bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical Role of Presynaptic Nicotinic ACh Receptor in the Formation of Long‐Term Potentiation: Implications for Development of Anti‐Dementia Drugs
Authors: Nishizaki Tomoyuki , Nomura Tamotsu , Matsuyama Shogo , Kondoh Takeshi , Fujimoto Etsuko , Yoshii Mitsunobu
Published: August 2007

Background: Since neuronal nicotinic ACh receptors are involved in the cognitive function, they have been studied as a target of anti‐dementia drugs. The present study was designed to understand the role of nicotinic ACh receptors in the expression of long‐term potentiation (LTP), a cellular model of learning and memory.

Methods: The ultrastructural localization of neuronal nicotinic ACh receptors in the rat hippocampus was examined electron‐immunohistochemically using an antibody against the α7 subunit, forming a brain‐type nicotinic ACh receptor. Miniature excitatory postsynaptic currents (mEPSCs) were monitored in cultured rat hippocampal neurons. Schaffer collateral‐CA1 LTP and perforant path LTP were analyzed by recording field excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs) in the CA1 region and the dentate gyrus of rat hippocampal slices or in the intact mouse hippocampus.

Results: α7 receptors are preferentially localized on presynaptic terminals, where the receptors are employed in the release of the excitatory neurotransmitter, glutamate. The probability of LTP development was markedly reduced in the presence of the neuronal nicotinic ACh receptor antagonists, α‐bungarotoxin and mecamylamine, in both the CA1 region and the dentate gyrus of rat hippocampal slices. Perforant path LTP was never induced in slices with selective cholinergic denervation using 192 IgG‐saporin, while it was not affected by atropine, a selective muscarinic ACh receptor antagonist, in normal slices. Nicotine facilitated hippocampal neurotransmission with the saturation occluding the potentiation induced by tetanic stimulation, and vice versa. A similar occlusion was also obtained with an intact mouse hippocampus. These types of LTP, which are dependent uponN‐methyl‐D‐aspartate (NMDA) receptors, were still induced by treatment with nicotine in the presence of D‐2‐amino‐5‐phosphonovaleric acid (APV), a selective NMDA receptor antagonist.

Conclusion: The results of the present study suggest that presynaptic nicotinic ACh receptors play a critical role as a target of retrograde messengers in the formation of NMDA receptor‐dependent LTP. This may account for the involvement of nicotinic ACh receptors in cognitive function. Drugs enhancing the activity of neuronal nicotinic ACh receptors, therefore, are capable of expressing LTP, conversely, ameliorating dementia.
Geriatric Neuropsychopharmacology: Unmet Needs
Authors: Cummings Jeffrey L. , Senanarong Vorapun
Published: August 2007

Abstract: Substantial progress has been made in developing new pharmacological agents for geriatric neurological diseases with behavioral manifestations such as Alzheimer's disease and Parkinson's disease as well as new psychotropic agents for psychogeriatric disorders including atypical anti‐psychotics, new antidepressants and anti‐agitation agents. The growth of the world elderly population demands improved psychogeriatric neuropharmacology. Disease mechanisms are increasingly well understood in geriatric degenerative disorders but remain obscure for idiopathic conditions such as depression, psychosis, and bipolar illness. Classifications of psychiatric disorders underemphasize issues important in psychogeriatrics such as apathy and agitation. Evolving regulatory requirements make it imperative that clinical trials be performed in geriatric populations if labeling for use in these populations is sought by pharmaceutical companies. There are unmet needs in almost all phases of drug development including identification of therapeutic targets; optimization of lead compounds; investigation of toxicity and pharmacokinetics; phase I, II and III trials; and post‐marketing investigation. Outcomes that are more relevant to clinical practice and more patient‐centered are needed in clinical trials. These include assessments of the impact of treatment on quality of life; changes in behavior; functional abilities; delayed pivotal endpoints, such as nursing home placement; and secondary effects on caregivers. Surrogate biological markers of drug effect on disease processes are urgently needed. Resolution of ethical issues including informed consent must be achieved to facilitate advances in drug development. Globalization of drug discoveries to enable use of therapeutic advances by patients throughout the world is necessary. Translational research, changes in public policy to enhance acceptance of new drug development, and harmonization of drug testing and regulatory guidelines will improve globalization of advances in psychogeriatric pharmacotherapy. Identification of these unmet needs in geriatric neuropsychopharmacology suggests an agenda for research activities.
Effect of Aging on Gene Expression of Metabotropic Glutamate Receptor 5 and Glutamate Transporter‐1 in the Prefrontal Cortex of Schizophrenics
Authors: Shimada Hideho , Ohnuma Tohru , Emson Piers C. , Aral Heii
Published: August 2007

Background: The involvement of the glutamatergic system in the patho‐physiology of schizophrenia is attracting interest because an antagonist of N‐methyl‐D‐aspartate (NMDA) glutamate receptor has been demonstrated to induce schizophrenic‐like symptoms in normal subjects. The results of previous studies have also suggested that glutamatergic function is reduced in the prefrontal cortex (PFC) of diagnosed schizophrenics. In order to provide additional evidence for this, we investigated whether expression of metabotropic glutamate receptor 5 (mGluR5) and glutamate transporter‐1 (GLT‐1) in the PFC is altered in schizophrenia.

Methods: We compared the expression of mGluRS and GLT‐1 by in situ hybridization in Brodmann area 9 (B9) and 10 (B10) of the prefrontal cortex in 5 normal individuals and 5 schizophrenics that were younger than in previous studies, and examined the relationship between age and mRNA expression.

Results: There were no significant differences in either mGluR5 or GLT‐1 mRNA expression between the schizophrenics and controls, however, there was a significant correlation to increase mGluR5 mRNA levels in the schizophrenics in both layer III and layer V of B9 with age, a finding not observed in the controls.

Conclusion: The results suggest that the brains of schizophrenics may be vulnerable to aging and that the glutamatergic dysfunctions previously reported in schizophrenics may be partly explained by the aging process.
Basic and Clinical Studies on the Measurement of β‐amyloid(1–42) in Cerebrospinal Fluid as a Diagnostic Marker for Alzheimer's Disease and Related Disorders: Multi Center Study in Japan
Authors: Takeda Masatoshi , Tanaka Toshihisa , Arai Hiroyuki , Sasaki Hidetada , Shoji Mikio , Okamoto Koichi , Urakami Katsuya , Nakashima Kenji , Matsubayashi Takeyuki , Sugita Mitsunori , Yoshida Hiroshi
Published: August 2007

Background: The development of diagnostic markers for earlier and more accurate clinical diagnosis of Alzheimer's disease (AD) is essential to identify unequivocally AD patients during life. This study is to investigate the basic performance and clinical significance of β‐amyloid(1–42) (Aβ42) level measurement in cerebrospinal fluid (CSF) alone or in combination with CSF tau for distinguishing AD from non‐AD disorders.

Methods: The basic characteristics of the reagent for measuring Aβ42, which used Sandwich ELISA, was examined. The clinical studies were done at 5 centers in Japan. CSF samples from 353 patients were collected and classified into the following six groups; AD (n=189), Mild Cognitive Impairment (MCI: n=25), Neurodegenerative disorders without AD (ND: n=66), Cerebrovascular disturbance (CVD: n=28), Other neurological disorders (OND: n=18) and Neurological control (NC: n=27) group.

Results: Mean levels of Aβ42 in CSF were significantly lower in AD (395 pg/mL) than MCI (586 pg/mL;p<0.001), ND (530 pg/mL; p<0.001), CVD (504 pg/mL; p<0.001) and NC (605 pg/mL; p<0.001), respectively. Mean levels of AD unit (tau/Aβ42) were significantly higher in AD (1.63) than MCI (0.79; p<0.001), ND (0.56; p<0.001), CVD (0.34; p<0.001) and NC (0.19; p<0.001), respectively. Discrimination of AD from other related disorders was significantly improved by the combined assessment of Aβ42 and tau. When the cut‐off level of an AD unit was 0.67, the sensitivity for AD was 80% and the specificity for other related disorders was 86%. The positive rate (AD unit>0.67) of MCI patients who had progressed to AD within a few years was 79% (15/19).

Conclusion: The combined measurement of CSF Aβ42 and tau is clinically a useful diagnostic marker to discriminate AD at an early stage including MCI from normal aging and other related disorders.
Reliability of a Rating Scale to Assess Post‐stroke Psychiatric Symptoms
Authors: Kusunoki Tadashi , Inomata Tomokazu , Homma Akira , Hirai Shunsaku
Published: August 2007

Background: Various rating scales for post‐stroke psychiatric symptoms such as cognitive impairment have long been used in drug efficacy trials in Japan. However, their reliability has not been established. The purpose of the present study was to examine the inter‐rater and intra‐rater reliability of a rating scale, which has been conventionally used in Japan.

Methods: The most frequent symptoms, including apathy, emotional and cognitive impairment, found in post‐stroke patients were assessed using a rating scale comprising 17 items and 4 global assessment scales. Semi‐structured interviews of 18 patients with symptoms with various degrees of severity were videotaped. Twelve physicians who were not interviewers independently assessed the severity of symptoms in the 18 patients by replaying the videotapes. This procedure was repeated twice with an interval of two months to examine inter‐rater and test‐retest reliability.

Results: The results revealed almost satisfactory reliability. Intraclass correlation coefficients were over 0.6 in the inter‐rater analysis for most items and the concordance correlation coefficients were over 0.7 in the intra‐rater analysis. The rating scale was considered to be reliable, although some items showed relatively low agreement.

Conclusion: The conventional rating scale to assess post‐stroke psychiatric symptoms showed satisfactory inter‐rater and intra‐rater reliability by the videotape method. The validity study should be further investigated.
Pacing Rhythms of “Wanderers” with Dementia
Authors: Hori Koji , Inada Toshiya , Tominaga Itaru , Oda Tatsuro , Teramoto Hiroshi , Kashima Haruo
Published: August 2007

Background: As wandering in the demented is difficult to define qualitatively, we tride to define it quantitatively. We investigated the relationship between wandering and rhythm abnormalities.

Methods: In order to study the pacing rhythms of wanderers observed in a subgroup of demented inpatients (dementia due to Alzheimer's disease and vascular dementia), we assessed 115 inpatients in terms of steps during four parts of a day and total daily steps using a pedometer.

As the mean+2 S.D. of total daily steps in the nondemented was 9,979, we defined 10,000 steps in a day as the cut off for defining demented wanderers versus nonwanderers. Then, the pacing rhythms (nadir part and amplitude) were compared among demented wanderers, demented nonwanderers and nondemented subjects.

Results: That there were no statistically significant differences among the three groups. But wandering groups defined by pedometer exhibited many of the same characteristics in wanderers observed in other studies.

Conclusion: The quantification of steps might provide a good hallmark of wandering behaviors in the demented, and these results might indicate hyperpacing rather than rhythm dysfunctions to be essential to wandering behavior.
Symptomatology of Late‐onset Schizophrenia and Paranoid Disorders
Authors: Hamada Hidemichi
Published: August 2007

Abstract: There is controversy concerning the classification of late‐onset paranoid disorders, but many interpret it as schizophrenia that is first manifested in old age. As a result of the revival of the concept of late‐onset catatonia in recent years, the classification of late schizophrenia has been reorganized. Late‐onset paranoid disorders have two characteristics in terms of their symptomatology: a transition from the boundaries of the self to material boundaries, and delusions of injury. In late‐onset paranoid disorders there is adherence of the boundaries of the self to physical boundaries in an external form that can be seen with the eyes. Delusions of injury, in which living space within physical boundaries is infringed, become manifestations, such as delusions of robbery, jealousy, and delusions of infestation.
The Present State of Charles Bonnet Syndrome
Authors: Terao Takeshi
Published: August 2007

Abstract: This review attempts to integrate the present, somewhat confusing, state of the research on Charles Bonnet syndrome (CBS). After a brief introduction giving the history of CBS and its diagnostic criteria, relevant case reports and studies are reviewed. As a result of this review, it is revealed that CBS may have heterogenous causes: peripheral (visual impairment), central (organic brain lesion), and both. The neuroimaging findings on CBS are inconsistent, but in the pharmacotherapy for CBS, it has been found that anticonvulsants may be effective, although randomized controlled studies are needed. Moreover, the time course of CBS seems to vary: remission, continuation, development into dementia, and so on. With respect to a possible association between CBS and dementia, it is suggested that clinicians follow such patients up longitudinally, because the available diagnostic criteria for CBS are almost exclusively based on cross‐sectional observations.
Delusional Parasitosis
Authors: Hayashi Takuji
Published: August 2007

Abstract: In order to examine the clinical characteristics of delusional parasitosis in a large sample, we previously analyzed 102 cases reported in Japan. In this article, these results are shown briefly, and psychopathological symptoms and nosological classifications are discussed.

In our study, 53 cases were classified in to pure type excluding endogenous psychoses, induced psychosis and somatically based psychoses. Two thirds of the pure type cases had visual experiences. These cases involved both hallucinatory and delusional factors, and symptoms considered delusional perception or bodily hallucinations “being made” by parasites were included in these experiences. Although these symptoms are thought to be specific to schizophrenia, some biological findings were often present. Furthermore, the facts concerning sex difference, age at onset, and no personality changes resembled late‐onset paraphrenia, that is, a type of atypical psychoses. Therefore, both psychopathological and biological studies should be carried out continuously from now on.
Paraphrenia and Late Paraphrenia
Authors: Sato Arata , Ihda Shin
Published: August 2007

Abstract: Paraphrenia is a clinical entity described by Kraepelin in the eighth edition of his textbook in 1913. He formed this concept to define a group of patients who exhibited symptoms characteristic of dementia praecox, but with minimal disturbances of emotion and volition, and marked delusions with or without hallucinations. Herein the four subtypes of paraphrenia classified by Kraepelin and the prognostic research of Mayer, who studied the outcomes of patients reported by Kraepelin are described. After the publication of Mayer's study in 1921, the view to differentiate paraphrenia from schizophrenia was considered to be unfounded in Germany. In the 1950s, Roth in the U. K. examined patients over age 60 with delusional states and with/without hallucinations, and introduced late paraphrenia as a clinical entity. Although the term (late) paraphrenia present in the ICD‐9 is not included in the recent diagnostic criteria, many researchers recognize that the concept of (late) paraphrenia has not lost its usefulness for the diagnosis of psychotic disorders in old age. As in the days of Kraepelin, the problems concerning paraphrenia cannot be neglected when considering the classification of psychotic disorders.
Region‐specific and Age‐related Decrease of Parvalbumin Gene Expression in the Prefrontal Cortex of Elderly Patients with Schizophrenia
Authors: Takahashi Tadashi , Emson Piers C. , Arai Heii
Published: August 2007

Background: Multiple studies on schizophrenia have suggested a dysfunction of γ‐aminobutyric acid (GABA) transmission in the prefrontal cortex (PFC) and some vulnerability of the central nervous system to the aging process. Since one of the calcium‐binding proteins, parvalbumin (PV) is a useful marker for a subpopulation of GABAergic local circuit neurons, we determined the PV gene expression in the PFC in schizophrenic brains to study a possible involvement of GABAergic system and its vulnerability, if any, to the aging process.

Methods: We attempted a detailed in situ hybridization to determine the PV gene expression throughout the three PFC subregions (Brodmann areas; BAs 9, 10, and 11) from six elderly patients with schizophrenia and five age‐matched normal individuals.

Results: The regional levels of PV messenger RNA (mRNA) were significantly decreased in BAs 9 and 10 of schizophrenics compared with controls. The cellular levels were significantly decreased in layers III, IV, and V in BAs 9 and 10 of schizophrenics. However, in BA 11 of schizophrenics, the cellular level was significantly decreased in layer in alone. There were significant reverse correlations between the PV mRNA levels in those areas and the age at death in the schizophrenic group, but not in the controls.

Conclusion: The present results not only provide further evidence of a disturbance in GABA transmission in the PFC of schizophrenics, but also suggest that such dysfunction may be region‐specific and vulnerable to the aging process.
Cognitive Patterns of Good and Poor Namers in Old Age
Authors: Nakaaki Shutaro , Nakanishi Masao , Fujiwara Nakako , Hamajima Hideki , Nakamura Hikaru , Yoshida Shinichi , Sato Junko , Tatsumi Hiroshi , Furuhashi Kyoko , Furukawa Toshiaki , Connor Lisa Tabor , Lindfield Kimberly C. , Albert Martin L.
Published: August 2007

Background: Word finding difficulties are common complaints among healthy elderly persons. Recently, both cross‐sectional and longitudinal studies have demonstrated a decline in naming ability, particularly in subjects 70 years old or over. It is unclear which cognitive mechanisms cause this reduction of lexical retrieval ability with advancing age.

Methods: Based on their performance in the Picture Naming Test, normal elderly subjects, predominantly in their 70's were divided into two groups, namely, good and poor namers. The two groups did not differ significantly with respect to age, education, or Mini‐Mental State Examination (MMSE) test score. We administrated a comprehensive neuropsychological battery involving a verbal and non‐verbal memory task, semantic memory task, and attention task. The performance in each test was compared between the two groups.

Results: Significant differences between the two groups were demonstrated in only two tasks, the Trail Making Test (part B) and the Stroop Colored Word Test.

Conclusion: Set‐switching and inhibitory processes in attentional control, as reflected on by the results in the Trail Making Test (part B) and the Stroop Colored Word Test, may contribute to lexical ability in normal aged people. There is little evidence that verbal and non‐verbal memory or semantic memory are associated with naming ability. Poor performance in naming tasks of elderly people may be attributable to their inability to suppress inappropriate responses.
Cross‐sectional Evaluation of Aged Schizophrenics at Home‐Influence of Aging and Social Support
Authors: Saito Haruna , Kanamatsu Naoya
Published: August 2007

Background: We carried out a cross‐sectional evaluation on the living state and social support in aged schizophrenic patients and the circumstances that enables them to live at home.

Methods: There were 19 aged schizophrenic outpatients at Nagano prefectural Kiso Hospital who were at home. Eight were male and 11 were female, and their age ranged from 65 to 82 years with a mean of 70.3 years. Based on medical records and interviews at the outpatient clinic, we investigated the following factors: the family environment, care providers, relations with medical institutions, present symptoms, and the influence of aging.

Results: Of the 19 patients, 18 were in remission. The characteristics of daily life common to them were the following: (1) They had a family as the care providers. The patients living alone depended on care providers in welfare activities in the community. (2) Seventeen patients continued to visit the hospital without admission. All of them were close to the medical institutions. (3) Dementia such as Alzheimer's dementia or cerebrovascular dementia was not suspected in 18 patients. Of the 19 patients, 9 had made an application for care insurance.

Conclusion: The characteristics common to the patients with remission were the presence of care providers, participation in community life, the presence of nearby medical institutions and ongoing treatment. These may be important for maintaining a healthy life not only in aged schizophrenic patients but also in the general aged population. Therefore, the results in this study support the theory that the social state and social adaptation in aged schizophrenic patients generally approaches that found with general aging.
What Environmental and Staffing Characteristics Predict Behavioural and Psychological Symptoms of Dementia in Nursing Home Residents?
Authors: Brodaty Henry , Draper Brian , Low Lee‐Fay
Published: August 2007

Background: Behavioural and psychological symptoms of dementia (BPSD) are common in nursing home residents and distressing. Factors leading to their occurrence are incompletely understood.

Aim:

To investigate environmental and staffing variables associated with the prevalence of BPSD.

Methods:

Survey of Directors of Nursing and 505 residents of 11 nursing homes in the eastern suburbs of Sydney. Resident variables included measures of cognition, dependency, and BPSD using the BEHAVE‐AD. Directors of nursing completed a questionnaire that rated physical design, staff and resident characteristics.

Results

There was a two‐to three‐fold difference in the prevalence of total and subscale scores on the BEHAVE‐AD. Higher scores were associated with higher resident to bedroom ratio, living with less functional residents, lower levels of staffing, less staff training, fewer activities for residents and management less geared towards managing difficult behaviours.

Conclusion:

The number of residents sharing a bedroom, the mix of residents' functional capacity, staff numbers and training and the use of activity programs may influence BPSD.
A Case with Striatocapsular Infarction that Developed Severe Depression which was Successfully Treated with Olanzapine and Paroxetine
Authors: Tagami Shinji , Niigawa Hisayoshi , Suzuki Junko , Mizoguchi Yuriko , Mikiya Ryosuke , Miyamae Yasuyuki , Takeda Masatoshi
Published: August 2007

Abstract: It is well known that depression can often occur after various kinds of cerebrovascular disorders and that antidepressants including selective serotonin reuptake inhibitor (SSRI) are effective against poststroke depression (PSD). But some cases of PSD, as in the case of endogenous depression, can be treatment‐resistant. Here we report a case that developed severe appetite loss and depression one month after the onset of left‐sided Striatocapsular infarction. The appetite loss was so severe that transnasal nutrition was necessary. Amantadine or sulpiride was administered to him, but neither of them were effective. The maximum tolerable dose of paroxetine gave him slight improvement, but it was not enough. Recently, it has been reported that a combination of olanzapine, which is a kind of multi‐acting receptor targeted agent (MARTA), and fluoxetine, a kind of SSRI, demonstrated superior efficacy for treatment‐resistant depression (TRD) compared to either agent alone. In our case, a combination of olanzapine and paroxetine showed a drastic improvement in appetite loss and depression. The result suggested that a combination of MARTA and SSRI can be as effective in treatment‐resistant PSD as in endogenous TRD.
The Ethical Issue in Caring for the Elderly with Dementia
Authors: Saito Masahiko
Published: August 2007

In recent decades, the demography of Japanese society has been changing very rapidly. In 1970, the population of the elderly in Japan was 7.1%, 17.6% in 2000, and expected to be 26.9% in 2020. However, the change in the structure of family for the elderly may be much more drastic than the increase of the elderly. In 1975, there were 1.53 million elderly living by themselves either alone or as a couple, 4.57 million in 1995, and it is estimated to be more than 9 millions in 2020. The decline of the traditional family unit in Japan resulted in the rapid increase of the elderly living by themselves.
A Risk of Alzheimer's Disease and Aluminum in Drinking Water
Authors: Meshitsuka Shunsuke , Aremu David A. , Nose Takayuki
Published: August 2007

Abstract: The epidemiological studies on the relation between Alzheimer's disease and aluminum in drinking water are reviewed. In descriptive studies, case‐control studies, and also cohort studies aluminum in drinking water turned out to be positive for the senile dementia of Alzheimer type. Negative results were obtained in the studies of presenile dementia or alminum levels lower than 0.1 mg/L. Aluminum is the third abundant element on earth, therefore, exposure to aluminum is inevitable in daily life. It is known that as over 95% of cases with Alzheimer's disease are sporadic, some environmental factors are expected to be etiological. Aluminum has been so far studied as a candidate for a neurotoxic factor. It is not known why attention has been given to only aluminum in drinking water as the cause of the neuro‐degenerative disease other than aluminum in foods or medications, and how aluminum acts as a toxicant in brain. Nonetheless, reduction of aluminum in drinking water is recommended, as well as investigations on the mechanism of neurotoxicity of aluminum to find out the way to be free from the fear of aluminum.
Frontal Theta Rhythm: Evaluation of its Clinical Electrophysiological Significance with a View Point of Aging
Authors: Ueda Yumiko , Matsubara Hiroo , Shinomiya Shigeko , Arai Heii
Published: August 2007

Background: Frontal theta rhythms can be observed in routine electroencephalogram (EEG) examinations. Their significance has been interpreted from pathological or physiological viewpoints by many previous studies. We evaluated the clinical electrophysiological significance including aging of the frontal theta rhythms to differentiate pathological theta activities.

Methods: Since 23 EEGs, out of 2,424 patients routinely taken in our hospital and 87 healthy volunteers, showed frontal theta rhythms during drowsiness, those subjects were re‐examined at rest and during a mental task. The morphological features of theta rhythms were compared between the two conditions and analyzed in terms of clinical conditions.

Results: In 16 subjects theta rhythms either disappeared or were suppressed during the mental task (“suppressed” group). In the seven subjects theta rhythms recorded during drowsiness were equivalent or were activated by the mental task (“activated” group). The subjects of the suppressed group were found to have clinical findings suggesting cerebral organic changes, while those of the activated group did not have such findings. In the morphological comparison between these groups, the frequency, amplitude, and duration were significantly different.

Conclusion: The differentiation of these two types of frontal theta rhythms may be possible by clinical information, morphological features of theta rhythms and their changes during a mental task. In the case of pathological theta rhythms appearing in middle and advanced age, they can sometimes be based on aging due to arteriosclerotic changes and others.
Plasma Concentration of Risperidone Showed a Correlation with Daily Dose, but not with Age nor Cytochrome P‐450 2D6 Gene Polymorphisms in Japanese Schizophrenics
Authors: Matsubara Yoichiro , Ohnuma Tohru , Shibata Nobuto , Takahashi Tadashi , Arai Heii
Published: August 2007

Background: Risperidone, a neuroleptic, is mainly metabolized by the enzyme cytochrome P‐450 2D6 (CYP2D6), which has over 20 genetic polymorphisms, to its major active metabolite, 9‐hydroxyrisperidone (9‐OH‐risperidone). The clinical outcome in risperidone treatment is highly dependent on the plasma concentration of risperidone.

Methods: In this study, in order to investigate whether individual plasma concentration of risperidone is affected by CYP2D6*4, CYP2D6*5 and major oriental mutation, CYP2D6*10A polymorphism, the genomic DNA from 53 subjects taking risperidone were analyzed by restriction fragment length polymorphism method for the determination of each genotype.

Results: Neither any plasma concentration of risperidone or 9‐OH‐risperidone nor metabolic ratio of risperidone/9‐OH‐risperidone was affected by CYP2D6 genotypes. “Plasma concentration of risperidone” and “plasma concentration of 9‐OH‐risperidone” showed a strong correlation with “risperidone dose/body weight” (r=0.60, p<0.0001; r=0.54, p<0.0001, respectively). “Age” of present subjects did not show any significant correlation with plasma concentration of risperidone (r=‐0.018), 9‐OH‐risperidone (r=0.211) nor the metabolic ratio (r=‐0.237, all p>0.05).

Conclusion: Based on these results that CYP2D6 genotypes and “age” showed no correlation with any plasma concentration of risperidone metabolites, it can be said that clinically the most important factor is to keep a small daily dose amount, regardless of the age of the subject. In this way, an unexpected high plasma concentration of risperidone can be avoided.
A Clinicopathological Study of Idiopathic Normal Pressure Hydrocephalus
Authors: Matsumoto Mitsuhiro , Kosaka Kenji , Horimoto Yoshihiko , Akatsu Hiroyasu , Yamamoto Takayuki , Matsukawa Noriyuki , Ueda Ryuzo , Ojika Kosei
Published: August 2007

Background: Since Hakim and Adams introduced the clinical entity of normal pressure hydrocephalus (NPH) in 1965, postmortem studies of idiopathic NPH have been few in number. Several autopsy cases reported with clinically probable “idiopathic NPH” were diagnosed with Alzheimer's disease (AD) or Binswanger's disease (BD) neuropathologically. Therefore, the neuropathological study of pathologically confirmed idiopathic NPH remains to be completed both quantitatively and qualitatively.

Methods: Out of 239 autopsy cases in Fukushimura Hospital, 13 patients had been diagnosed clinically as having NPH. After excluding seven cases diagnosed neuropathologically with other diseases or secondary NPH, we investigated the clinicopathological findings of six patients with idiopathic NPH.

Results: Four patients presented with the complete classic triad consisting of progressive dementia, gait disturbance, and urinary incontinence. All cases exhibited progressive ventricular enlargement with periventricular lucency by computed tomography images. We found (1) diffuse marked dilatation of the lateral ventricles of unknown etiology, and (2) the changes of ependymal cells and subependymal tissue around the callosocaudate angle. Furthermore, no complications were suspected neuropathologically in all cases, such as AD, BD, or Lewy body disease.

Conclusion: We experienced six autopsy cases with pathologically confirmed idiopathic NPH. They had two pathological features of NPH but no other pathological disorders that might cause NPH. Several “idiopathic NPH” cases reported previously have been diagnosed neuropathologically with other disorders. However, the presented cases could be clearly distinguished from such “idiopathic NPH.” Therefore, our cases should be defined as idiopathic NPH neuropathologically. By accumulating more cases and investigating further we hope to elucidate the pathogenesis and further develop treatment for idiopathic NPH.
SPECT and Alzheimer's Disease
Authors: Bhriain Siobhan Ni , Lawlor Brian A.
Published: August 2007

Abstract: This article is review of the role of single photon emission tomography (SPECT) in the diagnosis and management of Alzheimer's disease (AD).

It begins by describing AD in terms of diagnosis, pathology and current pharmacological treatment. The relevance of the pathological changes in relation to SPECT is outlined. This is discussed in terms of receptor abnormalities and atrophic changes which in turn effect cerebral blood flow.

A detailed description of SPECT methodology describes how the quality of the image is effected by SPECT instrumentation, image reconstruction techniques and a number of subject factors.

The article goes on to discuss the role SPECT in the diagnosis of AD and its potential for facilitating early diagnosis. The main focus here is on the changes which occur in cerebral blood flow in AD and the sensitivity and specificity of regional changes in cerebral blood flow is described.

Image analysis is an area in which there has been many developments in the last number of years and the authors describe the differences between qualitative and quantitative image analysis, with a particular focus on statistical parametric mapping (SPM).

There is a brief discussion concerning receptor ligands and their potential use in the diagnosis and management of AD, although this remains an undeveloped area in SPECT imaging as yet.

Finally, the authors discuss the future possibilities for SPECT and AD, and conclude that there is considerable potential for SPECT in the diagnosis and management of AD with further refinement of image analysis techniques and the development of cholinergic receptor ligands.
Color Responses of Flash Visual Evoked Potentials in Normal Adults, Normal Elderly Subjects and Dementia of the Alzheimer Type Using Light Emitting Diodes
Authors: Yuki Asana
Published: August 2007

Background: Since initially we could only employ the red light goggle‐shaped stimuli equipment with flash light emitting diodes (LEDs), we had little information concerning different color responses of visual evoked potentials (VEPs). On our request, Nihon Kohden (Tokyo, Japan) developed green light goggle‐shaped stimuli equipment with LEDs in 1999.

The purpose of this study was to determine the effects of green and red flash VEPs in normal adults, normal elderly subjects and patients with dementia of the Alzheimer type (DAT).

Methods: Subjects consisted of a normal adult group (n=30), normal elderly group (n=10), and DAT patients (n=7). Transient VEPs of 1 Hz were measured. The recording electrodes were placed at midline‐occipital, left‐occipital and right‐occipital sites in accordance with the ten‐twenty electrode system.

Results: In the normal adult group, peak latencies of green flash VEPs increased significantly compared to those of red flash VEPs (N2, P3: p<0.01, N3: p<0.05). The N2 and P3 latencies of both red and green flash VEPs were delayed in the normal elderly and DAT groups compared with those in the normal adult group. The delayed latencies of red flash VEPs were greater than those of green flash VEPs.

Conclusion: The difference in latency between green and red flash VEPs corresponds to the difference in the conducting time from three rods (each spectrum peak is 419–420 nm, 530–534 nm, and 558–564 nm) to the visual central system. Each channel from the three rods to the visual central system may have an individual speed reaction, individual ageing and pathological changes. The results indicate that the peak latency of red light reveal elderly and pathological change more easily than that of green light.
Apolipoproteins and β Amyloid Transport Pathway
Authors: Kamino Kouzin , Kida Tomoyuki , Tanaka Toshihisa , Tanii Hisashi , Okochi Masayasu , Kudo Takashi , Kobayashi Toshiko , Takeda Masatoshi
Published: August 2007

Abstract: Cholesterol metabolism has been viewed as an important step in the development of Alzheimer's disease, since it was shown that the ɛ4 allele of apolipoprotein E (APOE) gene is a genetic risk and modifies age‐at‐onset of Alzheimer's disease. Although the knowledge of the effect of cholesterol in the neuronal cell has been recently accumulated, the link between systemic and brain cholesterol metabolism remains to be elucidated. Lipoproteins in cerebrospinal fluid (CSF) are fractionated only to high‐density lipoprotein (HDL), and contain apolipoprotein (apo) A‐I, E, A‐II, and J. Whereas apoE is produced in the brain, apoA‐I and apoA‐II in cerebrospinal fluid, the major components of plasma HDL cholesterol, originate from plasma. Plasma HDL is thought to act in reverse cholesterol transport, and in vitro experiments indicated that these apolipoproteins and albumin show a high affinity binding to β amyloid. In patients with Alzheimer's disease, plasma apoA‐I and apoA‐II levels are significantly decreased, which is possibly related to the deposition of β amyloid in the brain, and to the β amyloid transport pathway.
An Overview of the Management of Treatment Resistant Depression in Late Life
Authors: Ng Chee Hong , Schweitzer Isaac
Published: August 2007

Abstract: Treatment resistant depression (TRD) significantly contributes to the morbidity and mortality associated with depression occurring in late life. Yet, depression in the elderly population remains largely under‐recognised and under‐treated. This paper aims to provide an overview of the contributing factors and current treatment approaches in TRD in late life. Consensus on the operational criteria for TRD is still emerging due to unresolved issues on different criteria of definition and diagnosing TRD. If there is treatment failure, a comprehensive diagnostic evaluation along with the assessment of treatment adequacy should be undertaken. Reasons for the lack of treatment response need to be adequately explored including non‐compliance, misdiagnosis and co‐morbid physical, psychiatric and cognitive disorders. Stabilising co‐existing medical conditions as well as addressing the psychological and social issues may be necessary to achieve optimal outcome. Other strategies including increasing the dose and duration of treatment, switching antidepressant, augmentation and combination treatments, and electroconvulsive therapy (ECT) may be appropriate. There is a growing range of treatment options available including newer agents and treatment strategies that may offer improved efficacy and safety for the elderly depressed patients. However, considerable research into such treatment approaches in TRD in late life is still needed. A systematic consideration of all the treatment options with the associated risks and benefits is recommended, together with close monitoring of symptoms, progress and adverse effects.
The Prognosis of Delirium
Authors: Bhat Ravi S. , Rockwood Kenneth
Published: August 2007

Abstract: This paper aims to undertake a systematic review of the published experience on the prognosis of delirium. Using a standard search strategy, we identified studies and assessed them using standard criteria for validity. Seventeen cohorts were identified, with length of follow‐up varying from hospital discharge to four years. Although delirium usually results in increased adverse outcomes in both the short and long term, the mechanism is unclear. A good case can be made, however, that, especially in older patients, delirium and dementia represent alternative expressions of the same underlying pathology.
Relationship between Hippocampal Atrophy and Cognitive Dysfunction in Early Alzheimer‐type Dementia
Authors: Kodama Naoki , Kawase Yasuhiro , Okamoto Koichiro , Fukumoto Ichiro
Published: August 2007

Background: We assessed the relationship between early cognitive dysfunction and morphologic changes in the brain, especially hippocampal atrophy, on MR images in Alzheimer‐type dementia (AID) patients to establish a technique for making an early clinical diagnosis of AID.

Methods: The subjects of this study were 82 individuals who visited Kawase Neurology Clinic. They consisted of 41 ATD patients and 41 elderly individuals without dementia who visited the clinic for a neurological checkup or because of vertigo or numbness as age‐matched controls. As an index for hippocampal atrophy, the hippocampal‐intracranial ratio (HIR) was calculated. Discriminant analysis was performed using HIR results and the correct answer rate for recall and calculation items in Mini‐Mental State Examination (MMSE).

Results: The mean ratio was significantly lower in the ATD patients than in the controls. This supports our previous results. The results of discriminant analysis with Mahalanobis generalized distance in the 41 controls and 22 ATD patients who scored 15 or higher. The sensitivity and specificity of HIR combined with the correct answer rate for recall and calculation items in MMSE were 95.5% and 95.1%, respectively, with an overall accuracy of 95.2%.

Conclusion: HIR combined with the correct answer rate for recall and calculation items in MMSE allows for an early diagnosis of ATD.
Late‐onset Psychosis with Agenesis of the Corpus Callosum
Authors: Suzuki Mitsuru , Kawamura Satoshi , Watanabe Harutomo , Sakai Akio
Published: August 2007

Abstract: A 57‐year‐old woman showing her first psychiatric episode was admitted and MRI revealed agenesis of the corpus callosum with a lipoma. Except for the fact that her elder sister had been diagnosed with schizophrenia at the age of 24, she had no special anamnesis or problems in her life history. At the age of 57, troublesome behavior based on auditory hallucinations and delusions of persecution were noted which made it necessary for her to be taken to a hospital. There were no clinical signs of dementia, pathological reflexes or any other malfunctions. The brain MRI showed complete defect of the corpus callosum with a lipoma at the anterior midline region. According to characteristic findings of agenesis of the corpus callosum, parallel lateral ventricles, colpocephaly, and upward extension of the third ventricle were also noted. There were no findings of vascular change or cortical atrophy. Electroencephalography showed sharp waves and spikes appearing frequently in the parietal and occipital lobes. After being hospitalized, anti‐psychotic drugs were effective against the symptoms which made it possible for her to be discharged after 8 weeks. She returned to her normal daily life and within 12 months there had been no signs of relapse and no considerable changes in MRI either. Although there have been many reports on schizophrenic patients with volumetric reduction of the corpus callosum, late‐onset psychosis with callosal agenesis is quite rare. Neuroimaging investigations for late‐onset psychosis are valuable to detect structural deficits or damages, and further cell‐biological studies on commissural white matter are required to understand the correlations in pathogenesis between developmental failure and acquired brain damage.
Porosity Formation and Prevention in Pulsed Laser Welding
Authors: Zhou Jun , Tsai Hai-Lung
Published: August 2007

Porosity has been frequently observed in solidified, deep penetration pulsed laser welds. Porosity is detrimental to weld quality. Our previous study shows that porosity formation in laser welding is associated with the weld pool dynamics, keyhole collapse, and solidification processes. The objective of this paper is to use mathematical models to systematically investigate the transport phenomena leading to the formation of porosity and to find possible solutions to reduce or eliminate porosity formation in laser welding. The results indicate that the formation of porosity in pulsed laser welding is caused by two competing factors: one is the solidification rate of the molten metal and the other is the backfilling speed of the molten metal during the keyhole collapse process. Porosity will be formed in the final weld if the solidification rate of the molten metal exceeds the backfilling speed of liquid metal during the keyhole collapse and solidification processes. Porosity formation was found to be strongly related with the depth-to-width aspect ratio of the keyhole. The larger the ratio, the easier porosity will be formed, and the larger the size of the voids. Based on these studies, controlling the laser pulse profile is proposed to prevent/eliminate porosity formation in laser welding. Its effectiveness and limitations are demonstrated in the current studies. The model predictions are qualitatively consistent with reported experimental results.
Metal Transfer and Arc Plasma in Gas Metal Arc Welding
Authors: Hu J. , Tsai H. L.
Published: August 2007

This article analyzes the transient complex heat transfer and fluid flow in molten metal and arc plasma during the gas metal arc welding process. The model predicts the formation, growth, detachment, and transfer of droplets from the tip of a continuously fed electrode under the influences of several competing forces including gravity, electromagnetic force, arc pressure, plasma shear stress, and surface tension. Simulations were conducted for five different current levels to study the effects of current on the distributions of temperature, velocity, pressure, and current density in the droplet and/or the arc plasma. Agreement between the simulated results and published experimental data was obtained.
Characterization of Variable Thermal Contact Resistance in Rapid Contact Solidification Utilizing Novel Ultrasound Technique
Authors: Hong F. J. , Qiu H.-H.
Published: August 2007

A method based on a novel ultrasound technique and inverse heat transfer analysis was developed to study the transient thermal contact resistance (TCR) at the early stage of a rapid contact solidification process. This promising technique is nonintrusive and, therefore, provides no distortion to the contact surface as well as the heat transfer process. The effects of impact velocity and initial molten metal temperature on TCR were investigated in detail. An empirical equation that correlates the variable TCR with the initial and interfacial conditions was introduced utilizing the experimental data.
Spatially and Temporally Resolved Temperature Measurements for Slow Evaporating Sessile Drops Heated by a Microfabricated Heater Array
Authors: Paik S. W. , Kihm K. D. , Lee S. P. , Pratt D. M.
Published: August 2007

The spatially and temporally resolved evaporation phenomena of a slowly evaporating water droplet are investigated using a microfabricated gold heater array consisting of 32 linear heater elements (100 μm wide and 15 mm long, each). Each of the gold microheater elements works both as a temperature sensor and as a heater. The experiment is performed under a constant voltage mode to examine the spatially resolved temperature history of the droplet contact surface for a period starting at initial contact with the heater and lasting to the point of complete dryout. The raw data obtained from the linear array have been tomographically deconvolved so that the radial temperature profile can be determined assuming a circular droplet contact surface.