer in all participants. RESULTS: In healthy individuals, ADP- and PAR4-AP-induced platelet aggregations were significantly inhibited depending on the cangrelor concentration in vitro, while PAR1-AP-induced platelet aggregation was slightly inhibited. In patients with stroke or TIA, clopidogrel inhibited ADP-induced platelet aggregation at all concentrations, and significantly inhibited PAR4-AP-induced platelet aggregation at 50 µmol/L of PAR4-AP (p<0.05), especially in 5 patients who showed high reactivity to PAR4-AP. PAR1-AP-induced platelet aggregation was also slightly inhibited. CONCLUSIONS: We showed significant inhibitory effects on PAR4-AP-induced platelet aggregation by clopidogrel in patients with stroke or TIA who had high reactivity to PAR4-AP.

[Role of the liaison officer in disaster countermeasures implemented by the Japanese Society of Neurology: Hope for the best and prepare for the worst].

Disaster countermeasures have been implemented by the Japanese Society of Neurology based on the experience of support to the areas affected by the Great East Japan Earthquake on March 11, 2011. The countermeasures activity began at the end of 2011. We, the Committee for Measures Against Disaster, officially started work in 2014. We developed a support network to urgently deal with patients with intractable neurological disease at the time of disaster and strengthen disaster measures, including effective disaster countermeasure training. During the 2016 Kumamoto earthquake, we realized the need to prepare for natural disasters, leading to a state of emergency, at normal times. A list of vulnerable people should be prepared and the individual support plan for disaster should be confirmed during normal times. Furthermore, during disaster, livelihood support is required for patients with intractable neurological disease living in evacuation centers in affected areas. Therefore, we compiled and published the book, titled "The manual of disaster countermeasures," in 2017. The Committee for Measures Against Disaster in the Japanese Society of Neurology has appointed a liaison officer for patients with intractable neurological disease in each prefecture. The liaison's role of is gathering and disseminating information on the disaster-hit areas, arranging medical support, and coordinating health activities, when natural disasters occur. It is hoped that the liaison officer will play an active role both at normal times and during disaster, even unforeseen ones. Although we hope for the best, we aim to be prepared for the worst.

Dashcam-captured moment of right hemispheric stroke.

A bus driver presented with neurological abnormalities following a driving mishap. He was diagnosed cardioembolic stroke. The bus was equipped with a dashboard camera that recorded the moment when the patient suffered the stroke. We reported the first case dashcam-captured images at the first sign of a right hemispheric stroke.

[Time-sparing screening method for mild cognitive impairment and early Alzheimer's disease: Self- and family reports using the TMIG index of competence].

AIM: To verify the clinical utility of instrumental activities of daily life evaluated using the Tokyo Metropolitan Institute of Gerontology index of competence (TMIG-IC) as a screening tool for patients with early-phase cognitive impairment, including mild cognitive impairment (MCI) and early Alzheimer's disease (AD). METHODS: We recruited healthy subjects from our community-based cohort and consecutive subjects with MCI and AD from our clinic. The TMIG-IC was investigated in all participants and their family members. The total and subscale scores were compared among all groups. We then statistically determined the accuracy of the differentiation of MCI and AD. RESULTS: We registered 187 normal controls (NC), 39 participants with MCI, 50 AD patients with functional assessment staging (FAST) 4, and 19 AD patients with ≥5 FAST. The family-report score was significantly lower in MCI patients than in others, followed by AD patients. The total score was able to differentiate MCI and AD with a sensitivity of 85.7% and a specificity of 90.9% (area under the curve [AUC]=0.913). Differentiation of MCI alone had a low accuracy (AUC=0.787). However, the AUC was 0.847 when only the items with inconsistent responses between self and family reports were used as indices. CONCLUSIONS: The TMIG-IC is a useful tool for evaluating the severity of AD, including early AD. These findings suggest that family-report scores can differentiate MCI and AD from cognitive normal aging with a sufficient degree of accuracy. It was also suggested that inconsistencies between self and family reports were higher when differentiating MCI than the self- and family-reports.

Safety and effectiveness of non-vitamin K oral anticoagulants versus warfarin in real-world patients with non-valvular atrial fibrillation: a retrospective analysis of contemporary Japanese administrative claims data.

Objective: To assess the safety (ie, risk of bleeding) and effectiveness (ie, risk of stroke/systemic embolism (SE)) separately for four non-vitamin K oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban and rivaroxaban) versus warfarin in Japanese patients with non-valvular atrial fibrillation (NVAF), including those at high risk of bleeding and treated with reduced doses of NOACs. Methods: We conducted a retrospective analysis of electronic health records and claims data from 372 acute care hospitals in Japan for patients with NVAF newly initiated on NOACs or warfarin. Baseline characteristics were balanced using inverse probability of treatment weighting with stabilised weights (s-IPTW). Bleeding risk and stroke/SE risk were expressed as HRs with 95% CIs. Two sensitivity analyses were conducted. Results: A total of 73 989 patients were eligible for analysis. Notably, 52.8%-81.9% of patients received reduced doses of NOACs. After applying s-IPTW, patient characteristics were well balanced across warfarin/NOAC cohorts. The mean within-cohort age, CHADS2 score and CHA2DS2-VASc score were 76 years, 2.2-2.3 and 3.8, respectively. In all age categories, the majority of the HRs for major bleeding, any bleeding and stroke/SE were equal to or below 1 for all NOACs versus warfarin. Apixaban was the only NOAC associated with a significantly lower risk of any bleeding. There was a trend towards increased risk reduction with NOACs versus warfarin in patients with body weight ≥60 kg. In patients with renal disease, the HRs for apixaban versus warfarin were below 1 for major bleeding, any bleeding and stroke/SE, with statistical significance observed for the risk reduction in stroke/SE versus warfarin. In the sensitivity analysis, there were no large differences in HRs between the two observational periods. Conclusions: In patients with NVAF primarily treated with reduced-dose NOACs, the risks of stroke/SE and major bleeding were significantly lower with NOACs versus warfarin.

Thrombin-induced platelet aggregation -effect of dabigatran using automated platelet aggregometry.

Dabigatran, a direct oral thrombin inhibitor, has two therapeutic effects: anticoagulation; and antiplatelet activity. In the clinical field, evaluation of the effect of dabigatran on thrombin-induced platelet aggregation is difficult because of fibrin clot formation and platelet aggregation. The aim of this study was to establish a new platelet aggregation method and to investigate the effects of dabigatran on thrombin-induced platelet aggregation. Platelet aggregation with thrombin was performed with automated light transmission aggregometry (CS2400; Sysmex, Kobe, Japan) in 40 healthy subjects. Thrombin-induced platelet aggregation was performed using thrombin and platelet-rich plasma (PRP), and thrombin-induced fibrin polymerization was inhibited by adding the peptide Gly-Pro-Arg-Pro (GPRP). The effect of dabigatran was then evaluated using the above method. Thrombin at < 0.2 U/mL did not induce platelet aggregation in most normal subjects. Median maximum aggregation percent (MA%) (25th-75th percentile) with 0.5 and 1.0 U/mL of thrombin was 87.0% (79.3-90.8%), and 90.2% (86.5-92.2%), respectively. The anti-platelet effects of dabigatran were then evaluated with these concentrations of thrombin. Dabigatran (final concentration, 2.5-1000 nM) inhibited platelet aggregation by 0.2-1.0 U/mL of thrombin in a concentration-dependent manner in vitro. Dabigatran showed potent inhibitory effects against platelet aggregation induced by 0.5 and 1.0 U/mL thrombin with half maximal inhibitory concentrations of 10.5 and 40.4 nM, respectively. A standard for thrombin-induced platelet aggregation was developed using the CS2400 in healthy subjects, and dabigatran was confirmed to inhibit thrombin-induced platelet aggregation in vitro with PRP.

Impaired metabolism of kynurenine and its metabolites in CSF of parkinson's disease.

AIM: The kynurenine (KYN) pathway plays an important role in degrading molecules responsible for oxidative stress in the central nervous system (CNS), but can also have neurotoxic effects. Both 3-hydroxykynurenine (3-HK) and quinolinic acid are neurotoxic metabolites produced from this pathway. In Parkinson's disease (PD), oxidative stress is suspected to represent a key pathogenic mechanism. This study aimed to investigate the function of the KYN pathway and interactions between oxidative stress and neuroinflammation in PD. METHODS: Participants comprised 20 patients with PD and 13 controls. Cerebrospinal fluid (CSF) levels of KYN and 3-HK were measured using high-performance liquid chromatography coupled with an electrochemical detector. CSF levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and interferon (IFN)-γ were measured with an enzyme-linked immunosorbent assay, and results were statistically compared between PD patients and controls. RESULTS: Median CSF levels of KYN and 3-HK were 49.0 nM and 4.25 nM in PD and 30.5 nM and 1.55 nM in controls, respectively, showing significantly higher levels in PD (p < 0.05). CSF levels of measured cytokines showed that TNF-α and IL-1ß were significantly higher in PD patients than in controls. No positive correlation between 3-HK and TNF-α was seen in PD. CONCLUSION: Dysfunction of the KYN pathway may induce oxidative stress in the CNS in PD, and may also induce cytokine-mediated neuroinflammation. Functional amelioration of the KYN pathway may facilitate modification of neurodegenerative processes in PD.

Gastrointestinal involvement in patients with vasculitis: IgA vasculitis and eosinophilic granulomatosis with polyangiitis.

Background and study aims Among vasculitides, IgA vasculitis (IgAV) and eosinophilic granulomatosis with polyangiitis (EGPA) frequently damage the gastrointestinal tract. However, only a few studies have investigated the entire gastrointestinal tract in patients with IgAV or EGPA by endoscopy. The aim of this study was to clarify endoscopic characteristics of patients with IgAV and those with EGPA. Patients and methods Clinicopathological and endoscopic findings were retrospectively compared between 33 patients with IgAV and 19 patients with EGPA. Results Gastrointestinal involvement was observed in 33 patients with IgAV (100 %) and in 8 patients with EPGA (42 %; P  = 0.0001). Duodenal involvement was more frequent in patients with IgAV (75.8 %) than in those with EGPA (21.1 %, P  = 0.0002). Jejunoileal involvement was frequent in both groups (IgAV 94.4 %; EGPA 77.8 %). Gastric mucosal erythema was more frequent in patients with IgAV (18.2 %) than in those with EGPA (0 %, P  = 0.0481). Duodenal mucosal erythema (IgAV 54.6 %; EGPA 21.1 %, P  = 0.0227), ulcer (IgAV 33.3 %; EGPA 0 %, P  = 0.0041), and hematoma-like protrusion (IgAV 21.1 %; EGPA 0 %, P  = 0.039) were more frequently observed in patients with IgAV than in those with EGPA. Conclusions Frequent duodenal involvement, gastric mucosal erythema, and duodenal lesions including erythema, ulcer, and hematoma-like protrusion are characteristic of patients with IgAV. Because jejunoileal involvement was frequent in both groups of patients, small-bowel endoscopies should be performed for diagnosis of small-bowel lesions in patients with IgAV and EGPA.

[A case of adult-onset mitochondrial encephalopathy due to m.4296G>A gene abnormality].

The case is a 30-year-old woman. From the age of 25 years, she had several episodes of cortical blindness and visited a local doctor. Mitochondrial disease was suspected based on findings of cerebral infarction-like imaging and a history of diabetes. However, serum and cerebrospinal fluid lactate levels were normal and no abnormal muscle pathology was found. At the age of 30 years, she visited our hospital with impaired consciousness, cortical blindness, and tremor-like involuntary movements in the neck and right fingers. Brain MRI showed abnormal signals in bilateral basal ganglia, with an increased lactate peak by magnetic resonance spectroscopy and high cerebrospinal fluid lactate levels. Mitochondrial gene analysis identified a m.4296G>A gene mutation. Consequently, we reached a diagnosis of mitochondrial encephalopathy. Adult-onset mitochondrial encephalopathy with m.4296G>A gene mutation is extremely rare. This case showed clinical features caused by damage of both the cerebral cortex and subcortical basal ganglia.

[Study of encoding and storage in memorization among patients with Alzheimer's disease].

AIM: Memorization comprises three stages: encoding, storage, and retrieval. Using neuropsychological tests, we investigated the stage at which encoding and storage are retained in Alzheimer's disease (AD) patients with progressive memory disorder. METHODS: The target patients were an amnestic mild cognitive impairment (MCI) group (21 cases) and FAST 4 (37 cases), 5 (10 cases), and 6 (4 cases) AD groups. The neuropsychological tests performed were the Rivermead behavioral memory test and Wechsler memory scale-revised. These were carried out in the MCI group as well as in each AD stage group. We investigated the delayed recall (free recall and cued recall) based on the disease stage and raw score of the sub-items in delayed recognition. RESULTS: The MCI group had 48% (median 0 point) correct respondents (providing ≥1 correct answer) for free recall, whereas FAST 4 and 5 groups had ≤14% correct respondents. In the verbal paired associates II evaluated in cued recall, the MCI group had 90% correct respondents, and the FAST 4, 5, and 6 groups had rates of 51%, 60%, and 50%, respectively. For the pictures and photos in the delayed recognition tasks, there were no significant differences in the percentage of correct respondents between the MCI group (100%) and the FAST 4 and 5 groups (70%-90%). CONCLUSIONS: Given that retrieval is impossible if encoding and storage are impaired, we inferred that the encoding and retrieval abilities were retained even in moderately advanced AD.

Diabetes care providers' manual for disaster diabetes care.

To ensure that experiences and lessons learned from the unprecedented 2011 Great East Japan Earthquake are used to improve future disaster planning, the Japan Diabetes Society (JDS) launched the "Research and Survey Committee for Establishing Disaster Diabetes Care Systems Based on Relevant Findings from the Great East Japan Earthquake" under the supervision of the Chairman of the JDS. The Committee conducted a questionnaire survey among patients with diabetes, physicians, disaster medical assistance teams (DMATs), nurses, pharmacists, and nutritionists in disaster areas about the events they saw happening, the situations they found difficult to handle, and the needs that they felt required to be met during the 2011 Great East Japan Earthquake. A total of 3,481 completed questionnaires were received. Based on these and other experiences and lessons reported following the 2011 Great East Japan Earthquake and the 2004 Niigata-Chuetsu Earthquakes, the current "Manual for Disaster Diabetes Care" has been developed by the members of the Committee and other invited authors from relevant specialties. To our knowledge, the current Manual is the world's first to focus on emergency diabetes care, with this digest English version translated from the Japanese original. It is sincerely hoped that patients with diabetes and healthcare providers around the world will find this manual helpful in promoting disaster preparedness and implementing disaster relief.