Ling-Chun Huang

Previous studies have shown that plasma amyloid-beta oligomers (AβOs), the toxic form of amyloid-beta (Aβ), are a critical issue in the development or worsening of Alzheimer’s disease (AD) and can be regarded as a blood marker for screening in dementia. We examined plasma AβOs with their related biomarkers in a case–control study to clarify these issues. A total of 16 patients diagnosed with Alzheimer’s dementia (AD) and 16 cognitively normal controls (NCs) were recruited to compare their plasma biomarkers, AβO, Aβ_1-40, and Aβ_1-42, also referring to other parameters like APOE ε4 status, Clinical Dementia Rating^®-Sum of Boxes (CDR^®-SB), and Mini Mental Status Examination (MMSE) scores. In plasma concentrations of Aβ_1-40, Aβ_1-42, and AβO, the mean concentrations were significantly different between the two groups. There is a significant increase in the concentrations of Aβ_1-40 and AβO, while Aβ_1-42 is decreased in individuals with AD compared to NC. AβO was statistically associated with the Aβ_1-40 and Aβ_1-42/Aβ_1-40 ratio. Higher plasma concentrations of AβO were significantly associated with AD compared to non-dementia controls. This suggests that AβOs can be potential plasma biomarkers to screen in AD. However, a study recruiting more individuals is necessary to examine the association, if any.

Background: Virtual reality (VR) interventions are emerging as promising nonpharmacological strategies for people with dementia, aiming to prevent cognitive decline, reduce behavioral and psychological symptoms of dementia (BPSD), and alleviate caregiver burden. Although some studies have reported beneficial effects, findings remain inconsistent, and little is known about the duration and sustainability of these effects, particularly in real-world care settings. Objective: This study aimed to examine both the immediate and long-term effects of an immersive VR reminiscence intervention on BPSD and caregiver burden in people with dementia attending day care centers. Methods: This longitudinal observational study was conducted in 10 dementia day care centers in Kaohsiung, Taiwan. A total of 82 participants with dementia were enrolled. The VR intervention consisted of twice-weekly sessions over one month, featuring culturally familiar live-action 360° scenes filmed in well-known Taiwanese locations. Each session lasted approximately 10‐12 minutes and included interactive elements. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory Questionnaire, and caregiver burden was assessed using the Zarit Caregiver Burden Interview. Measurements were taken at 3 time points: preintervention, immediately postintervention, and 2 months after the intervention ended. The Wilcoxon signed-rank test was used for statistical comparisons, and rank-biserial correlation was calculated as the effect size. Results: Significant improvements were observed after 1 month of VR intervention in both caregiver burden (Z=−3.095, P=.002, r=0.34) and neuropsychiatric symptoms (Z=−2.929, P=.003, r=0.32). At the two-month follow-up, neuropsychiatric symptoms remained significantly improved (Z=−4.327, P<.001, r=0.48), although caregiver burden returned to preintervention levels. Regarding specific neuropsychiatric symptoms, significant improvements were observed immediately after the intervention in dysphoria or depression, anxiety, and sleep or nighttime behaviors. These effects were sustained over time, with additional long-term improvements noted in euphoria or elation, apathy or indifference, irritability or lability, aberrant motor behavior, and appetite or eating behaviors. Conclusions: A 1-month immersive VR reminiscence intervention appears to improve neuropsychiatric symptoms and temporarily reduce caregiver burden in people with dementia, with some symptom improvements lasting up to 2 months. These findings suggest that VR may offer a meaningful therapeutic option in day care settings. Future studies with control groups, including nonimmersive 2D conditions, and comparisons to traditional reminiscence therapy are needed to validate and expand upon these findings.

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.

Background: Non-invasive 40 Hz gamma frequency stimulation has shown improved cognition and memory recall in Alzheimer’s disease (AD). Purpose: The present study investigates the effects of white light stimulation at gamma frequency on SH-SY5Y cells using Delta M + BrainCare Light without causing discomfort. Methods: SH-SY5Y cells were exposed to The Delta M + BrainCare Light for 15, 30, 45, and 60 minutes. The secretion of amyloid-β42 (Aβ42), p-AKT (Ser473), AKT, p-mTOR (Ser2448), mTOR, p-4E-BP1 (Thr37/46), 4E-BP1, p-tau (Thr181), and tau were analyzed. Aβ42 fibril aggregation and phagocytosis of FITC-Aβ42 in BV-2 cells were also observed. Results: Delta M + BrainCare Light reduced tau, AKT, and p-mTOR and increased p-4E-BP1 in SH-SY5Y cells. Further, it inhibited secretion and aggregation of Aβ42, alongside increased phagocytosis in microglial cells. Conclusion: These findings underscore the potential of the Delta M + BrainCare Light in mitigating the associated proteins and pathways implicated in AD.

Background: Machine learning (ML) applied to healthcare is increasingly and it provides innovative solutions to solve complex real‐world problems. In dementia, ML has been applied to dementia detection, discriminating different types of dementia, and prediction progression of diseases. The aim of the study was to develop a new, brief clinical tool based on machine learning for dementia screening.Method: The training data was from 533 participants (311 dementia and 202 non‐demented participants) screened with “Six‐Question Dementia Screening Test” (6Q‐DS). The 6Q‐DS contained six simple questions to evaluate mood, memory, orientation, and concentration. We used e‐Xtreme Gradient Boosting (XGBoost) algorithm, an ensemble ML based on decision trees, to establish the prediction model for dementia.Result: A total 533 participants, 186 men and 347 women with mean age 77.6 ± 8.2 (mean± SD) years, were recruited. The dementia group was significantly older and had lower education years compared to non‐dementia group (p < 0.01 for both). The receiver‐operator characteristic (ROC) analysis showed that the area under the curve (AUC) was 0.91 for discriminating non‐dementia vs. dementia, with the sensitivity as 0.86, specificity 0.81 and accuracy 0.84. We found that the top 3 features are the second calculations for serial 3’s test, feeling of depression and the third calculations for serial 3’s test. We hypothesized that the second and third calculations required more cognitive demands because of holding information longer and depression is frequent in dementia. In our sixth question “Please count down 100 by 3 for 5 times (Serial 3’s)”, we found that the second and third calculations for serial 3’s test were important features to discriminating dementia from non‐dementia. We also found that the feeling of depression is the second important feature to distinguish dementia in our data set.Conclusion: We proposed the new, ease‐to‐use instrument with good classification of screening dementia based on ML. The 6Q‐DS showed an acceptable accuracy with a relatively high sensitivity and specificity. Further works are warranted to validate the model in different clinical settings and disease severity.

Background: Dementia, which presents as cognitive decline in one or more cognitive domains affecting function, is increasing globally. Early diagnosis of dementia for general population is important, which needs a screening tool capable of identifying dementia efficiently.Most cognitive tests for screening dementia are based on verbal administration, which will be influenced by cultural background and language differences, if any.Developing a screening tool less depended on verbal administration is crucial for these necessities.Method: Participants aged from 50 to 89 years old were recruited from department of Neurology, Kaohsiung Municipal Ta‐Tung Hospital, Taiwan. Dementia was diagnosed based on clinical diagnosis with referring to cognitive test performance by psychologists by 2011 National Institute on Aging and Alzheimer’s Association (NIA‐AA) criteria for all‐cause dementia .Participants were assessed with Clinical dementia rating (CDR), Cognitive Abilities Screening Instrument (CASI), derived Mini‐Mental State Examination (MMSE) and the non‐verbal cognitive test consisted of visual memory test, digital connection test, clock puzzle, shape color matching and simple card sorting test. These tests were designed to capture cognitive function including visual memory, visuospatial ability, and executive function. Statistical analysis was performed using MedCalc, version 20.14.Result: In total, 160 demented patients and 81 non‐demented participants were recruited. The performance of the dementia group was worse than that of the control group in all non‐verbal tests. Among these tests, visual memory had the greatest ability to examine dementia with its percentage of recalled visual memory with optimal cut‐off point 70% having a sensitivity 73.38%,specificity 85.19% and area under the curve (AUC) as 0.87. Combining visual memory test, the digital connection test‐1 and the clock puzzle‐1 to discriminate dementia, the AUC was 0.93 and was superior to the AUC of MMSE (AUC = 0.88).Conclusion: Compared to traditional pencil‐paper tests, non‐verbal tests shown its potentials in screening dementia with fewer language limitation.

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.

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.

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.