Association Between Polymorphisms in Dopamine-Related Genes and Orthopedic Pain Expression in a Chinese Elderly Population.

OBJECTIVES: The dopaminergic pathway plays a vital role in pain expression. Here, our aim was to investigate the effects of polymorphisms in genes encoding the dopamine active transporter (SLC6A3) and dopamine receptor D2 (DRD2) on preoperative pain expression among patients preparing for orthopedic surgery. METHODS: Chinese elderly patients scheduled for orthopedic surgery were enrolled. The VAS was used to evaluate pain intensity (score range 0 to 10; 0 = no pain; 10 = worst pain possible). Depressive symptoms were evaluated via the 15-item Geriatric Depression Scale. DNA was isolated from venous blood samples, and single-nucleotide polymorphisms of SLC6A3 and DRD2 were genotyped. Multiple linear regressions analyses were carried out to adjust the results for confounders. RESULTS: A total of 294 patients with a mean age of 73.82 ± 8.03 years were enrolled in this study. After adjustment for confounders, rs393795 in SLC6A3 showed a significant association with preoperative VAS scores. Patients with the A/A genotype reported lower mean pain scores than did those with the A/C genotype (P = 0.026). Subsequent depression-stratified analysis of rs6276 in DRD2 revealed that patients with the A/A genotype had higher pain scores than did those with the G/G genotype (P = 0.043). No associations were found for DRD2 rs6277 in the whole study population or depression-stratified groups. CONCLUSION: Genetic variations in SLC6A3 and DRD2 may play an important role in pain expression among the elderly prior to orthopedic surgery.

Epidemiology of benign essential blepharospasm: A nationwide population-based retrospective study in Taiwan.

IMPORTANCE: This study provides a nationwide, population-based data on the incidence of benign essential blepharospasm in Asian adults. BACKGROUND: To describe the incidence, patient demographics, and risk factors associated with benign essential blepharospasm. DESIGN: Population-based retrospective study. PARTICIPANTS AND SAMPLES: A total of 1325 patients with benign essential blepharospasm were identified. METHODS: Patients with diagnosis of blepharopsasm between January 2000 and December 2013 were sampled using the Longitudinal Health Insurance Database 2000. Secondary blepharospasm that may be related to neurological, trauma, and ocular surface disease were excluded. MAIN OUTCOME MEASURED: Multivariate conditional logistic regression was used to estimate the odds ratios for potential risk factors of benign essential blepharospasm. RESULTS: The mean annual incidence was 0.10‰ (0.07‰ for males, and 0.12‰ for females). The peak incidence was in the 50 to 59-year-old age group (0.19‰). People living in urban regions have more risk of developing blepharospasm comparing to people living in less urban regions (p <0.01). White-collar workers also have higher chance of having blepharospasm (p<0.001). Significant difference between control group and case group in hyperlipidemia (p <0.001), sleep disorders (p <0.001), mental disorders (depression, anxiety, obsessive compulsive disorder) (p <0.001), dry eye-related diseases (dry eye, Sjögren's syndrome) (p <0.001), Parkinson's disease (p <0.004), and rosacea (p <0.021) were also identified. CONCLUSIONS AND RELEVANCE: Higher level of urbanization, white-collar work, sleep disorders, mental health diseases, dry eye-related diseases, Parkinsonism, and rosacea are possible risk factors for benign essential blepharospasm.

Decreased IL-1ra and NCAM-1/CD56 Serum Levels in Unmedicated Patients with Schizophrenia Before and After Antipsychotic Treatment.

OBJECTIVE: Schizophrenia (SZ) has been associated with the inflammatory-related and immunological pathogenesis. This study investigates the aberration of cytokines in patients with SZ. METHODS: Thirty patients with SZ without antipsychotic treatment for at least two weeks participated. We measured the serum levels of fourteen cytokines at hospital admission and after 8-week antipsychotic treatment. Severity was measured by expanded version of 24-items brief psychiatric rating scale (BPRS-E). Repeated measure analyses of variance were conducted. RESULTS: The interleukin-1 receptor antagonist (IL-1ra) was significantly decreased after 8-week antipsychotic treatment than those of before antipsychotic treatment (F=12.15, df=1/30, p=0.002). Neural cell adhesion molecule 1/CD56 (NCAM-1/CD56) was significantly decreased (F=6.61, df=1/30, p=0.016) among those with second-generation antipsychotics but not first-generation antipsychotics treatment. The changes of BPRS-E-manic and BPRS-E-anxiety scores correlated with the baseline IL-1ra (r=-0.393), IL-6 (r=-0.407), and insulin like growth factor binding protein 3 (r=-0.446). Additionally, the changes of BPRS-E and BPRS-E-negative scores correlated with the changes of brain-derived neurotrophic factor (r=0.372) and interferon-gamma (r=0.375). CONCLUSION: Our study supports that IL-1ra and NCAM-1/CD56 may be considered as markers of developing SZ.

Serum nerve growth factor beta, brain- and glial-derived neurotrophic factor levels and psychopathology in unmedicated patients with schizophrenia.

BACKGROUND: There is accumulating evidence that neurotrophic factors may be involved in the pathophysiology of patients with schizophrenia. This study aimed to explore the relationship between serum nerve growth factor beta (NGF-beta), brain-derived neurotrophic factor (BDNF), and glial-derived neurotrophic factor (GDNF) levels and psychopathology in unmedicated patients with schizophrenia. METHODS: Serum NGF-beta, BDNF, and GDNF levels were determined using enzyme-linked-immunosorbent assay (ELISA) in the serum of 30 unmedicated patients with schizophrenia. Symptomatology was assessed with the expanded version of the 24-items brief psychiatric rating scale (BPRS-E), which was divided into four conceptual domains: manic excitement/disorganization, depression/anxiety, negative symptoms, and positive symptoms. Kolmogorov-Smirnov one sample test was performed to test non-parametric variables. Spearman's correlation was performed to examine the correlations between the cytokines of interest and psychopathology. Benjamini-Hochberg procedure was applied for multiple corrections. RESULTS: Serum GDNF levels correlated negatively with the BPRS-total (r = -0.533, corrected p = 0.002) and BPRS-manic (r = -0.456, corrected p = 0.011) subtests. BDNF levels showed a positive correlation with BPRS-total (r = 0.480, corrected p = 0.007). In addition, NGF-beta did not associate with psychopathology measured by BPRS scores. CONCLUSION: Neurotrophic factors play a vital role in the regulation of neuroplasticity and neurogenesis in humans. This study suggests that BDNF and GDNF may be contributing to the pathological mechanisms involved in unmedicated patients with schizophrenia.

Mini-Nutritional Assessment Short-Form as a useful method of predicting poor 1-year outcome in elderly patients undergoing orthopedic surgery.

AIM: The present study aimed to determine whether the Mini-Nutritional Assessment Short-Form (MNA-SF) can predict the 1-year outcome of orthopedic fracture surgery in elderly patients. METHODS: This 1-year prospective study assessed nutrition using the MNA-SF at baseline, and postoperatively at 6 and 12 months. Repeated measures analysis of covariance was used to examine functional change over time for two MNA-SF categories. Multivariable logistic regression analysis with forward stepwise modeling was carried out to identify risk factors of functional decline, emergency department visit, hospital readmission and mortality at follow up. RESULTS: There were 312 participants, 11 of whom died (3.53%) during 1-year follow up. The mean age was 74.04 ± 7.65 years. A total of 88.1% and 11.9% of the participants were well nourished (MNA-SF 12-14 points) or at risk of undernutrition (0-11 points), respectively. For MNA-SF as a continuous variable, lower MNA-SF scores were associated with a significantly higher risk of emergency department visit at 6-month follow up, and mortality at 12-month follow up (emergency room visit, adjusted odds ratio 0.78, 95% CI 0.63-0.96, P < 0.05; mortality, adjusted odds ratio 0.73, 95% CI 0.57-0.94, P < 0.05). No association was found between functional decline and hospital readmission, and MNA-SF scores. For MNA-SF categories, functional decline was more profound in patients at risk of undernutrition than in well-nourished patients, especially 6-12 months postoperatively. CONCLUSIONS: The MNA-SF could be an effective and non-invasive preoperative screening tool to predict functional decline, emergency department visit and mortality during the year after surgery. Geriatr Gerontol Int 2017; 17: 2361-2368.

Serum DHEA-S concentration correlates with clinical symptoms and neurocognitive function in patients with bipolar II disorder: A case-controlled study.

OBJECTIVES: Dysregulation of the neuroendocrine system including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and pregnenolone may play a role in the pathophysiology of bipolar II disorder (BP-II). The aims of the current study are to determine (a) the differences in DHEA, DHEA-S and pregnenolone in patients with BP-II and controls; and (b) the correlation of levels of the above hormones, cognitive function, and clinical symptoms. METHODS: Patients diagnosed with BP-II and healthy controls were recruited from psychiatric department. Blood samples were collected to measure the levels of DHEA, DHEA-S and pregnenolone in all participants, followed by assessment of cognitive function using the Brief Assessment of Cognition in Affective Disorders (BACA). RESULTS: A total of 32 patients BP-II and 30 healthy control subjects were recruited. The BP-II group was found with significantly elder age, fewer years of education, and lower BACA composite scores compared to the healthy controls. The level of DHEA-S was significantly associated with performance in BACA when controlling for age, gender, years of education and having BP-II (P=0.018). The DHEA-S level was significantly correlated with mania score (r=-0.498, P=0.010). CONCLUSION: Our findings support that serum level of DHEA-S may be a biomarker representing clinical manic symptoms and cognitive performance.

Lack of Association between Pre-Operative Insulin-Like Growth Factor-1 and the Risk of Post-Operative Delirium in Elderly Chinese Patients.

OBJECTIVE: Postoperative delirium (POD) is a highly prevalent complex neuropsychiatric syndrome in elderly patients. However, its pathophysiology is currently unknown. Early detection and prevention of POD is important; therefore, the aim of this study was to investigate the link between preoperative insulin growth factor 1 (IGF-1) levels in the serum and POD in the Chinese elderly patients. METHODS: One hundred and three patients who were undergoing an orthopedic operation took part in the study. Preoperative serum IGF-1 levels were measured. POD was determined daily using the Confusion Assessment Method (CAM) and DSM-IV TR. Baseline serum IGF-1 levels were compared between patients who did and did not develop POD. Correlation coefficients were calculated to evaluate relationship between baseline characteristics and serum IGF-1 levels. The relationship between baseline biomarkers and delirium status was investigated using logistic regression analysis, adjusting for potential confounding variables. RESULTS: Twenty-three patients developed POD. The POD group had lower MMSE scores and higher CCI scores and proportions of acute admission. Preoperative serum IGF-1 levels were correlated with MMSE scores and age (MMSE: r=0.230, p<0.05; age: r=-0.419, p<0.001). Baseline serum IGF-1 levels did not differ between patients who did and did not develop POD, even after adjusting for potential confounding factors, MMSE score, and age. CONCLUSION: No association was found between preoperative IGF-1 levels and POD, suggesting that they are not direct biomarkers of the incidence of POD among the Chinese elderly population. Further research with larger sample sizes is warranted to clarify the relationship.

Short-Form Mini Nutritional Assessment as a useful method of predicting the development of postoperative delirium in elderly patients undergoing orthopedic surgery.

OBJECTIVE: Postoperative delirium (POD) is a major cause for concern among elderly patients undergoing surgery, often resulting in poor outcome. It is therefore important to predict and prevent POD. The aim of this study was to evaluate the Mini Nutritional Assessment Short-Form (MNA-SF) as a predictor of POD after orthopedic surgery. METHODS: Elderly patients undergoing orthopedic surgery between April 2011 and March 2013 were included in the study (n=544; mean age, 74.24 ± 7.92 years). The MNA-SF was used to evaluate preoperative nutritional status. Delirium was assessed daily after surgery using the confusion assessment method. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria were used to confirm delirium diagnosis. Univariate and multivariate logistic regression analyses were performed to identify key factors associated with POD. RESULTS: POD occurred in 52 patients (9.6%). According to the MNA-SF, 17.5% of subjects were at risk of undernutrition. Adjusting for all potential factors in the final model, age, male gender and lower Mini-Mental State Examination and higher Charlson Comorbidity Index scores were associated with significantly increased likelihood of POD. Subjects who were identified preoperatively as at risk of undernutrition were 2.85 times more likely to develop POD compared to normally nourished subjects (odds ratio: 2.85, 95% confidence interval: 1.19-6.87). CONCLUSIONS: These results suggest that the MNA-SF is a simple and effective tool that can be used to predict incident delirium in elderly patients after orthopedic surgery.

Developing a Prediction Model for Post-Operative Delirium and Long-Term Outcomes Among Older Patients Receiving Elective Orthopedic Surgery: A Prospective Cohort Study in Taiwan.

This study aimed to develop a prediction model for post-operative delirium among older patients receiving elective orthopedic surgery and to evaluate its effectiveness in predicting long-term health outcomes. This prospective cohort study screened all subjects aged over 60 years who were admitted for elective orthopedic surgery in a tertiary medical center in Taiwan from April, 2011, to December, 2013. Demographic characteristics, surgery-related factors, and results of comprehensive geriatric assessment (CGA) were all used to develop the prediction model. Long-term health outcomes, including mortality, nursing home admission, and functional status in the first year after surgery, were used to further evaluate the effectiveness of the prediction model. Overall, 461 patients (median age, 73 years; interquartile range [IQR], 67-80 years; 42.3% males) were enrolled, and 37 patients (8.0%) developed post-operative delirium. Prediction models were developed on the basis of demographic characteristics and surgery-related factors (model 1) and of demographic characteristics, surgery-related factors, and geriatric assessment variables (model 2). Although both models effectively predicted the occurrence of post-operative delirium, duration of post-operative delirium, total hospital days, nursing home admission, and mortality, model 2 was more likely to differentiate cases with functional decline during the first year after surgery. In conclusion, a prediction model developed by using demographic characteristics, surgery-related factors, and results of CGA was highly predictive for post-operative delirium, as well as long-term health and functional outcomes.

Interrelationship of postoperative delirium and cognitive impairment and their impact on the functional status in older patients undergoing orthopaedic surgery: a prospective cohort study.

BACKGROUND: The impact of postoperative delirium on post-discharge functional status of older patients remains unclear, and little is known regarding the interrelationship between cognitive impairment and post-operative delirium. Therefore, the main purpose was to evaluate the post-discharge functional status of patients who experience delirium after undergoing orthopaedic surgery and the interrelationship of postoperative delirium with underlying cognitive impairment. METHOD: This prospective cohort study, conducted at a tertiary care medical center from April 2011 to March 2012, enrolled all subjects aged over 60 years who were admitted for orthopaedic surgery. The baseline characteristics (age, gender, BMI, and living arrangement), surgery-related factors (ASA class, admission type, type of surgery, and length of hospital stay), results of geriatric assessment (postoperative delirium, cognition, depressive mood, comorbidity, pain, malnutrition, polypharmacy, ADL, and instrumental [I]ADL) and 1-12-month postoperative ADL and IADL functional status were collected for analysis. RESULTS: Overall, 9.1% of 232 patients (mean age: 74.7 ± 7.8 years) experienced postoperative delirium, which was significantly associated with IADL decline at only 6 and 12 months postoperatively (RR: 6.22, 95% CI: 1.08-35.70 and RR: 12.54, 95% CI: 1.88-83.71, respectively). Delirium superimposed on cognitive impairment was a significant predictor for poor functional status at 6 and 12 months postoperatively (RR: 12.80, 95% CI: 1.65-99.40 for ADL at the 6th month, and RR: 7.96, 95% CI: 1.35-46.99 at the 12th month; RR: 13.68, 95% CI: 1.94-96.55 for IADL at the 6th month, and RR: 30.61, 95% CI: 2.94-318.54 at the 12th month, respectively). CONCLUSION: Postoperative delirium is predictive of IADL decline in older patients undergoing orthopaedic surgery, and delirium superimposed on cognitive impairment is an independent risk factor for deterioration of ADL and IADL functional status. Early identification of cognitive function and to prevent delirium are needed to improve functional status following orthopaedic surgery.

Decreased plasma brain-derived neurotrophic factor levels in institutionalized elderly with depressive disorder.

OBJECTIVES: To compare the differences in plasma brain-derived neurotrophic factor (BDNF) levels among institutionalized ethnic Chinese elderly participants with major depression, those with subclinical depression, and a nondepressed control group. DESIGN: A cross-sectional study. SETTING: The veterans' home in southern Taiwan. PARTICIPANTS: One hundred sixty-seven residents. MEASUREMENTS: Questionnaires including the Minimum Data Set Nursing Home 2.1, Chinese-language version, and the short-form Geriatric Depression Scale, Chinese-language version. Depressive disorder was diagnosed by a well-trained psychiatrist using DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision) criteria. We measured plasma BDNF levels in the following 3 groups: nondepressive subjects (n = 122), subclinically depressive subjects (n = 33), and subjects with major depression (n = 12). Plasma BDNF was assayed using the sandwich ELISA method. RESULTS: We noted a significantly negative association between age and plasma BDNF in the regression model. There was no significant correlation between BDNF plasma levels and body weight or platelet counts. We found that plasma BDNF was significantly lower in the major depressive group (mean, 115.1 pg/mL; SD, 57.2) than in the nondepressive group (mean, 548.8 pg/mL; SD, 370.6; P < .001). The BDNF plasma concentrations in the subclinically depressive group (mean, 231.8 pg/mL; SD, 92.4; P < .001) and control group were also significantly different. CONCLUSIONS: Our findings revealed that plasma BDNF levels were reduced not only in ethnic Chinese elderly patients with major depressive disorder but also in those with subclinical depression. This makes the plasma BDNF level a potential biological marker for clinical or subclinical depression.

Regain of visuospatial capacity after coenzyme Q10 in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes: a case report.

OBJECTIVE: MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) is a neurodegenerative disorder caused by mitochondrial dysfunction. Multiple systems of the body, including cognitive function and heart conduction, can be affected by this disorder. We report a case with global cognitive impairment. METHOD: A single-case report. RESULTS: The patient got improved cognitive function, especially visuospatial function, under coenzyme Q10 treatment. CONCLUSION: First, coenzyme Q10 may give some benefit to control MELAS. Second, cognitive functions and intellectual abilities decline with disease progression. Routine neuropsychological tests should be performed.

Fear of falling (FF): Psychosocial and physical factors among institutionalized older Chinese men in Taiwan.

Fear of falling (FF) can have multiple adverse consequences in the elderly. Although there are various fall prevention programs, little is known of FF and its associated characteristics. This study examined FF-associated physical and psychosocial factors in older Chinese men living in a veterans home in southern Taiwan. Subjects with a recent episode of delirium, of bed-ridden or wheelchair-bound status, severe hearing impairment or impaired cognition were excluded. Overall, 371 residents (mean age 82.1 ± 5.11 years, all males) participated. The prevalence of FF was 25.3%. Univariate analysis revealed that subjects in the FF group were older age, having lower education level, poorer sitting and standing balance, poorer activities of daily living (ADL), more depressive symptoms, higher chances of using walking aids, neurologic diseases, and a history of fall within the past 6 months. Logistic regression showed that depressive symptoms (odds ratio = OR = 6.73, 95%CI: 3.03-14.93, p < 0.001), activities of daily living (OR = 2.48, 95%CI: 1.08-5.71, p = 0.033), history of fall in the past 6 months (OR = 2.47, 95%CI: 1.04-5.9, p = 0.041), and neurological diseases (OR = 2.75, 95%CI: 1.15-6.56, p = 0.023) were all independent risk factors for FF.