One week after CS, the NTRM in male patients was significantly hi

One week after CS, the NTRM in male patients was significantly higher. Metoprolol had no significant effect in either sex. At 6 months, females with metoprolol (n=18) showed a significantly lower NTRM and significantly lower PTSD symptom scores than females without BBs (n=15, p=0.02). By contrast, selleck the totally administered dosage of epinephrine correlated with NTRM in males (r=0.33, p<0.01) but not in females (r=0.21, p=0.29).

Conclusions. beta-Adrenergic stimulation with epinephrine enhances memory for adverse experiences in males but not in females whereas beta-blockade selectively reduces memory for post-operative adverse events and PTSD symptoms in females.”

previous studies have demonstrated that application of the inflammatory irritant mustard oil (MO) to the tooth pulp produces trigeminal central sensitization that includes increases in mechanoreceptive

field size and responses to noxious stimuli and decrease in activation threshold in brainstem nociceptive neurons of trigeminal subnucleus caudalis (the medullary dorsal horn, MDH). The aim of the present study was to test if central noradrenergic processes are involved in the central sensitization of MDH neurons and if alpha 1-adrenoceptors or alpha 2-adrenoceptors or both are involved. In urethane/alpha-chloralose-anesthetized rats, the activity of extracellularly recorded and functionally identified single nociceptive neurons in the MDH was studied. Continuous intrathecal (i.t.) superfusion of the adrenergic modulator Selisistat mw guanethidine and alpha-adrenoceptor blocker phentolamine or selective alpha 1-adrenoceptor antagonist prazosin over the medulla strongly attenuated all three MO-induced parameters of central sensitization in the MDH nociceptive neurons, compared to phosphate-buffered saline (as vehicle control).

In contrast, i.t. superfusion of the selective alpha 2-adrenoceptor antagonist yohimbine had little effect on the mechanoreceptive field expansion and the decreased mechanical activation threshold, and indeed facilitated SC75741 supplier responses to noxious stimuli of sensitized nociceptive neurons. Superfusion of each of the four chemicals alone did not affect baseline nociceptive neuronal properties. These findings provide the first documentation of the involvement of central noradrenergic processes in MDH in the development of the central sensitization, and that alpha 1- and alpha 2-adrenoceptors may be differentially involved. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Cholinergic system is important for respiratory control from the first days of life. Disturbances in cholinergic pathway due to early life stress like hypoxic shock can adversely affect the ventilatory response. The present study evaluates neonatal hypoxic insult mediated cholinergic disturbances and the role of glucose, oxygen and epinephrine resuscitation.

Effect of solvents on (i) the cell morphology and structure (ii)

Effect of solvents on (i) the cell morphology and structure (ii) surface hydrophobicity Fedratinib mouse and (iii) permeability of cell membrane have been examined using transmission electron microscopy, atomic force microscopy and other biochemical

techniques. The results show that (i) less hydrophobic (low log P-value) solvent cyclohexane alters the cell membrane integrity and (ii) cells adapt to organic solvents by changing morphology, size, permeability and surface hydrophobicity. However, no such changes were observed in the cells grown in tetradecane.


It may be concluded that P. aeruginosa PseA responds differently to solvents of different hydrophobicities. Bacterial cell membrane is more permeable to less

hydrophobic solvents that eventually accumulate in the cytoplasm, while highly hydrophobic solvents have lesser tendency to access the membrane.

Significance and Impact of the Study:

To the best of our knowledge, these are first time observations that show that way of bacterial solvent adaptability depends on nature of solvent. Difference in cellular responses towards solvents of varying log P-values (hydrophobicity) might prove useful to search for a suitable solvent for carrying out whole-cell biocatalysis.”

To study the effect of biosurfactant on aqueous phase solubility and biodegradation of chlorpyrifos.

Methods and Results:

A Pseudomonas sp. (ChlD), isolated from agricultural soil by enrichment culture technique in the presence of chlorpyrifos, was capable JQ-EZ-05 research buy of producing biosurfactant (rhamnolipids) and degrading chlorpyrifos (0 center dot 01 g l(-1)). The partially purified rhamnolipid biosurfactant preparation, having a CMC of 0 center dot 2 g l(-1), was evaluated for its ability to enhance aqueous phase partitioning and degradation of chlorpyrifos (0 center dot 01 g l(-1)) by ChlD strain. The best degradation efficiency was observed at 0 center dot 1 g l(-1) supplement of biosurfactant, as validated by GC and HPLC studies.


The addition

of biosurfactant at 0 center dot 1 g l(-1) resulted in more than 98% this website degradation of chlorpyrifos when compared to 84% in the absence of biosurfactant after 120-h incubation.

Significance and Impact of the Study:

This first report, to the best of our knowledge, on enhanced degradation of chlorpyrifos in the presence of biosurfactant(s), would help in developing bioremediation protocols to counter accumulation of organophosphates to toxic/carcinogenic levels in environment.”

To determine whether the extracellular products (ECPs) from Aeromonas hydrophila, a frog bacterial pathogen that is resistant to skin antimicrobial peptides of three different frog species Xenopus laevis, Litoria aurea and Litoria raniformis, can modulate the activity of these peptides.

This study investigated whether dietary cholesterol modulates rab

This study investigated whether dietary cholesterol modulates rabbit hippocampal CM neuron membrane properties known to be involved in rabbit eyeblink conditioning. Whole-cell current clamp recordings in hippocampal neurons from rabbits fed 2% cholesterol or normal chow for 8 weeks revealed changes including

decreased after-hyperpolarization amplitudes (AHPs) – an index of membrane excitability shown to be important for rabbit eyeblink conditioning. This index was reversed by adding copper to drinking water – a dietary manipulation that can retard rabbit eyeblink conditioning. Evidence of cholesterol effects on membrane excitability was provided by application of methyl-beta-cyclodextrin, a compound that reduces membrane cholesterol, which increased the excitability of hippocampal CA1 neurons. (C) 2010 Elsevier Ireland Tucidinostat Ltd. All rights reserved.”
“Bullous pemphigoid (BP) is Lapatinib mouse the most common autoimmune blistering disease, and has been associated with many diseases; most autoimmune. It has never previously been associated

with a reperfused limb. A 74-year-old female underwent a right femoroanterior tibial polytetrafluoroethylene (PTFE) bypass for tissue loss and rest pain ill the right foot. After surgery she was treated for recurrent infection which exacerbated tissue loss and was eventually diagnosed as BP. There was a delay in diagnosis due to the similarity to dry gangrene. This case highlights the potential difficulties of BP diagnosis in a revascularized limb and the importance of multidisciplinary management of atypical infection. (J Vasc Surg 2010;51:732-4.)”
“Previous studies have consistently suggested that the epsilon 4 allele of apolipoprotein E (APOE) gene is a major risk factor for Alzheimer’s

disease (AD). However, whether the epsilon 2 allele, a possible protective factor for AD, will express its protective effect in terms of cortical KU-60019 thickness in healthy elderly carriers is unclear. The goal of this study is to clarify the effects of APOE genotypes on cortical thickness in nondemented elderly subjects. We used 164 healthy, cognitively normal, elderly subjects, who were grouped into epsilon 2 carriers, epsilon 3 homozygotes, and epsilon 4 carriers respectively. The APOE epsilon 2 carriers had a significant thicker (corrected p < 0.05)cortical thickness in the superior temporal cortex compared with the epsilon 3 homozygotes. In addition to this area, the APOE epsilon 2 carriers had a significantly thicker region in the dorsolateral prefrontal cortex (corrected p < 0.05) than did the epsilon 4 carriers. These findings suggest that the different alleles of the APOE gene have distinct neuroanatomic effects in elderly healthy subjects and may play specific roles in the development of AD. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Effects on the functional performance were assessed 5 weeks after

Effects on the functional performance were assessed 5 weeks after surgery by conductance catheters, followed by histologic and molecular assessment.

Results: Contractile performance was significantly improved in the PAB+AO group versus the PAB group for both ventricles. Relative to sham-operated animals, both banding ROCK inhibitor groups showed significant differences in myocardial histologic and molecular responses. Relative to the PAB group, the PAB+AO group showed significantly decreased RV cardiomyocyte diameter, decreased RV collagen content, and reduced RV expression of endothelin

receptor type B, matrix metalloproteinase 9, and transforming growth factor beta genes.

Conclusions: Aortic constriction in an experimental model of chronic RV pressure overload not only resulted in improved biventricular systolic function but also improved myocardial remodeling. These data suggest that chronically increased left ventricular afterload leads to a more physiologically hypertrophic buy Pritelivir response in the pressure-overloaded RV. (J Thorac Cardiovasc Surg 2012;144:1494-501)”
“Negative symptoms

of schizophrenia (NSS), related to hypodopaminergic activity in the mesocortical pathway and prefrontal cortex, are predictive of poor outcomes and have no effective treatment. Use of dopamine-enhancing drugs (eg, psychostimulants) has been limited by potential adverse effects. This multicenter study examined lisdexamfetamine dimesylate (LDX), a d-amphetamine prodrug, as adjunctive therapy to antipsychotics in adults with clinically stable Omipalisib schizophrenia and predominant NSS.

Outpatients with stable schizophrenia, predominant NSS, limited positive symptoms, and maintained on stable atypical antipsychotic therapy underwent a 3-week screening, 10-week open-label adjunctive LDX (20-70 mg/day), and 4-week, double-blind, randomized, placebo-controlled withdrawal. Efficacy measures included a modified Scale for the Assessment of Negative Symptoms (SANS-18) and Positive and Negative Syndrome Scale (PANSS) total and subscale scores. Ninety-two participants received open-label LDX; 69 received double-blind therapy with placebo (n = 35) or LDX (n = 34). At week 10 (last observation carried forward; last open-label visit), mean (95% confidence interval) change in SANS-18 scores was -12.9 (-15.0, -10.8; P<0.0001). At week 10, 52.9% of participants demonstrated a minimum of 20% reduction from baseline in SANS-18 score. Open-label LDX was also associated with significant improvement in PANSS total and subscale scores. During the double-blind/randomized-withdrawal phase, no significant differences (change from randomization baseline) were found between placebo and LDX in SANS-18 or PANSS subscale scores.

V All rights

reserved “
“INTRODUCTION: A high-speed

V. All rights

“INTRODUCTION: A high-speed power-drilling technique of anterior clinoidectomy has been advocated in all publications on paraclinoid region surgery. The entire shaft of the power drill is exposed in the operative field; thus, all neurovascular structures QNZ concentration in proximity to any portion of the full length of the rotating drill bit are at risk for direct mechanical and/or thermal injury. Ultrasonic bone removal has recently been developed to mitigate the potential complications of the traditional power-drilling technique of anterior clinoidectomy. However, ultrasound-related cranial neuropathies are recognized complications of its use, as well as the increased cost of device acquisition and maintenance.

METHODS: A retrospective review of a cerebrovascular/cranial base

fellowship-trained neurosurgeon’s 45 consecutive cases of anterior clinoidectomy using the “”no-drill”" technique is presented. Clinical indications have been primarily small to giant aneurysms of the proximal internal carotid artery; however, in addition to ophthalmic click here segment aneurysms, selected internal carotid artery-posterior communicating artery aneurysms and internal carotid artery bifurcation aneurysms, and other large/giant/complex anterior circulation aneurysms, this surgical series of “”no-drill”" anterior clinoidectomy includes tuberculum sellae meningiomas, clinoidal meningiomas, cavernous sinus lesions, pituitary macroadenomas with significant Selleckchem Foretinib suprasellar extension,

other perichiasmal lesions (sarcoid), and fibrous dysplasia. A bony opening is made in the mid- to posterior orbital roof after the initial pterional craniotomy. Periorbita is dissected off the bone from inside the orbital compartment. Subsequent piecemeal resection of the medial sphenoid wing, anterior clinoid process, optic canal roof, and optic strut is performed with bone rongeurs of various sizes via the bony window made in the orbital roof.

RESULTS: No power drilling was used in this surgical series of anterior clinoidectomies. Optimal microsurgical exposure was obtained in all cases to facilitate complete aneurysm clippings and lesionectomies. There were no cases of direct injury to surrounding neurovascular structures from the use of the “”no-drill”" technique. The surgical technique is presented with illustrative clinical cases and intraoperative photographs, demonstrating the range of applications in anterior and central cranial base neurosurgery.

CONCLUSION: Power drilling is generally not necessary for removal of the anterior clinoid process, optic canal roof, and optic strut. Rigorous study of preoperative computed tomographic scans/computed tomographic angiography scans, magnetic resonance imaging scans, and angiograms is essential to identify important anatomic relationships between the anterior clinoid process, optic strut, optic canal roof, and neighboring neurovascular structures.

8 I) paint can be typical of those used as a chamber for metaboli

8 I) paint can be typical of those used as a chamber for metabolism and evaporative water loss studies. For an otherwise empty polished metal chamber, the effective temperature could be 2-5.5 degrees C warmer than in a chamber with flat black walls at the same air temperature. However,

if the chamber is prepared as in typical metabolism studies with 1 cm mineral oil in the bottom covered with a 12 mm x 12 mm hardware cloth, difference in effective temperature between a black painted and a polished metal chamber was negligible. As long as the floor of the metabolism chamber is covered with oil, or other high thermal absorptivity material such as feces, urine, or rust, the use of metabolism chambers with polished metal walls is not reason to reject data obtained therein. (C) 2011 Elsevier Ltd. All rights reserved.”
“Two men from northwestern Missouri independently presented to a medical facility with fever, fatigue,

Lazertinib datasheet diarrhea, thrombocytopenia, and leukopenia, and both had been bitten by ticks 5 to 7 days before the onset of illness. Ehrlichia chaffeensis was suspected as the causal agent but was not found on serologic analysis, polymerase-chain-reaction (PCR) assay, or cell culture. Electron microscopy revealed viruses consistent with members of the Bunyaviridae family. Next-generation selleck screening library sequencing and phylogenetic analysis identified the viruses as novel members of the phlebovirus genus. Although Stem Cells antagonist Koch’s postulates have not been completely fulfilled, we believe that this phlebovirus, which is novel in the Americas, is the cause of this clinical syndrome.”
“When examining the diurnal profile of the hormone cortisol in children and adolescents developmental issues are particularly relevant. Previous findings regarding relationships between cortisol secretory activity and reproductive (pubertal) maturation lack clarity and may reflect methodological inconsistencies between studies. This study examined the

diurnal cortisol profile across female adolescence, with a particular focus on an obvious and unique marker of development: menarche.

In a cross-sectional design, 61 healthy female adolescents aged 9-18 years (mean age 13.89 years, S.D. +/- 2.72) collected eight saliva samples per day on two consecutive weekdays. Samples were collected at awakening, 15, 30 and 45 min and 3, 6, 9 and 12 h post-awakening in order to capture both the cortisol awakening response (CAR) and the subsequent period of decline. Demographic information was recorded and participants also completed the Spielberger State-Trait Anxiety Inventory.

Patterns of cortisol secretion exhibited good intra-individual stability across the two sampling days. Participants evidenced a robust diurnal pattern, with cortisol levels peaking approximately 30-45 min post-awakening (the CAR) and steadily declining concentrations over the remainder of the day.

Among men, the risks associated with smoking have plateaued at th

Among men, the risks associated with smoking have plateaued at the high levels seen in the 1980s, GSK1904529A except for a continuing, unexplained increase in mortality from COPD.”
“Cyclic AMP response element binding protein (CREB) plays a critical role in fear memory formation. Here we determined the role of CREB selectively within the amygdala in reconsolidation and extinction of auditory fear. Viral overexpression of the inducible cAMP early repressor (ICER) or the dominant-negative mCREB, specifically within the lateral amygdala disrupted

reconsolidation of auditory fear memories. In contrast, manipulations of CREB in the amygdala did not modify extinction of fear. These findings suggest that the role of CREB in modulation of memory after retrieval is dynamic selleck products and that CREB activity in the basolateral amygdala is involved in fear memory reconsolidation.”
“Objectives: To examine whether an impaired ability to infer emotion in people with autism spectrum disorder (ASD) and difficulty with emotional theory of mind (eToM) are limited to the ill state or if this condition is a stable deficit that persists with recovery in adults with anorexia nervosa (AN). This is in keeping with observations

of similarities between the disorders. Methods: Twenty-four participants fully recovered from AN were compared against a sample of currently ill AN patients (n = 40) and healthy controls (HCs) (n = 47) on forced-choice PF-02341066 mouse tasks assessing emotion recognition, basic or advanced eToM in other people,

using sensory stimuli and on a written task measuring eToM ability for the self as well as for others. Results: Recovered participants performed well on eToM tasks and were significantly better than currently ill patients at inferring emotions in the self and in others. However, participants recovered from AN had some slight impairment in emotion recognition relative to HCs, particularly when recognizing positive emotions. Conclusions: These findings indicate almost complete normalization of emotion recognition ability as well as the restoration of eToM in recovered patients, despite the observation of difficulties in both domains in currently ill patients. Findings suggest that similarities between AN and ASD in poor eToM are restricted to the currently ill AN state and such difficulties in AN may be a factor of starvation.”
“A 57-year-old man with a history of alcohol dependence comes for an annual examination. He reports that he has reduced his drinking to two beers two to three times per week and has not had five or more drinks on any occasion or any adverse consequences for the past 2 years. He states that he drinks “”for his health”" and that “”it is under control.”" How should his case be assessed and managed?”
“Kv4.2 channels contribute to the transient, outward K+ current (A-type current) in hippocampal dendrites, and modulation of this current substantially alters dendritic excitability. Using Kv4.

However, through the sale and promotion of tobacco, alcohol, and

However, through the sale and promotion of tobacco, alcohol, and ultra-processed food and drink (unhealthy commodities), transnational corporations are major drivers of global epidemics of NCDs. What role then should these industries have in NCD prevention and control? We emphasise the rise in sales of these unhealthy commodities in low-income and middle-income countries, and consider the common strategies that the transnational corporations use to undermine NCD prevention and control. We assess the effectiveness of self-regulation, public-private partnerships, and public regulation models of interaction with these industries and conclude that unhealthy commodity industries

should have no role in the formation of national or international NCD policy. Despite the common reliance on industry self-regulation and public-private partnerships, there is no evidence HDAC inhibitor of their effectiveness or safety. Public regulation and market intervention are the only evidence-based mechanisms to prevent

harm caused by the unhealthy commodity industries.”
“Phospholipases A(2) (PLA(2)) are the enzymatic keys for the activation of the arachidonic acid (AA) cascade and the subsequent synthesis of pro-inflammatory prostanoids (prostaglandins and tromboxanes). Prostanoids buy OTX015 play critical roles in the initiation and modulation of inflammation and their levels have been reported increased in several neurological and neurodegenerative disorders, including multiple sclerosis (MS).

Here, we aimed to determine whether brain expression PLA(2) enzymes and the terminal prostagland in levels are changed during cuprizone-induced demyelination and in the subsequent

remyelination phase.

Mice were given the neurotoxicant cuprizone through the diet for six weeks to induce brain demyelination. Then, cuprizone was withdrawn and mice were returned to a normal diet for 6 weeks to allow spontaneous remyelination.

We found that after 4-6 weeks of cuprizone, sPLA(2)(V) and cPLA(2), but not iPLA(2)(VI), gene expression was upregulated in the cortex, concomitant see more with an increase in the expression of astrocyte and microglia markers. Cyclooxygenase (COX)-2 gene expression was consistently upregulated during all the demyelination period, whereas COX-1 sporadically increased only at week 5 of cuprizone exposure. However, we found that at the protein level only sPLA(2)(V) and COX-1 were elevated during demyelination, with COX-1 selectively expressed by activated and infiltrated microglia/macrophages and astrocytes. Levels of PGE(2), PGD(2), PGI(2) and TXB(2) were also increased during demyelination. During remyelination, none of the PLA(2) isoforms was significantly changed, whereas COX-1 and -2 were sporadically upregulated only at the gene expression level. PGE(2), PGI(2) and PGD(2) levels returned to normal, whereas TXB(2) was still upregulated after 3 weeks of cuprizone withdrawal.

“Background Potential disparities in health care utilizat

“Background. Potential disparities in health care utilization were examined using overnight hospitalization data from the University of Alabama at Birmingham Study of Aging, a longitudinal investigation of a stratified sample of Medicare beneficiaries.

Methods. Racial differences in self-reported surgical and nonsurgical overnight hospital admissions were examined using Cox proportional hazards models. Andersen’s Behavioral Model provided the conceptual framework to identify other

potential predictors of admission.

Results. Nine hundred and forty-two participants, 50.1% African American, provided data at baseline and at least one follow-up assessment (mean age = 75.3 years, range: 65-106). African Americans were less learn more likely to utilize surgical admissions compared with Caucasians in

a bivariate model (hazard ratio = 0.63, 95% confidence interval = 0.41-0.98). This effect was not significant after controlling for demographics and self-reported physical health. Additional bivariate predictors of surgical admission were intact mental status, having private insurance, and higher education. African Americans were less likely to utilize nonsurgical admissions in both bivariate (hazard ratio = 0.74, 95% confidence interval = 0.59-0.93) and covariate-adjusted models (hazard ratio this website = 0.64, 95% confidence interval = 0.50-0.84). This effect was significantly stronger for men than for women, with African American men only 0.50 times as likely as Caucasian men to report a nonsurgical admission. Other bivariate predictors of nonsurgical admission were increased age, poor physical health, negative

psychological characteristics, higher levels of social support, and low perceived discrimination.

Conclusion. Underutilization of services has been linked to increased mortality in African Americans. Modifications in mutable domains associated with service utilization such as perceived discrimination, social support, and having private insurance may be beneficial.”
“At least five symptoms must occur for a DSM diagnosis of major depressive disorder about (MDD), one of which must be sadness or anhedonia. The present study is the first known investigation of the implications of the presence or absence of these prioritized symptoms on symptom expression and clinical characteristics among 564 young adults with MDD. Differences in symptom expression and clinical characteristics occurred among MDD participants with sadness relative to those without sadness as well as among MDD participants with anhedonia relative to those without anhedonia. Differential symptom expression could have important implications for the etiology, prevention, and treatment of MDD. (c) 2007 Elsevier Ireland Ltd. All rights reserved.”
“BACKGROUND: Nitric oxide (NO) depletion and periadventitial inflammation contribute to the pathogenesis of cerebral vasospasm. L-Citrulline increases L-arginine levels, thereby raising NO synthesis.

The role of the UPS in neurodegeneration in vivo is reviewed by d

The role of the UPS in neurodegeneration in vivo is reviewed by discussing the currently available murine models showing a neurological phenotype induced by genetic manipulation of the UPS. (C) 2008 Elsevier Ltd. All rights reserved.”
“Oncolytic viruses have been tested against many carcinomas of ectodermal and endodermal origin; however, sarcomas, arising from mesoderm, have received relatively little attention. Using 13 human sarcomas representing seven

tumor types, we assessed the efficiency of infection, cytolysis, and replication of green fluorescent protein (GFP)-expressing vesicular stomatitis virus (VSV) and its oncolytically enhanced mutant VSV-rp30a. Both viruses efficiently infected and killed 12 of 13 sarcomas. VSV-rp30a showed a faster rate of infection and replication. In vitro and in vivo, VSV was selective for sarcomas compared with normal mesoderm. A-1210477 mw A single intravenous injection of VSV-rp30a selectively infected all subcutaneous human sarcomas tested in mice and arrested the growth Elafibranor manufacturer of tumors that otherwise grew 11-fold. In contrast to other sarcomas, synovial sarcoma SW982 demonstrated remarkable resistance, even to high titers of virus (multiplicity of infection [MOI] of 100). We found no dysfunction in VSV binding or internalization. SW982 also resisted infection by human cytomegalovirus and Sindbis virus, suggesting a virus resistance mechanism based on an altered antiviral state.

Quantitative reverse transcriptase (qRT)-PCR analysis revealed a heightened basal expression of interferon-stimulated genes (ISGs). Pretreatment, but not cotreatment, with interferon attenuators valproate, Jak1 inhibitor, or vaccinia virus B18R protein rendered SW982 highly susceptible, and this correlated with downregulation of ISG expression. Jak1 inhibitor pretreatment also enhanced Tacrolimus (FK506) susceptibility in moderately VSV-resistant liposarcoma and bladder carcinoma. Overall, we find that the potential efficacy of VSV as an oncolytic agent extends to nonhematologic mesodermal tumors and that unusually strong

resistance to VSV oncolysis can be overcome with interferon attenuators.”

Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimer’s disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease.


We assigned 295 community-dwelling patients who had been treated with donepezil for at least 3 months and who had moderate or severe Alzheimer’s disease (a score of 5 to 13 on the Standardized Mini-Mental State Examination [SMMSE, on which scores range from 0 to 30, with higher scores indicating better cognitive function]) to continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, or continue donepezil and start memantine. Patients received the study treatment for 52 weeks.