Background: Electrical muscle stimulation (EMS) is effective for increasing physical function. However, there is no evidence regarding the effects of EMS on muscle mass and physical function in older adults with dementia. The aim of the present study was to quantify the effects of EMS on muscle mass and balance in older adults with dementia. Methods: A total of 32 participants were randomly assigned to an intervention group ( = 16, age = 89.4 ± 4.8 years) and a control group ( = 16, age = 88.1 ± 5.2 years). Participants in the intervention group underwent a general rehabilitation program (20 min for three days/week) and an EMS intervention (23 min for three days/week) for 23 weeks. Participants in the control group underwent general rehabilitation only. The efficacy of EMS was evaluated by lower limb muscle mass, the Berg Balance Scale (BBS), and the functional independence measure (FIM). Results: Muscle mass was significantly increased in the intervention group after 12 weeks ( = 0.008), but average muscle mass in the control group did not change ( = 0.18). Participants in the control group showed a significant decrease in BBS after 12 weeks ( = 0.007), unlike those in the intervention group. Furthermore, there was a strong correlation between the mini-mental state examination (MMSE) results and the change in muscle mass, the BBS, and the FIM in the control group ( < 0.05). Conclusions: These findings suggest that EMS is a useful intervention for increasing muscle mass and maintaining balance function in older adults with dementia.

In addition to photic reflex function, the temporal behavior of the pupil diameter reflects levels of arousal and attention and thus internal cognitive neural activity. Recent studies have reported that these behaviors are characterized by baseline activity, temporal complexity, and symmetricity (i.e., degree of symmetry) between the right and left pupil diameters. We hypothesized that experimental analysis to reveal relationships among these characteristics and model-based analysis focusing on the newly discovered contralateral projection from the locus coeruleus (LC) to the Edinger-Westphal nucleus (EWN) within the neural system for controlling pupil diameter could contribute to another dimension of understanding of complex pupil dynamics. In this study, we aimed to validate our hypothesis by analyzing the pupillary hippus in the healthy resting state in terms of sample entropy (SampEn), to capture complexity, and transfer entropy (TranEn), to capture symmetricity. We also constructed a neural model embedded with the new findings on neural pathways. The following results were observed: first, according to surrogate data analysis, the complexity and symmetricity of pupil diameter changes reflect a non-linear deterministic process. Second, both the complexity and the symmetricity are unimodal, peaking at intermediate pupil diameters. Third, according to simulation results, the neural network that controls pupil diameter has an inverted U-shaped profile of complexity and symmetricity vs. baseline LC activity; this tendency is enhanced by the contralateral synaptic projections from the LCs to the EWNs. Thus, we characterized the typical relationships between the baseline activity and the complexity and symmetricity of the pupillometric data in terms of SampEn and TranEn. Our evaluation method and findings may facilitate the development of estimation and diagnostic tools for exploring states of the healthy brain and psychiatric disorders based on measurements of pupil diameter.

The efficacy of antiplatelet therapy may vary among different disease subtypes. Prasugrel is generally a more potent, consistent, and fast-acting platelet inhibitor than clopidogrel. This sub-analysis of the phase III comparison of PRAsugrel and clopidogrel in Japanese patients with ischemic STROke (PRASTRO-I) trial aimed to assess the differences in efficacy of these treatments for each stroke subtype.

In the PRASTRO-I trial, a total of 3,753 patients with ischemic stroke were recruited from 224 centers throughout Japan and randomized (1:1) to prasugrel (3.75 mg/day) or clopidogrel (75 mg/day) for 96 weeks. For the sub-analysis, strokes were classified as large-artery atherosclerosis, small-artery occlusion (lacunar), stroke of other etiology, and stroke of undetermined etiology. The cumulative incidence of primary events (ischemic stroke, myocardial infarction, and death from other vascular cause) and hazard ratios (HRs) were calculated for each subgroup.

For patients with large-artery atherosclerosis, the primary event incidence was 3.8% in the prasugrel group and 4.8% in the clopidogrel group (HR 0.79; 95% confidence interval [CI] 0.45–1.41). For patients with small-artery occlusion, the incidence was 3.3% in the prasugrel group and 3.9% in the clopidogrel group (HR 0.82; 95% CI 0.45–1.50). For patients with stroke of undetermined etiology, the incidence was 4.6% in the prasugrel group and 3.0% in the clopidogrel group (HR 1.56; 95% CI 0.90–2.72). The incidence of bleeding was similar across subtypes.

Although statistical significance was not reached, the efficacy of prasugrel was potentially different between stroke subtypes, warranting further studies.

Spinocerebellar ataxia (SCA) 42 is caused by a mutation in , which encodes the low voltage-gated calcium channel Ca3.1 (T-type). Patients with SCA42 exhibit a pure form of cerebellar ataxia. We encountered a patient with the p.Arg1715His mutation, suffering from intractable resting tremor, particularly head tremor. This symptom improved with the administration of low-dose of zonisamide (ZNS), a T-type calcium channel blocker effective for treating Parkinson’s disease and epilepsy. Previous electrophysiological studies showed that the voltage dependence of this mutant Ca3.1 was shifted toward the positive potential. This abnormal shift was considered a factor related to disease onset and symptoms. In this study, we performed whole-cell recordings of GFP-expressing HEK293T cells that expressed wild-type or mutant Ca3.1 and investigated the changes in the abnormal shift of voltage dependence of the mutant Ca3.1. The results showed that ZNS in an amount equivalent to the patient’s internal dose significantly ameliorated the abnormal shift in the mutant Ca3.1, giving values close to those in the wild-type. On the other hand, ZNS did not affect the voltage dependence of wild-type Ca3.1. Because Ca3.1 is known to be involved in tremogenesis, modulation of the voltage dependence of mutant Ca3.1 by ZNS might have contributed to improvement in the intractable tremor of our patient with SCA42. Moreover, efonidipine, another T-type calcium channel blocker, had no effect on tremors in our patient with SCA42 and did not improve the abnormal shift in the voltage dependence of the mutant Ca3.1. This indicates that ZNS is distinct from other T-type calcium channel blockers in terms of modulation of the voltage dependence of the mutant Ca3.1.

UDP‐‐acetylglucosamine 2‐epimerase/‐acetylmannosamine kinase (GNE) is necessary for sialic acid biosynthesis. GNE myopathy is caused by a defect in , and hyposialylation is a key factor in the pathomechanism of GNE myopathy. Although candidates for evaluating hyposialylation have been reported, it is difficult to measure them in routine clinical practice. Sialylation is necessary for synthesis of various glycoproteins, including Krebs von den Lungen‐6 (KL‐6)/mucin 1 (MUC1). Here we report that KL‐6/MUC1 is decreased in GNE myopathy. We observed that KL‐6 levels were decreased in the serum of patients with GNE myopathy, and that KL‐6 and MUC1‐C were also decreased in muscle biopsy specimens from these patients. An immunofluorescent study revealed that KL‐6 and MUC1‐C were not present in the sarcolemma but were, instead, localized in rimmed vacuoles in specimens from patients with GNE myopathy. KL‐6 is already used to detect lung diseases in clinical practice, and this glycoprotein may be a novel candidate for evaluating hyposialylation in GNE myopathy.

To assess the influence of periodontal disease on cerebral hemorrhage and its clinical course, we examined the association of the serum IgG titer of periodontal pathogens with hemorrhage growth and 3-month outcome. We consecutively enrolled 115 patients with acute cerebral hemorrhage (44 females, aged 71.3 ± 13.1 years) and used ELISA to evaluate the serum IgG titers of 9 periodontal pathogens: , (.) , , , (.) , , , , and . Significant hematoma growth was defined as an increase in the volume of >33% or an absolute increase in the volume of >12.5 mL. A poor outcome was defined as a 3 or higher on the modified Rankin Scale. We observed hemorrhage growth in 13 patients (11.3%). Multivariate analysis revealed that increased IgG titers of . independently predicted the elevated hemorrhage growth (odds ratio 5.26, 95% confidence interval 1.52–18.25, = 0.01). Notably, augmented IgG titers of . but not . led to a poorer 3-month outcome (odds ratio 7.86, 95% confidence interval 1.08–57.08, = 0.04). Thus, we demonstrate that elevated serum IgG titers of . are an independent factor for predicting cerebral hemorrhage growth and that high serum IgG titers of . may predict a poor outcome in patients with this disease. Together, these novel data reveal how systemic periodontal pathogens may affect stroke patients, and, should, therefore, be taken into consideration in the management and treatment of these individuals.

Despite growing evidence that high creativity leads to mental well-being in older individuals, the neurophysiological bases of creativity remain elusive. Creativity reportedly involves multiple brain areas and their functional interconnections. In particular, functional magnetic resonance imaging (fMRI) is used to investigate the role of patterns of functional connectivity between the default network and other networks in creative activity. These interactions among networks play the role of integrating various neural processes to support creative activity and involve attention, cognitive control, and memory. The electroencephalogram (EEG) enables researchers to capture a pattern of band-specific functional connectivity, as well as moment-to-moment dynamics of brain activity; this can be accomplished even in the resting-state by exploiting the excellent temporal resolution of the EEG. Furthermore, the recent advent of functional connectivity analysis in EEG studies has focused on the phase-difference variable because of its fine spatio-temporal resolution. Therefore, we hypothesized that the combining method of EEG signals having high-temporal resolution and the phase synchronization analysis having high-spatio-temporal resolutions brings a new insight of functional connectivity regarding high creative activity of older participants. In this study, we examined the resting-state EEG signal in 20 healthy older participants and estimated functional connectivities using the phase lag index (PLI), which evaluates the phase synchronization of EEG signals. Individual creativity was assessed using the S-A creativity test in a separate session before the EEG recording. In the analysis of associations of EEG measures with the S-A test scores, the covariate effect of the intelligence quotient was evaluated. As a result, higher individual S-A scores were significantly associated with higher node degrees, defined as the average PLI of a node (electrode) across all links with the remaining nodes, across all nodes at the alpha band. A conventional power spectrum analysis revealed no significant association with S-A scores in any frequency band. Older participants with high creativity exhibited high functional connectivity even in the resting-state, irrespective of intelligence quotient, which supports the theory that creativity entails widespread brain connectivity. Thus, PLIs derived from EEG data may provide new insights into the relationship between functional connectivity and creativity in healthy older people.

The aim of this study was to examine the effect of electrical muscle stimulation on muscle atrophy caused by neuromyelitis optica. Two neuromyelitis optica patients with flaccid paralysis participated. The participants underwent a general rehabilitation program (transfer, balance, and gait training) and electrical muscle stimulation on the quadriceps femoris muscle of their paralyzed side. The change in the thickness of the vastus lateralis muscle ranged from −0.6 to 1.4 mm. These changes were minimal and did not indicate muscle atrophy. These findings suggest that in addition to general physiotherapy, electrical muscle stimulation seems safe and feasible in the acute phase of neuromyelitis optica.

Oral health conditions and cerebral small vessel disease, such as white matter lesions or cerebral microbleeds (CMBs), are associated with the incidence of stroke. The purpose of this study was to examine the associations between oral health conditions (serum IgG titers of periodontal pathogens) with the presence or severity of CMBs in acute stroke patients. From January 2013 to April 2016, acute stroke patients were registered in two hospitals. Serum samples were evaluated for antibody titers against 9 periodontal pathogens using the ELISA method. The cut-off points for reactivity (the positive decision point) to each antigen were defined as more than a mean ELISA unit + 1 standard deviation (after logarithmic transformation) in all subjects. CMBs were evaluated on T2*-weighted MRI. In all, 639 patients were evaluated (ischemic, n = 533 and hemorrhagic, n = 106; 73.1 ± 12.9 years old). Among these patients, 627 were available for CMB evaluation. Among the 9 evaluated periodontal pathogens, only (. ) was associated with the presence of CMBs. the prevalence of positive serum antibody titers against . was higher among patients with CMBs than among those without CMBs (14.6% vs. 8.7%, P = 0.025). In addition, positive serum antibody titers against . remained one of the factors associated with the presence of CMBs in multivariate logistic analysis (odds ratio 2.03, 95% confidence interval 1.19–3.47, P = 0.010). A positive serum antibody titer against . was associated with the presence of CMBs in acute stroke patients.

Associations between cognitive decline and cerebral microbleeds (CMBs) have received increasing attention. An association between CMB distribution (deep or lobar) and cognitive decline has been reported, but these findings are controversial. We investigated the association between magnetic resonance imaging (MRI) findings, including CMBs, and cognitive function in patients with first-ever lacunar infarction. We retrospectively included consecutive patients admitted with first-ever lacunar infarction identified by MRI from July 1, 2011, to December 31, 2018. We excluded patients diagnosed with dementia, including strategic single-infarct dementia, before or after the onset of stroke. The Mini-Mental State Examination (MMSE) was performed within 3 days of admission. We searched the records of 273 patients (age 72.0 ± 11.2 years, 95 females). The median MMSE score was 27 (interquartile range 25.5–29). In a univariate analysis, the MMSE score was associated with age, body mass index (BMI), education, dyslipidemia, chronic kidney disease (CKD), periventricular hyperintensity, medial temporal atrophy, lobar CMBs, and mixed CMBs (p < 0.20). The lacunar infarction location was not associated with the MMSE score. In a multivariate analysis of these factors, lobar CMBs (p < 0.001) and mixed CMBs (p = 0.008) were independently associated with the MMSE score. Lobar CMBs were associated with cognitive impairment.