In an effort better to understand the application of pharmaceutical services in the operating room (OR) we conducted a survey among OR department directors of 526 hospitals throughout Japan. A total of 202 directors responded to the survey. Pharmacists are expected to achieve better outcomes in pharmacotherapy as well as play major roles as members of diverse perioperative care teams. Besides implementing medication safety standards, pharmacists' roles include optimizing drug therapy and other clinical interventions, both in OR and wards. Presently, few pharmacists in Japan participate in perioperative care, which is one of the reasons that the majority of pharmacy schools in Japan have been providing fewer lectures or rotations related to perioperative care. Yet, developing general perioperative management as another crucial role OR pharmacists play and incorporating it into pharmaceutical education would be important. Enriching perioperative care provided by pharmacists can contribute toward improving clinical competence in these professionals.
With the revisions to the pay for performance of pharmaceutical service of inpatients in April 2012, the ward permanent time of pharmacists grew longer than previously; however, there are as yet few reports on the pharmaceutical outcome of the new medical service. To improve the pharmaceutical service requires that pharmacists collect useful medical information and extract the problems of pharmaceutical care for inpatients. Since many cases of treatment with multidrug regimens are regularly performed, pharmacists cannot contribute to medical treatment only by knowledge of a single disease. Therefore quick and comprehensive judgment of pharmacists is necessary in addition to acquisition of pharmaceutical knowledge. We especially highlight medical emergencies such as severe cases of sepsis and infection to which physicians require rapid judgment. Pharmacists alike require appropriate knowledge of drug administration to avoid medical treatment failure. Moreover, it is necessary for pharmacists to apply advanced drug monitoring in difficult cases. On the other hand, integrated team medical treatment is now advancing, although pharmacists' roles in clinical decision making are increasing, and pharmacists have a greater burden of responsibility than before.
A strategy named “Japan is back” adopted in June 2013 specifies that pharmacies shall be regarded as community-based places where health-related information is provided, and the public shall be encouraged to use the services of pharmacies and pharmacists who can advise on health and appropriate use of over-the-counter (OTC) drugs, and promote self medication. In Japan there are approximately 55000 pharmacies and 260000 pharmacists, and community residents are recommended to use these resources. As advisors on healthcare in the community, pharmacists are required to make judgments regarding drug use in individuals performing self medication and using OTC drugs in consideration of their symptoms and level of understanding of their health conditions, and recommend that they consult a medical center if necessary. To meet these requirements pharmacists need to have the skills to monitor each individual's lifestyle, behavior, and environment as well as trends in society, and assess their health status. However, education that allows pharmacists to practice such skills remains insufficiently developed. We consider that to be able to detect diseases early among community residents and appropriately support them using pharmacotherapy, it is very important to train pharmacists to do the following at pharmacies: 1) determine individuals who should be treated early using symptomatologic skills; 2) promote public awareness of disease; and 3) perform biochemical examination (blood is collected by fingerprick promptly to obtain biochemical data) in cooperation with the Department of Clinical Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hiroshima University.
Pharmaceutical education was expanded to a 6-year system in 2006, in an efforts to enhance clinical pharmaceutical research and education. Since that time, pharmacists have attempted to participate in medical all aspects of medical care, but an environment in which they can master direct pharmaceutical techniques for patients has not yet been sufficiently developed. This is because pharmaceutical education emphasizes the acquisition of knowledge and has not reached the point where it cultivates minds that can adapt to the multitude of situations that are envisaged in medical settings. By incorporating physical assessment in pharmaceutical settings, it is believed that a mind-set of treating patients can be formed in students, leading to the development of pharmacists skilled in the implementation of their area of treatment. We feel that, by shifting to clinical pharmaceutical education and research we will realize an integrated ability in pharmacists to treat patients, which will earn multifaceted appreciation from both patients themselves and medical practitioners. The pharmaceutical consultation clinic established at Mie University offers second opinions by pharmacists, but patients' opinions of pharmacists are tepid and the letter sometimes became the target of acerbic comments. This is a reflection of the current state in which pharmacists have not made their role in medicine clear. Ultimately, efforts must be made to resolve anxiety with respect to the things patients want to hear, without evading this responsibility even when under pressure. Pharmaceutical science should always be cognizant of what the pharmacists' contribution to medicine, should be, and research a means to help that individual acquire the ability to make quick though careful judgments while gathering needed findings.
Physical assessment skills are now being more widely accepted by pharmacists and pharmaceutical departments than in the past. This is explained by the realization that pharmacists can prevent serious adverse effects and evaluate drug efficacy for their patients through assessment, thus providing effective medical care. However, is that all physical assessment can provide to pharmacists and pharmaceutical students? These students, in turn, should recognize the “need for skill” and the “pleasure to be gained in acquiring that skill” through the physical assessment performed by doctors. They should also recognize the importance of medical devices (e.g., stethoscope, electrocardiograph and endoscope) and take responsibility for creating their own techniques for their use. Here they will consider valuable pharmaceutical skills. “Yaku-jutsu” is a pharmaceutical diagnosis to determine the time required to achieve maximum beneficial effects and effective drug administration based on that diagnosis. Pharmacists cannot gain public trust unless they relieve a patient's pain using Yaku-jutsu which has been made available to them by the research support of a pharmaceutical department.
Quinones play critical roles in biological systems, but are also regarded as a class of toxins that can cause oxidative stress in living cells, and the involvement of quinone-based reactive oxygen species in oxidative stress has been reported. In biological systems, quinones are reduced to semiquinone radicals by the enzyme NADPH:quinone reductase. Next, semiquinone radicals react with dissolved oxygen to form superoxide anion, which reacts with biological molecules to cause oxidative stress. On the other hand, chemiluminescence reagents such as luminol can emit chemiluminescence after oxidation by reactive oxygen species. Therefore, chemiluminescence reagents have been used widely to investigate reactive oxygen species. We have developed a sensitive and selective assay for quantifying quinones using luminol chemiluminescence. This chemiluminescence assay is based on the generation of reactive oxygen species through the redox reaction between quinone and dithiothreitol, a reductant, followed by detection of the generated reactive oxygen by luminol. Additionally, this assay can be used to quantify the toxic herbicide, paraquat, which produces reactive oxygen species in the same manner as quinones. This review describes the development of a sensitive and selective chemiluminescence assay for investigating quinones and paraquat by utilizing their ability to generate reactive oxygen species.
It is routine to search for and recognized genetic defects in human disorders to provide knowledge for diagnosis, treatment, and protection against diseases. It is also important to investigate and demonstrate the cause of a disease from the proteomic perspective, because intracellular signaling systems depend on protein dynamics. Demonstrating changes in protein levels enables us to understand biochemical events during the initiation and progression of a disease. To understand changes in protein levels in tissues and cells, we have developed a novel proteomics approach, FD-LC-MS/ MS. This consists of fluorogenic derivatization (FD), HPLC separation and detection/quantification of proteins in a biological sample, followed by the isolation and tryptic digestion of target proteins, and then their identification using HPLC and tandem mass spectrometry (MS/MS) with a database-searching algorithm. The method is highly sensitive (femtomole-level detection) through the use of less noisy fluorogenic rather than fluorescence derivatization, and enables precise and comprehensive relative quantitation of protein levels (between-day relative standard deviation of peak heights of ca. 20%) by combining FD with HPLC separation. In this paper, after a simple review of differential profiling using FD-LC-MS/MS, for example the analysis of stimulated vs. unstimulated samples, we introduce the development and application of the FD-LC-MS/MS method for comprehensive differential proteomics of several tissues, including mouse liver, mouse brain, and breast cancer cell lines, to reveal protein levels and biochemical events in tissues and cells.
Perfluoroalkyl-containing compounds are highly fluorous, meaning that they have a remarkable affinity for one another and effectively exclude non-fluorous species. Utilizing this unique property, we have developed a fluorous derivatization with a liquid chromatographic analysis method for highly selective analysis of target analytes. Although most previous methods focused on extremely sensitive detection-oriented derivatization, the fluorous derivatization method involves highly specific separation for analytes. This method includes perfluoroalkylation of analytes with a fluorous reagent, and separation of the derivatives using a perfluoroalkyl-modified stationary phase LC column. The derivatives can be selectively retained on the fluorous-phase LC column, whereas the non-fluorous derivatives are poorly retained under the same separation conditions. The combination of this method with LC-tandem mass spectrometry (MS/MS) is very useful for complex biological sample analysis, because matrix-induced suppression effects, which are a common problem in LC-MS/MS analysis arising from components of a biological endogenous matrix, have not been observed. We have successfully applied this method to precise and accurate LC-MS/MS analysis of some biogenic compounds, such as sialic acids and biogenic amines, in complex biological samples.
Therapeutic monoclonal antibody (mAb) preparations are produced from cultured cells; therefore, detailed and multidimensional analyses of their heterogeneities are required. We analyzed five commercially available mAb preparations by high-temperature reversed-phase LC using a wide-pore core-shell column for pluralistic quality assessment. At a highly elevated column temperature, isopropanol with high eluotropic strength coefficients and a wide-pore core-shell type octyl column showed good peak resolution of the investigated mAbs and their related constituents. We used this method to estimate the residual rate of intact mAbs after a heat aggregation treatment and conducted fragmentation analysis by analyzing their pepsin digests. Each peak component was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. All results were compared with those of reversed-phase and size exclusion analyses.
In this symposium we focused on trade-offs which might occur in the process of development of many types of formulation and corresponding dissolution methods. Firstly, we focused on a solubility-permeability trade-off in the case of micelle with surfactant or molecular complex with CyD. The micelle would be successful in increasing drug solubility, however it rather decreased permeability of model drug progesterone (Biopharmaceutics Classfication System (BCS) Class II) as an overall flux. Secondly in order to reduce bitterness of branched chain amino acid (BCAA), increasing particle sizes of each amino acid crystals involved in formulation was effective since the release rate of amino acid was restricted efficiently. Thirdly, in the case of injection of paclitaxel (BCS Class II)formulation, the drug was adsorbed to albumin. Thereby the risk of allergy was dramatically decreased compared to the case when non-ionic surfactant was used as an additive. Fourth, anticancer drug was incorporated into the internal (core) phase of an orally disintegrating tablet (ODT), this is also merit to avoid exposure of the drug to a nursing person or individual working person in manufacturing process. Fifth, the convenient syringe type kit pharmaceutical preparation for administration of total parenteral nutrition (TPN) to avoid incompatibility and its risk management effect was briefly discussed. Finally, the risk of an additive such as alcohol for a preterm infant was described.
Drug products are developed to meet multiple targets, thereby increasing their value. Pharmaceutical scientists encounter several trade-offs during the development of novel oral formulations. These trade-offs are generated by their desire to supply the highest possible quality products under the prevailing conditions of limited time and cost, and feasible options. When there are two incompatible factors, it is sometimes difficult to dismiss one element. This is because a quality target product profile (QTPP) is critical for each product being developed, and all elements should basically be satisfied with the criteria. Therefore, technological innovation becomes important to overcome the trade-offs. This article introduces examples of such innovations which have been successful in doing this, as well as some encountered in the oral formulation development and in the selection of proper dosage forms. Based on these examples, points to be considered in order to produce the drug product are thoroughly discussed.
Orally disintegrating tablets (ODTs) are currently widely used in drug therapy and are clinically attractive, because they are suitable for administration to patients with dysphagia and improve adherence, both of which increase the possibility of achieving the expected therapeutic effect. These properties of ODTs, which increase treatment effectiveness, are termed their “clinical functionality”, and ODTs with a high clinical functionality are required to meet the increasing need for these tablets. For example, there is a need for development of a clinically effective ODT with superior disintegrating properties while maintaining high tablet strength, bioequivalence with normal tablets while masking the bitterness with a fine particle coating, and a disintegration mechanism while maintaining moisture resistance and good storage quality. Thus, next-generation ODTs that overcome these conflicting properties, “trade-offs”, will be developed, using innovative formulation research technology. In this symposium, we will discuss a next-generation OD formulation known as PLETAAL OD, a high-dose antiplatelet agent, and will present the results of validation tests performed in our laboratory pertaining to high tablet strength, superior disintegration property, high wicking capacity, and storage stability with high moisture resistance. We will also introduce a second-generation antihistamine ALLELOCK OD and discuss its high clinical functionality achieved by masking the bitterness and obtaining bioequivalence with normal tablets by using granules while maintaining high tablet strength with EXLUB and SOLBLET technology.
Children generally reject taking medicine which does not have a favorable shape, taste, flavor, etc. However, if a child who needs to take a medicine, rejects taking it, he might never recover from his condition. When a child is unable to take medicine orally, it is intravenously administered, and he and his caregivers then may experience stress. Syrups and suspensions are considered as favorable types of dosage forms in which to orally administer medicine to infants and children. However, they may have disadvantages such as solubility, a bad taste, portability problems or required refrigerator storage. World Health Organization (WHO) currently favors that infants and children be treated with oral solid medicines. New oral solid tablets, such as a mini-tablet, instead of liquid medicines are proposed for this group, however, there are a few reports that mini-tablets are suitable for infants and children. Palatability is one of the main elements of patient acceptability of an oral pediatric medicine. Palatability is defined as the overall appreciation of an oral medicinal product in relation to its smell, taste, aftertaste and feeling in the mouth. Design of the formulation of an oral pediatric medicine should be considered together with its palatability.
Deterioration of the swallowing function in elderly persons and drug refusal among the behavioral abnormalities in Alzheimer's disease (AD) are commonly reported. Therefore, we developed an easy-to-swallow jelly formulation of Donepezil HCl which AD patients can take as a dessert. The development process, however, was full of trade-off problems. (1) Need for evaluating the taste of a drug product vs. Safety of human sensory evaluation of the taste. The trade-off was resolved by using a taste sensor. (2) Speed of development vs. Safety of the manufacturing process. We put priority on the safety rather than speed, and a safer antioxidant agent was found. (3) Usability of the container for AD patients with dysphagia vs. Size of the container. We put priority on its being user-friendly rather than on the size and chose a stable wide-mouth cup. (4) Suitable texture of jelly for swallowing the drug product vs. Residual volume of jelly in the cup. We designed the texture so that the residual volume of jelly in the cup was reduced. (5) Easy peeling properties of aluminum seal vs. High sealing strength for sterilization. The sealing strength was adjusted so that it was adequate to sterilize the drug product. (6) One cup in a heat-sealed aluminum pillow package to prevent overdose vs. Seven cups in a pillow package. A single-dose package was relatively expensive, but it was chosen to assure safety. We faced many difficult trade-off problems in the development of process. However, they were resolved using technical innovations and a people-friendly policy. Finally, we were able to launch a novel oral jelly formulation for elderly patients.
Recently, there has been a transition from glass to plastic injection containers in Japan. In our previous study, we suggested that plastic containers had less impurity contamination than glass containers. However, the use of some plasticizers has been limited because of their endocrine disrupting effects. Therefore, contamination has been a concern due to chemicals in injection solution packed with plastic containers. Indeed, in our recent study, photoinitiators were detected in an injection solution coming from plastic containers. Photoinitiators mainly exist in ink. We therefore speculated that ink originating from a photoinitiator directly printing on plastic containers had migrated into the injection solutions. In a clinical setting, plastic containers are very tractable because they are lightweight and less breakable. On the other hand, from a safety view point, these containers may be hazardous because of permeation by steam, ambient air or photoinitiators. In the present symposium, we will discuss the risk of photoinitiators leaking into injection solution packed with plastic containers, and countermeasures to avoid this risk.
The importance of vaccination has recently been widely recognized among Japanese people with a growing interest in vaccine. On the other hand, because vaccine is administrated to healthy people, it has had a difficult history due to overreaction to adverse events. With the recent rapid increase in the rate of vaccination, however, it is essential to correct the understanding of the public as to the risk and benefit of vaccine. Life spans around the world and infectious diseases are closely related, and vaccine certainly contributes to the control of the latter. Research and Development (R&D) of novel antigens is necessary for creating a next generation vaccine, a high performance device for efficient antigen delivery, and a safe adjuvant for adequate immunological response are also a key to the future. Moreover, various initiatives involving industry, academia, and government cooperation are essential to benefit the people of Japan and appropriate vaccination could actually be viewed as national security.
Safety information on drugs is provided through package inserts, which are the most basic tool offered by pharmaceutical companies, “Emergency Safety Information” and “Pharmaceuticals and Medical Devices Safety Information”, etc. issued by the Ministry of Health, Labour and Welfare (MHLW). In addition, the Pharmaceuticals and Medical Devices Agency (PMDA) recently established an information website, and the provision of enhanced information is now being promoted not only for health care professionals but also for patients. “Drug Guide for Patients” is one of the information tools for patients. The “Drug Guide for Patients” is presented so that the patient understands the correct use of the prescribed drug and serious adverse drug reactions can be recognized at an early stage. It is expected to contribute to the prevention of such adverse reactions by early detection and rapid cure. However, the guides have a low profile and are not yet fully exploited. They are currently being prepared without the direct involvement of patients although they are prepared from a patient point of view. These issues need to be resolved by encouraging broad use, a review of the contents and the involvement of patient groups to provide truly useful information. It is hoped that with these steps the guides will aid in further increasing risk communication to patients reading them.
Patients and consumers have desired high quality drug information in their pharmacotherapy, and are entitled to receive it. It is desirable that the information should be aimed at shared decision-making between patients and healthcare professionals about medications. The quality of drug information available to patients should also be assured. With an aim to improve the quality of “Drug Guide for Patients”, we investigated Patient Information Leaflets (PILs) which are approved by the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom (UK) with regard to the criteria of development and user testing for assuring the quality of the PILs. In the European Union (EU), these are called Package Leaflets (PLs). PILs have been a legal requirement in the UK since 1999 for all medications. The user testing of PILs has been implemented as evidence since 2005 so that people can rely on the information provided in the leaflet. Execution of PILs which follow the guidance of the user testing, according to the guidance of this user testing, would reflect the views of patients. Here, we introduce the development process and implementation of user testing of PILs. In terms of readability, accessibility and understandability of drug information for patients, we need to discuss involving the public in decisions on how its quality should be assured and how it can be made easily be comprehensible for patients, in order to make effective use of “Drug Guide for Patients” in the future in Japan.
Risks for patients and consumers can be minimized depending on how they are provided appropriate drug information. Therefore, from the viewpoint of hospital pharmacists, I would like to report on how information should be provided in order to minimize patient risk. For example, there is an ongoing opinion that the provision of easy-to-understand drug information to patients and consumers “does not appear necessary”. The reasons for this include the following: Because the level of understanding varies greatly among patients, it is difficult to define what “easy-to-understand” information entails; rather, it may cause misunderstanding. These problems occur repeatedly if they are resolved by individual institutions. Therefore, it is essential to standardize the drug information provided to patients, that is, to establish a system to transmit drug information to patients and consumers. Regardless of whether the development of a hospital information system is in progress or not, it can be said that the development of such information systems is gradually spreading outside of hospitals and the situation is changing. From the viewpoint of patients, medical services are not limited to those from hospitals. Patient-centered collaboration between hospitals/clinics and pharmacies (but not the collaboration between hospital pharmacists and community pharmacists (why not?)) can provide good medical services only if patient information is shared. It is essential to establish a system for providing a drug guide for patients, in order to have patients understand drug information. The preparation of Drug Information for Patients would provide health care specialists a communication tool that helps minimize patient risk.
Draft versions of two products of based on a “Drug Guide for Patients” have been prepared the guidelines proposed in “Research on risk communication between patients and healthcare professionals regarding information on safety measures for drugs, etc.” by Health and Labour Sciences Research Grants. We conducted a questionnaire survey on the draft to identify issues regarding the contents and their preparation from the viewpoint of pharmaceutical companies as authors. The questionnaire results indicated that, the segments of the contents of the “Drug Guide for Patients” based on the new guidelines are generally acceptable. In this paper, the author offers proposals to address issues regarding the preparation of easy-to-read contents for patients and strategies to promote the overall understanding recognition of Drug Guide for Patients. Drug Guide for Patients are expected to be utilized as materials providing information to be used for routine risk minimization activities of the Risk Management Plan in the future.
In order for a patient to read a medication guide and develop appropriate behavior regarding use of the medication, the guide should suit patients' needs. In medical care, the primary needs of patients are preventing/curing disease and/or relieving symptoms. Certainly, patients would like knowledge about what can be expected after taking a medication. However, current “Drug Guides for Patients” are based on drug labeling, which is essentially a medically sophisticated instruction manual for medical professionals who have existing knowledge about the medical treatment of the disease. Thus, there seems to be a gap in patients' needs and the contents of existing drug guides. Consequently, this disconnect may be part of the reason Drug Guides for Patients have been underused. If a patient treatment guide, which gives an overview of the disease and possible treatment strategies, is provided in conjunction with a drug guide, this combination may be useful for satisfying patients' needs. In addition, patients generally prefer detailed drug information. Consistently, surveys have revealed that many patients would like to get more information about prescribed medicine than what is frequently provided in medical practice. Furthermore, one survey reported that detailed information about possible side effects resulted in improved compliance. The need to provide patients with drug information can be considered from three points of view: patients' rights, best decision-making by the patient, and minimizing risks. Although in daily practice doctors and pharmacists may have some difficulty providing detailed medication information that includes all possible risks, more effective ways to communicate this information to patients have been suggested.
Metallomics is newly coined terms and defined as a comprehensive analysis of the entirety of metal and metalloid species within a cell or tissue type. Then, metallome is defined as the entire category of metalloproteins and any other metal-containing biomolecules. Metallomics and research on metallome require analytical techniques that can provide information on the identification and quantification of metal/metalloid-containing biomolecules. This concept has been called speciation, and the acquisition of data according to the concept is performed using hyphenated techniques involving both separation and detection methods. In this review, the author intends to present several applications of complementary use of HPLC-inductively coupled plasma mass spectrometry (ICP-MS) and HPLC-electrospray ionization tandem mass spectrometry for identification of unknown selenium-containing metabolites, and also to present a newly developed technique, capillary LC-ICP-MS to be used for the analysis of metal-binding proteins.
Crush syndrome (CS) is characterized by ischemia/reperfusion-induced rhabdomyolysis and subsequent systemic inflammation and has a high mortality rate, even when treated with conventional therapy. In previous studies, we demonstrated that treatment of rats with acute lethal CS using dexamethasone (DEX) had therapeutic effects in laboratory findings and improved the clinical course of CS. However, because the application of DEX in CS therapy is unknown, evaluation of the pharmacokinetic parameters of DEX was considered essential to support its clinical use. Here, we investigated the pharmacokinetic characteristics of DEX in a rat model of CS. Anesthetized rats were subjected to bilateral hind limb compression using rubber tourniquets for 5 h, followed by reperfusion for 0 to 24 h. Rats were divided randomly into 4 groups: saline-treated sham (S) and CS groups and 5.0 mg/kg DEX-treated S (S-DEX) and CS (CS-DEX) groups. Blood and tissue samples were collected for HPLC analysis. In the CS-DEX group, the pharmacokinetic parameters of the area under the concentration-time curve, mean residence time, and distribution volume levels increased significantly compared to the S-DEX group, whereas total body clearance, elimination rate constant, and renal clearance levels decreased significantly. Moreover, decrease of muscle tissue DEX concentration and of CYP3A activity were observed in the CS-DEX group. These results show the pharmacokinetic characteristics of DEX in the rat CS model and support the potential use of DEX in disaster medical care.
In addition to cognitive decline, Alzheimer's disease patients also exhibit non-cognitive symptoms commonly referred to as behavioral and psychological symptoms of dementia, or BPSD. These symptoms have a serious impact on the quality of life of these patients, as well as that of their caregivers, but there are currently no effective therapies. The amyloid β-peptide (Aβ) is suspected to play a central role in the cascade leading to Alzheimer's disease, but the precise mechanisms are still incompletely known. To assess the influence of Aβ pathology on cognitive and non-cognitive behaviors, we examined locomotor activity, motor coordination, and spatial memory in male and female APPswePS1dE9 mice (Alzheimer's disease model, double transgenic mice expressing an amyloid precursor protein with Swedish mutation and a presenilin-1 with deletion of exon 9) at 5 months of age, when the mice had subtle Aβ deposits, and again at 9 months of age, when the mice had numerous Aβ deposits. Compared to wild-type mice, the male and female APPswe/PS1dE9 mice showed normal motor coordination in the rotarod test at both 5 and 9 months. In the Morris water maze test, male and female APPswe/PS1dE9 mice showed impaired spatial memory at 9 months; however, no such deficits were found at 5 months. In a locomotor activity test, male APPswe/PS1dE9 mice exhibited locomotor hyperactivity at 9 months, while females exhibited locomotor hyperactivity at both 5 and 9 months compared to the control mice. Together, these results indicate that APPswe/PS1dE9 mice developed spatial memory impairment and BPSD-like behavioral alterations resulting from Aβ accumulation.