Decreased perfusion of the posterior cingulate gyri shown by a cingulate island score is a possible marker of vulnerability to behavioural and psychological symptoms of Alzheimer's disease: a pilot study.

BACKGROUND: The cingulate island score (CIScore), which indicates the Z-score ratio of the posterior cingulate gyri to the medial occipital area, has been shown to be useful for differentiating dementia with Lewy bodies from Alzheimer's disease (AD). Our aim was to investigate associations between the clinical symptoms of AD and the CIScore as an index of the relative decrease in perfusion of the posterior cingulate gyri that occurs in the early stages of AD. METHODS: Seventeen patients with early-stage AD and 13 patients with amnesic mild cognitive impairment were examined. Z-score maps of technetium-99m ethyl cysteinate dimer single-photon emission computed tomography images acquired from the patients were converted, and the CIScore was determined by using the easy Z-score imaging system. The relationships between the CIScore and clinical symptom scores were tested. RESULTS: A significant correlation was identified between the CIScore and the Neuropsychiatric Inventory Questionnaire score. No significant correlations were identified between the CIScore and other measures of cognitive function. Based on a CIScore of 0.39, we correctly differentiated patients with and without behavioural and psychological symptoms of dementia (BPSD), with a sensitivity of 72.2% and specificity of 75.0%. DISCUSSION: Using technetium-99m ethyl cysteinate dimer single-photon emission computed tomography, we observed that decreased posterior cingulate gyri perfusion, relative to the medial occipital area, in prodromal and early AD was closely associated with behavioural and psychological symptoms of dementia. Therefore, our findings suggest that CIScore is not only useful for discriminating dementia with Lewy bodies from AD, but it can also be clinically used as a specific indicator of the vulnerability to behavioural and psychological symptoms of dementia in the early stages of AD.

Microstructural changes of the nucleus accumbens due to increase of estradiol level during menstrual cycle contribute to recurrent manic episodes--a single case study.

We examined a rapid-cycling bipolar disorder patient who demonstrated manic episode regularly at around day 7 of the menstrual cycle. We hypothesize that gonadal hormones may induce a state-dependent change in cerebral microstructure and function. Following this hypothesis, the serum levels of estradiol and progesterone were analyzed and diffusion tensor imaging data were examined between the manic and euthymic states of the patient. Estradiol levels increased in the late follicular phase at manic state when compared to the luteal or early follicular phase at euthymic state. DTI results showed that the patient had increased fractional anisotropy values at manic state in the bilateral nucleus accumbens (NAc) and its connected areas, which is a major projection field of the mesolimbic dopamine (DA) system, perhaps reflecting microstructural changes due to neuronal activation related to manic episodes. According to these results, we consider that the mesolimbic DA system of this patient has hypersensitivity to estradiol, and elevation of the estradiol level increases the activity of the dopaminergic system, which in turn may contribute to recurrent manic episodes. Our findings provide a clue for understanding how fluctuations in gonadal hormone may amplify or ameliorate the symptomatology of psychiatric disorders related to the menstrual cycle.

Combination of antioxidant supplements improved cognitive function in the elderly.

Although nutrients or agents with antioxidant properties were reported to show a preventive effect on cognitive decline in animal studies, epidemiologic data on select antioxidants have shown conflicting results. We investigated whether a combination of antioxidants from supplements is effective for the improvement of cognitive function of elderly. Forty-one subjects from a community dwelling aged 65 years and older took supplements containing n-3 polyunsaturated fatty acids (n-3 PUFA), lycopene, and Ginkgo biloba extracts (GE) daily for 3 years. The data of 622 subjects without supplement intake were used as control. We investigated the changes in cognitive function during a 3-year follow-up. We also investigated the influence of apolipoprotein E (APOE) genotype on the effect of antioxidants. We found that a combination of antioxidants improved cognitive function of aged persons after 3 years. Our present study also indicated this improvement in cognitive function with supplement intake in both APOE4 non-carrier (E4-) and APOE4 carrier (E4+) groups. Especially, in E4+, we found a large effect size of the improvement of cognition. When multiple antioxidants are used in combination, they protect against vulnerability to other agents and synergistically potentiate their antioxidant properties. These synergistically potentiated antioxidant effects of agents contribute to the improvement of cognitive function.

Effects of smoking on the lung accumulation of [11C]McN5652.

OBJECTIVE: The lung is one of the key organs for determining the distribution of drugs in the human body. Various factors influence the accumulation of drugs. In this study, we investigated the effects of smoking on drug distribution to the lung using radiolabeled drugs. METHODS: We measured the lung uptake of [11C](+)McN5652, a radioligand for serotonin transporter (5-HTT), and inactive enantiomer [11C](-)McN5652 in 19 healthy men (12 nonsmokers and 7 smokers) using positron emission tomography. Pretreatment study was performed by the administration of clomipramine (50 mg), a potent 5-HTT inhibitor. RESULTS: The mean lung uptake of [11C](+)McN5652 and [11C](-)McN5652 was significantly higher in smokers than in nonsmokers. The lung uptake of [11C](+)McN5652 decreased after pretreatment with clomipramine, whereas that of [11C](-)McN5652 was not affected by clomipramine. CONCLUSIONS: Lung uptake of [11C](-)McN5652 was influenced by smoking, possibly because the probable nonspecific binding accumulation was changed as [11C](-)McN5652 was reported to have negligible affinity to 5-HTT. Smoking might be one of the important factors when distribution of radioligands is considered.

Role of ventral striatal dopamine D1 receptor in cigarette craving.

BACKGROUND: Several theories of cigarette craving suggest that dopaminergic function in the ventral striatum plays an important role. The objective of this study was to determine correlations between craving-related brain activation and dopamine D1 receptor (D1R) binding in smokers. METHODS: Twelve smokers and 12 nonsmoking controls underwent [(15)O]H(2)O-positron emission tomography activation study and D1R-binding study using [(11)C]SCH 23390, and the correlations between receptor binding and cue-induced regional cerebral blood flow (rCBF) changes were assessed. Consecutive D1R-binding changes were examined during a period of 6 months of postsmoking abstinence in five smokers. RESULTS: Cue-induced activation was observed in the left ventral striatum including the nucleus accumbens in smokers. D1R binding in the ventral striatum showed a negative relationship with cue-induced craving and rCBF changes. D1R binding was significantly low in smokers, and there was a trend of increase after smoking abstinence. CONCLUSIONS: D1R binding and cue-induced rCBF changes in the ventral striatum suggest the important role of D1R in this region in cigarette craving.