Anserine, HClO-scavenger, protected against cognitive decline in individuals with mild cognitive impairment.

Neuroinflammation has been recognized as a promising target when considering strategies for treating AD. In particular, it has been shown that neutrophils and MPO-mediated neuroinflammatory responses with the production of HClO play a role in the progression of AD. In this study, we aimed to evaluate the effects of anserine, a scavenger of HClO, on the protection of cognitive declines in persons with MCI. Fifty-eight elderly volunteers were screened, and 36 MCI individuals were assigned either to an active arm, who received 500 mg anserine per day, or a placebo arm, for 12-weeks. To assess cognitive function, we performed MMSE at baseline and after the ingestion. The data of the MMSE for 30 subjects who completed the follow-up tests were analyzed. A significant difference was detected in the change score of MMSE between the active arm (1.9 ± 2.0; n = 15) and the placebo arm (0 ± 2.8; n = 15) (p = 0.036). After the correction with the daily intake of anserine, the significance was elevated (p = 0.0176). Our results suggest that anserine protects elderly persons with MCI from cognitive declines by suppressing MPO-mediated neuroinflammatory responses.

Influence of Imidazole-Dipeptides on Cognitive Status and Preservation in Elders: A Narrative Review.

The worldwide increase in the number of patients with dementia is becoming a growing problem, while Alzheimer's disease (AD), a primary neurodegenerative disorder, accounts for more than 70% of all dementia cases. Research on the prevention or reduction of AD occurrence through food ingredients has been widely conducted. In particular, histidine-containing dipeptides, also known as imidazole dipeptides derived from meat, have received much attention. Imidazole dipeptides are abundant in meats such as poultry, fish, and pork. As evidenced by data from recent human intervention trials conducted worldwide, daily supplementation of carnosine and anserine, which are both imidazole dipeptides, can improve memory loss in the elderly and reduce the risk of developing AD. This article also summarizes the latest researches on the biochemical properties of imidazole dipeptides and their effects on animal models associated with age-related cognitive decline. In this review, we focus on the results of human intervention studies using supplements of poultry-derived imidazole dipeptides, including anserine and carnosine, affecting the preservation of cognitive function in the elderly, and discuss how imidazole dipeptides act in the brain to prevent age-related cognitive decline and the onset of dementia.

Relationship between elevated impulsivity and cognitive declines in elderly community-dwelling individuals.

Impulse control disorders are recognized as one of the behavioral and psychological symptoms of dementia (BPSD). Majority of studies on the treatment of BPSD related to impulsivity have rather focused on the aggression and agitation. In particular, it has not been investigated how cognitive declines are associated with impulsivity in community-dwelling elderly people. Here, we have measured the cognitive and memory functions and impulsivity of 212 elderly community-dwelling people using a psychometric test battery and analyzed the correlation between their level of impulsivity and cognitive functions by multiple regression analysis. We found an elevation of impulsivity, which was evaluated by the Barratt Impulsiveness Scale-11, closely related to decline of cognitive functions, which were evaluated by the Montreal Cognitive Assessment and the Mini-Mental State Examination, and Logical Memory function, which were evaluated by the Wechsler Memory Scale-Delayed Recall. Then we have divided them into groups based on the severity of cognitive decline and conducted an analysis of each group, the result of which showed that as this tendency was particularly noticeable in the suspected dementia group. Therefore, we have concluded that heightened impulsivity is negatively associated with cognitive and memory functions in community-dwelling elderly people.

Effects of Matcha Green Tea Powder on Cognitive Functions of Community-Dwelling Elderly Individuals.

Matcha Green Tea Powder contains a variety of active ingredients beneficial to health, such as tea catechins, lutein and vitamin K. It is also known that these ingredients confer benefits upon cognitive functions of elderly people. Therefore, we aimed to investigate the relationship between a daily supplementation of Matcha and the change in cognitive functions of community-dwelling elderly people. A randomized, double-blind, placebo-controlled 12-week trial was performed. Sixty-one participants were recruited and randomly assigned to receive test drink containing 3g powder from fresh Matcha or placebo powder per day. Changes in cognitive function were assessed utilizing a psychometric test battery. Daily food intake was assessed by a Brief-type Self-administered Diet History Questionnaire (BDHQ). In the gender-specific analysis, a significant cognitive enhancement was observed in the Montreal Cognitive Assessment (MoCA) score in the active group of women. In dietary analysis, we found a significant inverse correlation between consumption of vitamin K in daily diet, excluding test drinks, and change in MoCA. The present study suggests that daily supplementation of Matcha Green Tea Powder has protective effects against cognitive decline in community-dwelling elderly women.

Effects of Anserine/Carnosine Supplementation on Mild Cognitive Impairment with APOE4.

BACKGROUND: Oral supplementation of anserine/carnosine helps preserve cognitive functions in healthy older adults. Mild cognitive impairment (MCI) is a transition between cognitive-normal and dementia. Therefore, it needs to investigate whether anserine/carnosine supplementation (ACS) has effects on subjects with MCI. METHODS: A randomized, double-blind, placebo-controlled 12-week trial was performed. Fifty-four subjects with MCI were randomized to an active group ingesting 750 mg of anserine and 250 mg of carnosine per day or a placebo (1:1). Evaluation of cognitive change was conducted utilizing a psychometric test battery. RESULTS: The score improvement in the global Clinical Dementia Rating (gloCDR) was superior in the active group than placebo (p = 0.023). No beneficial effect in the active group was detected in the other psychometric tests including the Mini-Mental State Examination (MMSE), the Wechsler Memory Scale, and the Alzheimer's Disease Assessment Scale (ADAS). When APOE4 positive (APOE4 (+)) or negative (APOE4 (-)) subjects were separately analyzed, beneficial change in the APOE4 (+) subjects was observed in MMSE (p = 0.025) as well as in gloCDR (p = 0.026). CONCLUSIONS: The present study might suggest that protective effects against cognitive decline in APOE4 (+) MCI subjects exist.

Effect of the interaction between mental stress and eating pattern on body mass index gain in healthy Japanese male workers.

BACKGROUND: The effect of the interaction between long-term mental stress and eating habits on weight gain has not been confirmed in humans. METHODS: A population of 1080 healthy Japanese male local government employees without lifestyle-related diseases at baseline were studied [corrected]. Height and weight were measured and perception of mental stress and the frequency of eating to satiety, drinking, smoking, and exercise were surveyed by means of a questionnaire in both 1997 and 2002. Exposure patterns during this 5-year period were classified as low or high. Information on daily food and energy intake was collected in 2002. The effect of the interaction between stress and the frequency of eating to satiety on change in BMI (DeltaBMI) during this 5-year period was examined by 2-way analysis of variance (ANOVA) and covariance (ANCOVA) adjusted for age, BMI at baseline, and other lifestyle habits. The association between satiation eating and DeltaBMI was compared between participants with high and low levels of stress. RESULTS: Stress and satiation eating were not significantly mutually correlated. Two-way ANCOVA showed a significant interaction (F = 4.90, P = 0.03) between mental stress and satiation eating. Among participants with a high level of stress, BMI gain was significantly larger in those who ate to satiety than in those who ate moderately, when DeltaBMI was unadjusted or adjusted for covariates (adjusted mean [SE]: 0.34 +/- 0.06 kg/m(2) vs. 0.12 +/- 0.07 kg/m(2), P = 0.002). Among participants with a low level of stress no such difference was observed. These results were unchanged after further adjustment for energy intake in 2002. CONCLUSION: In this population, eating pattern interacted with long-term mental stress to produce a larger body mass gain in satiation eaters than in moderate eaters among participants with a high level of stress, independent of energy intake or other lifestyle habits.

Analysis of PU.1/ICSBP (IRF-8) complex formation with various PU.1 mutants: molecular cloning of rat Icsbp (Irf-8) cDNA.

We isolated cDNA encoding a full-length Interferon (IFN) consensus sequence binding protein [Icsbp; also called IFN regulatory factor-8 (Irf-8)] from rat and analyzed interaction between ICSBP and PU.1, an Ets-family transcription factor regulating hematopoietic cell-specific promoters. Electrophoretic mobility shift assay indicated that PU.1 with deletion of the PEST domain could not bind to ICSBP, although loss of the PEST domain had no effect on DNA-binding ability of PU.1 itself. An amino-acid replacement of Ser147 by Ala of the PEST domain of PU.1 did not affect DNA-binding ability of PU.1 to form a binary complex, PU.1/DNA, but clearly decreased the ternary complex formation of PU.1/ICSBP/DNA. Phosphatase treatment of the ternary complex markedly decreased PU.1/ICSBP/DNA-complex formation. These results indicated that Ser147 of PU.1 is definitively required for forming a complex with ICSBP and phosphorylation of PU.1 and/or ICSBP is critical for formation of the ternary complex.

Evidence against requirement of Ser41 and Ser45 for function of PU.1 -- molecular cloning of rat PU.1.

The transcription factor PU.1 plays an important role in the development of the myeloid and lymphoid lineages and regulates the transcription of several genes expressed in these cells. Ser41 is conserved in the acidic region (33-47) of PU.1 from a variety of eukaryocytes and has been reported to be one of the two important Ser residues (S41 and S45) for the function of PU.1. In the present study, however, we found that rat PU.1 has Gly at position 41. To elucidate the role of amino acid residues at 41 and 45 in functions of PU.1, we generated mutants of rat PU.1, G41S, G41A, and S45A, and analyzed their transcription-enhancing activities by using two different systems, transient reporter assay system and retroviral transfection system. The amino acid substitution at 41 of PU.1 causes no effect on both transcription-enhancing activity for M-CSF receptor promoter and the cooperative transcription-enhancing activity with GATA-1 for FcRI alpha-chain promoter. Furthermore, the substitution at 41 also had no effect on the activity to induce monocyte-specific gene expression in the bone marrow-derived hematopoietic cells. From these results, we conclude that Ser41 as well as Ser45 are not essential for the promoter-upregulating function of PU.1.

Functional analysis of PU.1 domains in monocyte-specific gene regulation.

The Ets family transcription factor PU.1 is required for the development of various lymphoid and myeloid cell lineages, and regulates the expression of several genes in a cell type-specific manner. Recently we found that overproduction of PU.1 in mouse bone marrow-derived mast cell progenitors induced the expression of monocyte-specific genes. This prompted us to analyze the functions of each domain of PU.1 in monocyte-specific gene expression, using transfection of mast cell progenitors with a series of retrovirus vectors for overexpression of various truncation mutants. Both the acidic region and the Ets domain of PU.1 were required for expression of monocyte-specific genes, and for enhanced interleukin-6 production in response to lipopolysaccharide. The Gln-rich region was suggested to be involved in expression of both MHC class II and F4/80. On the other hand, when PU.1 protein lacking the PEST domain was produced in the progenitor cells, expression of monocyte-specific genes was substantially enhanced, suggesting that the PEST domain plays a negative role in monocyte-specific gene expression.

Overproduction of PU.1 in mast cell progenitors: its effect on monocyte- and mast cell-specific gene expression.

The Ets family transcription factor PU.1 is required for development of various lymphoid and myeloid cell lineages, and regulates the expression of several genes in a cell type-specific manner. Mouse bone marrow-derived hematopoietic progenitor cells are programmed to differentiate into mast cells, when the cells are maintained in the presence of pokeweed mitogen-stimulated spleen-conditioned medium. However, by retroviral introduction of PU.1 cDNA, the progenitor cells expressed MHC class II, CD11b, CD11c, and F4/80, and acquired the ability to stimulate T cells. Furthermore, PU.1-overproducing cells exhibited the morphology, in part, similar to that of monocyte. These results indicate that the mast cell progenitors still have the ability to express monocyte-specific genes by increased expression of PU.1.