Assessment of High Risk for Alzheimer's Disease Using Plasma Biomarkers in Subjects with Normal Cognition in Taiwan: A Preliminary Study.

BACKGROUND: In Alzheimer's disease (AD), cognitive impairment begins 10-15 years later than neurodegeneration in the brain. Plasma biomarkers are promising candidates for assessing neurodegeneration in people with normal cognition. It has been reported that subjects with the concentration of plasma amyloid-ß 1-42×total tau protein higher than 455 pg2/ml2 are assessed as having a high risk of amnesic mild impairment or AD, denoted as high risk of AD (HRAD). OBJECTIVE: The prevalence of high-risk for dementia in cognitively normal controls is explored by assaying plasma biomarkers. METHODS: 422 subjects with normal cognition were enrolled around Taiwan. Plasma Aß1-40, Aß1-42, and T-Tau levels were assayed using immunomagnetic reduction to assess the risk of dementia. RESULTS: The results showed that 4.6% of young adults (age: 20-44 years), 8.5% of middle-aged adults (age: 45-64 years), and 7.3% of elderly adults (age: 65-90 years) had HRAD. The percentage of individuals with HRAD dramatically increased in middle-aged and elderly adults compared to young adults. CONCLUSION: The percentage of HRAD in cognitively normal subjects are approximately 10%, which reveals that the potentially public-health problem of AD in normal population. Although the subject having abnormal levels of Aß or tau is not definitely going on to develop cognitive declines or AD, the risk of suffering cognitive impairment in future is relatively high. Suitable managements are suggested for these high-risk cognitively normal population. Worth noting, attention should be paid to preventing cognitive impairment due to AD, not only in elderly adults but also middle-aged adults.

Human platelet lysate biotherapy for traumatic brain injury: preclinical assessment.

Traumatic brain injury (TBI) leads to major brain anatomopathological damages underlined by neuroinflammation, oxidative stress and progressive neurodegeneration, ultimately leading to motor and cognitive deterioration. The multiple pathological events resulting from TBI can be addressed not by a single therapeutic approach, but rather by a synergistic biotherapy capable of activating a complementary set of signalling pathways and providing synergistic neuroprotective, anti-inflammatory, antioxidative, and neurorestorative activities. Human platelet lysate might fulfil these requirements as it is composed of a plethora of biomolecules readily accessible as a TBI biotherapy. In the present study, we tested the therapeutic potential of human platelet lysate using in vitro and in vivo models of TBI. We first prepared and characterized platelet lysate from clinical-grade human platelet concentrates. Platelets were pelletized, lysed by three freeze-thaw cycles, and centrifuged. The supernatant was purified by 56°C 30 min heat treatment and spun to obtain the heat-treated platelet pellet lysate that was characterized by ELISA and proteomic analyses. Two mouse models were used to investigate platelet lysate neuroprotective potential. The injury was induced by an in-house manual controlled scratching of the animals' cortex or by controlled cortical impact injury. The platelet lysate treatment was performed by topical application of 60 µl in the lesioned area, followed by daily 60 µl intranasal administration from Day 1 to 6 post-injury. Platelet lysate proteomics identified over 1000 proteins including growth factors, neurotrophins, and antioxidants. ELISA detected several neurotrophic and angiogenic factors at ∼1-50 ng/ml levels. We demonstrate, using two mouse models of TBI, that topical application and intranasal platelet lysate consistently improved mouse motor function in the beam and rotarod tests, mitigated cortical neuroinflammation, and oxidative stress in the injury area, as revealed by downregulation of pro-inflammatory genes and the reduction in reactive oxygen species levels. Moreover, platelet lysate treatment reduced the loss of cortical synaptic proteins. Unbiased proteomic analyses revealed that heat-treated platelet pellet lysate reversed several pathways promoted by both controlled cortical impact and cortical brain scratch and related to transport, postsynaptic density, mitochondria or lipid metabolism. The present data strongly support, for the first time, that human platelet lysate is a reliable and effective therapeutic source of neurorestorative factors. Therefore, brain administration of platelet lysate is a therapeutical strategy that deserves serious and urgent consideration for universal brain trauma treatment.

Dementia screening for elderly in-patients and its association with nursing care satisfaction-an observational study.

Inappropriate care for patients with cognitive dysfunction in the hospital could worsen quality of care and medical service satisfaction.All elderly participants were recruited from acute wards of 5 departments in an university hospital. They were administered the Chinese version of Ascertain Dementia 8 (AD8) at admission and the Nursing Service Satisfaction Questionnaire before discharge.A total of 345 participants completed the study. There were 91 (26.4%) participants with AD8 ≥ 2, the cut-off value of high risk of dementia. The prevalence was much higher than prior community-based reports. The Nursing Service Satisfaction Score was significantly lower in AD8 ≥ 2 than in AD8 < 2 (56.99 ±â€Š0.94 vs 60.55 ±â€Š0.48, P < .01).Using AD8 in hospital-based screening might be more efficient than in the community in terms of cost-effectiveness due to higher positive rate and easier approach to diagnostic facilities. AD8 ≥ 2 is also an indicator to identify care dissatisfaction among inpatients. By identifying patients with cognitive dysfunction, such as its related communication barriers, care systems could be tailored for more friendly services.

Increased diabetes risk and interaction with social and medical events in patients upon stroke: Two nationwide studies.

BACKGROUND & AIMS: The relationship between stroke and diabetes is not completely understood. This study evaluated diabetes risk and post-diabetes adverse events in patients with stroke. METHODS: We identified 10,255 adults, newly diagnosed with stroke from 2000 to 2005, using the Taiwan's National Health Insurance Research Database. A comparison cohort of 41,020 adults without stroke was randomly selected from the same dataset, frequency matched by age and sex. Diabetes events from 2000 to 2013 were ascertained from medical claims. Adjusted hazard ratios (HRs) and 95% CIs were calculated for diabetes associated with stroke. A nested cohort study of 33,437 patients with inpatient care for diabetes between 2008 and 2013 was conducted to calculate the adjusted odds ratios (ORs) and 95% CIs for adverse events after diabetes, in patients with and without stroke. RESULTS: During 489,561 person-years of follow-up, there were 10,742 newly diagnosed diabetes cases. The incidence of diabetes for people with and without stroke was 43.9 and 17.8 per 1000 person-years, respectively (p < 0.0001). Compared to that for people without stroke, the adjusted HR for diabetes was 2.69 (95% CI 2.56-2.82) for stroke patients. The ORs of post-diabetes pneumonia, urinary tract infection, and mortality associated with stroke were 1.35 (95% CI 1.17-1.55), 1.52 (95% CI 1.36-1.70), and 1.71 (95% CI 1.27-2.29), respectively. CONCLUSIONS: We provide evidence that the consequences of stroke are not limited to the neurological defect, but evoke diabetes and a plethora of associated medical, psychological and social impacts the physician must be strongly aware of if evaluating and treating stroke patients.

Dynamic Cerebral Autoregulation Assessment Using Extracranial Internal Carotid Artery Doppler Ultrasonography.

Transcranial Doppler ultrasonography of the middle cerebral artery (MCA) is frequently used to assess dynamic cerebral autoregulation (dCA); however, this is difficult in patients with poor temporal bone windows. In the study described here, we investigated the agreement and sensitivity of dCA indices determined from the extracranial internal carotid artery (ICA) and those determined from the MCA. Measurements for 32 stroke patients and 59 controls were analyzed. Measurement of the mean flow correlation index (Mx) and transfer function analysis based on spontaneous blood pressure fluctuation were simultaneously performed for the extracranial ICA and MCA. The mean values of Mx and phase shift did not significantly differ between the ICA and MCA (mean difference: Mx = 0.01; phase shift of very low frequency [VLF] = 0.7°, low frequency [LF] = 3.3° and high frequency = 4.5°), but the gains in VLF and LF in the ICA were significantly lower than those in the MCA (mean difference: gain of VLF = -0.13, gain of LF = -0.10). The intra-class correlation coefficient between the dCA indices of the ICA and MCA was favorable in Mx (0.76) and the phase shift of VLF (0.72). The area under the receiver operating characteristic curve for stroke diagnosis did not differ among the dCA indices. We conclude that dCA assessed from the ICA is as effective as that from the MCA, but the results are not interchangeable.

Using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) for Predicting Institutionalization of Patients With Dementia in Taiwan.

World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is an assessment tool and it has been applied for disability status assessment of Taiwanese dementia patients since July 2012. The aim of this study was to investigate the predicting accuracy of WHODAS 2.0 for institutionalization of dementia patients.Of these patients, 13,774 resided in a community and 4406 in a long-term care facility. Demographic data and WHODAS 2.0 standardized scores were analyzed using the Chi-square test and independent t test to compare patients with dementia in an institution with those in a community. The receiver operating characteristic (ROC) curve was applied to investigate accuracy in predicting institutionalization, and the optimal cutoff point was determined using the Youden index. Binary logistic regression was used to analyze variables to determine risk factors for the institutionalization of patients with dementia.WHODAS 2.0 scores in all domains were higher in patients with dementia in a long-term care facility than in those in a community (P < 0.01). The ROC curve showed moderate accuracy for all domains of WHODAS 2.0 (area under curve 0.6~0.8). Binary logistic regression revealed that the male gender, severity of disease, and standardized WHODAS 2.0 scores surpassing the cutoff values were risk factors for the institutionalization of patients with dementia.Although the accuracy of WHODAS 2.0 in predicting institutionalization is not considerably high for patients with dementia, our study found that the WHODAS 2.0 scores, the male gender, education status, urbanization level, and severity of disease were risk factors for institutionalization in long-term care facilities.

High risk of gastrointestinal hemorrhage in patients with epilepsy: a nationwide cohort study.

OBJECTIVE: To examine the association between epilepsy and gastrointestinal hemorrhage. PATIENTS AND METHODS: We conducted a nationwide retrospective cohort study by using data from Taiwan's National Health Insurance Research Database. Patients 20 years and older newly diagnosed as having epilepsy and nonepileptic adults were identified between January 1, 2000, and December 31, 2003, and were observed through December 31, 2008. Cox proportional hazards models were performed to calculate adjusted hazard ratios (HRs) and 95% CIs of gastrointestinal hemorrhage associated with epilepsy. RESULTS: Compared with the nonepileptic group (n=449,541), epileptic patients (n=1412) had a higher incidence of gastrointestinal hemorrhage (13.4 vs 2.9 per 1000 person-years), with an HR of 2.97 (95% CI, 2.49-3.53). The HRs of gastrointestinal hemorrhage for patients with generalized epilepsy, inpatient care, emergency care, and frequent outpatient visits for epilepsy were 3.50 (95% CI, 2.59-4.72), 3.96 (95% CI, 2.85-5.50), 4.35 (95% CI, 3.15-6.01), and 4.96 (95% CI, 3.97-6.21), respectively. Risks were significantly higher in epileptic patients with mental disorders (HR, 3.20; 95% CI, 2.55-4.01), aged 70 years and older (HR, 4.08; 95% CI, 2.89-5.77), and in the first year after epilepsy (HR, 4.81; 95%, CI, 3.14-7.34). CONCLUSION: Epilepsy is an independent determinant for gastrointestinal hemorrhage in a chronological and severity-dependent pattern. We urge the development of an adequate surveillance policy and strategy for the early prevention of gastrointestinal hemorrhage in epileptic patients.

Risk of epilepsy after traumatic brain injury: a retrospective population-based cohort study.

OBJECTIVE: To investigate the associated risk of epilepsy after traumatic brain injury (TBI) in a population-based retrospective cohort study. METHODS: Using Taiwan's National Health Insurance Research Database of reimbursement claims, we conducted a retrospective cohort study of 19 336 TBI patients and 540 322 non-TBI participants aged ≥15 years as reference group. Data on newly developed epilepsy after TBI with 5-8 years' follow-up during 2000 to 2008 were collected. HRs and 95% CIs for the risk of epilepsy associated with TBI were analysed with multivariate Cox proportional hazards regressions. RESULTS: Compared with the non-TBI cohort, the adjusted HRs of developing epilepsy among TBI patients with skull fracture, severe or mild brain injury were 10.6 (95% CI 7.14 to 15.8), 5.05 (95% CI 4.40 to 5.79) and 3.02 (95% CI 2.42 to 3.77), respectively. During follow-up, men exhibited higher risks of post-TBI epilepsy. Patients who had mixed types of cerebral haemorrhage were at the highest risk of epilepsy compared with the non-TBI cohort (HR 7.83, 95% CI 4.69 to 13.0). The risk of post-TBI epilepsy was highest within the first year after TBI (HR 38.2, 95% CI 21.7 to 67.0). CONCLUSIONS: The risk of epilepsy after TBI varied by patient gender, age, latent interval and complexity of TBI. Integrated care for early identification and treatment of post-trauma epilepsy were crucial for TBI patients.

The impact factors on the cost and length of stay among acute ischemic stroke.

BACKGROUND: Understanding hospital costs and length of stay (LOS) can optimize the in-hospital management of acute stroke. We investigated cost and LOS in first-ever and recurrent stroke patients in Taiwan. METHODS: Data were examined in patients at Chang Gung Memorial Hospital in Chiayi County of Taiwan from April 1, 2008, to March 31, 2010 [corrected]. Predictors of hospital cost and LOS in these patients were studied. RESULTS: The study included 1021 patients with 1084 stroke episodes. Mean age was 68.1 ± 10.8 years (range: 32-93). The average cost was NTD$45,709.30 ± NTD$66,697.40 (US$1408.70 ± US$2084.30; US$1 = NTD$32) and average LOS was 13.9 ± 14.1 days (range: 1-129). After multivariate regression analysis, the significant predictive factors for cost were LOS, smoking, and medication for secondary prevention. The significant predictive factors for LOS were diabetes mellitus, atrial fibrillation, recurrence, and stroke subtype. CONCLUSIONS: Age 65 and over, atrial fibrillation, stroke treatment, and subtypes were the significant predictive factors affecting hospital costs and LOS. Compared to other countries, Taiwan spent the least while Canada had the highest expense. The United States had the shortest LOS (6 days) in contrast to Canada with the longest LOS (34-47 days). Regarding mean daily cost of stroke, the United States had the highest cost per day while China spent the least.

Postoperative adverse outcomes in surgical patients with dementia: a retrospective cohort study.

BACKGROUND: Dementia patients often present with coexisting medical conditions and potentially face higher risk of complications during hospitalization. Because the general features of postoperative adverse outcomes among surgical patients with dementia are unknown, we conducted a nationwide, retrospective cohort study to characterize surgical complications among dementia patients compared with sex- and age-matched nondementia controls. METHODS: Reimbursement claims from the Taiwan National Health Insurance Research Database were studied. A total of 18,923 surgical patients were enrolled with preoperative diagnosis of dementia for 207,693 persons aged 60 years or older who received inpatient major surgeries between 2004 and 2007. Their preoperative comorbidities were adjusted and risks for major surgical complications were analyzed. RESULTS: Dementia patients who underwent surgery had a significantly higher overall postoperative complication rate, adjusted odds ratio (OR) 1.79 (95 % confidence interval [CI] 1.72-1.86), with higher medical resources use, and in-hospital expenditures. Compared with controls, dementia patients had a higher incidence of certain postoperative complications that are less likely to be identified in their initial stage, such as: acute renal failure, OR = 1.32 (1.19-1.47); pneumonia, OR = 2.18 (2.06-2.31); septicemia, OR = 1.8 (1.69-1.92); stroke, OR = 1.51 (1.43-1.6); and urinary tract infection, OR = 1.62 (1.5-1.74). CONCLUSIONS: These findings have specific implications for postoperative care of dementia patients regarding complications that are difficult to diagnose in their initial stages. Acute renal failure, pneumonia, septicemia, stroke, and urinary tract infection are the top priorities for prevention, early recognition, and intervention of postoperative complications among surgical patients with dementia. Further efforts are needed to determine specific protocols for health care teams serving this population.