A Nationwide Multi-Center Questionnaire Survey on the Real-World State and Clinical Management of Poststroke Dementia in Japan.

BACKGROUND: Poststroke dementia (PSD) is a serious problem for stroke survivors. However, there is still limited data on the real-world state and clinical management of PSD worldwide, and several countries already have a super-aged society. OBJECTIVE: We conducted a nationwide questionnaire survey to examine the real-world state and management of PSD in Japan. METHODS: A survey was conducted in the top 500 Japanese hospitals regarding the number of stroke patients treated between July 2018 and August 2019. Thirteen questions regarding PSD were mailed to doctors responsible for stroke management. RESULTS: Responses were obtained from 251 hospitals (50.2%). The chief doctors responsible for stroke management answered the questionnaires. The median numbers of patients admitted annually with stroke in the departments of neurology and neurosurgery in the hospitals were 281.0 (interquartile range [IQR], 231.8-385.3) and 253.5 (IQR, 210.0-335.3), respectively, and most hospitals were acute care hospitals. Executive dysfunction was the most common cognitive dysfunction (10.9%), followed by amnesia (9.5%) and apathy (4.1%). Surprisingly, many stroke survivors lived alone at home (23.7%). Montreal Cognitive Assessment was significantly uncommon compared to Mini-Mental State Examination (p < 0.01). Furthermore, objective evaluation tests for behavioral and psychological symptoms of dementia were not often performed. Cognitive rehabilitation treatments were performed more often and earlier than drug treatments. The first drug of choice for PSD was predominantly donepezil (79.1%), followed by galantamine (6.1%), cilostazol (4.9%), memantine (2.5%), and rivastigmine (1.8%). CONCLUSION: Our study provides real-world evidence for the state of clinical practice related to PSD in Japan.

A Nationwide Multi-Center Questionnaire Survey on the Real-World State and Issues Regarding Post-Stroke Complications in Japan.

OBJECTIVES: Post-stroke complications affect stroke survivors across the world, although data on them are limited. We conducted a questionnaire survey to examine the real-world state and issues regarding post-stroke complications in Japan, which represents a super-aged society. MATERIALS AND METHODS: In 2018, a nationwide multi-center questionnaire survey was conducted in the top 500 Japanese hospitals regarding the number of stroke patients treated. Three questionnaires regarding post-stroke complications were mailed to the doctors responsible for stroke management. RESULTS: Responses were obtained from 251 hospitals (50.2%). The chief doctors responsible for stroke management answered the questionnaires. The number of stroke patients in the departments of neurology and neurosurgery was 338.3 ± 195.3 and 295.8 ± 121.8. Hospitals were classified using the categories secondary (n =142) and tertiary hospitals (n = 106); most hospitals were acute hospitals. Dementia was the most common complication (30.9%), followed by dysphagia (29.3%), and apathy (16.3%). Dementia was thought to be more common by neurologists than neurosurgeons, while apathy and bladder-rectal disorder were thought to be more common by neurosurgeons than neurologists (p = 0.001). The most difficult complication to treat was dysphagia (40.4%), followed by dementia (33.9%), epilepsy (4.1%), and fall (4.1%). Dementia was considered to lack clinical evidence regarding treatment (32.8%), followed by dysphagia (25.3%), and epilepsy (14.1%). Epilepsy was considered to lack clinical evidence among hospitals with a larger number of stroke cases (p = 0.044). CONCLUSION: This study revealed the current state and issues regarding post-stroke complications in Japan. Clinicians should be aware of the importance of post-stroke complications, although data on them remain unsatisfactory.

Dose-rate effect was observed in T98G glioma cells following BNCT.

BACKGROUND: It is generally said that low LET radiation produce high dose-rate effect, on the other hand, no significant dose rate effect is observed in high LET radiation. Although high LET radiations are produced in BNCT, little is known about dose-rate effect of BNCT. MATERIALS AND METHODS: T98G cells, which were tumor cells, were irradiated by neutron mixed beam with BPA. As normal tissue derived cells, Chinese hamster ovary (CHO-K1) cells and DNA double strand breaks (DNA-DSBs) repair deficient cells, xrs5 cells were irradiated by the neutrons (not including BPA). To DNA-DSBs analysis, T98G cells were stained immunochemically with 53BP1 antibody. The number of DNA-DSBs was determined by counting 53BP1 foci. RESULTS: There was no dose-rate effect in xrs5 cells. D0 difference between 4cGy/min and 20cGy/min irradiation were 0.5 and 5.9 at the neutron and gamma-ray irradiation for CHO-K1, and 0.3 at the neutron for T98G cells. D0 difference between 20cGy/min and 80cGy/min irradiation for T98G cells were 1.2 and 0.6 at neutron irradiation plus BPA and gamma-ray. The differences between neutron irradiations at the dose rate in T98G cells were supported by not only the cell viability but also 53BP1 foci assay at 24h following irradiation to monitor DNA-DSBs. CONCLUSION: Dose-rate effect of BNCT when T98G cells include 20ppm BPA was greater than that of gamma-ray irradiation. Moreover, Dose-rate effect of the neutron beam when CHO-K1 cells did not include BPA was less than that of gamma-ray irradiation These present results may suggest the importance of dose-rate effect for more efficient BNCT and the side effect reduction.

Relative biological effects of neutron mixed-beam irradiation for boron neutron capture therapy on cell survival and DNA double-strand breaks in cultured mammalian cells.

Understanding the biological effects of neutron mixed-beam irradiation used for boron neutron capture therapy (BNCT) is important in order to improve the efficacy of the therapy and to reduce side effects. In the present study, cell viability and DNA double-strand breaks (DNA-DSBs) were examined in Chinese hamster ovary cells (CHO-K1) and their radiosensitive mutant cells (xrs5, Ku80-deficient), following neutron mixed-beam irradiation for BNCT. Cell viability was significantly impaired in the neutron irradiation groups compared to the reference gamma-ray irradiation group. The relative biological effectiveness for 10% cell survival was 3.3 and 1.2 for CHO-K1 and xrs5 cells, respectively. There were a similar number of 53BP1 foci, indicators of DNA-DSBs, in the neutron mixed-beam and the gamma-ray groups. In addition, the size of the foci did not differ between groups. However, neutron mixed-beam irradiation resulted in foci with different spatial distributions. The foci were more proximal to each other in the neutron mixed-beam groups than the gamma-ray irradiation groups. These findings suggest that neutron beams may induce another type of DNA damage, such as clustered DNA-DSBs, as has been indicated for other high-LET irradiation.

Hypercholesterolemia accelerates intraneuronal accumulation of Aß oligomers resulting in memory impairment in Alzheimer's disease model mice.

AIMS: Hypercholesterolemia is known to be a risk factor for Alzheimer's disease (AD), and diet-induced hypercholesterolemia has been shown to accelerate amyloid pathology in animals. While growing evidence has shown that synaptic and cognitive dysfunction in AD is associated with intraneuronal accumulation of Aß, the relationships between hypercholesterolemia, memory impairment, and intraneuronal Aß remains unclear. The present study aims to clarify this association. MAIN METHODS: Transgenic mice expressing amyloid precursor protein (APP) harboring the Osaka (E693∆) mutation (APP(OSK)-Tg mice) were used. These mice exhibit intraneuronal Aß oligomers and memory impairment from 8months of age. Five-month-old male APP(OSK)-Tg mice and non-Tg littermates were fed a high-cholesterol diet for 1 month to induce hypercholesterolemia. At 6 months of age, their cognitive function was evaluated by the Morris water maze. Intraneuronal Aß, synaptic density, and tau phosphorylation were examined by immunohistochemistry. KEY FINDINGS: Serum and brain cholesterol levels were significantly higher in APP(OSK)-Tg mice and non-Tg littermates that were fed a high-cholesterol diet than in control mice that were fed normal chow, indicating that hypercholesterolemia was successfully induced. Hypercholesterolemic APP(OSK)-Tg mice, but not control APP(OSK)-Tg mice or hypercholesterolemic non-Tg littermates, exhibited impaired spatial reference memory, which was accompanied with intraneuronal accumulation of Aß oligomers, reduced synaptophysin immunoreactivity, and abnormal tau phosphorylation in the hippocampus. Hypercholesterolemia-accelerated accumulation of intraneuronal Aß oligomers was also observed in another model mouse, Tg2576. SIGNIFICANCE: Our findings suggest that hypercholesterolemia accelerates intraneuronal accumulation of Aß oligomers and subsequent synapse loss, resulting in memory impairment.

Oligomeric amyloid beta-protein as a therapeutic target in Alzheimer's disease: its significance based on its distinct localization and the occurrence of a familial variant form.

Oligomer Abeta is the term utilized for multimeric but non-fibrillar forms of amyloid beta-protein (Abeta). The most prominent property of oligomer Abeta is considered to be its solubility and structure. Here, we examined the histochemical localization of oligomer Abeta in AD brains. At present, little information is available on the structure and function of cerebral oligomer Abeta. We therefore studied the molecular localization of oligomer Abeta using a newly generated polyclonal mouse antisera against a variant Abeta with a deletion mutation of the 22(nd) glutamate that we found recently in a patient with familial Alzheimer's disease. Intracellular as well as extracellular oligomer Abeta are herein discussed to define their structure and pathological roles in disease.