A review of SaiLuoTong (MLC-SLT) development in vascular cognitive impairment and dementia.

The dementia epidemic, attributed to aging populations, represents a growing socio-economic burden. It is estimated that in 2019 about 55 million people worldwide were living with dementia. With many possible causes of dementia and the possibility of mixed dementia combining Alzheimer's disease (AD) and vascular dementia the question is whether diagnostic uncertainty exists or whether diagnostic constructs based on single etiologies are incorrect. Vascular Cognitive Impairment and Dementia (VCID) designates the extent of cognitive dysfunctions from the most benign state to that of dementia, of vascular origin. We reviewed epidemiological, pathophysiological and clinical data on VCID with a focus on VaD, as well as key data on the development of a new therapeutic solution, SaiLuoTong (MLC-SLT). From documentary research executed on different web sources (PubMed, Clintrials.gov, Z-library and Google), our initial selection for the short review of VCID and VaD was based on keywords contained in each paragraph subtitles of this article with exclusion of publications in a language other than English or published before 2010. For the review of SaiLuoTong development, there was just the language exclusion criterion. Sorted by relevance and publication date, 47 references were selected from 140 shortlisted for review. With new evidence-based classification systems, vascular cognitive impairment was proposed as umbrella term covering all forms of cognitive deficits related to vascular causes. The scope of application expanded with the VCID which includes VaD and mixed pathologies. No drugs are approved for the treatment of VaD by major Western regulatory agencies, while some traditional Chinese medicines are registered in China. VCID treatment should have a dual focus: managing the underlying cerebrovascular disease and dementia symptoms. This is the objective set for the development of the MLC-SLT, the essential data of which are reviewed in detail. To strengthen VCID and VaD research, consensus groups should attempt to consolidate scattered local research initiatives into coordinated international programs. In two VaD clinical trials, MLC-SLT improved cognitive symptoms and activities of daily living, with good safety and potential disease-modifying effect. In a placebo-controlled study in 325 patients with mild to moderate VaD and randomized according to a delayed-start design, MLC-SLT demonstrated significant improvement in memory tests and performance in executive function tasks, expanding its place in the management of VCID. At week 26, changes in VADAS-cog scores (SD) from baseline were 23.25 (0.45) for MLC-SLT 180 mg bid), 23.05 (0.45) for MLC-SLT 120 mg bid (both p < 0.0001), and 20.57 (0.45) for placebo (p = 0.15). At week 52, differences between both groups MLC-SLT and placebo were 2.67 and 2.48, respectively (p < 0.0001), without significant difference between MLC-SLT groups.

Effectiveness of Early Multimodal Non-pharmacological Interventions in Cognitive Preservation in the Elderly.

INTRODUCTION: Multimodal non-pharmacological interventions (MNPI) have been determined as effective in delaying cognitive deterioration. The effectiveness of timing of such interventions in elderly is less discussed. We compared the different effectiveness of MNPI in cognitive preservation in elderly subjects with and without dementia. METHODS: We enrolled volunteer the elderly subjects. Subjects were classified as dementia group and non-dementia group by instrument of ascertainment of dementia 8. All were assigned to attend 3 hours of MNPI (physical fitness training, Chinese capillary, and Chinese drawings and paintings) twice a week over a 16-week period. Neuropsychiatric tests, including Mini-Mental State Examination (MMSE), Cognitive Assessment Screening Instrument (CASI), clinical dementia rating (CDR), and neuropsychiatric inventory (NPI), were administered before and 1 year after MNPI. We demonstrated the changes of cognition and behavioral and psychological symptoms of dementia (BPSD) before and after MNPI. We compared the different effectiveness of cognition preservation between two groups. RESULTS: In total, there were 43 participants in our study, including 18 with non-dementia and 25 with dementia. The non-dementia group had a significantly higher proportion of cognitive preservation in remote memory (100.0% vs 68.0%, P = .007), orientation (94.4% vs 48.0%, P = .001), drawing (94.4% vs 64.0%, P = .021) and language (77.8% vs 48.0%, P = .049) than the dementia group. The highest proportion of preserved cognition after MNPI was remote memory (100%), followed by orientation (94.4%) and drawing (94.4%) in the non-dementia group. The highest proportion of preserved cognition after MNPI was attention (72%) followed by remote memory (68%), recent memory (64%) and drawing (64%) in the dementia group. Overall, their improved rate in behavioral and psychological symptoms was 55.6%. CONCLUSION: Our study concluded the benefits of early MNPI in cognition preservation in the elderly, especially in the field of remote memory, orientation, drawing and language.

Quetiapine Oral Solution in Alzheimer's Disease: Efficacy and Dosage Insights from a Real-World Retrospective Study.

BACKGROUND: Neuropsychiatric symptoms (NPS) are distressing for patients with dementia, often accelerating functional decline and nursing home placement. Medications such as quetiapine are used to alleviate NPS, but their side effects require cautious use. Liquid formulations such as quetiapine oral suspension suit specific populations; however, real-world data on their use in patients with dementia are limited. OBJECTIVE: The purpose of this retrospective, naturalistic study was to provide preliminary data on the effects of treatment with quetiapine oral suspension on behavioral and psychiatric disturbances in Alzheimer's disease (AD) outpatients in Taiwan. METHODS: Between January 2022 and June 2023, data were collected from outpatients with a diagnosis of probable AD who received treatment with Qting® (quetiapine oral solution 25 mg/ml). Primary outcome measures were changes in Neuropsychiatric Inventory (NPI) total score and its sub-items from baseline to the endpoint. RESULTS: We recruited 66 AD patients with a mean age of 72.1±7.6 years, most of whom were female (69.7%). Twenty-three patients had data on neuropsychological test and NPI scores before and after quetiapine treatment. There was no significant change in global cognitive function from baseline to the endpoint. A significant reduction in NPI total score after quetiapine treatment was noted, while the effect on NPI sub-items was limited. The average maintenance dose was 1.5±0.6 ml. CONCLUSIONS: We demonstrated our clinical experience of the use of quetiapine oral solution in AD patients with NPS. Our results showed that quetiapine oral solution treatment significantly improved these symptoms at a relatively low dose.

A 12-Year Comparison of Alzheimer's Dementia Patients With Their Informants in Taiwan.

BACKGROUND: To update the characteristics of patients with Alzheimer's disease (AD) and their informants in Taiwan and compare them from 12 years ago. METHODS: 1218 patients with AD and their informants were recruited from six hospitals in Taiwan. The uniform data set version 3.0 (UDS3, form A1-A3) were administered. RESULTS: Compared with the first registration from 2010-2012 (n = 691), the mean clinical dementia rating sum of boxes score was significantly lower, more patients living independently, and more informants not living together with the patients. A total of 11.2%, 4.1%, 12.8%, and 0.5% of the patients had a reported history of cognitive impairment in their mothers, fathers, siblings, and children, respectively. CONCLUSION: Compared with the data from 2010, patients have been diagnosed at a milder disease stage, and their informants used telephone contact more frequently instead of living with the patients. Family histories of cognitive impairment in patients with AD remain frequent.

Association between pain and cognitive and daily functional impairment in older institutional residents: a cross-sectional study.

BACKGROUND: Pain is often neglected in disabled older population, especially in Taiwan where the population of institutional residents is rapidly growing. Our study aimed to investigate pain prevalence and associated factors among institutional residents to improve pain assessment and management. METHODS: This nationwide study recruited 5,746 institutional residents in Taiwan between July 2019 and February 2020. Patient self-report was considered the most valid and reliable indicator of pain. A 5-point verbal rating scale was used to measure pain intensity, with a score ranging from 2 to 5 indicating the presence of pain. Associated factors with pain, including comorbidities, functional dependence, and quality of life, were also assessed. RESULTS: The mean age of the residents was 77.1 ± 13.4 years, with 63.1% of them aged over 75 years. Overall, 40.3% of the residents reported pain, of whom 51.2% had moderate to severe pain. Pain was more common in residents with comorbidities and significantly impacted emotions and behavior problems, and the mean EQ5D score, which is a measure of health-related quality of life (p < .001). Interestingly, pain was only related to instrumental activities of daily living (IADL) and not activities of daily living (ADL). On the other hand, dementia was significantly negatively associated with pain (p < .001), with an estimated odds of 0.63 times (95% CI: 0.53-0.75) for the presence of pain when compared to residents who did not have dementia. CONCLUSIONS: Unmanaged pain is common among institutional residents and is associated with comorbidities, IADL, emotional/behavioral problems, and health-related quality of life. Older residents may have lower odds of reporting pain due to difficulty communicating their pain, even through the use of a simple 5-point verbal rating scale. Therefore, more attention and effort should be directed towards improving pain evaluation in this vulnerable population .

Analyzing Facial Asymmetry in Alzheimer's Dementia Using Image-Based Technology.

Several studies have demonstrated accelerated brain aging in Alzheimer's dementia (AD). Previous studies have also reported that facial asymmetry increases with age. Because obtaining facial images is much easier than obtaining brain images, the aim of this work was to investigate whether AD exhibits accelerated aging patterns in facial asymmetry. We developed new facial asymmetry measures to compare Alzheimer's patients with healthy controls. A three-dimensional camera was used to capture facial images, and 68 facial landmarks were identified using an open-source machine-learning algorithm called OpenFace. A standard image registration method was used to align the three-dimensional original and mirrored facial images. This study used the registration error, representing landmark superimposition asymmetry distances, to examine 29 pairs of landmarks to characterize facial asymmetry. After comparing the facial images of 150 patients with AD with those of 150 age- and sex-matched non-demented controls, we found that the asymmetry of 20 landmarks was significantly different in AD than in the controls (p < 0.05). The AD-linked asymmetry was concentrated in the face edge, eyebrows, eyes, nostrils, and mouth. Facial asymmetry evaluation may thus serve as a tool for the detection of AD.

Association between subclinical epileptiform discharge and the behavioral and psychological symptoms in patients with Alzheimer's dementia.

OBJECTIVES: Behavioral and psychological symptoms of dementia (BPSD) are highly prevalent in patients with Alzheimer's disease (AD), causing burdens on caregivers. Behavioral and psychological symptoms of dementia and subclinical epileptiform discharge (SED) increased with the disease course of AD. However, the interaction between them was still unknown. The present study aimed to evaluate the associations between SED and BPSD. METHODS/DESIGN: Patients with AD from Kaohsiung Municipal Ta-tung Hospital were included in this study. International 10-20 system scalp electroencephalography (EEG) for 13 min was performed to detect SED. Behavioral and psychological symptoms of dementia was assessed by neuropsychiatric inventory (NPI) questionnaires. The occurrence of BPSD subsyndromes was compared between patients with and without SED. RESULTS: Two hundred sixty-three adult patients qualified for the inclusion criteria and were enrolled in this study. The mean age of patients was 80.2 years, and approximately 62% were women. 17.1% of patients showed SED on EEG. Apathy was the most commonly reported BPSD subsyndrome in this cohort. There was no significant difference in the prevalence of BPSD between patients with and without SED. (75.6% vs. 67.4%, p = 0.2806). However, the NPI score of irritability subsyndrome was significantly higher in the SED (+) group (2.6 ± 3.7 vs. 1.2 ± 2.7, p = 0.0028). In addition, subclinical epileptiform discharge in the frontal lobe was associated with a considerably higher occurrence of hyperactivity subsyndrome, including irritability. CONCLUSIONS: SED may not be a direct cause of BPSD, but the presence of SED may affect the manifestation of BPSD.

The Use of Verbal and Nonverbal Memory Tests for Alzheimer's Disease Screening in Taiwan Chinese.

Patients with Alzheimer's disease typically have initial deficits in memory. Memory testing can be categorized as verbal or nonverbal by the modality of the stimuli used. We compared the discriminative validity of selected verbal and nonverbal memory tests between non-dementia and Alzheimer's disease in Taiwan. Ninety-eight patients with mild Alzheimer's disease and 269 non-dementia individuals underwent story recall test (immediate and delayed recall), and constructional praxis test (copy and delayed recall). The receiver-operating characteristic curve and area under the curve were evaluated to compare between tests. Patients with Alzheimer's disease performed poorly across all memory tests, and the receiver-operating characteristic curve analysis indicated that story recall immediate and relayed recall, and constructional praxis delayed recall had good classification accuracy with area under the curve of .90, .87 and .87 respectively. These results provide support that both verbal and nonverbal memory tests are reliable measure for screening patients with Alzheimer's disease.

Age and sex differences in the association between APOE genotype and Alzheimer's disease in a Taiwan Chinese population.

Introduction: The Apolipoprotein E (APOE) epsilon (ε) 4 allele is a well-established risk factor for late-onset Alzheimer's disease (AD). Reports on white ancestry populations have showed that age, sex, and ethnicity have different effects on the association between APOE genotype and AD. However, studies on Asian populations such as Taiwan Chinese populations are limited. This study aimed to evaluate the association between APOE genotype and AD in a Taiwan Chinese population, and to explore if the association varies by age and sex. Methods: We conducted a case-control study in 725 patients with AD and 1,067 age- and sex- matched controls without dementia from a Taiwan Chinese population. Logistic regression models were used to test the association between AD and APOE genotypes. Secondary analyses considered age (<75 or ≥75 years old), and sex stratified models. Results: The risk of AD was significantly increased for people with at least one copy of APOE ε4 (OR = 2.52, 95% CI = 2.01-3.17, p < 0.001) and in a dose-dependent manner. Our results did not show an statistically significance different in AD risk when women and men carrying APOEε4 were compared. Despite not reaching statistical significance, the risk of APOE ε4 for AD was higher among younger participants (OR = 3.21, 95% CI = 2.26-4.56, p < 0.001) compared to older ones (OR = 2.13, 95% CI = 1.53-2.97, p < 0.001). When considering both sex and age, the risk of AD was higher among older men carrying APOE ε4 (OR = 2.64, 95% CI = 1.51-4.60 in men; OR = 1.90, 95% CI = 1.26-2.86 in women), while women carrying APOE ε4 appeared to have an increased risk at a younger age (OR = 3.29, 95% CI = 2.20-4.93 in women; OR = 2.91, 95% CI = 1.40-6.05 in men). Discussion: The APOE ε4 allele represents a major risk factor for AD in the Taiwanese population. The effect of APOE ε4 allele on AD risk appeared to be stronger among men aged 75 years or more and among younger women.

The Association Between Subjective Mental Impairment and Objective Cognitive Performance in Non-Demented, Very Mild and Mild Demented Individuals.

OBJECTIVES: Explore associations between subjective mental impairment, objective cognitive performance, and subsequent decline in older individuals with different cognitive statuses in Taiwan. METHODS: Use self-reported questionnaire and cognitive abilities screening instrument to assess subjective and objective cognitive function. Categorize participants as reporters or non-reporters based on subjective reports. Conduct t-tests and regression analysis. RESULTS: 206 participants were assessed: 99 cognitively intact (CI), 44 very mild dementia, and 63 mild dementia. In the CI group, reporters in memory, orientation, daily life, community affairs, and judgement domains performed worse than non-reporters. In very mild dementia group, reporters in memory and personality domains performed better than non-reporters. No association found between subjective reports and 1-year cognitive decline in dementia groups. CONCLUSION: Association between subjective impairment and objective performance differs in CI and very mild dementia groups. Subjective reports do not predict 1-year cognitive decline in dementia patients. Longer follow-up studies needed.

Optical Coherence Tomography Assessment of Macular Thickness in Alzheimer's Dementia with Different Neuropsychological Severities.

This retrospective case-control study aimed to investigate associations between disease severity of Alzheimer's dementia (AD) and macular thickness. Data of patients with AD who were under medication (n = 192) between 2013 and 2020, as well as an age- and sex-matched control group (n = 200) with normal cognitive function, were included. AD patients were divided into subgroups according to scores of the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). Macular thickness was analyzed via the Early Treatment Diabetic Retinopathy Study (ETDRS) grid map. AD patients had significant reductions in full macula layers, including inner circle, outer inferior area, and outer nasal area of the macula. Similar retinal thinning was noted in ganglion cells and inner plexiform layers. Advanced AD patients (MMSE score < 18 or CDR ≥ 1) showed more advanced reduction of macular thickness than the AD group (CDR = 0.5 or MMSE ≥ 18), indicating that severe cognitive impairment was associated with thinner macular thickness. Advanced AD is associated with significant macula thinning in full retina and inner plexiform layers, especially at the inner circle of the macula. Macular thickness may be a useful biomarker of AD disease severity. Retinal imaging may be a non-invasive, low-cost surrogate for AD.

Prevalence and the associated factors of cognitive impairment among people living with HIV in Taiwan: a cross-sectional study.

Cognitive impairment impacts the quality of life and increases morbidity and mortality rates. The prevalence of and factors associated with cognitive impairment have become important issues as the age of people living with HIV(PLWH) increases. In 2020, We conducted a cross-sectional study to survey the cognitive impairment among PLWH in three hospitals in Taiwan with Alzheimer Disease-8 (AD8) questionnaire. The average age of 1,111 individuals was 37.54 ± 10.46 years old, and their average duration to live with HIV was 7.12 ± 4.85 years. The rate of impaired cognitive function was 2.25% (N = 25) when AD8 score ≥ 2 was a positive finding for cognitive impairment. Aging (p = .012), being less educated (p = 0.010), and having a longer duration to live with HIV (p = .025) were significantly associated with cognitive impairment. Multivariate logistic regression analysis revealed that only the duration of living with HIV was a significant factor related to the tendency of cognitive impairment (p = .032). The risk of cognitive impairment increased by 1.098 times for every additional year to live with HIV. In conclusion, the prevalence of cognitive impairment among PLWH in Taiwan was 2.25%. Healthcare personnel should be sensitive to the changes in PLWH's cognitive function as they age.

Developing Biomarkers for the Skin: Biomarkers for the Diagnosis and Prediction of Treatment Outcomes of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory decline and cognitive impairment. Research on biomarkers can aid in early diagnosis, monitoring disease progression, evaluating treatment efficacy, and advancing fundamental research. We conducted a cross-sectional longitudinal study to see if there is an association between AD patients and age-matched healthy controls for their physiologic skin characteristics, such as pH, hydration, transepidermal water loss (TEWL), elasticity, microcirculation, and ApoE genotyping. The study used the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating-Sum of the Boxes (CDR-SB) scales as references to quantify the presence of disease, if any. Our findings demonstrate that AD patients have a dominantly neutral pH, greater skin hydration, and less elasticity compared to the control subjects. At baseline, the tortuous capillary percentage negatively correlated with MMSE scores in AD patients. However, AD patients who carry the ApoE E4 allele and exhibit a high percentage of tortuous capillaries and capillary tortuous numbers have shown better treatment outcomes at six months. Therefore, we believe that physiologic skin testing is a rapid and effective way to screen, monitor progression, and ultimately guide the most appropriate treatment for AD patients.

Cognitive effects of cilostazol in Alzheimer's dementia patients with peripheral arterial occlusive disease: A case-control study.

AIM: Alzheimer's dementia (AD) is a slowly progressing neurodegenerative disease, characterized by beta-amyloid deposition and neurofibrillary tangles. Peripheral atherosclerosis may deteriorate these processes via endothelial cell dysfunction and microvascular impairment. Cilostazol - a phosphodiesterase 3 inhibitor - is a standard treatment for peripheral arterial occlusive disease and a potential treatment for preserving cognitive function in AD patients. We aimed to determine whether cilostazol is beneficial in AD patients with peripheral arterial occlusive disease by evaluating Cognitive Abilities Screening Instrument (CASI) domains. METHODS: We conducted a retrospective case-control study of 62 AD patients in Taiwan. Thirty-one patients had peripheral arterial occlusive disease and were receiving cilostazol plus acetylcholinesterase inhibitors (AchEIs) or N-methyl d-aspartate antagonists, whereas 31 others were receiving AchEIs. Therapeutic responses were measured using neuropsychological assessments. The CASI was administered at baseline and 12 months later; different domains were analyzed between the groups using univariate and multivariate analyses. RESULTS: Age, sex, education duration, ApoE ε4 gene status, and initial Mini-Mental State Examination scores were not different between the two groups. Except for fluency, no CASI domains showed a statistical difference between the groups. A significant difference was observed in category fluency (P = 0.010). In the logistic regression analysis, after adjusting for covariate effects, category fluency still showed a significant difference between the groups (P = 0.013). CONCLUSIONS: In AD patients with peripheral arterial occlusive disease who have received Food and Drug Administration-approved pharmacotherapy, cilostazol, as an antiplatelet, may help to preserve general cognitive function, with significant preservation in category fluency. Geriatr Gerontol Int 2023; 23: 194-199.

A review of cognitive and behavioral outcomes of Brivaracetam.

Anti-seizure medications (ASMs) can cause cognitive or behavioral adverse drug reactions, which is an important consideration when selecting an appropriate ASM. Brivaracetam (BRV) is a newer synaptic vesicle protein 2A ligand, which is expected to result in fewer neuropsychiatric adverse effects due to its mechanism of action. To understand the impact of BRV on cognition and behavior compared with other ASMs, we conducted a review of the literature using the Cochrane Library, PubMed/MEDLINE, and Embase. After the screening process, a total of two animal studies, one randomized controlled trial, one pooled analysis of clinical trials, one controlled study, and nine observational studies were included. The animal studies showed that BRV did not worsen cognitive or behavioral performance in rodents. The human studies showed that BRV was associated with fewer cognitive adverse events compared with other second- or third-generation ASMs. In addition, BRV was less associated with behavioral disturbance than levetiracetam. In summary, this review revealed that BRV has a limited impact on cognition and behavior. For patients who are intolerant to levetiracetam and have levetiracetam-related behavioral side effects, switching to BRV could be beneficial. However, heterogeneity between studies resulted in low-quality of evidence, and further trials are needed to confirm the findings.

Prevalence and Risk Factors of Neuropsychiatric Symptoms in Institutionalized Patients with Parkinson's Disease in Taiwan: A Nationwide Observational Study.

Neuropsychiatric symptoms (NPSs) are known to be frequent in Parkinson's disease (PD) with great impacts on the quality of life, but reports about the prevalence in institutions are few. Our aim was to investigate the prevalence of and risk factors for NPSs in institutionalized patients with PD in Taiwan. The National Health Research Institute executed a cross-sectional, community-based, observational study on residential long-term care service institutions. The diagnosis of PD was determined by physicians with the estimated Hoehn and Yahr stage of PD according to the EQ-5D-5L questionnaire. A total of 370 patients with PD (80.1 ± 9.94 years old, 55.1% females) were included, and 139 (37.6%) had more than one NPS in the prior 3 months. The top three NPSs were nighttime behavior (65 (17.6%)), depression (53 (14.3%)), and fear/anxiety (49 (13.2%)). There were no differences between those with NPS and those without NPS in terms of age, gender, education, Mini-Mental State Examination, or Hoehn and Yahr stage. However, multivariate logistic regression analysis showed that genitourinary disease (odds ratio (OR) = 3.13; 95% confidence interval (95%CI) = 1.77-5.51) and psychiatric disorders (OR = 5.18; 95%CI = 3.09-8.69) may be associated with increased risk of NPSs. Increased physical restraint was observed in residents with advanced PD. Genitourinary disease and psychiatric disorders appear to increase the risk of NPSs in institutionalized residents with PD.

What factors contribute to the need for physical restraint in institutionalized residents in Taiwan?

BACKGROUND: In Taiwan, physical restraint is commonly used in institutions to protect residents from falling or injury. However, physical restraint should be used cautiously to avoid side effects, such as worse cognition, mobility, depression, and even death. OBJECTIVES: To identify the rate of physical restraint and the associated risk factors in institutionalized residents in Taiwan. METHODS: A community-based epidemiological survey was conducted from July 2019 to February 2020 across 266 residential institutions. Among the estimated 6,549 residents being surveyed, a total of 5,752 finished the study. The questionnaires were completed by residents, his/her family or social workers. The cognition tests were conducted by specialists and a multilevel analysis approach was used to identify cognition/disability/medical history/special nursing care/BPSD risk factors for physical restraints. RESULTS: Of the 5,752 included institutionalized residents, 30.2% (1,737) had been previously restrained. Older age, lower education level, lower cognitive function, higher dependence, residents with cerebrovascular disease, pulmonary disease, dementia, and intractable epilepsy, all contributed to a higher physical restraint rate, while orthopedic disease and spinal cord injury were associated with a lower physical restraint rate. Furthermore, residents with special nursing care had a higher restraint rate. Residents with most of the behavior and psychological symptoms were also associated with an increased restraint rate. CONCLUSIONS: We studied the rate of physical restraint and associated risk factors in institutionalized residents in Taiwan. The benefits and risks of physical restraint should be evaluated before application, and adjusted according to different clinical situations.

Effects of Perampanel on Seizure Control, Cognition, Behavior, and Psychological Status in Patients With Epilepsy: A Systematic Review.

BACKGROUND AND PURPOSE: Thoroughly acquainting physicians with the effects of antiseizure medications (ASMs) is essential for developing appropriate therapeutic regimens for seizure management. This review summarizes the available evidence regarding patients receiving the antiseizure agent perampanel (PER) and its effects on the cognition, behavior, and psychological status of patients. METHODS: The PubMed and Google Scholar databases were searched for all relevant articles published during 2015-2021 and without any other publication limitations, and also manually searched the reference lists in the identified articles. Outcomes of interest were changes in seizure frequency relative to baseline, 50% responder rate, seizure-free rate, and retention rate (proportion of participants continuing PER at study endpoints). Safety outcomes included adverse effects and the percentage of patients experiencing effects on cognitive, psychiatric, and behavioral symptoms. RESULTS: We identified 139 studies, of which 28 were included after screening. Most studies found reduced seizure frequencies and satisfactory responder and retention rates, demonstrating the effectiveness and tolerability of PER. No negative effects were found for cognitive function, but a nonnegligible impact on aggressive behavior was noted when compared with other ASMs. Patients with previous psychiatric comorbidities had a greater risk of psychiatric side effects under PER treatment. PER induces an overall improvement in quality of life. CONCLUSIONS: After synthesizing the study results, PER was a safe and effective choice as an additional therapy for patients with refractory epilepsy. A comprehensive evaluation of behavior and psychiatric risk is suggested before implementing PER.

Gamma Frequency Inhibits the Secretion and Aggregation of Amyloid-ß and Decreases the Phosphorylation of mTOR and Tau Proteins in vitro.

BACKGROUND: Alzheimer's disease (AD) was the main cause of dementia in an aging society; unfortunately, there is no effective treatment for AD now. Meditation has been reported to thicken the cerebral cortex, and gamma wave at a frequency of 40 hertz (Hz) was recorded during the meditation process from the brain. Previous study showed that non-invasive scintillation gamma frequency oscillation increased the space in recognition and memory of auditory cortex hippocampal gyrus in AD mice model. However, the AD-related molecular change by exposure of 40 Hz gamma frequency in brain cells was still unclear. OBJECTIVE: We investigated the AD-related molecular change by exposure of 40 Hz gamma frequency in SH-SY5Y cells. METHODS: We designed the light and sound generators at 40 Hz gamma frequency for this study. SH-SY5Y cells were exposed to sound or light of 40 Hz gamma frequency, respectively. The concentrations of amyloid-ß40 (Aß40) and amyloid-ß42 (Aß42) were quantified by enzyme-linked immunosorbent assay. The protein levels were examined by Western blotting. The aggregation of Aß42 was examined by thioflavin T assay. RESULTS: Our results showed that the secretion of Aß, phosphorylation of AKT, mTOR, and tau, and aggregation of Aß42 were significantly inhibited by 40 Hz gamma frequency in SH-SY5Y cells. The phosphorylation of 4E-BP1, downstream of mTOR, was induced by 40 Hz gamma frequency in SH-SY5Y cells. CONCLUSION: Our study showed 40 Hz gamma frequency involved in the inhibition of secretion and aggregation of Aß and inhibition of p-Tau protein expression through the mTOR/4E-BP1/Tau signaling pathway.

Association between Cerebral Coordination Functions and Clinical Outcomes of Alzheimer's Dementia.

Background: Alzheimer's dementia (AD) is a degenerative disease that impairs cognitive function, initially, and then motor or other function, eventually. Motor coordination function impairment usually accompanies cognition impairment but it is seldom examined whether it can reflect the clinical outcomes of AD. Methods: 113 clinically diagnosed AD patients with a mean age of 78.9 ± 6.9 years underwent an annual neuropsychological assessment using the Mini-Mental State Examination (MMSE), the Cognitive Abilities Screening Instrument (CASI), the Sum of Boxes of Clinical Dementia Rating (CDR-SB), and the CDR. The cerebral coordination function was evaluated through correlations among 15 joints with a kinetic depth sensor annually. An intra-individual comparison of both cognitive and motor coordination functions was performed to examine their correlations. Results: The changes in coordination function in the lower limbs can significantly reflect the clinical outcomes, MMSE (p < 0.001), CASI (p = 0.006), CDR (p < 0.001), and CDR-SB (p < 0.001), but the changes in upper limbs can only reflect the clinical outcome in CDR (p < 0.001). Conclusions: The use of a kinetic depth sensor to determine the coordination between joints, especially in lower limbs, can significantly reflect the global functional and cognitive outcomes in AD. Such evaluations could be another biomarker used to evaluate non-cognitive outcomes in AD for clinical and research purposes.