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Background and objectivesThis study aimed to confirm the effectiveness of the virtual passport for dementia care.Research design and methodsThe virtual passport is an application (app) tool connecting healthcare professionals, dementia care sites, and people living with dementia (PLWD) and their family caregivers. This tool assists case managers in hospitals by providing individualized care plans and health education to PLWD and their caregivers. The dementia quality indicator achievement rates, care needs investigation and fulfillment, severity of behavioral and psychological symptoms of dementia (BPSD), and changes in caregiver burden and depression are measured at the initial interview and 6 and 12 months after the intervention.ResultsWe enrolled 57 and 54 patients and their caregivers in the virtual passport and routine care groups, respectively. Compared to the control group, six quality indicators in the passport group showed significantly higher achievement at 6 months after using the virtual passport. Case managers addressed more care needs at 6 months (1.37 vs 0, p < 0.001) and 12 months (1.32 vs 0, p < 0.001). Improvement in severity of neuropsychiatric symptoms (neuropsychiatric inventory (NPI) irritability/lability difference: -0.58 vs 0.22, p = 0.044; NPI agitation/aggression difference =-0.78 vs 0.00, p = 0.042) were also observed. No obvious influence was found in caregiver burden and depression after using the virtual passport.Discussion and implicationsThe virtual passport is an effective information technology tool in improving the quality of dementia care, assisting case management in identifying more care needs, and reducing the severity of BPSD.

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.

Abstract 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

Xanthoxylin, a bioactive phenolic compound extracted from the traditional herbal medicine Penthorum Chinense Pursh, is renowned for its anti-inflammatory effects. While previous studies have highlighted the anti-inflammatory and antioxidant properties of Xanthoxylin, its precise mechanisms, particularly concerning immune response and organ protection, remain underexplored. This study aimed to elucidate the effects of Xanthoxylin on inflammation and associated signaling pathways in a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced via intratracheal administration of LPS, followed by intraperitoneal injections of Xanthoxylin at doses of 1, 2.5, 5, and 10 mg/kg, administered 30 min post-LPS exposure. Lung tissues were harvested for analysis 6 h after LPS challenge. Xanthoxylin treatment significantly mitigated lung tissue damage, pathological alterations, immune cell infiltration, and the production of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Additionally, Xanthoxylin modulated the expression of key proteins in the protein kinase B (Akt)/hypoxia-inducible factor 1-alpha (HIF-1α)/nuclear factor-kappa B (NF-κB) signaling pathway, as well as nuclear factor erythroid 2-related factor 2 (Nrf2) and oxidative markers such as superoxide dismutase (SOD) and malondialdehyde (MDA) in the context of LPS-induced injury. This study demonstrates that Xanthoxylin exerts protective and anti-inflammatory effects by down-regulating and inhibiting the Akt/HIF-1α/NF-κB pathways, suggesting its potential as a therapeutic target for the prevention and treatment of ALI or acute respiratory distress syndrome (ARDS).

Abstract 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.

IntroductionThe 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.MethodsWe 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 (

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.

Background/purpose: Donepezil was approved for the treatment of Alzheimer's disease (AD) but causes variable therapeutic responses. Thus, identifying specific genetic polymorphisms, which can predict a therapeutic response to donepezil, would enable a development of personalized strategy to treatment for patients with AD. The research aimed to exam the impact of the cytochrome P450 2D6 (CYP2D6) single nucleotide polymorphism (SNP) rs1080985 on the concentration of and therapeutic response to donepezil in AD. Methods: In total, 40 newly diagnosed AD patients who had a clinical dementia rating (CDR) of 0.5–2 and who were on donepezil were enrolled and followed up. Plasma concentrations of donepezil were determined after 6 months of donepezil treatment. Cognitive and functional statuses were evaluated annually during follow-up. The response to therapy was defined based on the change in CDR. Results: At a mean of 21.8 ± 5.7 months of follow-up, 10 of 40 patients (25.0%) were nonresponders to donepezil treatment. Patients who were homozygous for the G allele exhibited a higher concentration of donepezil and concentration-to-dose ratio than those with other genotypes. Furthermore, a significantly higher proportion of patients with the G/G genotype were responders than nonresponders (90.0% vs 50.0%, P = 0.015, effect size of V: 0.457) to donepezil treatment. Conversely, patients carrying the C allele had a significantly high risk of poor responses to donepezil treatment (odds ratio: 9.00, 95% confidence interval: 1.611–50.275). Conclusion: The CYP2D6 SNP rs1080985 might be a useful pharmacogenetic marker of the long-term therapeutic response to donepezil in patients with AD.

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.

Family history (FH) of late-onset Alzheimer’s disease (AD) is associated with changes in several cerebrospinal fluid (CSF) biomarkers in cognitively normal individuals. However, potential changes in plasma biomarkers remain unknown. This study aimed to evaluate potential plasma biomarkers and their correlation in cognitively normal adult children (AC) and to compare this data with their AD parents and unrelated non-demented controls (NC). Participants with dementia due to AD, their AC and NC were recruited. Plasma samples were assessed for amyloid beta (Aβ)1–42, Aβ1–40, total tau (T-tau) and phosphorylated tau (P-tau). Kruskal–Wallis test was used for the comparison of this data between the three groups. Spearman rank correlation was used for evaluation of the correlations between Aβ1–40 and Aβ1–42, and T-tau and P-tau in the AD and AC groups. A total of 99 subjects completed the assessment (30 had AD; 38 were AC group; and 31 were NC). Compared with the NC group, there were significantly higher levels of Aβ1–40, P-tau, and P-tau/T-tau ratio, and lower levels of Aβ1–42 and Aβ1–42/Aβ1–40 ratio in the AD and AC groups. The correlation between the level of Aβ1–42 and Aβ1–40 and level of T-tau and P-tau was only observed in the AC but not in the AD group. AC of AD parents demonstrate some indicators of AD like their parents. Disruption to the correlation between Aβ and tau in AD may be a biomarker for the development of AD in AC, which should be examined in a longitudinal cohort.

BackgroundNovel nonpharmacological therapies are being developed to prevent cognitive decline and reduce behavioral and psychological symptoms in patients with dementia. Virtual reality (VR) reminiscence was reported to improve anxiety, apathy, and cognitive function immediately after intervention in individuals at residential aged care facilities. However, its effect on elderly patients with dementia and how long this effect could last remain unknown. ObjectiveThe aim of this paper is to investigate the effect of immersive VR reminiscence in people with dementia both immediately after and 3-6 months after intervention. MethodsA pilot study was conducted in 2 dementia care units. VR reminiscence therapy sessions were conducted twice per week for a 3-month period. Cognitive function, global status, depressive symptoms, and caregiver burden were assessed before and immediately after VR intervention in 20 participants. Subsequently, 7 participants were reassessed 3-6 months after the VR intervention. Wilcoxon sign-rank test was used for statistical comparisons of the changes. ResultsThere were no significant changes in cognitive function, global status, and caregiver burden immediately after the VR intervention, but there was a significant reduction in depressive symptoms (P=.008). Moreover, compared with the cognitive function immediately after VR, it kept declining 3-6 months after. ConclusionsImmersive VR reminiscence can improve mood and preserve cognitive function in elderly patients with dementia during the period of the intervention. Studies using a control group and comparing the use of VR with traditional forms of reminiscence should be conducted in the future to confirm and expand on these findings.

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.

Abstract Age-related white matter lesion (WML) is considered a manifestation of sporadic cerebral small vessel disease and an important pathological substrate for dementia. Asia is notable for its large population with a looming dementia epidemic. Yet, the burden of WML and its associated risk factors across different Asian societies are unknown. Subjects from 9 Asian cities (Bangkok, Bandung, Beijing, Bengaluru, Hong Kong, Kaohsiung, Manila, Seoul, and Singapore) were recruited (n = 5701) and classified into (i) stroke/transient ischemic attack (TIA), (ii) Alzheimer’s disease (AD)/mild cognitive impairment (MCI), or (iii) control groups. Data on vascular risk factors and cognitive performance were collected. The severity of WML was visually rated on MRI or CT. The prevalence of moderate-to-severe WML was the highest in subjects with stroke/TIA (43.3%). Bandung Indonesia showed the highest prevalence of WML, adjusted for age, sex, education, disease groups, and imaging modality. Hypertension and hyperlipidemia were significant risk factors for WML, and WML was negatively associated with MMSE in all groups. WML is highly prevalent in Asia and is associated with increasing age, hypertension, hyperlipidemia, and worse cognitive performance. Concerted efforts to prevent WML will alleviate the huge dementia burden in the rapidly aging Asian societies.

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.

Amyloid-β(1–42) [Aβ(1–42)] oligomer accumulations are associated with physiologic alterations in the brains of individuals with Alzheimer’s disease. In this study, we demonstrate that a nanostructured gold electrode with deposited gold nanoparticles, induced via electrochemical impedance spectroscopy (EIS), may be used as an Aβ(1–42) conformation biosensor for the detection of Alzheimer’s disease. Monoclonal antibodies (12F4) were immobilized on self-assembled monolayers of the electrochemical sandwich immunoassay biosensor to capture Aβ(1–42) monomers and oligomers. Western blot and fluorescence microscopy analyses were performed to confirm the presence of Aβ(1–42) monomers and oligomers. EIS analysis with an equivalent circuit model was used to determine the concentrations of different Aβ(1–42) conformations in this study. We identified conformations of Aβ(1–42) monomers and Aβ(1–42) oligomers using probe antibodies (12F4) by employing EIS. RAβ(1−42) indicates the sum resistance of impedance measured during Aβ(1–42) immobilization. ΔR12F4 refers to the concentration of probe antibody (12F4) binding with Aβ(1–42). The concentration of Aβ(1–42) oligomer was defined as the percentage of Aβ(1–42) aggregation R12F4/RAβ(1−42). The experimental results show that the biosensor has high selectivity to differentiate Aβ(1–40) and Aβ(1–42) monomers and Aβ(1–42) oligomers and that it can detect Aβ(1–42) oligomer accurately. The linear detection range for Aβ(1–42) oligomers was between 10 pg/ml and 100 ng/ml. The limit of detection was estimated to be 113 fg/ml.

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.

(1) Background: Alzheimer’s disease (AD) is the most common form of dementia. Increased levels of inflammatory proteins have been observed in brain and plasma samples of AD patients; however, it is not clear if other serum proteins correlate to the development or disease progression of AD. (2) Methods: Micro-Western Array (MWA) is a high-throughput antibody-based proteomics system which allows detection of the expression levels of 24–96 different proteins within 6–30 samples simultaneously. We applied MWA to explore potential serum protein biomarkers correlated to the development and progression of AD by examining the difference in serum protein profile of 31 healthy control (HC), 30 patients with AD and 30 patients’ adult children (ACS). (3) Results: Compared to HC, AD and ACS express similar pattern of serum proteins, including higher protein levels of ABCA1, ABCG1, SREBP1 and LXRβ but lower protein levels of ApoD, ApoE, ApoH, c_Myc, COX2 and Hippo-YAP signaling proteins. AD patients had higher serum levels of ABCG1, ApoD, ApoH, COX2, LXRα and YAP, but lower levels of ABCA1, ApoE, c_Myc, LATS1, MST1, MST2, Nanog, NFκB_p50, PPARγ and SREBP2, as compared to ACS. Pearson’s correlation analysis revealed that the protein expression level of ApoE, c_Myc, LATS1, MST2, NFκB p50, PPARγ and SREBP1 was negatively correlated to age, while that of ApoE, c_Myc, LATS1, MST1, MST2, Nanog, NFκB p50 and PPARγ was positively correlated to age. (4) Conclusions: We identified a group of serum proteins which may correlate to disease progression of AD and can be potential diagnostic serum protein biomarkers.

Objectives This study aimed to investigate the associations between biochemical markers, renal function, health behaviours and dementia among older people.Design A retrospective cohort study.Setting Community-based health examination database from Taipei city.Participants In total, 35 434 older people were included from February 2005 to December 2012. To assess changes in renal function, we selected participants who attended health examinations at least twice and responded to the AD8 questionnaire in 2012. We excluded those with dementia at baseline.Primary outcome measures Early dementia was assessed using the AD8 questionnaire in 2012. Explanatory variables included demographic factors, health behaviours, biochemical markers and renal function. We used a Cox proportional hazard model to estimate the HR for early dementia onset.Results Individuals with mild albuminuria (HR 1.228; 95% CI 1.066 to 1.414), lower eGFR (HR 1.549; 95% CI 1.319 to 1.820) and higher age (HR 1.022; 95% CI 1.015 to 1.028) were associated with a high risk of early dementia. Older people with no alcohol intake (HR 0.872; 95% CI 0.794 to 0.958), and higher education levels (HR 0.647; 95% CI 0.589 to 0.710) were at a low risk of early dementia.Conclusions Elevated mild albuminuria and low eGFR were associated with a high risk of early dementia in this community-based cohort. Routine health examinations for older people can help screen out the high-risk population, and clinical management might reduce or delay the risk of early dementia.

Background: As the average life expectancy of global citizens has increased, the prevalence of dementia has increased rapidly. The number of patients with dementia has increased by 6.7 times, reaching 300,000 in the past three decades in Taiwan. To realize the latest actual situation, the need for institutional care for elderly patients with dementia, and also a reference basis for government agencies to formulate dementia-related care policies, we investigated the institutional prevalence of dementia. Methods: We randomly sampled 299 out of the 1607 registered long-term care facilities including senior citizens’ institutions, nursing homes, and veteran homes in every administrative region of Taiwan. Then, a two-phase survey including MMSE screening, CDR, and clinical confirmation was conducted on each subject from 2019 to 2020. Results: Among 5753 enrolled subjects, 4765 from 266 facilities completed the examinations with a response rate of 82.8%. A total of 4150 subjects were diagnosed with dementia, 7.4% of whom had very mild dementia. The prevalence of all-cause dementia, including very mild dementia, was 87.1% in all facilities, 87.4% in senior citizens’ institutions, 87.1% in nursing homes, and 83.3% in veteran homes. Advanced age, low education, hypertension, Parkinsonism, respiratory disease, stroke, and intractable epilepsy were associated with dementia risk. Conclusions: We show that in an aged society, the prevalence of all-cause dementia in long-term care institutions can be as high as 87.1%. This study was completed before the outbreak of COVID-19 and provides a precious hallmark for future epidemiological research. We recommend that the long-term care policy in an aged society needs to take into account the increasing high prevalence of dementia in the institution.

Amyloid-beta (Aβ) is produced by the cleavage of amyloid precursor proteins in the cell membrane by β-secretase and γ-secretase into a monomeric form with peptides of different lengths such as Aβ1–40 or Aβ1–42, which is then transformed into oligomeric and fibril forms and is considered to be one of the hallmarks of Alzheimer’s disease (AD). The plasma concentrations of Aβ1–40 and Aβ1–42 are unstable after blood samples have been obtained. In order to examine the dynamic changes of plasma Aβ1–42 and Aβ1–40 in blood samples, we used fresh blood samples in ethylenediaminetetraacetic acid tubes from 32 clinically diagnosed AD patients. Each sample was subdivided into eight sub-samples, and levels of Aβ1–40 and Aβ1–42 were measured at 0 (baseline), 0.5, 1, 2, 3, 5, 8, and 24 h, respectively. All samples were incubated at 37°C before being measuring. The results showed that compared to baseline, 87.5 and 62.5% of the patients had higher plasma levels of Aβ1–42 and Aβ1–40 at 24 h, respectively. The patients with an increased amyloid level did not have a significantly different apo-lipoprotein E4 allele (APOE4) gene status for either Aβ1–40 (p = 0.422) or Aβ1–42 (p = 1.000). However, for plasma Aβ1–42, the APOE4 carriers had a significantly lower level than the non-carriers at baseline [31.2 ± 6.5 (mean ± SD) ng/ml vs. 50.4 ± 47.7 ng/ml, p = 0.031] and 0.5 h (37.5 ± 7.6 ng/ml vs. 51.9 ± 30.8 ng/ml, p = 0.043). There were no significant differences between the APOE4 carriers and non-carriers in plasma Aβ1–42 concentration at 1, 2, 3, 5, 8, and 24 h (p = 0.112, p = 0.086, p = 0.112, p = 0.263, p = 0.170 and p = 0.621, respectively). The Aβ1–40 level was related to disease severity as assessed using the clinical dementia rating (CDR) scale. Patients with advanced stages of dementia (CDR = 1 and CDR = 2) had a significantly higher Aβ1–40 level compared to those with very mild stage dementia (CDR = 0.5) at all time points (p < 0.05) except for 24 h (p = 0.059). Our findings illustrate the effects of APOE4 status on dynamic changes in plasma Aβ1–40 and Aβ1–42 levels, and significant associations between Aβ1–40 level and disease severity. Further studies are needed to investigate the exact mechanisms of how APOE4 affects the dynamic changes in plasma Aβ1–40 and Aβ1–42, and the association between Aβ1–40 and advanced dementia.

Rivastigmine has been widely used in mild-to-moderate Alzheimer's disease (AD), but the therapeutic response rate varies from 20 to 60%. A dose-dependent effect has been suggested, but the plasma concentration of rivastigmine and its metabolite, NAP 226-90, were not measured in previous studies. The influencing factors of therapeutic response are complicated and discordant in various studies among different ethnic groups. Hence, we analyzed the therapeutic responses of rivastigmine, measured by neuropsychological assessments, among 63 clinically diagnosed AD patients taking a daily dosage of 6–9 mg in relation to their plasma concentration of rivastigmine and NAP 226-90, apolipoprotein E (APOE) genotype and demographic characteristics. Our reports revealed that 41.3% of recruited AD patients had improvement in cognition, measured by Mini-Mental Status Examination (MMSE), and 63.5% in global status, by Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score. In cognition, the clinically improving group had a significantly higher rivastigmine concentration [p = 0.049, odds ratio (OR) = 1.029, 95%CI = 1.000–1.058], lower initial MMSE score (p = 0.010, OR = 0.708, 95%CI = 0.546–0.920), and lower initial CDR-SB score (p = 0.003, OR = 0.552, 95%CI = 0.372–0.817). The patients with APOE ε4 allele had worsening cognition (p = 0.037, OR = 3.870, 95%CI = 1.082–13.840). In global status, only higher education (p = 0.043, OR = 1.222, 95%CI = 1.007–1.484) was significantly associated with clinical improvement. In conclusion, high concentrations of rivastigmine may benefit cognitive function of AD patients, especially in APOE ε4 (−) carriers.

Background Galantamine has been approved for the treatment of Alzheimer’s disease (AD). However, there are few studies which have reported the association between cognitive responses and galantamine plasma concentration. The aim of this study was to determine the correlation between galantamine plasma concentration and the subsequent cognitive response following treatment in AD patients. Methods AD sufferers who continuously took 8 mg/d galantamine for at least 6 months without previous exposure to other kinds of AChEI such as donepezil, rivastigmine, or memantine were included in this cohort study. The assessments included the Mini Mental Status Examination (MMSE), Clinical Dementia Rating Scale (CDR) and the Cognitive Assessment Screening Instrument (CASI). Each subdomain of the CASI assessment was conducted at baseline and after 6 months of galantamine. The plasma concentrations of galantamine were measured by capillary electrophoresis after 6 months of the treatment. Logistic regression was performed to adjust for age, gender, apolipoprotein E ε4 genotype status, and baseline score to investigate the association between galantamine plasma concentrations and the cognitive response. Results The total sample consisted of 33 clinically diagnosed AD patients taking galantamine 8 mg/d for 6 months. There was no linear correlation between galantamine concentration and cognitive response in patients. However, 22 patients were responsive to the treatment in the long-term memory domain. In CASI subset domain, concentration improved during the 6 months follow up. Conclusions In the limited samples study, galantamine mostly benefitted the cognitive domain of long-term memory. The benefits were not related to the galantamine plasma concentration. Objective intra-individual evaluation of therapeutic response should be encouraged.

The combined effects of metabolic syndrome and the apolipoprotein E and CYP46 genotypes on the risk of cognitive decline has yet to be determined among Taiwanese Chinese. Two hundred and nine mentally healthy middle-aged and older adults were assessed for metabolic syndrome, cognitive function using the Cognitive Abilities Screening Instrument, Mini-Mental State Examination, ApoE, and CYP46 polymorphisms. There were no differences in cognitive performance, ApoE epsilon4 (ε4) carrier status, or CYP46 genotypes between participants with and those without metabolic syndrome. The ε4 carriers and participants with the AA allele of CYP46 had significantly lower mental manipulation score. Metabolic syndrome and ε4 had synergistic effects on cognitive decline. Therefore, the ε4 carriers and participants with the AA allele of CYP46 have decreased mental manipulation ability. The metabolic syndrome may play a role in subtle cognitive dysfunction in ε4 carriers among Taiwanese Chinese.

Alzheimer’s disease (AD) is traditionally thought of as a neurodegenerative disease. Recent evidence shows that beta amyloid-independent vascular changes and beta amyloid-dependent neuronal dysfunction both equally influence the disease, leading to loss of structural and functional connectivity. White matter changes (WMCs) in the brain are commonly observed in dementia patients. The effect of vascular factors on WMCs and the relationship between WMCs and severity of AD in patients remain to be clarified. We recruited 501 clinically diagnosed probable AD patients with a series of comprehensive neuropsychological tests and brain imaging. The WMCs in cerebral CT or MRI were rated using both the modified Fazekas scale and the combined CT-MRI age related WMC (ARWMC) rating scale. Periventricular WMCs were observed in 79.4% of the patients and deep WMCs were also seen in 48.7% of the patients. WMC scores were significantly higher in the advanced dementia stage in periventricular WMCs (p = 0.001) and total ARWMCs (p < 0.001). Age and disease severity were both independently associated with WMCs score, particularly in the total, frontal and parieto-occipital areas. Vascular factors including hypertension, diabetes mellitus, and gender were not significantly associated with WMCs. In conclusion, both age and severity of dementia were significantly associated with WMCs in AD patients. These associations highlight future research targets.

Frontal lobes are great and are a late-developing region of the neocortex that play a critical role in human behavior and executive function. The aim of this study was to clarify the role of event-related potentials (ERPs) in executive dysfunction and its relationship between generator mechanism and cognitive significance. We recruited 20 patients with frontal lobe lesion (FLL) and 27 age-matched controls. All patients submitted to comprehensive Frontal Test Battery and auditory ERPs measurement. In comparison with controls, the patients with FLL had significantly decreased executive function and manifested the delay of P300 latency, which reflected a delay of mental processing speed in these patients. Our findings suggest that patients with FLL may have prolonged P300 latency, which has a good correlation with executive dysfunction, poor performance, and longer P300 latencies. P300 ERPs are considered to be a useful method to identify the alteration of frontal-parietal connection.

Using neuropsychological investigation and visual event-related potentials (ERPs), we aimed to compare the ERPs and cognitive function of nondemented Parkinson’s disease (PD) patients with and without visual hallucinations (VHs) and of control subjects. We recruited 12 PD patients with VHs (PD-H), 23 PD patients without VHs (PD-NH), and 18 age-matched controls. All subjects underwent comprehensive neuropsychological assessment and visual ERPs measurement. A visual odd-ball paradigm with two different fixed interstimulus intervals (ISI) (1600 ms and 5000 ms) elicited visual ERPs. The frontal test battery was used to assess attention, visual-spatial function, verbal fluency, memory, higher executive function, and motor programming. The PD-H patients had significant cognitive dysfunction in several domains, compared to the PD-NH patients and controls. The mean P3 latency with ISI of 1600 ms in PD-H patients was significantly longer than that in controls. Logistic regression disclosed UPDRS-on score and P3 latency as significant predictors of VH. Our findings suggest that nondemented PD-H patients have worse cognitive function and P3 measurements. The development of VHs in nondemented PD patients might be implicated in executive dysfunction with altered visual information processing.

The biggest hurdle for early hospital presentation is the narrow therapeutic window after stroke. The aims of our study were to investigate the time lags and the factors causing pre‐hospital and emergency department (ED) delay during acute ischemic stroke attack. Between June 2004 and October 2005, we prospectively studied 129 acute ischemic stroke patients who presented to the ED of the study hospital within 4 hours after symptom onset. Chi‐square testing for trend, uni‐variate and multiple logistic regression analyses was performed to evaluate the factors influencing delays in the ED presentation of acute ischemic stroke patients. The median time from symptom onset to ED arrival was 71 (mean ± SD, 82.7 ± 57.7) minutes. The median times from ED arrival to neurologic consultation, computed tomography scan, electrocardiogram, and laboratory data completion were 10 (11.3±9.9) minutes, 17 (9.6±11.3) minutes, 14 (23.3±55) minutes, and 39 (44.4±24.5) minutes, respectively. Univariate and multiple logistic regression models revealed that age < 65 years, illiteracy and awakening with symptoms were the most significant factors related to a delay in ED presentation. This study indicates that 2 hours of pre‐hospital delay is the cutoff point for thrombolytic therapy. Organization of a stroke team and standardized stroke pathways may help to shorten in‐hospital time consumption. Educational efforts should not only focus on the public, but also on the training of ED physicians and other medical personnel.

Although the Blessed Dementia Rating Scale (BDRS), a clinical screening instrument, has been applied extensively, no suitable cut-off values and clinical application have been proposed, particularly in mild cognitive impairment (MCI), the precursor of dementia. The BDRS, Mini Mental State Examination (MMSE), and Clinical Dementia Rating Scale (CDR) were administrated in people aged 65 years and above, who were enrolled from southern Taiwan with multistep stratified random sampling and followed-up for 2 years. All subjects (total number = 3,027), with new onset of MCI (defined as CDR = 0.5) in the first year and dementia (defined as CDR ≥ 1) in the second and third years were subjected to statistical analysis. In distinguishing normal from MCI, except in the literate group aged 65-74 years, MMSE was superior to BDRS, with cut-off values of 1 in both literate groups aged 65-74 years and ≥ 75 years, and 1.5 and 2 in less educated groups aged 65-74 and ≥ 75 years, respectively. In distinguishing MCI from dementia, BDRS had cut-off values of 2.5 in both literate groups aged 65-74 and ≥ 75 years, and 2.5 and 3 in less educated groups aged 65-74 and ≥ 75 years, respectively. These values were better than those for MMSE in all groups. BDRS might be considered as a better tool than MMSE to screen for MCI and dementia in the increasing proportion of literate elderly aged 65-74 years in the aging population.

Cerebral venous thrombosis (CVT) is not uncommon, but CVT associated with bilateral internal jugular vein stenosis (BIJVS) is rare. Bilateral internal jugular vein stenting is also a rare procedure. We report on a patient with CVT associated with BIJVS, who was treated successfully using direct thrombolysis and bilateral internal jugular vein stenting.

We present a case of cerebral venous thrombosis diagnosed by magnetic resonance venography, magnetic resonance imaging, and angiography. Selective direct thrombolytic treatment with streptokinase via highly selective venography was successful.

Depression is a crucial public health problem because of its relatively high association with suicidal attempts, prolonged social isolation, poor physical health, and dementia. However, the available data and study on the prevalence of depression in Taiwan were mostly completed within the previous 1 to 2 decades, and these studies were limited to certain areas or populations. Little is known regarding the current status of depression in Taiwan. We used a brief tool, the Center for Epidemiological Studies Depression Scale (CES-D), to screen depression in 4 areas among the general and aged population. The results showed a higher CES-D score in the southern area among general (mean ± SD: 7.8 ± 8.4) or aged participants (mean ± SD: 7.2 ± 8.0) compared with other areas. The ratio of suspected depression patients was 16.4% of all recruited participants and 13.3% of aged participants. These results may provide information for this public health issue.

Alzheimer's disease (AD) has increased in its prevalence due to the increasing aged population. Currently there is no updated data on the prevalence of dementia including its very mild stage in Taiwan. Under the extensive coverage of Mentality Protection Center (MPC), Fo Guang Shan, Taiwan, the volunteers of MPC have conducted the medicine-related services and the screening of dementia by AD8 (ascertainment of dementia 8) that can screen the dementia even at its very mild stage in general population in all Taiwan. From 2011 to 2013, in total, 2,171 participants, 368 in the northern, 549 in the central, 877 in the southern, and 377 in the eastern part, were recruited with the mean age being 66.9 ± 10.2 years old. The ratio of suspected dementia patients, AD8 score greater than or equal to 2, was 13.6% of all recruited participants with their mean AD8 score being 2.9±1.3, mean age being 69.4±10.8 years old, and female predominance being 73.0%. Although this is a screening study, it has extensive coverage of all Taiwan and the use of AD8 is capable of screening very mild dementia. A further study with a randomized sampling to examine the prevalence and incidence of dementia including its very mild stage is encouraged.

The targeted screening for individuals at the risks of having dementia would be crucial to the further public health issues for dementia. This study aimed to conduct a screening study in an outpatient department of a regional hospital to screen people who were at risk of developing comorbid dementia. Patients who visited Kaohsiung Municipal Ta-Tung Hospital (KMTTH) clinics during the period from June 1, 2013, to May 31, 2014, were invited to participate in this screening voluntarily. The trained interviewer collected all participants’ demographic characteristics and used the instrument of ascertainment of dementia 8 (AD8) to find out suspected dementia ones. The result showed a higher ratio (24.1%) of suspected dementia in the outpatient department of a hospital, 500 out of 2017 subjects, than that in the general population. The median (interquartile range) age was significantly higher in the suspected dementia participants (70, (62, 77)) compared to that in nonsuspected dementia ones (65, (60, 73)), and the probability of suspected dementia was significantly increasing with age (P

Objective. To evaluate the effect of eradication of Helicobacter pylori (H. pylori) on the progression of dementia in Alzheimer’s disease (AD) patients with peptic ulcer. Methods. Participants with the diagnosis of AD and peptic ulcer were recruited between 2001 and 2008. We examined the association between eradication of H. pylori and the progression of AD using the multiple regression models. Medication shift from Donepezil, Rivastgmine, and Galantamine to Mematine is defined as progression of dementia according to the insurance of National Health Insurance (NHI) under expert review. Results. Among the 30142 AD patients with peptic ulcers, the ratio of medication shift in AD patients with peptic ulcers is 79.95%. There were significant lower incidence comorbidities (diabetes mellitus, hypertension, cerebrovascular disease, coronary artery disease, congestive heart failure and hyperlipidemia) in patients with H. pylori eradication as compared with no H. pylori eradication. Eradication of H. pylori was associated with a decreased risk of AD progression (odds ratio [OR] 0.35 [0.23–0.52]) as compared with no H. pylori eradication, which was not modified by comorbidities. Conclusions. Eradication of H. pylori was associated with a decreased progression of dementia as compared to no eradication of H. pylori in AD patients with peptic ulcers.

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 diseasemodifying 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 MLCSLT 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 MLCSLT and placebo were 2.67 and 2.48, respectively (p < 0.0001), without significant difference between MLC-SLT groups. [ABSTRACT FROM AUTHOR]