Cholinesterase inhibitors for Alzheimer disease: do they provide more than symptomatic benefits?

OBJECTIVE: This study aims to examine survival of patients with Alzheimer disease (AD) receiving clinical efficacy of cholinesterase inhibitors (ChEIs) and to compare their survival with those of patients with AD who never received ChEIs and cognitively intact old psychiatric outpatients. DESIGN, SETTING, AND PARTICIPANTS: The retrospective cohort study used national mortality data provided by the Korean National Statistics Office and electronic database of 15 general hospitals on older patients who began outpatient treatment with psychiatric medications including ChEIs (N = 3,813). The authors controlled for confounding by using multivariate models and propensity scoring methods. MEASUREMENTS: Mortality rate of patients with AD receiving ChEIs was compared with those of patients with AD who never received ChEIs and cognitively intact old psychiatric outpatients. RESULTS: Observed additional survival of patients with AD receiving ChEIs (mortality rate: 13.1%), when compared with patients with AD who never received ChEIs (15.4%) was not statistically significant (p = 0.74; hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 0.67-1.59). Patients with AD receiving ChEIs showed higher mortality rate (13.1%) compared with that of cognitively intact old psychiatric outpatients (8.6%) (p <0.001; HR: 1.60, 95% CI: 0.96-2.68). CONCLUSION: This study does not support that ChEIs increase survival of patients with AD, compared with patients with AD who have never treated with ChEIs. Therefore, all ChEIs should be considered for symptomatic use only and not to be capable of modifying mortality of patients with AD.

Effects of alcohol hangover on cytokine production in healthy subjects.

A hangover is the syndrome of physical and mental symptoms that occurs 8 to 16 h after alcohol consumption with a zero level of alcohol. The aim of the current study was to investigate the effects of the alcohol hangover on cytokine production in healthy subjects. The hangover state was defined as 13 h after drinking 1.5 g/kg of alcohol (blood alcohol level=0). A venous blood sample was taken from 20 healthy adult men before consumption of alcohol and during the hangover state. Peripheral blood mononuclear cells were separated and stimulated with phytohemagglutinin. An enzyme-linked immunosorbent assay was used to measure the production of the following cytokines: interleukin (IL)-1beta, IL-4, IL-6, IL-10, IL-12, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). We found that the concentrations of IL-10, IL-12, and IFN-gamma were significantly increased during the hangover state compared with the concentrations in normal conditions. These results support the suggestion that the dysregulated cytokine pathway (IL-10, IL-12, and IFN-gamma) is associated with the symptoms of hangovers.

Aberrant development of functional connectivity among resting state-related functional networks in medication-naïve ADHD children.

OBJECTIVE: The aim of this study was to investigate the compromised developmental trajectory of the functional connectivity among resting-state-related functional networks (RSFNs) in medication-naïve children with attention-deficit/hyperactivity disorder (ADHD). SUBJECTS AND METHODS: Using both independent component analysis and dual regression, subject-specific time courses of 12 RSFNs were extracted from both 20 medication-naïve children with ADHD, and 20 age and gender-matched control children showing typical development (TDC). Both partial correlation coefficients among the 12 RSFNs and a resting-state resource allocation index (rsRAI) of the salience network (SN) were entered into multiple linear regression analysis to investigate the compromised, age-related change in medication-naïve ADHD children. Finally, correlation analyses were performed between the compromised RSFN connections showing significant group-by-age interaction and rsRAI of SN or clinical variables. RESULTS: Medication-naïve ADHD subjects failed to show age-related increment of functional connectivity in both rsRAI of SN and two RSFN connections, SN-Sensory/motor and posterior default mode/precuneus network (pDMN/prec)--anterior DMN. Lower SN-Sensory/motor connectivity was related with higher scores on the ADHD Rating Scale, and with poor scores on the continuous performance test. The pDMN/prec-aDMN connectivity was positively related with rsRAI of SN. CONCLUSIONS: Our results suggest that medication-naïve ADHD subjects may have delayed maturation of the two functional connections, SN-Sensory/Motor and aDMN-pDMN/prec. Interventions that enhance the functional connectivity of these two connections may merit attention as potential therapeutic or preventive options in both ADHD and TDC.

The effect of paliperidone extended release on subjective well-being and responses in patients with schizophrenia.

OBJECTIVE: This study aimed to evaluate the subjective well-being and attitudes toward antipsychotic medication of patients with schizophrenia who had switched to paliperidone extended release (ER). METHODS: A total of 291 patients with schizophrenia treated with antipsychotics participated in this open-label, 24-week switching study. The primary outcome measures were the Subjective Well-Being under Neuroleptic Treatment Scale-short version (SWN-K) and the Drug Attitude Inventory (DAI). The Krawiecka scale, Clinical Global Impression-Schizophrenia (CGI-SCH), Personal and Social Performance scale (PSP) were used to evaluate psychopathology and psychosocial functioning, respectively. RESULTS: Data from a total of 243 subjects who received the study medication and had at least one follow-up assessment without a major protocol violation were analyzed. Scores on the DAI and SWN-K showed significant improvement between baseline and end-point measurements beginning during the second week. Scores on the Krawiecka scale, all five subscales of the CGI-SCH scale, and the PSP scale were also significantly improved at the end point compared with the baseline. Significant predictors of improvements in the SWN-K and DAI after a switch to paliperidone ER were baseline scores, reductions in scores on the Krawiecka scale, and previous risperidone use. A clinically relevant increase in body weight (≥7% weight gain) occurred in one-fourth of the participants who completed the 24-week study. CONCLUSION: Switching to paliperidone ER improved the subjective well-being and attitudes towards antipsychotic medication in patients with schizophrenia. Exploratory analyses revealed that these improvements were particularly pronounced in patients who had been treated with risperidone before treatment with paliperidone ER.

A combination of green tea extract and l-theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebo-controlled study.

A combination of green tea extract and l-theanine (LGNC-07) has been reported to have beneficial effects on cognition in animal studies. In this randomized, double-blind, placebo-controlled study, the effect of LGNC-07 on memory and attention in subjects with mild cognitive impairment (MCI) was investigated. Ninety-one MCI subjects whose Mini Mental State Examination-K (MMSE-K) scores were between 21 and 26 and who were in either stage 2 or 3 on the Global Deterioration Scale were enrolled in this study. The treatment group (13 men, 32 women; 57.58 ± 9.45 years) took 1,680 mg of LGNC-07, and the placebo group (12 men, 34 women; 56.28 ± 9.92 years) received an equivalent amount of maltodextrin and lactose for 16 weeks. Neuropsychological tests (Rey-Kim memory test and Stroop color-word test) and electroencephalography were conducted to evaluate the effect of LGNC-07 on memory and attention. Further analyses were stratified by baseline severity to evaluate treatment response on the degree of impairment (MMSE-K 21-23 and 24-26). LGNC-07 led to improvements in memory by marginally increasing delayed recognition in the Rey-Kim memory test (P = .0572). Stratified analyses showed that LGNC-07 improved memory and selective attention by significantly increasing the Rey-Kim memory quotient and word reading in the subjects with MMSE-K scores of 21-23 (LGNC-07, n = 11; placebo, n = 9). Electroencephalograms were recorded in 24 randomly selected subjects hourly for 3 hours in eye-open, eye-closed, and reading states after a single dose of LGNC-07 (LGNC-07, n = 12; placebo, n = 12). Brain theta waves, an indicator of cognitive alertness, were increased significantly in the temporal, frontal, parietal, and occipital areas after 3 hours in the eye-open and reading states. Therefore, this study suggests that LGNC-07 has potential as an intervention for cognitive improvement.

The effects of alcohol hangover on cognitive functions in healthy subjects.

A hangover is characterized by the constellation of unpleasant physical and mental symptoms that occur between 8 and 16 h after drinking alcohol. We evaluated the effects of experimentally-induced alcohol hangover on cognitive functions using the Luria-Nebraska Neuropsychological Battery. A total of 13 normal adult males participated in this study. They did not have any previous histories of psychiatric or medical disorders. We defined the experimentally-induced hangover condition at 13 h after drinking a high dose of alcohol (1.5 g/kg of body weight). We evaluated the changes of cognitive functions before drinking alcohol and during experimentally-induced hangover state. The Luria-Nebraska Neuropsychological Battery was administrated in order to examine the changes of cognitive functions. Cognitive functions, such as visual, memory, and intellectual process functions, were decreased during the hangover state. Among summary scales, the profile elevation scale was also increased. Among localization scales, the scores of left frontal, sensorimotor, parietal-occipital dysfunction, and right parietal-occipital scales were increased during the hangover state. These results indicate that alcohol hangovers have a negative effect on cognitive functions, particularly on the higher cortical and visual functions associated with the left hemisphere and right posterior hemisphere.

A naturalistic study of risperidone treatment in seven affiliated university hospitals in Korea.

This retrospective naturalistic study, conducted on patients with schizophrenia, was undertaken to examine the differences in the clinical characteristics of subjects who were treated with risperidone, but who were discontinued soon after administration, and those who were maintained on the drug for a long-term period. Data on 210 of 580 inpatients with schizophrenia who were treated with risperidone and whose complete medical records were available, were analyzed. Patients maintained on risperidone for at least 2 years were assigned to a 'long-term maintenance' (LTM) group and those who were discontinued within 6 months of risperidone administration were assigned to an 'early drop-out' (ED) group. The parameters used for comparisons included the patients' demographic characteristics, the presence/absence of physical or psychiatric comorbidities, the severity of the psychopathology, the typology of the schizophrenia, the nature and subjects' responses to previous antipsychotic treatments (if any) and dosages of risperidone treatment. Of the 210 subjects, 67 (31.9%) belonged to the ED group, whereas 143 (68.1%) were maintained on risperidone at 2 years. There were no significant differences in the demographics, nor in the severity of the psychopathology, nor were there significant differences in the starting or maximal dosages of risperidone administered between the two groups. Exposure to any previous antipsychotic and the longest maintained final dosage of risperidone were significantly different in the two groups. We believed that a multicenter-based retrospective naturalistic study would provide useful information about the efficacy and other practical aspects of antipsychotic administration.