Biomedical subjects

Nobuyuki Okamura

Publications and source records attributed to Nobuyuki Okamura.

22 records · Page 2Linked to original sources

PubMed2002

The effects of a sedative antihistamine, d-chlorpheniramine, on visuomotor spatial discrimination and regional brain activity as measured by positron emission tomography (PET).

Although most people taking antihistamines have experienced sedation and impaired performance, the neural correlates of these sedative properties are not well understood in man. Brain imaging can be used to demonstrate how regional brain activities are altered during such sedative effects. The aim of this study was to visualize the brain mechanism of impaired visuomotor spatial cognition with orally administered d-chlorpheniramine, a first-generation sedative antihistamine, using H(2) (15)O and positron emission tomography (PET). Normal subjects were randomly assigned to two groups (chlorpheniramine and placebo) and performed a spatial discrimination task after the oral administration of 6 mg d-chlorpheniramine or a placebo. The administration of d-chlorpheniramine impaired visuomotor spatial discrimination and altered cortical and subcortical activity. Decreased and increased activities were observed in the right parietal cortex (BA 40) which is related to visuomotor spatial cognition and the posterior cingulate cortex which constitutes the attention system of the brain, respectively. In particular, the brain activities of BA 40 were negatively and positively correlated to those of bilateral caudate nuclei and the dorsolateral prefrontal cortex, respectively. These findings clearly suggest that the alteration in the cortical and subcortical activity contributes to impaired spatial cognition caused by treatment with d-chlorpheniramine.

Adult↗

PubMed2002

Neuroanatomical correlates of low body weight in Alzheimer's disease: a PET study.

Weight loss is a common problem in patients with Alzheimer's disease (AD) and this might be associated with an increased risk for mortality. Recent evidences have suggested that certain brain dysfunctions may result in impaired nutritional status in AD patients. However, the mechanism of body weight loss in AD remains enigmatic. To investigate a possible association between low body weight and regional brain dysfunction, the authors conducted the correlational analysis of body mass index (BMI) with regional brain glucose metabolism using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG). Twenty-seven patients with probable AD were divided into two groups: the low BMI group and the normal BMI group. Regional brain glucose metabolic ratios were calculated using the cerebellar hemisphere as a reference region. Comparisons were made of regional brain metabolic ratios between the low BMI group and the normal BMI group. Correlations of the glucose metabolic ratio with BMI were also assessed in all patients with AD. In the comparison between the two groups, glucose metabolic ratio in the anterior cingulate cortex (ACC) was significantly lower in the low BMI group, whereas no significant differences were found in all the other brain regions. Furthermore, regional glucose metabolism in the ACC had a significant and positive correlation with BMI (r=.450, P=.018). After adjustment for age, gender and disease duration, regional glucose metabolism in the ACC was independently associated with BMI. Our findings suggest that the ACC may be preferentially involved in the regulation of nutritional status in AD patients, and provides a new insight into developing strategies for prevention and treatment of undernutritional demented patients.

Age Factors↗

PubMed2002

Differential cognitive effects of ebastine and (+)-chlorpheniramine in healthy subjects: correlation between cognitive impairment and plasma drug concentration.

AIMS: It has been widely recognized that classical antihistamines induce sedation as an adverse effect, while second-generation antihistamines have few if any sedative effects. In order to evaluate the sedative properties of ebastine, a second-generation antihistamine, its effect on cognitive performance in healthy subjects was compared with placebo and (+)-chlorpheniramine. METHODS: Twelve healthy male subjects were instructed to perform six types of attention-demanding cognitive tasks, and objective measurements of reaction times and accuracy was made before and after drug administration. Their sleepiness levels were also monitored. Test drugs were ebastine 10 mg, placebo and two doses of (+)-chlorpheniramine 2 mg and 6 mg, as positive controls. Plasma drug concentrations at the end of the study were analysed. RESULTS: After treatments with (+)-chlorpheniramine, the reaction times of the tasks were significantly prolonged (e.g. ratios of after/before dosing: placebo (0.998 +/- 0.113) vs (+)-chlorpheniramine 2 mg (1.103 +/- 0.083; P<0.05) or (+)-chlorpheniramine 6 mg (1.170 +/- 0.139; P<0.001) in a 7 ms visual discrimination time task) and the accuracy was significantly decreased (e.g. ratios: placebo (1.038 +/- 0.158) vs (+)-chlorpheniramine 2 mg (0.792 +/- 0.202; P<0.01) or (+)-chlorpheniramine 6 mg (0.837 +/- 0.222; P<0.05) in a 7 ms task). On the other hand, performance was not affected by ebastine or placebo treatment (e.g. ebastine 10 mg (reaction time ratio; 1.014 +/- 0.067 and accuracy ratio; 0.990 +/- 0.146) in a 7 ms task). Subjective sleepiness was also not affected by ebastine but (+)-chlorpheniramine significantly increased sedation. With respect to the relationship between plasma drug concentrations and task performance, the latter deteriorated with an increase in plasma (+)-chlorpheniramine concentration (e.g. r=0.439 (P=0.007) in a 5 ms and r = 0.352 (P=0.039) in a 7 ms task), but it did not correlate with the plasma concentration of carebastine, an active metabolite of ebastine. CONCLUSIONS: Ebastine 10 mg did not cause any cognitive impairment or subjective sleepiness. On the other hand, (+)-chlorpheniramine impaired cognitive function and induced sleepiness even at 2 mg, the recommended dose in over-the-counter medication. In addition, impaired CNS performance was significantly correlated with plasma (+)-chlorpheniramine concentration.

Administration, Oral↗

PubMed2002

Combined Analysis of CSF Tau Levels and [(123)I]Iodoamphetamine SPECT in Mild Cognitive Impairment: Implications for a Novel Predictor of Alzheimer's Disease.

OBJECTIVE: The aim of this study was to establish an objective and reliable index to predict the development of Alzheimer's disease in a large pool of elderly patients with mild cognitive impairment. METHOD: Twenty-three patients with probable Alzheimer's disease, 22 patients with mild cognitive impairment who eventually developed Alzheimer's disease, eight patients with mild cognitive impairment who did not develop dementia, and 19 cognitively normal subjects were included in the study. The authors constructed a new diagnostic index, the CSF-CBF index, based on CSF tau levels divided by regional cerebral blood flow (CBF) in the posterior cingulate cortex. RESULTS: Receiver operating characteristic analysis showed that applying a cutoff value for the CSF-CBF index of 296.0 achieved a sensitivity of 88.5% and a specificity of 90.0% in discriminating mild cognitive impairment that progressed to Alzheimer's disease from mild cognitive impairment that did not progress to Alzheimer's disease. CONCLUSIONS: The CSF-CBF index is useful in predicting Alzheimer's disease in subjects with mild cognitive impairment.

Aged↗