Metformin decelerates aging clock in male monkeys.

In a rigorous 40-month study, we evaluated the geroprotective effects of metformin on adult male cynomolgus monkeys, addressing a gap in primate aging research. The study encompassed a comprehensive suite of physiological, imaging, histological, and molecular evaluations, substantiating metformin's influence on delaying age-related phenotypes at the organismal level. Specifically, we leveraged pan-tissue transcriptomics, DNA methylomics, plasma proteomics, and metabolomics to develop innovative monkey aging clocks and applied these to gauge metformin's effects on aging. The results highlighted a significant slowing of aging indicators, notably a roughly 6-year regression in brain aging. Metformin exerts a substantial neuroprotective effect, preserving brain structure and enhancing cognitive ability. The geroprotective effects on primate neurons were partially mediated by the activation of Nrf2, a transcription factor with anti-oxidative capabilities. Our research pioneers the systemic reduction of multi-dimensional biological age in primates through metformin, paving the way for advancing pharmaceutical strategies against human aging.

CHIT1-positive microglia drive motor neuron ageing in the primate spinal cord.

Ageing is a critical factor in spinal-cord-associated disorders1, yet the ageing-specific mechanisms underlying this relationship remain poorly understood. Here, to address this knowledge gap, we combined single-nucleus RNA-sequencing analysis with behavioural and neurophysiological analysis in non-human primates (NHPs). We identified motor neuron senescence and neuroinflammation with microglial hyperactivation as intertwined hallmarks of spinal cord ageing. As an underlying mechanism, we identified a neurotoxic microglial state demarcated by elevated expression of CHIT1 (a secreted mammalian chitinase) specific to the aged spinal cords in NHP and human biopsies. In the aged spinal cord, CHIT1-positive microglia preferentially localize around motor neurons, and they have the ability to trigger senescence, partly by activating SMAD signalling. We further validated the driving role of secreted CHIT1 on MN senescence using multimodal experiments both in vivo, using the NHP spinal cord as a model, and in vitro, using a sophisticated system modelling the human motor-neuron-microenvironment interplay. Moreover, we demonstrated that ascorbic acid, a geroprotective compound, counteracted the pro-senescent effect of CHIT1 and mitigated motor neuron senescence in aged monkeys. Our findings provide the single-cell resolution cellular and molecular landscape of the aged primate spinal cord and identify a new biomarker and intervention target for spinal cord degeneration.

Salivary Antimicrobial Peptide in Patients With Dementia Before and After Clinical Oral Rehabilitation Programme: A Randomised Controlled Trial.

BACKGROUND: Emerging evidence suggests a link between salivary metabolite changes and neurodegenerative dementia, with antimicrobial peptides (AMPs) implicated in its pathogenesis. OBJECTIVE: 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). METHODS: 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. RESULTS: At the 3-month follow-up, EG showed significantly lower histatin 5 (HTN-5) levels (ß = -0.08; effect size [ES] = 0.72) than CG. At 6 months, EG exhibited improved salivary flow rate (ß = 0.89; ES = 0.89) and OHRQoL (ß = 6.99; ES = 1.31) compared to CG. Changes in salivary flow rate (ß = 4.03), HTN-5 level (ß = -0.78) and beta-defensin 2 level (BD-2) (ß = -0.91) at 3 months predicted improved OHRQoL at 6 months (all p < 0.05). CONCLUSIONS: 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.

Xanthoxylin Attenuates Lipopolysaccharide-Induced Lung Injury through Modulation of Akt/HIF-1α/NF-κB and Nrf2 Pathways.

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

Prevalence and the associated factors of cognitive impairment among people living with HIV in Taiwan: a cross-sectional study.

Cognitive impairment impacts the quality of life and increases morbidity and mortality rates. The prevalence of and factors associated with cognitive impairment have become important issues as the age of people living with HIV(PLWH) increases. In 2020, We conducted a cross-sectional study to survey the cognitive impairment among PLWH in three hospitals in Taiwan with Alzheimer Disease-8 (AD8) questionnaire. The average age of 1,111 individuals was 37.54 ± 10.46 years old, and their average duration to live with HIV was 7.12 ± 4.85 years. The rate of impaired cognitive function was 2.25% (N = 25) when AD8 score ≥ 2 was a positive finding for cognitive impairment. Aging (p = .012), being less educated (p = 0.010), and having a longer duration to live with HIV (p = .025) were significantly associated with cognitive impairment. Multivariate logistic regression analysis revealed that only the duration of living with HIV was a significant factor related to the tendency of cognitive impairment (p = .032). The risk of cognitive impairment increased by 1.098 times for every additional year to live with HIV. In conclusion, the prevalence of cognitive impairment among PLWH in Taiwan was 2.25%. Healthcare personnel should be sensitive to the changes in PLWH's cognitive function as they age.

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.

Association between pain and cognitive and daily functional impairment in older institutional residents: a cross-sectional study.

BACKGROUND: Pain is often neglected in disabled older population, especially in Taiwan where the population of institutional residents is rapidly growing. Our study aimed to investigate pain prevalence and associated factors among institutional residents to improve pain assessment and management. METHODS: This nationwide study recruited 5,746 institutional residents in Taiwan between July 2019 and February 2020. Patient self-report was considered the most valid and reliable indicator of pain. A 5-point verbal rating scale was used to measure pain intensity, with a score ranging from 2 to 5 indicating the presence of pain. Associated factors with pain, including comorbidities, functional dependence, and quality of life, were also assessed. RESULTS: The mean age of the residents was 77.1 ± 13.4 years, with 63.1% of them aged over 75 years. Overall, 40.3% of the residents reported pain, of whom 51.2% had moderate to severe pain. Pain was more common in residents with comorbidities and significantly impacted emotions and behavior problems, and the mean EQ5D score, which is a measure of health-related quality of life (p < .001). Interestingly, pain was only related to instrumental activities of daily living (IADL) and not activities of daily living (ADL). On the other hand, dementia was significantly negatively associated with pain (p < .001), with an estimated odds of 0.63 times (95% CI: 0.53-0.75) for the presence of pain when compared to residents who did not have dementia. CONCLUSIONS: Unmanaged pain is common among institutional residents and is associated with comorbidities, IADL, emotional/behavioral problems, and health-related quality of life. Older residents may have lower odds of reporting pain due to difficulty communicating their pain, even through the use of a simple 5-point verbal rating scale. Therefore, more attention and effort should be directed towards improving pain evaluation in this vulnerable population .

Developing Biomarkers for the Skin: Biomarkers for the Diagnosis and Prediction of Treatment Outcomes of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory decline and cognitive impairment. Research on biomarkers can aid in early diagnosis, monitoring disease progression, evaluating treatment efficacy, and advancing fundamental research. We conducted a cross-sectional longitudinal study to see if there is an association between AD patients and age-matched healthy controls for their physiologic skin characteristics, such as pH, hydration, transepidermal water loss (TEWL), elasticity, microcirculation, and ApoE genotyping. The study used the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating-Sum of the Boxes (CDR-SB) scales as references to quantify the presence of disease, if any. Our findings demonstrate that AD patients have a dominantly neutral pH, greater skin hydration, and less elasticity compared to the control subjects. At baseline, the tortuous capillary percentage negatively correlated with MMSE scores in AD patients. However, AD patients who carry the ApoE E4 allele and exhibit a high percentage of tortuous capillaries and capillary tortuous numbers have shown better treatment outcomes at six months. Therefore, we believe that physiologic skin testing is a rapid and effective way to screen, monitor progression, and ultimately guide the most appropriate treatment for AD patients.

The effects of caregiver characteristics on behavioral and psychological symptoms of dementia of patients with dementia.

OBJECTIVE: To determine the association between caregiver characteristics and behavioral and psychological symptoms of dementia (BPSD) in patients with dementia (PWD) in a Taiwanese community-dwelling population. METHODS: This cross-sectional study was conducted using the data of 190 patients with Alzheimer's disease/dementia and 190 informal matched caregivers in Taiwan. BPSD were examined using the Neuropsychiatric Inventory-Questionnaire (NPI-Q). Correlation and regression analyses were used to explore associations between caregiver characteristics and the presence, severity, and distress of NPI-Q items. RESULTS: Only spouse primary caregiver was positively associated with presence of delusions in PWD. Caregiver education was positively correlated to severity of hallucinations, agitation/aggression, and apathy/indifference in PWD, while child primary caregiver was positively related to severity of disinhibition in PWD but negatively related to severity of anxiety in PWD. Spouse primary caregiver was positively related to severity of anxiety and appetite/eating in PWD while sole primary caregiver was positively related to severity of anxiety and nighttime behaviors in PWD. Caregiver education was positively correlated to distress of agitation/aggression in caregivers while child primary caregiver was positively related to distress of disinhibition in caregivers. Spouse primary caregiver was positively related to distress of anxiety and appetite/eating in caregivers while spouse caregiver was positively related to distress of nighttime behaviors in caregivers. CONCLUSIONS: Caregiver education, child and spouse primary caregiver were relevant to severity of PWD and distress of caregivers of BPSD. It is suggested that healthcare professionals provide caregivers with proper individualized interventions based on these results to enhance caring quality.Key pointsCaregiver education was positively correlated to severity of hallucinations, agitation/aggression, and apathy/indifference, and distress of agitation/aggression.Child primary caregiver was positively related to severity and distress of disinhibition but negatively related to severity of anxiety.Spouse primary caregiver was positively related to severity and distress of anxiety and appetite/eating, and distress of nighttime behaviors.

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.

Clinical-based oral rehabilitation programme improved the oral diadochokinesis and swallowing function of older patients with dementia: A randomised controlled trial.

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 [ß = 0.7; effect size (ES) = 0.45], the syllables /pa/ (ß = 3.1; ES = 0.37) and /ka/ (ß = 2.7; ES = 0.40) in oral DDK, PI (ß = -0.2; ES = 0.52) and WTCI (ß = -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.

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 Long-Term Risk of Dementia after Transient Global Amnesia: A Population-Based Cohort Study in Taiwan.

BACKGROUND: Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of larger anterograde and milder retrograde amnesia that lasts up to 24 h. OBJECTIVES: We aimed to investigate the long-term risk of dementia up to 8 years in subjects with TGA. METHOD: We conducted a control cohort study using the Taiwan National Health Insurance Research database from 2005 to 2012 with an 8-year follow-up period. From all potential participants >18 years of age without dementia history, we identified TGA subjects and non-TGA controls with age, gender and comorbidities matched in a 1:3 ratio. The yearly incidence of dementia was compared in TGA and non-TGA cohorts. The cumulative hazard ratio (HR) of dementia was estimated. The risk factors of dementia after TGA were investigated. RESULTS: A total of 181 TGA subjects and 543 non-TGA controls were included in the study. There were 14 dementia cases in the 181 TGA cohorts during the follow-up period with yearly incidence rates of 20.14 per 1,000 person. The adjusted HR for dementia in TGA cohorts was 2.23 (95% CI 1.12-4.44, p = 0.023) compared with non-TGA cohorts after adjusting for age, gender and comorbidities. Age and diabetes were significantly associated with dementia in TGA. CONCLUSIONS: TGA increased the long-term risk of dementia. Age and diabetes were notable factors associated with dementia after TGA.

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.

Hormone therapy for prostate cancer increases the risk of Alzheimer's disease: a nationwide 4-year longitudinal cohort study.

INTRODUCTION: Androgen-deprivation therapy (ADT) is recognized to be the preferred first-line treatment for advanced prostate cancer. However, the risk-benefit ratio of ADT remains poorly defined and the relationship between androgen depletion and dementia is not clear. AIM: To investigate the risk of developing Alzheimer's disease (AD) in patients undergoing ADT for prostate cancer. METHODS: Data from 24 360 prostate cancer patients were collected from the Longitudinal Health Insurance Database of Taiwan. In total, 15 959 patients who underwent ADT were included in the study cohort, and another 8401 patients who did not receive ADT were included as a non-ADT cohort. RESULTS: During the average 4-year follow-up period, the incidence of AD was 2.78 per 1000 person-years in the non-ADT cohort and 5.66 per 1000 person-years in the ADT cohort. After adjusting for age and all comorbidities, the combined ADT cohort was found to be 1.84 times more likely to develop AD than the non-ADT control group (95%CI 1.33-2.55, p < 0.001). CONCLUSIONS: The present results suggest that ADT use is associated with an increased risk of developing AD.

Cilostazol as an add-on therapy for patients with Alzheimer's disease in Taiwan: a case control study.

BACKGROUND: Combination therapy using acetylcholinesterase inhibitors (AChEIs) and cilostazol is of unknown efficacy for patients with Alzheimer's disease (AD). METHODS: We explored the therapeutic responses by using a case-control study, which was conducted in Taiwan. We enrolled 30 participants with stable AD who were receiving cilostazol (50 mg) twice per day as an add-on therapy combined with AChEIs, and 30 participants as controls who were not receiving cilostazol as an add-on therapy. The therapeutic responses were measured using neuropsychological assessments and analyzed in relation to cilostazol use, apolipoprotein E genotype, and demographic characteristics. Mini-mental state examination (MMSE) and clinical dementia rating sum of boxes (CDR-SB) were administered at the outset of the study and 12 months later. Multiple logistic regression analysis was used to estimate the association between the therapeutic response and cilostazol use. RESULTS: For the therapeutic indicator of cognition, Cilostazol use (adjusted odds ratio (aOR) = 0.17, 95% confidence interval (CI) = 0.03-0.80), initial CDR-SB score (aOR = 2.06, 95% CI = 1.31-3.72), and initial MMSE score (aOR = 1.41, 95% CI = 1.11-1.90), but not age, sex, education, or ApoE ε4 status, were significantly associated with poor therapeutic outcomes. For the therapeutic indicator of global status, no significant association was observed between the covariates and poor therapeutic outcomes. CONCLUSIONS: Cilostazol may reduce the decline of cognitive function in stable AD patients when applied as an add-on therapy.

Impact of Alzheimer's Disease in Nine Asian Countries.

BACKGROUND: Asia will soon have the majority of demented patients in the world. OBJECTIVE: To assess dementia using a uniform data system to update the current status of dementia in Asia. METHODS: A uniformed data set was administered in Taiwan, China, Hong Kong, Korea, Japan, Philippines, Thailand, Singapore, and Indonesia to gather data with regard to Alzheimer's disease (AD) and its related issues for these countries. RESULTS: In total, 2,370 AD patients and their caregivers were recruited from 2011 to 2014. The demographic characteristics of these patients and the relationships between patients and caregivers were different among individuals in these countries (p < 0.001). Of note, the family history for having dementia was 8.2% for females in contrast to 3.2% for males. CONCLUSION: Our study highlighted the differences in dementia assessment and care in developing versus developed countries. Greater effort with regard to studying dementia, especially in developing countries, is necessary.