Perampanel (PER) is a selective blocker of AMPA receptors showing efficacy in treating various epileptic disorders including brain tumor-related epilepsy and also potential in treating motor neuron disease. However, besides its inhibition of AMPA-induced currents, whether PER has any other direct ionic effects in different types of neurons remains largely unknown. We investigated the effects of PER and related compounds on ionic currents in different types of cells, including hippocampal mHippoE-14 neurons, motor neuron-like NSC-34 cells and U87 glioma cells. We found that PER differentially and effectively suppressed the amplitude of voltage-gated Na+ currents (INa) in mHippoE-14 cells. The IC50 values required to inhibit peak and late INa were 4.12 and 0.78 μM, respectively. PER attenuated tefluthrin-induced increases in both amplitude and deactivating time constant of INa. Importantly, PER also inhibited the amplitude of M-type K+ currents (IK(M)) with an IC50 value of 0.92 μM. The suppression of IK(M) was attenuated by the addition of flupirtine or ZnCl2 but not by L-quisqualic acid or sorafenib. Meanwhile, in cell-attached configuration, PER (3 μM) decreased the activity of M-type K+ channels with no change in single-channel conductance but shifting the activation curve along the voltage axis in a rightward direction. Supportively, PER suppressed IK(M) in NSC-34 cells and INa in U87 glioma cells. The inhibitory effects of PER on both INa and IK(M), independent of its antagonistic effect on AMPA receptors, may be responsible for its wide-spectrum of effects observed in neurological clinical practice.

Objective Delusions are common neuropsychiatric symptoms in patients with dementia with Lewy bodies (DLB). The aim of this study was to investigate the associated factors of delusions in patients with DLB. Method A retrospective study of outpatients with DLB registered in a regional hospital's database was performed. The associated factors including cognitive performance, clinical features, vascular risk factors, and neuropsychiatric symptoms between delusional and nondelusional patients with DLB were compared. Results Among 207 patients with DLB, 106 (51.2%) were delusional and 101 (48.8%) were not. Delusion of other persons are stealing was the most common symptom (35.3%). The delusional group had a significantly higher diagnostic rate of probable than possible DLB, higher disease severity, poorer cognitive performance, more severe neuropsychiatric symptoms, and higher caregiver burden (all p < 0.05). In addition, the delusional group had a significantly lower frequency of diabetes compared to the nondelusional group (odds ratio = 0.28, p < 0.001). Conclusion Delusion of other persons are stealing was the most common delusional symptom. The patients with DLB who presented with delusions had poorer cognitive function and more severe neuropsychiatric symptoms. A novel finding is that the DLB patients with diabetes had a lower frequency of delusions.

Introduction: Freezing phenomenon is a striking feature of Parkinson's disease. However, it has never been studied in people with dementia with Lewy bodies (DLB). We designed a freezing of speech single questionnaire (FOSSQ) and investigated the frequency and association of freezing of speech (FOS) in patients with DLB and other types of dementia.Methods: This is a retrospective analysis of data from the project of historybased artificial intelligent computerized dementia diagnostic system. We compared the frequencies of FOS among non-demented (ND) participants, patients with Alzheimer's disease (AD), vascular dementia (VaD), and DLB. Further, we explored the association factors of FOS in all the participants.Results: We enrolled 666 individuals with the following disease distribution: 190, ND; 230, AD; 183, VaD; and 63, DLB. Compared to individuals with ND (2.1%), patients with AD (6.1%), or VaD (18.0%), DLB (54.0%) showed a significantly higher frequency of positive FOS (all p < 0.001). The association factors of FOS were older age, more severe dementia, more severe motor dysfunction, fluctuating cognition, visual hallucinations, parkinsonism, rapid eye movement sleep behavior disorder, attention, mental manipulation, and language. Conclusion:Our study showed that the informant-based FOSSQ may be a practical screening tool for discriminating DLB from individuals with ND or other forms of dementia. The FOSSQ can be applied in clinical practice as well as on the artificial intelligent platform.

Objectives: Tremor is common in patients with Lewy body disease (LBD) and not rare in normal individuals. Prevalence of tremor in patients with vascular cognitive impairment (VCI) and its association with other comorbidities are seldom studied. The aim of this study was to investigate the patient characteristics of VCI associated with tremor and to evaluate the possibility of mixed pathology with LBD in these patients. Methods: Retrospective analysis of a large population with VCI registered in the database of a regional healthcare system was performed. VCI patients were divided into tremor and non-tremor groups. The associated characteristics including demographics, clinical features in motor and non-motor domains, vascular risk factors, and neuroimaging features were compared between the tremor group and the nontremor group. Results: Among 1337 patients with VCI, 292 (21.8%) had tremor, while 1045 (78.2%) did not have tremor. The tremor group had significantly higher prevalence of all motor and non-motor LBD clinical features than the non-tremor group. The tremor group also demonstrated more severe neuropsychiatric symptoms. Among patients with tremor, patients having tremor onset earlier than stroke onset showed significantly higher prevalence of rapid eye movement sleep behavior disorder. All comparisons were adjusted for age and severity of dementia. Conclusion: Tremor is a common comorbidity of VCI. VCI patients with tremor had a higher prevalence of motor and non-motor LBD features. These findings raised the possibility of VCI patients with tremor having high possibility of mixed pathology with LBD.