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.

Consistencies among miscellaneous scales for evaluation of post-stroke dysphagia.

PURPOSE: Post-stroke dysphagia (PSD) is the most common type of dysphagia. Stroke patients with sustained dysphagia have poorer outcomes. The severity of PSD is assessed using miscellaneous scales with unknown consistencies. We aim to investigate the consistencies among miscellaneous scales, which could aid in the assessment of PSD. METHODS: A total of 49 PSD patients were enrolled. Functional Oral Intake Scale (FOIS), Dysphagia Severity Scale (DSS), Ohkuma Questionnaire, Eating Assessment Tool-10, and Repetitive Saliva Swallowing Test were performed. FOIS was performed by physicians, and DSS was conducted by both the physicians and nurses; the physicians used either videofluoroscopy (VF) or videoendoscopy (VE) for evaluation; while, the nurses assessed PSD by observation and subjective judgment. RESULTS: When using VF (VF-DSS and VF-FOIS) as the gold standard for the evaluation, VE-FOIS (κ = 0.625, 95% CI 0.300-0.950, p < 0.001) has a substantial agreement with VF-FOIS, and VE-DSS (κ = 0.381, 95% CI 0.127-0.636, p = 0.007) has a fair agreement with VF-DSS. The weighted kappa of FOIS to DSS in VE (weighted κ = 0.577, 95% CI 0.414-0.740, p < 0.001) is not lower than that in VF (weighted kappa = 0.249, 95% CI 0.136-0.362, p < 0.001). CONCLUSION: For both DSS and FOIS, only VE has a statistically significant agreement with VF. Though VF has been viewed as the traditional gold standard of dysphagia screening, it has the limitations of being invasive and equipment dependent. For PSD, VE could be considered as a substitution when VF is not available or suitable.

Videofluoroscopy dysphagia severity scale is predictive of subsequent remote pneumonia in dysphagia patients.

Introduction: Dysphagia-associated pneumonia is a critical health issue especially in the elders and stroke patients which carries a poorer prognosis. Therefore, we aim to identify methods with the potentials to predict subsequent pneumonia in dysphagia patients, which will be of great value in the prevention and early management of pneumonia. Methods: One-hundred dysphagia patients were enrolled and measurements including Dysphagia Severity Scale (DSS), Functional Oral Intake Scale (FOIS), Ohkuma Questionnaire, and Eating Assessment Tool-10 (EAT-10) were assessed by either videofluoroscopy (VF), videoendoscopy (VE), or the study nurse. The patients were categorized into mild or severe groups based on each screening method. All the patients were assessed for pneumonia at 1, 3, 6, and 20 months after the examinations. Results: VF-DSS (p=0.001) is the only measurement being significantly associated with subsequent pneumonia with sensitivity and specificity of 0.857 and 0.486. The Kaplan-Meier curves revealed that significant differences between the mild/severe groups start to emerge 3 months after VF-DSS (p=0.013). Cox regression models used for adjusted hazard ratio of severe VF-DSS in association with subsequent pneumonia of different timepoints after controlling the important covariates showed the following results: 3 months, p=0.026, HR=5.341, 95%CI=1.219-23.405; 6 months, p=0.015, HR=4.557, 95%CI=1.338-15.522; 20 months, p=0.004, HR=4.832, 95%CI=1.670-13.984. Conclusions: Dysphagia severity evaluated by VE-DSS, VE-FOIS, VF-FOIS, Ohkuma Questionnaire, and EAT-10 is not associated with subsequent pneumonia. Only VF-DSS is associated with both short-term and long-term subsequent pneumonia. In patients with dysphagia, VF-DSS is predictive of subsequent pneumonia.

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.

Risk of cognitive impairment from exposure to incense smoke.

Incense is aromatic biotic material that releases fragrant smoke when burned. We aim to investigate the cognition risks from incense smoke. We obtained data from Taiwan Biobank in community. Cognition function was assessed by mini-mental state examination (MMSE). There were 978 participants in our study, including incense exposure (N = 131) and without incense exposure (N = 847). MMSE scores and registration sub-scores were lowered in incense exposure group than the other group. Incense exposure is one of the independent risk factors for cognitive decline in MMSE and registration sub-scores after adjusting confounding factors We concluded the risk of cognitive impairment, with predominant in registration in healthy individuals with incense exposure in community.

Pharmacological Management of Dysphagia in Patients with Alzheimer's Disease: A Narrative Review.

Alzheimer's disease (AD) and dysphagia are important health and socioeconomic problems in the aging population. Currently, the medical treatment of dysphagia in AD patients remains insufficient, and there are significant gaps in the management and clinical needs to postpone tube feeding. Literatures published over the last 30 years were searched in the PubMed and Embase databases. All relevant and promising pharmacological management studies were included. Because of the heterogeneity in design and methodology, only narrative reports were mentioned. Nine studies were included with two case reports, two case series, and two observational and three randomized controlled trials. The key approaches and clinical problems related to dysphagia include onset pattern, dementia stage, review of offending drugs and polypharmacy, and comorbidities (cerebrovascular disease, hypertension, parkinsonism, depression, and anorexia). The corresponding strategies of pharmacological treatments are further proposed and discussed comprehensively, with transient receptor potential channel modulators as promising treatment. With the integration of adequate and potential pharmacomanagement, AD patients with dysphagia can achieve a good prognosis and postpone tube feeding to maintain a better quality of life. More rigorous studies are needed to verify the effectiveness of innovative strategies and develop targets for neurostimulation.

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.

Effects of Dabigatran on Dementia Pathogenesis and Neuropsychological Function: A Review.

BACKGROUND: Patients with atrial fibrillation (AF) carry higher risks of cognitive consequences and psychological burden. An optimal anticoagulant therapy would be expected to better preserve neuropsychological function in addition to effective prevention of stroke and systemic thromboembolism. OBJECTIVE: The aim of this review is to explore the effects of the non-vitamin K antagonist oral anticoagulant (NOAC) dabigatran, a direct thrombin inhibitor, on cognitive and psychological function as well as dementia pathogenesis. METHODS: We performed a comprehensive search of PubMed/Medline for all types of relevant articles using a combination of dabigatran and associated keywords updated to August 31, 2021. All titles and abstracts were screened for eligibility, and potentially relevant papers were collected for inclusion. RESULTS: The pooled results demonstrated neutral to positive impacts of dabigatran on cognitive and psychological outcomes, including laboratory results in animal models of Alzheimer's disease, and reduced incidences of anxiety/depression and dementia for AF patients. Dabigatran also exhibited better therapeutic profiles than warfarin in preclinical and observational research. CONCLUSION: Given limited strength of evidence from heterogeneous studies, our review proposed modest beneficial effects of dabigatran on neuropsychological function. Further clinical trials are warranted to affirm the pleiotropic protective effects of NOACs on dementia treatment.

Real-world Evaluation of Tolerability, Safety and Efficacy of Rivastigmine Oral Solution in Patients with Mild to Moderate Alzheimer's Disease Dementia.

OBJECTIVE: The purpose of this study is to investigate the safety, tolerability and efficacy of titrating dose of rivastigmine oral solution in patients with mild to moderate Alzheimer's disease (AD) in Taiwan. METHODS: We recruited 108 mild to moderate AD patients with RivastⓇ (rivastigmine oral solution 2 mg/ml) treatment for 52 weeks. We recorded the demographic characteristics, initial cognition by mini-mental state examination (MMSE), initial global status by clinical dementia rating (CDR) with CDR-Sum of Boxes (CDR-SB), initial dose, and titrating dose at each visit. We investigated the adherence, proportion of possible side effects, optimal dose, and time to optimal dose. We demonstrated the proportion of cognitive decline and its possible risk factors. RESULTS: During the course, 9 patients discontinued the rivastigmine oral solution due to poor compliance or preference. Twelve out of 99 patients (12.1%) reported possible side effects. Among 87 patients, the mean age was 77.2 ± 9.0 years ago with female predominant (65.2%). The optimal dose was 3.6 ± 1.4 ml in average and 4 ml (n = 31, 35.6%) in mode. The duration to optimal dose was 12.5 ± 10.2 weeks and 24 weeks (n = 35, 40.2%) in mode. It presented 25% with cognitive decline in MMSE, 27% with global function decline in CDR and 63% with global function decline in CDR-SB. CONCLUSION: We demonstrated the clinical experience of rivastigmine oral solution in mild to moderate AD patients. It suggested rivastigmine oral solution 4ml is the optimal dose with 24 weeks to the optimal dose for at least one third of patients.

Behavioral and psychological symptoms in institutional residents with dementia in Taiwan.

AIM: Behavioral and psychological symptoms of dementia (BPSD) are important predictors for institutional placement, caregiver distress and depression for patients with dementia. We aim to investigate BPSD in institutional residents with dementia in Taiwan. METHODS: We conducted a nationwide study surveying institutional residents in Taiwan. Institutional residents from 22 counties and cities in Taiwan were recruited and analyzed in our study. We recorded demographic data, severity of dementia and disability, presence of BPSD, and past medical history of institutional residents in Taiwan. We recorded the characteristics of BPSD and analyzed the possible risks of BPSD in residents with dementia. RESULTS: A total of 4722 institutional residents were recruited and analyzed in our study. The prevalence of dementia was 87.2% (4119 residents). Among residents with dementia, 1546 (37.5%) had presented BPSD in the past 3 months. The most frequent three types of BPSD were nighttime behavior (17.9%), resistance against care (13.4%) and depression (12.9%). Old age, female gender, and lower MMSE (Mini-Mental State Examination) scores were associated with BPSD. Moderate dementia (OR = 1.73, 95% CI = 1.30-2.31) and mild activities of daily living (ADL) dependence (OR = 2.13, 95% CI = 1.06-4.27) increased the risks of BPSD. Reviews of past medical history showed that orthopedic disease, eye disease, genitourinary disease, dementia, psychiatric disorder and intellectual disability were associated with increasing risks of BPSD. CONCLUSIONS: We concluded that moderate dementia and mild ADL dependence increased the risks of BPSD in institutional residents with dementia. Geriatr Gerontol Int 2021; 21: 718-724.

The Role of Cilostazol and Inflammation in Cognitive Impairment After Ischemic Stroke.

PURPOSE: The aim of this study is to examine the potential effect of cilostazol and inflammation on cognitive impairment after stroke in an Asian population. METHODS: Forty-five patients with cognitive impairment after ischemic stroke using cilostazol were enrolled as the study group and 45 patients using aspirin or clopidogrel were enrolled as the control group. Neuropsychiatric assessments were administered at the start of the study and after 6 months. Multiple logistic regression analysis was used to estimate the association between the cognitive change and cilostazol use. Macrophage polarization were assessed using flow cytometry in 7 patients. RESULTS: There were a significantly higher number of patients with peripheral arterial occlusive disease in the cilostazol group. No significant differences were observed in the cognitive change between the cilostazol and control groups. M1 macrophage subset increment were observed in the patient having a declined cognitive change. CONCLUSION: Cilostazol did not make a significant difference in cognitive change after ischemic stroke. M1 macrophage subset increment may indicate post stroke cognitive decline. Due to limited number of subjects, these findings should be examined further in large-scale randomized clinical trials.

Poor Cognitive Function Is Associated with Obstructive Lung Diseases in Taiwanese Adults.

Previous studies have reported an association between the impairment of cognitive performance and lung diseases. However, whether obstructive or restrictive lung diseases have an impact on cognitive function is still inconclusive. We aimed to investigate the association between cognitive function and obstructive or restrictive lung diseases in Taiwanese adults using the Mini-Mental State Examination (MMSE). In this study, we used data from the Taiwan Biobank. Cognitive function was evaluated using the MMSE. Spirometry measurements of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained to assess lung function. Participants were classified into three groups according to lung function, namely, normal, restrictive, and obstructive lung function. In total, 683 patients enrolled, of whom 357 participants had normal lung function (52.3%), 95 had restrictive lung function (13.9%), and 231 had obstructive lung function (33.8%). Compared to the normal lung function group, the obstructive lung function group was associated with a higher percentage of cognitive impairment (MMSE < 24). In multivariable analysis, a low MMSE score was significantly associated with low FVC, low FEV1, and low FEV1/FVC. Furthermore, a low MMSE score was significantly associated with low FEV1 in the participants with FEV1/FVC < 70%, whereas MMSE was not significantly associated with FVC in the participants with FEV1/FVC ≥ 70%. Our results showed that a low MMSE score was associated with low FEV1, low FVC and low FEV1/FVC. Furthermore, a low MMSE score was associated with obstructive lung diseases but not with restrictive lung diseases.

Air Pollution Is Associated with Poor Cognitive Function in Taiwanese Adults.

The issue of air pollution is gaining increasing attention worldwide, and mounting evidence has shown an association between air pollution and cognitive decline. The aim of this study was to investigate the relationships between air pollutants and cognitive impairment using the Mini-Mental State Exam (MMSE) and its sub-domains. In this study, we used data from the Taiwan Biobank combined with detailed daily data on air pollution. Cognitive function was assessed using the MMSE and its five subgroups of cognitive functioning. After multivariable linear regression analysis, a high level of particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5), low ozone (O3), high carbon monoxide (CO), high sulfur dioxide (SO2), high nitric oxide (NO), high nitrogen dioxide (NO2), and high nitrogen oxide (NOx) were significantly associated with low total MMSE scores. Further, high SO2 and low O3 were significantly associated with low MMSE G1 scores. Low O3, high CO, high SO2, high NO2, and high NOx were significantly associated with low MMSE G4 scores, and high PM2.5, high particulate matter with an aerodynamic diameter of ≤10 µm (PM10), high SO2, high NO2, and high NOx were significantly associated with low MMSE G5 scores. Our results showed that exposure to different air pollutants may lead to general cognitive decline and impairment of specific domains of cognitive functioning, and O3 may be a protective factor. These findings may be helpful in the development of policies regarding the regulation of air pollution.

Dynamic Blood Concentrations of Aß1-40 and Aß1-42 in Alzheimer's Disease.

Amyloid-beta (Aß) is produced by the cleavage of amyloid precursor proteins in the cell membrane by ß-secretase and γ-secretase into a monomeric form with peptides of different lengths such as Aß1-40 or Aß1-42, 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 Aß1-40 and Aß1-42 are unstable after blood samples have been obtained. In order to examine the dynamic changes of plasma Aß1-42 and Aß1-40 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 Aß1-40 and Aß1-42 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 Aß1-42 and Aß1-40 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 Aß1-40 (p = 0.422) or Aß1-42 (p = 1.000). However, for plasma Aß1-42, 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 Aß1-42 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 Aß1-40 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 Aß1-40 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 Aß1-40 and Aß1-42 levels, and significant associations between Aß1-40 level and disease severity. Further studies are needed to investigate the exact mechanisms of how APOE4 affects the dynamic changes in plasma Aß1-40 and Aß1-42, and the association between Aß1-40 and advanced dementia.

The long-term risk of epilepsy after transient global amnesia: A population-based cohort study.

OBJECTIVE: Transient global amnesia (TGA) is characterized by sudden onset of larger anterograde and milder retrograde amnesia lasting up to 24 h. We aimed to investigate the long-term risk of epilepsy up to 8 years in subjects after TGA in the population-based cohort study. PATIENTS AND METHODS: We conducted a control cohort study with an 8-year follow-up period. All data was collected retrospectively. From all potential participants more than 18 years of age without epilepsy and TGA history, we identified TGA subjects and non-TGA controls with age, gender and comorbidities matched in a 1:3 ratio. The yearly incidence of epilepsy was compared in TGA and non-TGA cohorts. The cumulative hazard ratio of epilepsy was estimated. The risk factors of epilepsy after TGA were investigated. RESULTS: A total of 185 TGA subjects and 555 non-TGA controls were included in the study. There were 7 epilepsy cases in the 185 TGA cohorts during the follow-up period with yearly incidence rates of 9.629 per 1000 person. The adjusted hazard ratio for epilepsy in TGA cohorts was 6.50 (95 % confidence interval 1.87-22.68, p = 0.003) compared with non-TGA cohorts after adjusting for age, gender and comorbidities. No notable factor was significantly associated with epilepsy after TGA. CONCLUSION: Our study highlighted TGA is associated with increased long-term risk of epilepsy.

A comparison of sociobehavioral impact on cognitive preservation in Alzheimer's disease between Taiwan and Korea: A cross-national study.

Both Taiwan and Korea are developed countries with different cultures. When encountering the issue of dementia, such sociobehavioral factors have various and different impacts on dementia. We aim to assess the cross-national difference of sociobehavioral impact on cognitive preservation in Alzheimer's disease (AD) between Taiwan and Korea.A uniformed data set was administered regarding AD. We evaluated annual cognitive function using the Mini-Mental State Examination (MMSE), Clinical Dementia Rating sum of box (CDR-SB), and CDR for 2 continuous years. Annual change of scores compared with the baseline indicated cognitive change as preservation or decline. We recorded the sociodemographic variables of interest, including education duration, level of independence, living situation, and marital status. Step-wise regression analyses were performed to determine the independent factors for cognitive preservation.In total, 503 participants in Taiwan and 77 participants in Korea were recruited from 2011 to 2014. The baseline demographic characteristics were different in levels of education, living situation, level of independence, and dementia severity between the 2 countries. With follow-up for 2 years, cognitive preservation was associated with CDR staging at baseline and independence [adjusted odds ratio (OR) = 1.657, 95% confidence interval (95% CI) = 1.109-2.477, P = .014] in the Taiwanese population, whereas cognitive preservation was related to living alone (adjusted OR = 3.316, 95% CI = 1.135-9.687, P = .028) in the Korean population. The levels of education showed inconsistency in cognitive preservation in both countries.Cognitive preservation was associated with independence in the Taiwanese population, whereas cognitive preservation was related to living alone in the Korean population. By practicing relevant socioeconomic support, this might contribute to lessening the negative impact of dementia and preserving cognition in different countries.

M2b macrophage subset decrement as an indicator of cognitive function in Alzheimer's disease.

AIM: Alzheimer's disease (AD) is a chronic neurodegenerative disease. Various inflammatory processes account for the pathology of AD, and macrophages in particular have a distinct polarization phenotype related to M1/M2 classification. We aimed to investigate macrophage polarization patterns as an indicator of cognitive function in AD. METHODS: We recruited 54 non-demented individuals as control and 105 AD patients as experimental groups respectively. Percentages of macrophage (PM2K+ CD14+ and PM2K+ CD14- ) and macrophage polarization subsets (M1, M2a, M2b, and M2c) were assessed using flow cytometry. All AD patients were classified by dementia severity using clinical Dementia Rating scale (CDR) as CDR 0.5, 1 and ≧2. AD patients had cognitive function evaluation using Mini-Mental State Examination (MMSE) and Cognitive Assessment Screening Instrument (CASI). We compared the macrophage polarization patterns between control and patient groups. Cognitive function was evaluated in association with macrophage polarization patterns in AD patients. RESULTS: The percentages of PM2K+ CD14+ and PM2K+ CD14- macrophages were higher in AD patients than in controls. M2b macrophage subset decrement and M1 macrophage subset increment of PM2K+ CD14+ and PM2K+ CD14- macrophages were observed in AD patients compared with controls. Although percentages of macrophage subsets were not consistent with CDR staging, PM2K+ CD14+ M2b macrophage subset decrement was correlated with worse cognitive functioning by MMSE and CASI in AD patients. CONCLUSION: M2b macrophage subset decrement and M1 macrophage subset increment were noted in AD patients, while PM2K+ CD14+ M2b macrophage subset decrement indicated worse cognitive function in such patients.

Gender differences in presentation of behavioral and psychological symptoms in Alzheimer's disease in Taiwan.

Objectives: Behavioral and psychological symptoms of dementia (BPSD) are frequently met in Alzheimer's disease (AD), especially in their late stages. BPSD has been reported to be associated with gender for its biological characteristics and severity of dementia. We aimed to investigate the gender differences in presentation of BPSD in AD in Taiwan.Methods: We recruited patients with clinically diagnosed AD by National Institute of Neurological Disorders and Stroke (NINCDS) - Alzheimer's Disease and Related Disorders Association (ADRDA) criteria. Demographic data and annual psychometrics, including Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR) and Neuropsychiatric Inventory (NPI), consisting sub-items of delusions, hallucinations, aggression, depression, anxiety, elation, apathy, disinhibition, irritability, aberrant motor, nighttime behavior and eating were all administered to evaluate BPSD. Apolipoprotein E (APOE) allele was genotyped for each recruited AD subject. Differences between gender and variables were compared and significant NPI sub-items associated with gender were determined, while linear regression analyses were determined as the independent factor for BPSD.Results: In total, 280 female and 180 male AD patients were recruited into statistical analyses. Males had longer education duration and higher MMSE scores than females. Female had higher presence of delusion and disinhibition. In linear regression, being female and CDR stage were two independent factors for delusion (for female, B = 0.95, 95% CI = 0.17-1.73, p = 0.017) and disinhibition (for female, B = 0.49, 95% CI = 0.08-0.90, p = 0.019) after adjusting for confounding factors.Conclusions: The presentation of delusion and disinhibition in BPSD is associated with the female gender and staging of AD. Disinhibition was not necessarily associated with late stage of AD.