Application of blood-based biomarkers of Alzheimer's disease in clinical practice: Recommendations from Taiwan Dementia Society.

Blood-based biomarkers (BBM) are potentially powerful tools that assist in the biological diagnosis of Alzheimer's disease (AD) in vivo with minimal invasiveness, relatively low cost, and good accessibility. This review summarizes current evidence for using BBMs in AD, focusing on amyloid, tau, and biomarkers for neurodegeneration. Blood-based phosphorylated tau and the Aß42/Aß40 ratio showed consistent concordance with brain pathology measured by CSF or PET in the research setting. In addition, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are neurodegenerative biomarkers that show the potential to assist in the differential diagnosis of AD. Other pathology-specific biomarkers, such as α-synuclein and TAR DNA-binding protein 43 (TDP-43), can potentially detect AD concurrent pathology. Based on current evidence, the working group from the Taiwan Dementia Society (TDS) achieved consensus recommendations on the appropriate use of BBMs for AD in clinical practice. BBMs may assist clinical diagnosis and prognosis in AD subjects with cognitive symptoms; however, the results should be interpreted by dementia specialists and combining biochemical, neuropsychological, and neuroimaging information. Further studies are needed to evaluate BBMs' real-world performance and potential impact on clinical decision-making.

Tackling challenges in care of Alzheimer's disease and other dementias amid the COVID-19 pandemic, now and in the future.

We have provided an overview on the profound impact of COVID-19 upon older people with Alzheimer's disease and other dementias and the challenges encountered in our management of dementia in different health-care settings, including hospital, out-patient, care homes, and the community during the COVID-19 pandemic. We have also proposed a conceptual framework and practical suggestions for health-care providers in tackling these challenges, which can also apply to the care of older people in general, with or without other neurological diseases, such as stroke or parkinsonism. We believe this review will provide strategic directions and set standards for health-care leaders in dementia, including governmental bodies around the world in coordinating emergency response plans for protecting and caring for older people with dementia amid the COIVD-19 outbreak, which is likely to continue at varying severity in different regions around the world in the medium term.

[Development and Psychometric Validation of a Tool for Assessing the Care Needs of Families of Patients With Dementia].

BACKGROUND: The rapid aging of the global population has sharply increased the prevalence of dementia. Most people with dementia (PwD) live at home and are cared for by family caregivers. The complicated care needs of PwD and family caregivers necessitate the provision of comprehensive and transdisciplinary assessment and service support. PURPOSE: The purpose of this study was to construct the contents of the "Assessment Tool for Family Care Needs of People with Dementia" using a transdisciplinary perspective and to establish the reliability and validity of this tool. METHODS: Based on a literature review and clinical experience, the preliminary items of the assessment tool were drawn up and pilot tests of the case were conducted in the Clinic for Dementia Care. The transdisciplinary research team discussed the pilot tests and verified the preliminary items, and then experts were invited to assess the content validity of the assessment tool. Next, quota sampling was conducted in accordance with the national proportion of the severity of dementia and the questionnaire surveys were administered in an outpatient department of neurology at a medical center in southern Taiwan. Two hundred dyads of PwD and their family caregivers participated in the survey. Reliability and validity analysis of the data were completed. RESULTS: The assessment tool contains 21 items of demographic data and 31 items in the eight subscales of "language and communication", "activities of daily living", "sleep", "activity arrangements", "nutrition and diet", "behavioral and psychological symptoms of dementia", "care stress", and "obtaining resources". The overall content validity of the assessment tool was .99 and the Cronbach's alpha of each subscale ranged between .625 and .905. The concurrent validities of the "activities of daily living" subscale and the "behavioral and psychological symptoms of dementia" subscale were, respectively, correlated with the Barthel Index (r = -.889, p < .001) and the Neuropsychiatric Inventory Questionnaire (r = .750, p < .001). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The assessment tool was assessed as having satisfactory validity and reliability. Moreover, the tool was clear and concise, and was able to be completed quickly by the caregivers. Transdisciplinary professionals involved in dementia care may use this assessment tool in outpatient departments, centers for integrated dementia care, and discharge preparation services to acquire information related to family care needs. The results of the assessment tool may be used as a reference in developing appropriate transdisciplinary care plans to improve the quality of care and quality of life of families of patients with dementia.

Predictors of caregiver burden and care costs for older persons with dementia in Taiwan.

ABSTRACTObjectives:As a degenerative disease, the progression of dementia needs continued care provision and poses both psychological and financial burden for family caregivers of persons with dementia (PWD). This study seeks to compare predictors of care costs and caregiver burden, and to identify modifiable factors that could alleviate the burden faced by dementia caregivers. METHODS: This study interviewed 231 PWD-caregiver dyads in a dementia clinic at a teaching hospital in southern Taiwan in 2013. A follow-up study was conducted a year later, and 167 dyads completed the second interview. Data collected included PWD characteristics, caregiver characteristics, relationship to PWD, and social support to caregivers. Caregiver burden was measured with the Zarit Burden Interview instrument. The association between each predictor variable and cost of care and caregiver burden scores was examined using linear mixed models. RESULTS: Predictors of care costs were found to be different from predictors of caregiver burden: functional declines measured by Katz's activities of daily living (ADL) scale were associated with total cost as compared to behavioral disturbance measured by Neuropsychiatric Inventory (NPI), which showed no impact on care costs. However, NPI was a significant predictor of caregiver burden. Caregivers who were better-off financially also reported significantly lower caregiver burden. CONCLUSIONS: Since predictors of care costs were different from the predictors of caregiver burden, providing training to caregivers in addressing PWD's behavioral disturbance and proving financial assistance to low income caregivers could be effective in reducing caregiver burden.

Factors Influencing Family Surrogates' Intention with Regard to Do-Not-Resuscitate Directive for Patients with Dementia.

Objective: To investigate the prevalence of family surrogates' do-not-resuscitate (DNR) intention for patients with dementia (PwD), and factors influencing family surrogates' decisions. Methods: This is a descriptive and cross-sectional study. Patients with dementia and their family surrogates from Dementia Outpatient Clinic of a teaching hospital in southern Taiwan were included. Data were collected using chart review and questionnaire survey. Influential factors were analyzed using multiple logistic regression. Results: One hundred and forty of the 223 participants (62.8%) have intention to sign DNR consents for their dementia relatives. Factors influencing the intention were: (1) Comorbid with musculoskeletal diseases or diabetes (p < .05); (2) psychological symptoms of repetitive wording and behavior (p < .05); (3) spouse (p < .05) and lineal relatives (p < .01); (4) previous discussion between families and patient about DNR directive (p = .001); (5) believers of Taiwan folk belief (Buddhism or Taoism) (p < .05). Conclusions: Advanced dementia patients cannot express intention about their end-of-life care and depend on family surrogates to decide for them. Our study showed that spouse and direct relatives, comorbidities of musculoskeletal disease or diabetes, psychological symptoms of repetitive wording and behavior, previous discussion about patients' intention, and believers of Taiwan folk belief are all positive influencing factors for surrogates to consent DNR directive for patients. Our findings are important in promoting DNR directive for PwD. Clinical implications: Our results may help to promote DNR decisions for dementia patients, especially in Chinese populations.

Cross-cultural study of caregiver burden for Alzheimer's disease in Japan and Taiwan: result from Dementia Research in Kumamoto and Tainan (DeReKaT).

BACKGROUND: Caregiver burden (CB) of Alzheimer's disease (AD) in Taiwan is becoming an urgent social issue as well as that in Japan. The comparison of CB may explain how caregiver feels burden in each country. METHODS: The participants were 343 outpatients with AD and their caregivers of Japan (n = 230) and Taiwan (n = 113). We assessed the CB using the Japanese and Chinese version of Zarit Caregiver Burden Interview (ZBI). The initial analysis was an exploratory factor analysis for each group to confirm the factor structure of ZBI. Then, the multiple-group structural equation modeling (MG-SEM) was used to assess the measurement invariance of ZBI such as configural, metric, and scalar invariances. Lastly, we compared the latent factor means of the ZBI between Japan and Taiwan. RESULTS: In both groups, the confirmatory factor analysis extracted 3 factors which were labeled "Impact on caregiver's life", "Embarrassed/anger", and "Dependency". The MG-SEM indicated an acceptable model fit, and established the partial scalar measurement invariance (comparative fit index (CFI) = 0.901, root mean square error of approximation (RMSEA) = 0.066). When we compared the latent factor means, the score of "Impact on caregiver's life" in Taiwanese caregivers was significantly higher than that in Japanese (p = 0.001). However, "Dependency" in Taiwanese caregivers was lower than that in Japanese (p < 0.001). CONCLUSIONS: Partial measurement invariance allowed comparing the latent factor mean across two countries. The results of comparisons suggested that there may be differences in the way of feeling CB between Japan and Taiwan.

The investigation and comparison of the underlying needs of common disruptive behaviours in patients with Alzheimer's disease.

BACKGROUND: Management of the disruptive behaviours is one of the most challenging aspects of caring for patients with Alzheimer's dementia (PwAD). The underlying needs of disruptive behaviours in PwAD had rarely been studied, especially the comparison of the underlying needs of disruptive behaviours in PwAD have never been mentioned. AIMS AND OBJECTIVES: The purpose of this study was to investigate and compare the underlying needs of five common disruptive behaviours including hoarding, aggressive behaviour, repetitive behaviour, altered eating behaviour and delusion in PwAD, as perceived by family caregivers, and to relate these needs from the perspective of Maslow's hierarchy. METHODS: An exploratory research design with qualitative data collection techniques was employed. Informed consent was obtained from each participant prior to the data collection. A total of 65 pairs of caregiver-patient with Alzheimer's disease participated in the study. A semi-structured interview guide was used during the interview, and the directed content analysis method was conducted to analyse data. RESULTS: Four themes related to the underlying needs of the five selected disruptive behaviours emerged from the data, and these included a desire for comfort (physical and psychological), a desire for security (psychological and economic), a need for a sense of belonging (including a need to connect with the outside world and a need for attention) and a need for self-control. These behaviour features were found closely related to Maslow's hierarchy model of human needs. CONCLUSION: Although the data were gathered from the caregivers, and the views of the patients were thus not included in the analysis, the findings provide information for health providers that can enable them to better understand the underlying needs of common disruptive behaviours in patients with Alzheimer's disease and thus help develop better patient-centred care plans.

Modulating the interference effect on spatial working memory by applying transcranial direct current stimulation over the right dorsolateral prefrontal cortex.

Spatial working memory (SWM) is the ability to temporarily store and manipulate spatial information. It has a limited capacity and is quite vulnerable to interference. Dorsolateral prefrontal cortex (DLPFC) has been shown to be a part of the SWM network but its specific functional role still remains unknown. Here we applied transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique that provides polarity-specific stimulation over the targeted region, to investigate the specific role of the right DLPFC in resolving interference in SWM. A forward- and backward-recall computerized Corsi Block Tapping task (CBT), both with and without a concurrent motor interference task (the modified Luria manual sequencing task) was used to measure SWM capacity and reaction time. The results showed that motor interference impeded accuracy and prolonged reaction time in forward and backward recall for SWM. Anodal tDCS over right DLPFC yielded the tendency to shorten participants' reaction time in the conditions with interference (forward with interference, and backward with interference). Most importantly, anodal tDCS significantly improved participants' SWM span when cognitive demand was the highest (the "backward-recall with motor interference" condition). These results suggest that (1) the right DLPFC plays a crucial role in dealing with the cross-domain motor interference for spatial working memory and (2) the anodal tDCS over right DLPFC improved SWM capacity particularly when task difficulty demands more complex mental manipulations that could be due to the facilitatory effect of anodal tDCS which enhanced the DLPFC function within central executive system at the top-down attentional level.

Use of cognitive enhancers and associated medical care costs among patients with dementia: a nationwide study in Taiwan.

BACKGROUND: Pharmaceutical therapy for patients with dementia including cholinesterase inhibitors (ChEI) and memantine is covered by Taiwan's National Health Insurance (NHI) but with strict reimbursement criteria. This study compared utilization of selected cognitive enhancers among elderly patients with dementia and estimated associated differences in medical care costs. METHODS: This study used medical claims and pharmacy claims from the NHI Research Database of Taiwan from 2009 to 2011, which included all patients 65 years or older diagnosed with dementia in their outpatient or inpatient claims. Both individual-level and market-level analysis were performed to calculate the average medical costs per person and the share of drug expenditures. Generalized linear models with propensity score adjustment estimated differences in medical care costs by use of selected cognitive enhancers. RESULTS: Users of ChEI had the highest medication and outpatient costs but the lowest inpatient costs among all users of cognitive enhancers. However, annual adjusted total medical care costs per ChEI user were not significantly different from those who used cerebral vasodilators (CBV). In 2011, 52.4% of the elderly with dementia in Taiwan used cognitive enhancers, but among them 88.3% used CBV while 9.2% used ChEI. Among patients with dementia who used at least one cognitive enhancer, the aggregated expenditure as a share of their total drug expenditures was 9.7% in 2011. CONCLUSION: Given that CBV had a much higher utilization rate than ChEI or memantine among elderly people with dementia, the strict reimbursement policy for ChEI and memantine may need to be revisited to increase access to those drugs by patients with dementia in Taiwan.

Delusions and underlying needs in older adults with Alzheimer's disease: influence of earlier life experiences and the current environment.

Delusions are one of the most severe psychiatric symptoms of individuals with Alzheimer's disease (AD), which often increase the stress experienced by caregivers. The purpose of this study was to understand the influences of earlier life experiences and the current environment on delusions, as well as the underlying needs of older adults with AD who experience delusions. Using an exploratory research design with a qualitative approach and purposive sampling, 20 family caregivers were interviewed. Two psychosocial types of attributes of delusion were categorized: Type A, the influence of earlier life experiences; and Type B, current environmental influences. The underlying needs of those with delusions include physical comfort, a desire to be secure, and a sense of belonging. The contents of delusions are easily influenced by patients' earlier negative experiences and responsibilities, whereas the current environment exerts a crucial influence on the occurrence, frequency, and severity of specific delusions. These results can facilitate planning for patient-centered care by enhancing health care providers' understanding of the psychosocial and environmental attributes and needs behind delusions.

The feasibility and practicality of auxiliary detection of spatial navigation impairment in patients with mild cognitive impairment due to Alzheimer's disease by using virtual reality.

Background: Spatial disorientation in patients with mild cognitive impairment due to Alzheimer's disease (MCI due to AD) has become a subject of great interest. Medical practitioners are concerned about the serious issue of these patients who are getting lost. Therefore, the early detection of MCI due to AD is crucial. New methods: We designed virtual reality (VR) protocols to test spatial recognition abilities. Our devices mainly included the Vive Pro Eye and the Steam VR program. We tested the three groups: young cognitively unimpaired (YCU), older cognitively unimpaired (OCU) and MCI due to AD. We also administered the Cognitive Abilities Screening Instrument and the Questionnaire on Everyday Navigational Ability for comparison. Results: We adopted the testing results of 2 YCU, 3 OCU, and 4 MCI due to AD for analysis. Concerning cognitive abilities, YCU and OCU had better performance than MCI due to AD respectively. It was consistent with the recent memory and the total scores of the Cognitive Abilities Screening Instrument. Comparison with existing methods: We introduced a real-life setting, the Tzu-Chiang campus at National Cheng Kung University, into the VR environment. It allowed us to assess daily road-recognizing abilities of participants in a controlled testing environment. Conclusions: Several limitations were considered in this study, such as limited number of participants and low-quality images on the screen. Nonetheless, this device has the potential to serve as a screening tool for MCI due to AD based on its feasibility and practicality.

Using eZIS to Predict Progression from MCI to Dementia in Three Years.

(1) Background: Mild cognitive impairment (MCI) due to Alzheimer's disease (AD) progresses to dementia at a higher annual rate, while other MCIs may remain stable or even improve over time. Discriminating progressive from non-progressive cases of MCI is crucial and challenging. (2) Methods: A retrospective study of individuals with MCI was conducted at a university hospital located in southern Taiwan. The researchers collected demographic data, comorbidities, the scores of cognitive tests, three easy Z-score imaging system (eZIS) indicators (severity, extent, and ratio), Fazekas scale scores, mesial temporal atrophy (MTA) scores, clinical outcomes including deterioration of Cognitive Abilities Screening Instrument, Mini-mental State Examination, Clinical Dementia Rating Sum of Box scores, and the conversion from MCI to dementia. Those who converted to dementia in three years and non-converters were compared by the three eZIS indicators to test the predictive utility, and the clinical outcomes were evaluated by regression and ROC curve analysis. (3) Results: The three eZIS indicators were significantly higher in the group of progressive MCI than in stable MCI. eZIS severity is positively correlated with a deterioration in the scores of the Cognitive Abilities Screening Instrument and Clinical Dementia Rating Sum of Box. eZIS severity is also positively correlated with conversion from MCI to dementia. The AUC for severity is 0.719, and the optimal cutoff value of severity for predicting conversion is 1.22. (4) Conclusions: During three years of follow-up, MCI individuals with greater eZIS severity were significantly associated with worse cognitive assessment scores and a higher conversion rate to dementia.

A Framework for Best Practices and Readiness in the Advent of Anti-Amyloid Therapy for Early Alzheimer's Disease in Asia.

Advances in biomarker-based diagnostic modalities, recent approval of anti-amyloid monoclonal antibodies for early Alzheimer's disease (AD; mild cognitive impairment or mild dementia due to AD) and late-stage clinical development of other disease-modifying therapies for AD necessitate a significant paradigm shift in the early detection, diagnosis and management of AD. Anti-amyloid monoclonal antibodies target the underlying pathophysiological mechanisms of AD and have demonstrated a significant reduction in the rate of clinical decline in cognitive and functional outcome measures in patients with early AD. With growing recognition of the benefit of early interventions in AD, an increasing number of people may seek diagnosis for their subjective cognitive problems in an already busy medical system. Various factors such as limited examination time, lack of expertise for cognitive assessment and limited access to specialized tests can impact diagnostic accuracy and timely detection of AD. To overcome these challenges, a new model of care will be required. In this paper, we provide practical guidance for institutional readiness for anti-amyloid therapies for early AD in Asia, in terms of best practices for identifying eligible patients and diagnosing them appropriately, safe administration of anti-amyloid monoclonal antibodies and monitoring of treatment, managing potential adverse events such as infusion reactions and amyloid-related imaging abnormalities, and cross-disciplinary collaboration. Education and training will be the cornerstone for the establishment of new pathways of care for the identification of patients with early AD and delivery of anti-amyloid therapies in a safe and efficient manner to eligible patients.

Classification Prediction of Alzheimer's Disease and Vascular Dementia Using Physiological Data and ECD SPECT Images.

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common forms of dementia. However, their neuropsychological and pathological features often overlap, making it difficult to distinguish between AD and VaD. In addition to clinical consultation and laboratory examinations, clinical dementia diagnosis in Taiwan will also include Tc-99m-ECD SPECT imaging examination. Through machine learning and deep learning technology, we explored the feasibility of using the above clinical practice data to distinguish AD and VaD. We used the physiological data (33 features) and Tc-99m-ECD SPECT images of 112 AD patients and 85 VaD patients in the Taiwanese Nuclear Medicine Brain Image Database to train the classification model. The results, after filtering by the number of SVM RFE 5-fold features, show that the average accuracy of physiological data in distinguishing AD/VaD is 81.22% and the AUC is 0.836; the average accuracy of training images using the Inception V3 model is 85% and the AUC is 0.95. Finally, Grad-CAM heatmap was used to visualize the areas of concern of the model and compared with the SPM analysis method to further understand the differences. This research method can quickly use machine learning and deep learning models to automatically extract image features based on a small amount of general clinical data to objectively distinguish AD and VaD.

Montreal Cognitive Assessment and Mini-Mental State Examination performance in patients with mild-to-moderate dementia with Lewy bodies, Alzheimer's disease, and normal participants in Taiwan.

BACKGROUND: The aim of this study was to examine and test the sensitivity, specificity, and threshold scores of the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) and determine those that best correspond to a clinical diagnosis of dementia with Lewy bodies (DLB). METHODS: Sixty-seven Alzheimer's disease (AD), 36 DLB, and 62 healthy participants without dementia (NC), aged 60 to 90, were enrolled. All three groups took the MoCA and MMSE tests at the same time. The Cochran-Mantel-Haenszel tests and receiver operating characteristics curve analysis were used to compare the different neuropsychological test results among the groups. RESULTS: The cut-off point of the MoCA for AD was 21/22 with a sensitivity of 95.5% and a specificity of 82.3% (area under the curve (AUC): 0.945), and the cut-off point for DLB was 22/23 with a sensitivity of 91.7% and a specificity of 80.6% (AUC: 0.932). For the MMSE, the cut-off points for AD and for DLB from NC were all 24/25, with a sensitivity of 88.1% and a specificity of 85.5% for AD (AUC: 0.92), and a sensitivity of 77.8% and a specificity of 85.5% for DLB (AUC: 0.895). After controlling sex, age, and education, AD and DLB had lower scores in all MoCA subscales than the NC group (p < 0.05), except for the orientation and naming in DLB. In addition, AD had a lower score in the MoCA orientation (p = 0.03) and short-term memory (p = 0.02) than did DLB. CONCLUSIONS: The MoCA is a more sensitive instrument than the MMSE to screen AD or DLB patients from non-dementia cases.

Driving practice effects for older drivers with mild cognitive impairment: A preliminary study.

BACKGROUND: Older drivers with mild cognitive impairment (MCI) often show declining driving performance. Evidence is lacking regarding whether their driving skills can be improved after practice. AIMS/OBJECTIVES: To compare the practice effects of older drivers with MCI and drivers with normal cognition in an unfamiliar, standardized driving course with three practices. MATERIALS AND METHODS: Single-blind two-group observational design. Twelve drivers with confirmed MCI as the experimental group and ten with normal cognition (NC) as the control, all ≥ 55 years old. The primary outcome was to assess the practice effects, measured with an in-car global-positioning-system mobile application to compare the speed and directional control of a complex manoeuvre after practices. Secondary outcomes were to assess the pass/fail rate and mistakes observed for the 3rd/final on-road driving practice. No instructions were given during practice. Descriptive statistics and the Mann-Whitney U test were used for data analysis. RESULTS: No significant inter-group difference in the pass/fail rate and number of mistakes. Some MCI drivers performed better in the speed and directional control of the S-Bend manoeuvre after practices. CONCLUSIONS: The driving performance of drivers with MCI may improve with practice. SIGNIFICANCE: Older drivers with MCI may potentially benefit from driver retraining. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT04648735).

The application of a neuropsychological measure of executive working memory in older adults with memory impairment.

The component of working memory that the frontal cortex subserves is frequently characterized as the executive working memory (EWM). This study applied a neuropsychological measure of EWM (NPM-EWM) in older adults with memory impairment to investigate the EWM. Thirty-two older adults from the community were recruited as older healthy controls (OHCs), and 58 older adults from a memory clinic were diagnosed with mild cognitive impairment (MCI) and mild dementia (MD). Significant differences were found among the three groups in the Clinical Dementia Rating (CDR), the Chinese version of Mini-Mental State Examination (MMSE-C), and the Cognitive Abilities Screening Instrument (CASI). The NPM-EWM was applied by using the learning task of the Comprehensive Nonverbal Memory Test Battery, where the 7 scores were divided into two categories: mnemonic capacity and executive error. All OHCs, more than 50% MCI, and less than 25% of MD patients passed the NPM-EWM. The MCI-passed and MD-passed subgroups showed similar mnemonic capacity and executive errors, and both the subgroups had significantly worse performance than the OHC group. The MD-passed subgroup had a higher Hamilton Depression Rating Scale (HDRS) score than did the MD-failed subgroup. The MCI-failed subgroup had a higher Hierarchy of Care Required (HCR) level in instrumental activities of daily living (IADL) than did the MCI-passed subgroup. These findings indicated that applying the NPM-EWM for older adults with memory impairment may offer precise and tailored care to a whole person, especially for the MCI patients with poorer EWM and the MD patients with relatively intact EWM.

The Effect of Agomelatine in Behavioral and Psychological Symptoms of Dementia.

Objective: Moderate and severe behavioral and psychological symptoms of dementia (BPSD) often need medical treatment to improve symptoms. Agomelatine is a selective melatonergic (MT1/MT2) agonist that has normalizing effects on disturbed circadian rhythms and disrupted sleep-wake cycles. Its activity of 5HT-2C receptor antagonism is associated with lessening depression and anxiety and increasing slow-wave sleep. Based on past clinical records and current findings it suggests that agomelatine can improve BPSD for patients. This retrospective cohort study was designed to compare the BPSD before and after using agomelatine. Methods: Records of dementia cases who had ever received agomelatine treatment for BPSD in a general hospital setting during the past 2.5 years were identified and reviewed. Scores from before and after 3 months of treatment with agomelatine were collected for Neuropsychiatric Inventory (NPI), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI) to compare and analyze the difference of psychological and behavioral symptoms pre- and post-agomelatine used. Results: Records of 144 cases of dementia with BPSD who had ever used agomelatine from January 2015 to June 2017 were collected. All of the 112 cases had BPRS and CGI scores, of which 75 cases had additional NPI scores. Among these 112 cases, the BPRS and CGI scores were significantly improved in all types of dementia. NPI scores indicated that the use of agomelatine alleviated obvious symptoms and decreased overall distress, especially in the depression/poor mood, anxiety, and sleep/night behavior. Conclusion: It is consistent with an effective result of agomelatine in improving BPSD.

Evidence of plasma biomarkers indicating high risk of dementia in cognitively normal subjects.

Subjects with comorbidities are at risk for neurodegeneration. There is a lack of a direct relationship between comorbidities and neurodegeneration. In this study, immunomagnetic reduction (IMR) assays were utilized to assay plasma Aß1-42 and total tau protein (T-Tau) levels in poststroke (PS, n = 27), family history of Alzheimer's disease (ADFH, n = 35), diabetes (n = 21), end-stage renal disease (ESRD, n = 41), obstructive sleep apnea (OSA, n = 20), Alzheimer's disease (AD, n = 65). Thirty-seven healthy controls (HCs) were enrolled. The measured concentrations of plasma Aß1-42 were 14.26 ± 1.42, 15.43 ± 1.76, 15.52 ± 1.60, 16.15 ± 1.05, 16.52 ± 0.59, 15.97 ± 0.54 and 20.06 ± 3.09 pg/mL in HC, PS, ADFH, diabetes, ESRD, OSA and AD groups, respectively. The corresponding concentrations of plasma T-Tau were 15.13 ± 3.62, 19.29 ± 8.01, 17.93 ± 6.26, 19.74 ± 2.92, 21.54 ± 2.72, 20.17 ± 2.77 and 41.24 ± 14.64 pg/mL. The plasma levels of Aß1-42 and T-Tau in were significantly higher in the PS, ADFH, diabetes, ESRD and OSA groups than controls (Aß1-42 in PS: 15.43 ± 1.76 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.005; T-Tau in PS: 19.29 ± 8.01 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aß1-42 in ADFH: 15.52 ± 1.60 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ADFH: 17.93 ± 6.26 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aß1-42 in diabetes: 16.15 ± 1.05 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in diabetes: 19.74 ± 2.92 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aß1-42 in ESRD: 16.52 ± 0.59 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ESRD: 21.54 ± 2.72 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aß1-42 in OSA: 15.97 ± 0.54 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in OSA: 20.17 ± 2.77 vs. 15.13 ± 3.62 pg/mL, p < 0.001). This evidence indicates the high risk for dementia in these groups from the perspective of plasma biomarkers.