Supplementation with Matured Hop Bitter Acids Improves Cognitive Performance and Mood State in Healthy Older Adults with Subjective Cognitive Decline.

BACKGROUND: Prevention of age-related cognitive decline and depression is becoming urgent because of rapid growing aging populations. Effects of vagal nerve activation on brain function by food ingredients are inadequately investigated; matured hop bitter acid (MHBA) administration reportedly improves cognitive function and depression via vagal nerve activation in model mice. OBJECTIVE: We investigated the effects of MHBA supplementation on cognitive function and mood state in healthy older adults with perceived subjective cognitive decline. METHODS: Using a randomized double-blind placebo-controlled trial design, 100 subjects (aged 45-69 years) were randomly assigned into placebo (n = 50) and MHBA (n = 50) groups, and received placebo or MHBA capsules daily for 12 weeks. RESULTS: Symbol Digit Modalities Test (SDMT) score assessing divided attention at week 12 was significantly higher (p = 0.045) and ß-endorphin at week 12 was significantly lower (p = 0.043) in the subjects receiving MHBA. Transthyretin in serum, a putative mild cognitive impairment marker, was significantly higher at week 12 in the MHBA group than in the placebo group (p = 0.048). Subgroup analysis classified by the subjective cognitive decline questionnaire revealed that in addition to improved SDMT scores, memory retrieval assessed using the standard verbal paired-associate learning tests and the Ray Verbal Learning Test at week 12 had significantly improved in the subgroup with perceived subjective cognitive decline and without requirement for medical assistance in the MHBA group compared with that in the placebo group. CONCLUSION: This study suggested that MHBA intake improves cognitive function, attention, and mood state in older adults.

No associations found between the genes situated at 6p22.1, HIST1H2BJ, PRSS16, and PGBD1 in Japanese patients diagnosed with schizophrenia.

Recent GWAS demonstrated an association between candidate genes located at region 6p22.1 and schizophrenia. This region has been reported to house certain candidate SNPs, which may be associated with schizophrenia at HIST1H2BJ, PRSS16, and PGBD1. These genes may presumably be associated with pathophysiology in schizophrenia, namely epigenetics and psychoneuroimmunology. A three-step study was undertaken to focus on these genes with the following aims: (1) whether these genes may be associated in Japanese patients with schizophrenia by performing a 1st stage case-control study (514 cases and 706 controls) using Japanese tagging SNPs; (2) if the genetic regions of interest for the disease from the 1st stage of analyses were found, re-sequencing was performed to search for new mutations; (3) finally, a replication study was undertaken to confirm positive findings from the 1st stage were reconfirmed using a larger number of subjects (2,583 cases and 2,903 controls) during a 2nd stage multicenter replication study in Japan. Genotyping was performed using TaqMan PCR method for the selected nine tagging SNPs. Although three SNPs situated at the 3' side of PGBD1; rs3800324, rs3800327, and rs2142730, and two-window haplotypes between rs3800327 and rs2142730 showed positive associations with schizophrenia, these associations did not have enough power to sustain significance during the 2nd stage replication study. In addition, re-sequencing for exons 5 and 6 situated at this region did not express any new mutations for schizophrenia. Taken together these results indicate that the genes HIST1H2BJ, PRSS16, and PGBD1 were not associated with Japanese patients with schizophrenia.

Effect of Rikkunshi-to on appetite loss found in elderly dementia patients: a preliminary study.

BACKGROUND: Functional gastrointestinal symptoms are frequently found in elderly dementia patients. In such a case, we attempt treatment by the administration of antidepressants or second-generation antipsychotics. However, these medications have a risk of side-effects. In the present study, we carried out oral administration of Rikkunshi-to to elderly dementia patients with appetite loss, and examined its effects on food intake. METHODS: Six elderly dementia patients were recruited from inpatients. They showed appetite loss, but no organic abnormalities of the gastrointestinal organs. These patients were given Rikkunshi-to, at 7.5 g per day, t.i.d. for 4 weeks. We examined the food intake, weight, total protein, albumin and potassium in plasma before administration and for 4 weeks after administration. In statistical analyses, the percentage of food consumed for 4 weeks was analyzed by anova. We also examined the side-effects of Rikkunshi-to. RESULTS: In patient 3, we stopped investigation after 3 weeks because of the development of cholecystitis. The values of 4 weeks in patient 3 were calculated as the mean values of 4 weeks in the other five patients. anova and Tukey's multiple comparison showed a marginally significant difference in weight between before Rikkunshi-to was given and 4 weeks after. In change of food intake, there were no significant differences between before Rikkunshi-to was given and 1 day after, 1 day and 2 days after, 2 days and 3 days after, 3 days and 1 week after, and 1 week and 2 weeks after; however, there were significant increases in food intake between other times. With regard to the side-effects, mild lower limb oedema appeared in the two patients. CONCLUSION: In the present study, we showed the effect of Rikkunshi-to in improving appetite loss in elderly dementia patients. The present study suggests that Rikkunshi-to might be useful in improving functional appetite loss in elderly dementia patients, because there are no serious side-effects.

Diffuse occipital hypometabolism on [18 F]-FDG PET scans in patients with idiopathic REM sleep behavior disorder: prodromal dementia with Lewy bodies?

BACKGROUND: Previous longitudinal studies have revealed that specific patterns on [(18) F]-fluoro-d-glucose (FDG) positron emission tomography (PET) scans in patients with amnesic mild cognitive impairment can predict Alzheimer's disease (AD). However, the significance of particular patterns on [(18) F]-FDG PET scans in prodromal patients with dementia with Lewy bodies (DLB) remains unclear. METHODS: Based on the prevailing evidence that rapid eye movement (REM) sleep behavior disorder (RBD) often precedes the onset of DLB, [(18) F]-FDG PET scans of nine non-demented patients reporting recurrent nocturnal dream-enactment behavior in our memory clinic were compared with the normative database using three-dimensional stereotactic surface projection (3D-SSP) images. All patients underwent clinical and neuropsychological examinations as well as cardiac [(123) I]-metaiodobenzylguanidine ([(123) I]-MIBG) scintigraphy. RESULTS: Four patients were found to have diffuse areas of reduced cerebral metabolic rate of glucose (CMRglc), predominantly in the occipital lobe, which is the preferentially affected region in DLB patients. In contrast, five patients showed no such occipital hypometabolism; instead, these five patients showed hypometabolism in the left anterior cingulate gyrus (Broadmann area (BA) 24), right frontal lobe (BA 32) and right anterior temporal lobe (BA 38), which are the preferentially affected regions in Parkinson's disease rather than DLB. The extent of the reduction in CMRglc in the left occipital lobe was correlated with scores on the Bender Gestalt Test, which reflects visuospatial ability, but not with global cognitive measures. All patients showed reduced cardiac [(123) I]-MIBG levels, consistent with underlying Lewy body disease. CONCLUSION: These variations in [(18) F]-FDG PET scans raise the possibility that the specific pattern of CMRglc reduction may predict developing DLB in patients with idiopathic RBD. Further follow-up studies are needed, particularly on patients with diffuse occipital hypometabolism.

Nicotine effects on mismatch negativity in nonsmoking schizophrenic patients.

BACKGROUND: The goal of the present study is to identify the effect of nicotine on auditory automatic processing, as reflected by mismatch negativity (MMN), in nonsmoking schizophrenic patients. METHODS: Ten nonsmoking schizophrenic patients and 10 healthy volunteers underwent a reference session and 2 test sessions. The test sessions involved administration of a placebo patch and a nicotine skin patch, which were counterbalanced. Nicotine was administered transdermally under controlled dosage. RESULTS: Nicotine administration shortened the MMN latencies (at Fz on nicotine/placebo: 134.8 +/- 5.7/157.6 +/- 6.4 ms) in healthy volunteers. In contrast, there were no significant differences in MMN latencies in schizophrenic patients (169.6 +/- 5.7/165.0 +/- 6.4 ms). CONCLUSION: Nicotine activates and accelerates preattentive and automatic processing in healthy controls, whereas there were no such effects observed in nonsmoking patients. The impaired MMN response to nicotine administration in nonsmoking schizophrenic patients may be attributed to low nicotinic receptor function, implicated in dysregulation of the glutamatergic system.

Requirement of tryptophan hydroxylase during development for maturation of sensorimotor gating.

Deficits in sensorimotor gating, a function to focus on the most salient stimulus, could lead to a breakdown of cognitive integrity, and could reflect the "flooding" by sensory overload and cognitive fragmentation seen in schizophrenia. Sensorimotor gating emerges at infancy, and matures during childhood. The mechanisms that underlie its development are largely unclear. Here, we screened the mouse genome, and found that tryptophan hydroxylase (TPH) is implicated in the maturation of sensorimotor gating. TPH, an enzyme involved in the biosynthesis of serotonin, proved to be required only during the weaning period for maturation of sensorimotor gating, but was dispensable for its emergence. Proper serotonin levels during development underlie the mature functional architecture for sensorimotor gating via appropriate actin polymerization. Thus, maintaining proper serotonin levels during childhood may be important for mature sensorimotor gating in adulthood.

Electroconvulsive therapy improves severe pain associated with fibromyalgia.

The pathophysiology of fibromyalgia remains unknown. Several reports have recently suggested the novel concept that fibromyalgia is due to the central nervous system becoming hyper-responsive to a peripheral stimulus. The effect of electroconvulsive therapy (ECT) as pain remedication in cases of fibromyalgia without major depressive disorder was studied in a prospective trial lasting three months. All of the patients taking part in the study fulfilled the American College of Rheumatology diagnostic criteria for fibromyalgia. Technetium-99m ethyl cysteinate dimer single photon emission computed tomography was used to assess regional cerebral blood flow (rCBF) before and after a course of ECT. Pain assessment in the patients was undertaken by use of the visual analog scale (VAS) and by evaluation of tender points (TPs). Beck's depression inventory (BDI) was further used to assess depressive mood change in the patients. Our study clearly demonstrated that pain was significantly less severe after ECT, as indicated by the VAS scale for pain and the evaluation of TPs. A further notable observation was that thalamic blood flow was also improved. We conclude that a course of ECT produced notable improvements in both intractable severe pain associated with fibromyalgia and also in terms of thalamic blood flow.