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ABSTRACT Background Objective Methods Results Conclusions Emerging evidence suggests a link between salivary metabolite changes and neurodegenerative dementia, with antimicrobial peptides (AMPs) implicated in its pathogenesis.We investigated the effects of a clinical oral rehabilitation programme tailored for dementia patients on salivary flow rate, AMP levels and oral health‐related quality of life (OHRQoL).Eligible patients were randomly assigned to either the experimental group (EG; n = 28) or the control group (CG; n = 27). Both groups received a leaflet on oral health. In addition, the EG received an oral care intervention that included individual lessons on oral muscle exercises and oral self‐care practices. Saliva samples and OHRQoL data were collected at baseline and follow‐up visits. Generalised estimating equation models were used to analyse the changes over time.At the 3‐month follow‐up, EG showed significantly lower histatin 5 (HTN‐5) levels (β = −0.08; effect size [ES] = 0.72) than CG. At 6 months, EG exhibited improved salivary flow rate (β = 0.89; ES = 0.89) and OHRQoL (β = 6.99; ES = 1.31) compared to CG. Changes in salivary flow rate (β = 4.03), HTN‐5 level (β = −0.78) and beta‐defensin 2 level (BD‐2) (β = −0.91) at 3 months predicted improved OHRQoL at 6 months (all p < 0.05).Our clinical oral rehabilitation programme reduced the level of salivary HTN‐5, increased salivary flow rate and enhanced OHRQoL in dementia patients. Furthermore, changes in salivary flow rate, HTN‐5 level and BD‐2 level were associated with improvements in patients' OHRQoL. [ABSTRACT FROM AUTHOR]

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. Key points: Behavioral and psychological symptoms of dementia (BPSD) and subclinical epileptiform discharge (SED) increase with the progression of Alzheimer's disease.In the present study, we aimed to evaluate the associations between SED and BPSD.Apathy was the most commonly reported subsyndrome in our cohort, followed by nighttime behavior and irritability.There was no significant difference in the prevalence of BPSD between patients with and without SED. However, the NPI score for irritability subsyndromes was significantly higher in the SED (+) group.SED may not be a direct cause of BPSD, but its presence may affect the manifestation of BPSD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of a clinical‐based oral function intervention on oral function and care behaviours in older patients with mild dementia. Method: Participants were randomly assigned to the experimental group (EG) and control group (CG). Both groups received a leaflet on oral health‐related knowledge, and the EG also received an oral function intervention, which was a brief one‐on‐one lesson concerning oral exercise and preventive oral care. Oral exercise included turning the head, pouting lips, bulging cheeks, stretching tongue, articulation exercise and salivary gland massages. A reminder phone call was made every 2 weeks. Perceived xerostomia and dysphagia, plaque index (PI), Winkel tongue‐coating index (WTCI), repetitive saliva‐swallowing test (RSST), oral diadochokinesis (DDK) and oral care behaviours were recorded at baseline and at 3‐month follow‐up. Generalised Estimating Equations (GEE) were used to analyse the indicated effects. Results: The EG (n = 59) exhibited greater improvement to the CG (n = 55) in RSST [β = 0.7; effect size (ES) = 0.45], the syllables /pa/ (β = 3.1; ES = 0.37) and /ka/ (β = 2.7; ES = 0.40) in oral DDK, PI (β = −0.2; ES = 0.52) and WTCI (β = −0.8; ES = 0.38). Moreover, the EG exhibited better preventive behaviours in regular dental visits [adjusted odds ratio (aOR) = 2.2], daily mouth cleaning frequency (aOR = 1.6) and mouth cleaning before sleep (aOR = 1.3). Conclusion: The brief clinical‐based intervention was effective in improving the swallowing function, oral DDK and plaque control of older patients with mild dementia at 3‐month follow‐up. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: We investigated the long‐term risk of dementia for up to 10 years in patients with stroke and broadened the correlates. Methods: We carried out a case–control study using the Taiwan National Health Insurance Research database in 2000 with a sampled population of 1 million. The study cohort comprised 8236 patients with stroke and no dementia history. We carried out a 1:1 case–control matched analysis on estimated propensity scores. Cox proportional hazards regressions were carried out to estimate the risk of dementia during the 5‐ and 10‐year follow‐up periods. The risk factors were also investigated. Results: The stroke cohort was significantly at more risk of dementia during the 5‐ and 10‐year follow‐up periods, with adjusted hazard ratios 1.87 and 1.53, respectively. The patients with ischemic stroke, transient ischemic attack and intracerebral hemorrhage had a significantly higher risk of dementia after 5 and 10 years, with adjusted hazard ratios of 1.81 and 1.49, 1.92 and 1.61, and 2.14 and 1.61, respectively. The significant risk factors of dementia were age ≥60 years, resident in southern and eastern regions, having low insurance range, and antiplatelet use. Conclusions: Stroke and the subtypes, including ischemic stroke, transient ischemic attack and intracerebral hemorrhage, increase the long‐term risk of dementia. The incidence of post‐stroke dementia increases yearly, but the relative risk decreases gradually. Older adults, residents in southern and eastern regions, having low insurance range and antiplatelet use were prominent risk factors of post‐stroke dementia in Taiwan. Careful management of stroke and risk factors of post‐stroke dementia with long‐term follow up of cognition should be reinforced. Geriatr Gerontol Int 2019; 19: 815–822. [ABSTRACT FROM AUTHOR]

Aim: The response to donepezil in patients with Alzheimer's disease varies, and it is important to identify the potential responder before therapy. Cerebral white matter changes (WMC) are frequently observed in older patients, and the effect of WMC on therapeutic response remains controversial. The present study aimed to investigate the relationships between the location of WMC, severe WMC and the response to donepezil. Methods: Among 418 patients with Alzheimer's disease receiving donepezil, 196 patients were eligible for analysis. Five brain areas on each side were analyzed using computed tomography scans and the Age‐Related White Matter Changes Rating Scale before therapy. The Cognitive Abilities Screening Instrument was used annually. Patients were defined as responders if their baseline Cognitive Abilities Screening Instrument score minus their follow‐up Cognitive Abilities Screening Instrument score was ≤0. Results: There was no significant difference in demographic data between responder and non‐responder groups. Patients in the responder group had significantly less involvement of WMC in the frontal area (P = 0.0213) and nearly a trend for less involvement of WMC in the basal ganglia (P = 0.1103). After adjustment for age, sex, education, polymorphism of apolipoprotein E, hypertension and diabetes, WMC in the frontal area (OR 0.446, P = 0.0139) and basal ganglia (OR 0.243, P = 0.0380) were significantly associated with a reduced therapeutic response. Conclusions: Patients with WMC in the frontal area and basal ganglia had significant decreases in their therapeutic response to donepezil. The location of WMC, independent of their severity, might be associated with the therapeutic response in patient with Alzheimer's disease. Geriatr Gerontol Int 2018; 18: 123–129. [ABSTRACT FROM AUTHOR]

Aim The presence of cerebral white matter changes (WMC) has been reported as an important predictor of the rapidity of cognitive decline in Alzheimer's disease (AD). The association between the angiotensin-converting enzyme ( ACE) insertion/deletion (I/D) polymorphism and WMC in AD is yet to be elucidated. The present study aimed to examine the association between the ACE I/D polymorphism and WMC among AD patients in Taiwan. Methods A total of 403 patients clinically diagnosed with AD were recruited in a cross-sectional study carried out in an area hospital in Kaohsiung, Taiwan. The ACE I/D polymorphism was genotyped, and cerebral white matter rating was carried out using the visual rating scale for age-related white matter changes. Results The I allele was associated with a significantly lower total age-related white matter changes scale score compared with the D allele (4.83 vs 5.93, P = 0.013). The total age-related white matter changes scale score was significantly lower for the I/I genotype than for the I/D (4.37 vs 5.87, P = 0.009) and I/D + D/D genotypes (4.37 vs 5.91, P = 0.006), with no differences observed between the I/I + I/D and the D/D genotypes (5.08 vs 6.09, P = 0.373), after adjustment for age and hypertension. A stratified analysis by sex demonstrated that the I/I genotype was associated with significant lower WMC than other genotypes in women, but not in men. Conclusions The present study supports the hypothesis that the ACE I/D polymorphism is associated with the severity of WMC in patients with AD. Patients with AD who are homozygous for the I allele might be less likely to develop WMC, especially women. Geriatr Gerontol Int 2017; 17: 945-950. [ABSTRACT FROM AUTHOR]

Aim The effects of Alzheimer's disease ( AD) are making a major impact on the socioeconomic status of older adults in society. The recognition of early symptoms and clinical presentation are crucial issues to foster early diagnosis and treatment in order to have better therapeutic outcomes. Methods We recruited clinically diagnosed AD patients at the very mild stage in the Clinical Dementia Rating scale 0.5 and mild stage Clinical Dementia Rating scale 1.0 in Taiwan and Japan. Psychometrics including the Ascertain Dementia 8 ( AD8) questionnaire were administered to collect and compare the differences of the clinical presentation of the participants from the two countries. Results A total of 1189 participants, 641 from Taiwan and 548 from Japan, were recruited in the present study. In the very mild dementia group with Clinical Dementia Rating scale 0.5, apart from AD8-2: reduced interest in hobbies/activities ( P = 0.056) and AD8-4: trouble learning how to use a tool, appliance or gadget ( P = 0.224), other AD8 subitems were significantly different between the two countries. Japanese participants had a higher reported frequency of AD8-5: forgetting the correct month or year (82.7%) than that (57.9%) in Taiwanese ( P < 0.001). Taiwanese participants had a higher reported frequency in AD8-1: problems with judgment (20.3%), AD8-3: repeats questions, stories or statements (67.5%), AD8-6: difficulty handling complicated financial affairs (32.5%); AD8-7: difficulty remembering appointments (53.8%); and AD8-8: consistent problems with thinking and/or memory (89.3%) than those in Japanese participants. Conclusion Early symptoms of AD in both countries are different. The frequently reported early symptoms are important for primary physicians and the general population so that they can recognize the disease in the early stage so as to have a better therapeutic outcome. Such efforts would increase the awareness of dementia in the general population. Geriatr Gerontol Int 2016; 16: 797-803. [ABSTRACT FROM AUTHOR]

Thirteen cases developed depression out of the 146 TGA subjects during the follow-up period with a yearly incidence rate of 23.85 per 1000 person years, while 27 cases developed depression in the 438 non-TGA subjects with a yearly incidence rate of 14.89 per 1000 person years. Although TGA patients have a high prevalence of emotional comorbid depressive symptoms and may experience a depressive mood during the TGA episode, the psychological effect is brief and does not increase long-term risk of depression after TGA. Cumulative hazard ratio of depression events by Kaplan-Meier analysis in transient global amnesia (TGA) cohort and non-TGA cohort during 8-year follow-up. [Extracted from the article]

Aim The angiotensin-converting enzyme gene ( ACE) insertion (I)/deletion (D) polymorphism is considered a biologically plausible gene for Alzheimer's disease (AD) in cross-sectional studies. The present study aimed to investigate the longitudinal effect of ACE I/D polymorphism on AD progression. Methods This 3-year observational study investigated the longitudinal effect of ACE I/D polymorphism on AD progression. Clinically diagnosed AD patients with a clinical dementia rating (CDR) of 0.5 or 1 were enrolled in the study. The Mini-Mental State Examination (MMSE), Cognitive Assessment Screening Instrument (CASI) and the CDR scale were carried out for all patients on the date of the initial interview and 36 ± 6 months after the initial evaluation. Results A total of 177 patients with sporadic AD were enrolled in this study. Among all patients, those with the I/I genotype showed a higher risk of CDR deterioration (I/I versus I/D + D/D: adjusted OR 2.103, 95% CI 1.113-3.972; adjusted P = 0.022). Among 74 AD patients without hypertension, those with the I/I genotype showed significantly greater differences in the MMSE, CASI and the CDR-sum of box scores, and a higher risk of CDR deterioration (I/I versus I/D + D/D: adjusted OR 3.255, 95% CI 1.099-9.639; adjusted P = 0.033) after adjustment for possible confounders during the 3-year follow up. Conclusions Patients with AD who were homozygous for the I allele presented with a more rapid AD deterioration than did those who had other ACE genotypes, particularly those patients without hypertension. Geriatr Gerontol Int 2017; 17: 1544-1550. [ABSTRACT FROM AUTHOR]