Koichi Miyakawa

A quantitative near-infrared spectroscopy study: a decrease in cerebral hemoglobin oxygenation in Alzheimer's disease and mild cognitive impairment.

A newly developed quantitative near-infrared spectroscopy (NIRS) system was used to measure changes in cortical hemoglobin oxygenation during the Verbal Fluency Task in 32 healthy controls, 15 subjects with mild cognitive impairment (MCI), and 15 patients with Alzheimers disease (AD). The amplitude of changes in the waveform, which was quantitatively calculated by a signal processing method, was significantly lower in the frontal, and the bilateral parietal areas in the AD group, whereas that in the MCI group was significantly lower only in the right parietal area. The NIRS system may be a potential tool for the primary screening of AD.

Maximal Response to Electroconvulsive Therapy for the Treatment of Catatonic Symptoms

Objectives: Because the number of medical lawsuits has recently increased in Japan, doses of medication above the upper limits have recently been avoided, even when treating catatonic patients. We treated catatonic symptoms with drugs within the upper limit of dosage and electroconvulsive therapy (ECT) to determine the maximal response. Methods: We examined 50 consecutive patients with catatonic symptoms admitted to a university hospital during a 32-month period who were treated with either drugs within the upper limit or ECT. Results: Response rates were as follows: ECT, 100%; chlorpromazine, 68%; risperidone, 26%; haloperidol, 16%; and benzodiazepines, 2%. Conclusions: The findings indicated that ECT is the treatment of choice for catatonic symptoms.

Quantitative evaluation of electroconvulsive therapy for Parkinson's disease with refractory psychiatric symptoms.

Patients with advanced-stage Parkinson’s disease (PD) occasionally experience refractory depression or catatonic stupor. Electroconvulsive therapy (ECT) has been reported as a successful procedure for both severe psychosis and motor symptoms in patients with PD. Four patients with PD who were receiving ECT were quantitatively evaluated using the Unified PD Rating scale part III, Hoehn and Yahr scale, Barthel index, Neuropsychiatric Inventory, mini-mental state examination, Revised Hasegawa’s Dementia scale, Beck’s Depression Inventory, and Hamilton Rating Scale for Depression-17. We adopted the “half-age” method, which is an age-based stimulus-dosing method. The patients showed improvement in symptoms of psychosis and motor symptoms without any adverse effects. The interval of improvement after ECT varied among patients. Of note, a decrease in psychiatric symptoms successfully alleviated the burden of caregivers. ECT may be useful to treat parkinsonism with refractory psychosis, major depression, or catatonic stupor, within the limitations of the patients enrolled.

Pulmonary embolism from persistent dilatation of the bladder secondary to anticholinergic side effects

OBJECTIVE To discuss the risk that bladder distention resulting from anticholinergic side effects of antipsychotics can cause iliac vein compression syndrome (IVCS) and subsequent pulmonary embolism (PE). METHOD Case report, review of the literature and discussion. RESULTS We report the case of a 65-year-old man with depression who experienced PE associated with IVCS due to a distended urinary bladder resulting from anticholinergic side effects. PE disappeared after conservative therapy with heparin followed by warfarin. CONCLUSION When drugs with anticholinergic effects are given to immobilized patients such as those with severe depression, close observation including monitoring of urine volume is needed to prevent IVCS caused by drug-induced urinary retention, and subsequent PE.

Long-term effect of donepezil for Alzheimer's disease: Retrospective clinical evaluation of drug efficacy in Japanese patients

Background:  Alzheimers disease (AD) is common in the Japanese population. In 1999, donepezil was authorized in Japan for the treatment of AD. However, because the time since donepezil was authorized is relatively short, there are few reports regarding the long‐term effects of donepezil in Japanese AD patients.

Safety and pharmacokinetics of bapineuzumab in a single ascending-dose study in Japanese patients with mild to moderate Alzheimer's disease.

To evaluate the safety, tolerability and pharmacokinetic profile of bapineuzumab after a single intravenous injection in Japanese patients with mild to moderate Alzheimers disease.

Recurrent cholecystitis in an elderly mentally retarded patient with pica.

The case of a 64‐year‐old patient with pica and severe mental retardation who was admitted to our hospital for treatment of recurrent cholecystitis is reported. Abdominal ultrasound showed sludge in the gallbladder, but no stones. Abdominal CT revealed a foreign body in the duodenum resembling a suction cup of the type commonly used in kitchens and bathrooms. The object could not be removed because it was deeply embedded in the hypertrophic intestinal mucosa. A nasogastric tube was inserted for feeding, since the object impeded the passage of solid foods. The patients fever and abdominal pain subsequently resolved, and laboratory data improved. The indwelling feeding tube prevented recurrence of cholecystitis. Since pica is common not only in patients with mental retardation but also in dementia patients, the present case may also relate to the treatment of acute abdominal conditions in dementia patients.

Phenytoin toxicity associated with hypoalbuminaemia and the paradoxical elevation of serum concentration

Phenytoin, one of the most widely used anti-epileptic drugs, has a narrow therapeutic range because of nonlinear pharmacokinetics. Serum albumin levels also alter serum concentrations of phenytoin because phenytoin is primarily bound to serum albumin (1). Here we report a patient who developed phenytoin toxicity associated with hypoalbuminaemia because of physical complications and the paradoxical elevation of serum concentration. A 64-year-old woman was transferred from a psychiatric hospital to our university hospital because of repeated cholecystitis. She suffered from severe mental retardation. She experienced generalised tonic–clonic seizures for the first time at 9 years of age. Since then, she has suffered from epilepsy and taken phenytoin in combination with sodium valproate. Daily doses of phenytoin and sodium valproate were 250 and 400 mg, respectively. Drug compliance was good and the total serum phenytoin and sodium valproate concentrations were 12.5 and 46.8 μg/ml, respectively (Fig. 1). Her serum albumin was 3.1 g/dl at the time of admission. Her body temperature was 38.0 ◦C and serum alkaline phosphatase was 1300 IU/l. Her diet was stopped and peripheral infusion was started, but oral phenytoin and sodium valproate continued. Treatment with antibiotics, i.e. ceftazidime hydrate 1200 mg for 5 days, clindamycin 2000 mg for 4 days and pazufloxacin mesilate 1000 mg for 17 days, resolved cholecystitis. Unexpectedly, generalised seizures occurred twice during fasting. Her serum albumin decreased to 2.1 g/dl. Surprisingly, the total serum phenytoin concentration increased, so we started to taper off phenytoin dosage. However, the serum phenytoin concentration did not decrease during the following 6 days (maximum 29.7 μg/ml). Intravenous hyperalimentation started and hypoalbuminaemia improved to 3.5 g/dl. Thereafter, total serum phenytoin concentration decreased and her generalised seizures were controlled. In the present case, seizures were coincident with toxic concentrations of phenytoin in serum (2). However, this toxicity appeared although the dose of Fig. 1. Clinical course. , serum albumin (g/dl); , serum concentration of phenytoin (μg/ml); , duration of somnolence and , occurrence of seizure.

P1-294: Genetic association between PCSK9 and USF1 polymorphisms and Japanese Alzheimer’s disease and plasma cholesterol level

(p .001) Apo 3/ 3 genotype was found in 23.08% of the control group against 14.12% in the patients group (p .001). No statistical differences were found in the isoforms 3/ 4 and 2/ 4. No statistical relevance was found with the only individual with the 2/ 2 isoform. Conclusions: Genotype 4/ 4 of apolipoprotein E has a greater prevalence in patients with Alzheimer’s disease confirming our working hypothesis. There is an important association between ApoE 4 as risk factor of Alzheimer’s disease in addition to clinical and diagnosis skills.