Comparative study of the effects of intranasal insulin on memory deficits in type 2 diabetes and early Alzheimer's dementia concept and study scope

2011 ◽  
Vol 26 (S2) ◽  
pp. 500-500
Author(s):  
H. Siemann ◽  
B. Müller ◽  
E.M. Stein ◽  
H. Esselmann ◽  
S. Loos ◽  
...  

IntroductionRecent data support the view that the neurodegeneration underlying sporadic Alzheimer's Disease (AD) is in part related to brain insulin deficiency and brain insulin resistance. There is a higher incidence of AD in patients with diabetes mellitus type II (T2D) and both diseases show a decline in memory function. In a preceding trial intranasal insulin improved memory function in healthy volunteers so that an increase of central-nervous insulin concentration may improve cognitive function in both amnestic patient groups.AimsWe want to analyse the effects of intranasal insulin on patients with early Alzheimers's disease (eAD) and patients with T2D in the state of amnestic mild cognitive impairment (aMCI).MethodsRecruitment of 30 patients with eAD, 30 patients with T2D in aMCI state and 30 age-matched healthy controls. All patients undergo a run-in period of 2 weeks with 4 × daily administration of placebo. It follows a double blinded trial with daily intranasal administration of 4 × 40 I.U. insulin vs. placebo for 8 weeks and another 8 weeks of follow-up. At 4 defined time points memory function is assessed by word lists comprising 30 items of emotional, nutritional and neutral content which have to be memorized and are recalled after one week. To assess structural changes of the brain, a quantitative analysis for hippocampal N-acetyl-aspartate, choline and creatine is performed by 3 Tesla magnetic resonance spectroscopy.Results: Since the study has not finished yet, we present experiences from the initiation and the beginning phase.

Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 221
Author(s):  
Do-Youn Jeong ◽  
Myeong Seon Ryu ◽  
Hee-Jong Yang ◽  
Sunmin Park

Fermented soybean paste is an indigenous food for use in cooking in East and Southeast Asia. Korea developed and used its traditional fermented foods two thousand years ago. Chungkookjang has unique characteristics such as short-term fermentation (24–72 h) without salt, and fermentation mostly with Bacilli. Traditionally fermented chungkookjang (TFC) is whole cooked soybeans that are fermented predominantly by Bacillus species. However, Bacillus species are different in the environment according to the regions and seasons due to the specific bacteria. Bacillus species differently contribute to the bioactive components of chungkookjang, resulting in different functionalities. In this review, we evaluated the production process of poly-γ-glutamic acid (γ-PGA)-rich chungkookjang fermented with specific Bacillus species and their effects on memory function through the modulation of brain insulin resistance, neuroinflammation, and the gut–microbiome–brain axis. Bacillus species were isolated from the TFC made in Sunchang, Korea, and they included Bacillus (B.) subtilis, B. licheniformis, and B. amyloliquefaciens. Chungkookjang contains isoflavone aglycans, peptides, dietary fiber, γ-PGA, and Bacillus species. Chungkookjangs made with B. licheniformis and B. amyloliquefaciens have higher contents of γ-PGA, and they are more effective for improving glucose metabolism and memory function. Chungkookjang has better efficacy for reducing inflammation and oxidative stress than other fermented soy foods. Insulin sensitivity is improved, not only in systemic organs such as the liver and adipose tissues, but also in the brain. Chungkookjang intake prevents and alleviates memory impairment induced by Alzheimer’s disease and cerebral ischemia. This review suggests that the intake of chungkookjang (20–30 g/day) rich in γ-PGA acts as a synbiotic in humans and promotes memory function by suppressing brain insulin resistance and neuroinflammation and by modulating the gut–microbiome–brain axis.


2020 ◽  
Vol 1 ◽  
pp. 27-34 ◽  
Author(s):  
Aleksey Oparin ◽  
Anton Kudriavtsev ◽  
Anatoliy Oparin

Diabetes mellitus is one of the most serious problems of the clinical medicine. This is determined by the fact that it is followed by multisystemic affects, as well as complications on the side of other organs and systems, among which a special place is occupied by gastroesophageal reflux disease. As for the combination and mutual influence of diabetes mellitus and gastroesophageal reflux disease, this issue has not been studied yet, the data of modern literature are not complete and quite contradictory. The aim of the study: to investigate the state of the factors of aggression and protection of the oesophageal mucosa in patients with diabetes mellitus type II with concomitant gastroesophageal reflux disease without associated pathology. Method. There were two groups of patients under observation. The first group included 45 patients with diabetes mellitus type II with concomitant gastroesophageal reflux disease (26 men and 19 women). The second group included 38 patients with gastroesophageal reflux disease without associated pathology – 20 men and 18 women. By sex, age, body weight, Helicobacter pylori infection, smoking and alcohol consumption, both groups were comparable. The surveillance program included determining the compensation ratio of carbohydrate metabolism and the state of the factor. The antioxidant protection factor was assessed by the level of catalase activity in the blood serum, as well as by the diameter of the celiac trunk and the blood flow velocity in it. Statistical processing of the obtained data was carried out with the aid of the program WINDOWS STATISTIKA 6.0. For all types of analysis, differences were considered statistically significant with p<0.05. Results. During the study, we found that in patients with diabetes mellitus type II with concomitant gastroesophageal reflux disease, as well as in patients with gastroesophageal reflux disease without associated pathology, the level of pH-metry was reduced, but with varying measures of confidence. At the same time, we found that patients with GERD without associated pathology had a decrease in the blood flow velocity in the celiac trunk. Concurrently, we ascertained that the decrease in the blood flow velocity in patients of both groups reduced the diameter of the celiac trunk. Conclusions. In patients with diabetes mellitus type II, concomitant gastroesophageal reflux disease has a subtle clinical presentation that is affected by a significant decline in mucosal sealing protection factors. In patients with GERD without associated pathology, typical clinical manifestations, accompanied by inflammation, acid regurgitation and dyspepsia, are more vivid.


Author(s):  
K.I. Avgerinos ◽  
R.J. Mullins ◽  
J.M. Egan ◽  
D. Kapogiannis

BACKGROUND: Ketone bodies have been proposed as an “energy rescue” for the Alzheimer’s disease (AD) brain, which underutilizes glucose. Prior research has shown that oral ketone monoester (KME) safely induces robust ketosis in humans and has demonstrated cognitive-enhancing and pathology-reducing properties in animal models of AD. However, human evidence that KME may enhance brain ketone metabolism, improve cognitive performance and engage AD pathogenic cascades is scarce. Objectives: To investigate the effects of ketone monoester (KME) on brain metabolism, cognitive performance and AD pathogenic cascades in cognitively normal older adults with metabolic syndrome and therefore at higher risk for AD. Design: Double-blinded randomized placebo-controlled clinical trial. Setting: Clinical Unit of the National Institute on Aging, Baltimore, US. Participants: Fifty cognitively intact adults ≥ 55 years old, with metabolic syndrome. Intervention: Drinks containing 25 g of KME or isocaloric placebo consumed three times daily for 28 days. Outcomes: Primary: concentration of beta-hydroxybutyrate (BHB) in precuneus measured with Magnetic Resonance Spectroscopy (MRS). Exploratory: plasma and urine BHB, multiple brain and muscle metabolites detected with MRS, cognition assessed with the PACC and NIH toolbox, biomarkers of AD and metabolic mediators in plasma extracellular vesicles, and stool microbiome. Discussion: This is the first study to investigate the AD-biomarker and cognitive effects of KME in humans. Ketone monoester is safe, tolerable, induces robust ketosis, and animal studies indicate that it can modify AD pathology. By conducting a study of KME in a population at risk for AD, we hope to bridge the existing gap between pre-clinical evidence and the potential for brain-metabolic, pro-cognitive, and anti-Alzheimer’s effects in humans.


Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1272
Author(s):  
Amira Bryll ◽  
Wirginia Krzyściak ◽  
Paulina Karcz ◽  
Natalia Śmierciak ◽  
Tamas Kozicz ◽  
...  

Schizophrenia is a complex mental disorder whose course varies with periods of deterioration and symptomatic improvement without diagnosis and treatment specific for the disease. So far, it has not been possible to clearly define what kinds of functional and structural changes are responsible for the onset or recurrence of acute psychotic decompensation in the course of schizophrenia, and to what extent personality disorders may precede the appearance of the appropriate symptoms. The work combines magnetic resonance spectroscopy imaging with clinical evaluation and laboratory tests to determine the likely pathway of schizophrenia development by identifying peripheral cerebral biomarkers compared to personality disorders. The relationship between the level of metabolites in the brain, the clinical status of patients according to International Statistical Classification of Diseases and Related Health Problems, 10th Revision ICD-10, duration of untreated psychosis (DUP), and biochemical indices related to redox balance (malondialdehyde), the efficiency of antioxidant systems (FRAP), and bioenergetic metabolism of mitochondria, were investigated. There was a reduction in the level of brain N-acetyl-aspartate and glutamate in the anterior cingulate gyrus of patients with schisophrenia compared to the other groups that seems more to reflect a biological etiopathological factor of psychosis. Decreased activity of brain metabolites correlated with increased peripheral oxidative stress (increased malondialdehyde MDA) associated with decreased efficiency of antioxidant systems (FRAP) and the breakdown of clinical symptoms in patients with schizophrenia in the course of psychotic decompensation compared to other groups. The period of untreated psychosis correlated negatively with glucose value in the brain of people with schizophrenia, and positively with choline level. The demonstrated differences between two psychiatric units, such as schizophrenia and personality disorders in relation to healthy people, may be used to improve the diagnosis and prognosis of schizophrenia compared to other heterogenous psychopathology in the future. The collapse of clinical symptoms of patients with schizophrenia in the course of psychotic decompensation may be associated with the occurrence of specific schizotypes, the determination of which is possible by determining common relationships between changes in metabolic activity of particular brain structures and peripheral parameters, which may be an important biological etiopathological factor of psychosis. Markers of peripheral redox imbalance associated with disturbed bioenergy metabolism in the brain may provide specific biological factors of psychosis however, they need to be confirmed in further studies.


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