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

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

Determinants of long-term care service use by persons with dementia: A national dementia registry study conducted in Taiwan.

BACKGROUND: This study investigated the determinants and use of Taiwan's long-term care (LTC) Plan Version 2.0 (LTC 2.0) services by persons with dementia (PWDs) and their caregivers. METHODS: In total, 1268 PWD-caregiver dyads were enrolled for analysis from a national dementia registry. Andersen's Behavioral Model of Health Services Use was used to investigate the association of LTC service use with several factors, namely the demographic data of PWDs and their caregivers, migrant caregiver employment, monthly household income, caregiver burden as determined by the Zarit Burden Interview (ZBI), Mini-Mental State Examination score, Clinical Dementia Rating scores, neuropsychiatric inventory scores for the behavioral and psychological symptoms of dementia, and PWDs' activities of daily living (ADLs). RESULTS: Among the studied family caregivers, 81.4% did not use LTC resources. A multivariable logistic analysis revealed that aberrant motor behaviors (odd ratio [OR] = 1.31, 95% confidence interval [CI] = 1.10-1.56, p = 0.003), dysfunction in ADLs (OR = 1.06, 95% CI = 1.02-1.10, p = 0.002), higher ZBI scores (OR = 1.02, 95% CI = 1.01-1.03, p = 0.004), not residing with family members (OR = 1.88, 95% CI = 1.32-2.66, p < 0.001), and not employing a migrant caregiver (OR = 4.41, 95% CI = 2.59-7.51, p < 0.001) were the factors most significantly associated with LTC service use. CONCLUSION: Factors such as whether PWDs live alone, specific neuropsychiatric symptoms, and impaired function should be considered in future policy amendments to provide required activities and care resources for PWDs and their caregivers.

Impact of the CYP2D6 single nucleotide polymorphism on the concentration of and therapeutic response to donepezil in mild-to-moderate Alzheimer's disease.

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.

Predictors of caregiver burden in aged caregivers of demented older patients.

BACKGROUND: Dementia in the oldest-old is projected to increase exponentially as is the burden of their caregivers who may experience unique challenges and suffering. Thus, we aim to investigate which factors are associated with older caregivers' burden in caring demented outpatients in a multicenter cohort. METHODS: Patients and their caregivers, both aged ≧65 years, in the National Dementia Registry Study in Taiwan (T-NDRS) were included in this study. Caregiver burden was measured with the short version of the Zarit Burden Interview (ZBI). The correlations between the ZBI scores and characteristics of caregivers and patients, including severity of dementia, physical comorbidities, instrumental activities of daily living (IADL), neuropsychiatric symptoms assessed by the Neuropsychiatric Inventory (NPI), and family monthly income, were analyzed. RESULTS: We recruited 328 aged informal caregiver-patient dyads. The mean age of caregivers was 73.7 ± 7.0 years, with female predominance (66.8%), and the mean age of patients was 78.8 ± 6.9 years, with male predominance (61.0%). Multivariable linear regression showed that IADLs (ß = 0.83, p < 0.001) and NPI subscores of apathy (ß = 3.83, p < 0.001)and irritability (ß = 4.25, p < 0.001) were positively associated with ZBI scores. The highest family monthly income (ß = - 10.92, p = 0.001) and caregiver age (ß = - 0.41, p = 0.001) were negatively correlated with ZBI scores. CONCLUSIONS: Older caregivers of older demented patients experience a higher care burden when patients had greater impaired functional autonomy and the presence of NPI symptoms of apathy and irritability. Our findings provide the direction to identify risky older caregivers, and we should pay more attention to and provide support for these exhausted caregivers.

The effects of lacosamide on cognitive function and psychiatric profiles in patients with epilepsy.

BACKGROUND: Cognitive and psychiatric problems are common in people with epilepsy. They can have multiple causes, including structural brain lesions, the active epilepsy, and the effect of anti-epileptic therapy. Since patients' treatment compliance and quality of life are affected by cognitive and emotional status, it is crucial for clinicians to understand how anti-seizure medications (ASMs) affect cognition and mood, and to choose the proper ASM. OBJECTIVE: To conduct a literature review of the impact on cognition and mood status of lacosamide (LCM) in people with epilepsy. METHODS: Wesearched PubMed, the Cochrane Database of Systematic Reviews and reference lists of articles for all types of articles with no limitations on publication date. RESULTS: A total of 251 records were obtained, including 247 articles in PubMed and 4 articles from reference lists. We included 2 meta-analyses, one randomized controlled trials and 14 observational studies after the screening process. Most studies agree LCM has low risk of treatment-emergent adverse events (TEAEs) on cognition. Comparisons with other ASMs, LCM may be preferable to carbamazepine, topiramate and perampanel, and not inferior to lamotrigine. In spite of low incident rate, depression is the most common psychiatric change of LCM. There are no consistent positive or negative psychiatric effects of LCM. CONCLUSION: Lacosamide has limited impact on cognitive and mood status in this review. Several factors including mechanism of co-administration of ASMs and personal history of psychiatric disorder should be considered as important in the development of cognitive and psychiatric side effects. However, the heterogeneity between studies make the quality of evidence weaker and further trials are needed.

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.

The Mortality and the Risk of Aspiration Pneumonia Related with Dysphagia in Stroke Patients.

BACKGROUND: Dysphagia may result in poor outcomes in stroke patients due to aspiration pneumonia and malnutrition. GOAL: The aim of the study was to investigate aspiration pneumonia and the mortality rate in stroke patients with dysphagia in Taiwan. METHODS: We selected 1220 stroke patients, divided them into dysphagia and nondysphagia groups, and matched them according to age; covariates and comediations from 2000 to 2005 were identified from the NHIRD 2000 database. The date of the diagnosed stroke for each patient was defined as the index date. All patients were tracked for 5 years following their index visit to evaluate mortality and the risk of aspiration pneumonia. We estimated the adjusted hazard ratio using Cox proportional hazard regression. RESULTS: Within 1 year, the dysphagia group was 4.69 times more likely to develop aspiration pneumonia than the nondysphagia group (adjusted hazard ratio [aHR], 4.69; 95% confidence interval [CI] 2.83-7.77; P < .001). The highest significant risk of aspiration pneumonia was in the cerebral hemorrhage patients within 3 years of the index visit (aHR, 5.04; 95% CI 1.45-17.49; P = .011). The 5-year mortality rate in the dysphagia group was significantly higher than that in the nondysphagia group (aHR, 1.84; 95% CI 1.57-2.16; P < .001). CONCLUSION: Dysphagia is a critical factor in aspiration pneumonia and mortality in stroke patients. Early detection and intervention of dysphagia in stroke patients may reduce the possibility of aspiration pneumonia.

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.

Exploring the impact of 40 Hz multi-luminaire light exposure in Alzheimer's dementia: insights from a convenient sampling, non-randomized case-control study.

BACKGROUND: Recent studies propose 40 Hz neural activity induction as a promising approach for managing Alzheimer's dementia (AD). However, traditional flickering light is suboptimal in addressing cognitive and neuropsychiatric symptoms (NPS) of AD. This study aims to investigate the clinical efficacy of a novel multi-luminaire lighting technology, with reduced perceptible flickering, for treating AD NPS. METHODS: This study is a prospective, convenient sampling, non-randomized case-control investigation involving seventy-eight clinically diagnosed AD patients from 7 daycare centers. Thirty-five were exposed to 40 Hz light through Delta M + BrainCare Light (M +), 4 h daily, 5 days/week, for 12 weeks. The other 43 patients served as controls. Sum of boxes of the Clinical Dementia Rating (CDR-SB) scale, Neuropsychiatric Inventory (NPI), and Zarit Burden Interview (ZBI) were assessed at baseline and the 13th week. RESULTS: At baseline, the cases had worse cognitive function, lower cognitive score (Mini-Mental State Examination, p = 0.04; Cognitive Abilities Screening Instrument, p = 0.04), and advanced caregiver burden with higher ZBI scores (p < 0.01) than the controls. After the intervention, the cases had significant improvements in NPS as assessed using the NPI (p = 0.02), especially depression and euphoria symptoms (p = 0.04 and < 0.01, respectively) and less caregiver burden (ZBI score, p < 0.01). In global function, the control group showed a significant decline in CDR-SB score (p < 0.01), while the cases did not. CONCLUSIONS: Results suggest M + may slow global function decline, preserve cognitive function, improve NPS, and reduce caregiver burden in AD patients. Larger studies with biomarkers are needed to explore underlying mechanisms.

Predictors of live-in migrant caregiver employment for people with dementia in Taiwan.

BACKGROUND: With the increasing number of individuals with dementia, families have hired an increasing number of live-in migrant caregivers (LIMCs). Currently, limited evidence is available regarding the influence of long-term care resource utilization on the hiring of LIMCs for caring for individuals with dementia in Taiwan. METHODS: We recruited individuals with dementia who did not hire LIMCs and their primary family caregivers from nine hospitals in Taiwan as baseline. Multivariable logistic regression was used to evaluate the utilization of long-term care resources for individuals with dementia and other factors that may affect the decision to hire LIMCs. RESULTS: The users of non-long-term care resources had the highest likelihood of hiring LIMCs (odds ratio [OR] = 4.24, 95% CI, 2.30-7.84). Compared with spouses, nonimmediate family caregivers (OR = 3.40, 95% CI, 1.16-9.90) were significantly more likely to hire LIMCs. A higher likelihood of hiring LIMCs was observed for those with Lewy body dementia compared with other individuals (OR = 2.31, 95% CI, 1.03-5.14). Compared with individuals who did not hire LIMCs, those who hired LIMCs exhibited higher scores on the Neuropsychiatric Inventory (NPI) and higher severity of individual NPI items. CONCLUSION: Hiring LIMCs is strongly correlated with the utilization of non-long-term care resources and is influenced by the dynamics between individuals with dementia and their primary family caregivers. A higher likelihood of hiring LIMCs was observed for individuals with Lewy body dementia and individuals with elevated NPI scores compared with their counterparts. Given these observations, various support strategies and interventions should be tailored to the specific requirements of individuals with dementia and their families.

Susceptibility-weighted imaging in patient with consciousness disturbance after traffic accident.

Both diffuse axonal injury (DAI) and fat embolism syndrome could be the cause of altered consciousness in patients who suffered from traffic accident. In some situations, distinguishing DAI from fat embolism syndrome may be difficult because routine brain imaging could not detect the lesions. Susceptibility weighted imaging is sensitive to detect petechial hemorrhages in cerebral fat embolism and DAI. The areas most vulnerable to DAI are the cerebral gray-white matter junction, splenium of the corpus callosum, and dorsolateral brainstem. However, cerebral and cerebellar white matter and splenium of corpus callosum are the areas most vulnerable to cerebral fat embolism. In additional to history, clinical manifestation, and prognosis, evaluating the distribution of hypointense lesions in susceptibility-weighted imaging could be useful to differentiate these 2 conditions.

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

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

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

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

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.

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

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

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

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

The Long-term Effects of Immersive Virtual Reality Reminiscence in People With Dementia: Longitudinal Observational Study.

BACKGROUND: Novel 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. OBJECTIVE: The 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. METHODS: A 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. RESULTS: There 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. CONCLUSIONS: Immersive 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.

Application of Micro-Western Array for Identifying Different Serum Protein Expression Profile among Healthy Control, Alzheimer's Disease Patients and Patients' Adult Children.

(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 LXRß 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.

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

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