leptin and Cognition-Disorders

Although the brain has long been considered an insulin-independent organ, recent research has shown that insulin has significant effects on the brain, where it plays a role in maintaining glucose and energy homeostasis. To avoid peripheral insulin resistance, the brain may act via hypoinsulinemic responses, maintaining glucose metabolism and insulin sensitivity within its own confines; however, brain insulin resistance may develop due to environmental factors. Insulin has two important functions in the brain: controlling food intake and regulating cognitive functions, particularly memory. Notably, defects in insulin signaling in the brain may contribute to neurodegenerative disorders. Insulin resistance may damage the cognitive system and lead to dementia states. Furthermore, inflammatory processes in the hypothalamus, where insulin receptors are expressed at high density, impair local signaling systems and cause glucose and energy metabolism disorders. Excessive caloric intake and high-fat diets initiate insulin and leptin resistance by inducing mitochondrial dysfunction and endoplasmic reticulum stress in the hypothalamus. This may lead to obesity and diabetes mellitus (DM). Exercise can enhance brain and hypothalamic insulin sensitivity, but it is the option least preferred and/or continuously practiced by the general population. Pharmacological treatments that increase brain and hypothalamic insulin sensitivity may provide new insights into the prevention of dementia disorders, obesity, and type 2 DM in the future.

Topics: Animals; Brain; Cognition Disorders; Dementia; Glucose; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Leptin; Liver; Receptor, Insulin; Signal Transduction

Anorexia nervosa is a frequent disorder especially among adolescent girls and young women, with high morbidity, mortality, and relapse rates. To date, no single therapeutic approach has proved to be superior to others (Herpertz et al., 2011). It remains unclear how its etiology and pathology are encoded within cognitive, neural, and endocrinological processes that modulate important mechanisms in appetitive processing and weight regulation. Yet, several trait characteristics have been identified in AN which might reflect predisposing factors. Further, altered levels of neuropeptides and hormones that regulate appetite and feeding behavior have been found during both the acute and the recovered state, pointing to dysfunctional mechanisms in AN that persist even after malnutrition has ceased. Researchers are also hoping that brain imaging techniques will allow for a more detailed investigation of the neural basis of reward and punishment sensitivity that appears to be altered in AN. The integration and extension of recent findings in these areas will hopefully provide a more comprehensive understanding of the disorder and hence enable the development of more effective treatments.. Anorexia nervosa ist eine psychosomatische Erkrankung mit hoher Morbidität und Mortalität, die meist bei Mädchen und jungen Frauen auftritt. Bisher gibt es keine Hinweise auf die Überlegenheit eines bestimmten Therapieverfahrens (Herpertz et al., 2011). Während der klinische Phänotyp bislang im Fokus stand, werden immer häufiger Methoden und Ansätze verwendet, die in der Anorexieforschung bisher unterrepräsentiert waren. Diese beinhalten zum einen die Untersuchung endokrinologischer Merkmale wie z. B. Hormone und andere Mediatoren, die wichtige Vorgänge der Gewichts- und Appetitregulation beeinflussen, aber auch die Erforschung von kognitiven Veränderungen und Persönlichkeitsmerkmalen, die oft auch nach Ende der akuten Krankheitsphase noch messbar sind. Dabei ist es vor allem wichtig, prädisponierende und die Krankheit aufrechterhaltende Faktoren zu identifizieren und zu unterscheiden. Nicht zuletzt ermöglichen bildgebende Verfahren seit einigen Jahren die genauere Untersuchung von funktionellen Zusammenhängen verschiedener Gehirnareale, die diesen prädisponierenden und aufrechterhaltenden Faktoren zugrunde liegen könnten. Letztendlich ist es das Ziel, mit Hilfe dieser neurowissenschaftlichen Methoden langfristig neuropsychologische und biologische Merkmale zu ermitteln, die ein besseres Verständnis der zugrundeliegenden Mechanismen von Anorexia nervosa ermöglichen und damit zur Verbesserung der Behandlung beitragen.

Topics: Adolescent; Anorexia Nervosa; Appetitive Behavior; Brain; Cognition Disorders; Female; Humans; Hypothalamus; Leptin; Magnetic Resonance Imaging; Neuropsychological Tests; Neurotransmitter Agents; Protein-Energy Malnutrition; Sense of Coherence; Weight Gain; Young Adult

Level of adiposity is linked to manifest dementia and Alzheimer's disease in epidemiological studies. Overweight and obesity in mid- and late-life may increase risk for dementia, whereas decline in body weight or body mass index and underweight in years preceding and at the time of a dementia diagnosis may also relate to dementia. The role of adiposity during the period of cognitive decline is, as yet, not understood; however, some hypotheses relating adipose tissue to brain can be drawn. This review focuses on potential, varied mechanisms whereby adipose tissue may influence or interact with the brain and/or dementia risk during the dynamic period of life characterized by both body weight and cognitive decline. These mechanisms relate to: a) adipose tissue location and cell types, b) body composition, c) endocrine adipose, and d) the interplay among adipose, brain structure and function, and genes. This review will illustrate that adipose tissue is a quintessential, multifunctional tissue of the human body.

Topics: Adiponectin; Adipose Tissue; Adiposity; Body Composition; Body Mass Index; Body Weight; Brain; Cognition Disorders; Cytokines; Dementia; Glucagon-Like Peptide 1; Humans; Leptin

Recent research indicates similarities between obesity and addictive disorders on both the phenomenological and neurobiological level. In particular, neuroendocrine and imaging studies suggest a close link between the homeostatic regulation of appetite on the on hand, and motivation and reward expectancy on the other. In addition, findings from neuropsychological studies additionally demonstrate alterations of cognitive function in both obesity and addictive disorders that possibly contribute to a lack of control in resisting consumption. In this review, recent findings on overlapping neurobiological and phenomenological pathways are summarized and the impact with regard to new treatment approaches for obesity is discussed.

Topics: Animals; Appetite; Behavior Therapy; Brain; Cognition Disorders; Cognitive Behavioral Therapy; Conditioning, Psychological; Energy Metabolism; Evidence-Based Practice; Genetic Predisposition to Disease; Ghrelin; Humans; Hunger; Intracellular Signaling Peptides and Proteins; Leptin; Motivation; Neuropeptides; Obesity; Orexins; Prefrontal Cortex; Receptors, Dopamine D2; Self-Help Groups; Substance-Related Disorders

Topics: Animals; Behavior, Animal; Brain Ischemia; Carotid Artery, Common; Cerebrovascular Circulation; Cognition Disorders; Corpus Callosum; Cytokines; Hypoxia; Inflammation; Leptin; Male; Memory, Short-Term; Mice; Mice, Inbred C57BL; Microglia; Neuroglia; Perfusion; Phenotype; Receptors, Leptin; White Matter

Low plasma leptin levels can be a risk factor for Alzheimer's disease (AD) but the relation of leptin with disease progression in clinical AD is unknown.. The aim of this study was to investigate the relation between serum leptin concentrations and cognitive decline in clinical AD.. Serum leptin levels were analyzed in 295 non-obese subjects including healthy controls (n = 65), patients with subjective memory complaints (n = 99), patients with AD (n = 100), and patients with vascular dementia (n = 31). Leptin levels were related to hippocampal atrophy, baseline Mini-Mental State Examination (MMSE) scores and annual decline in MMSE measured over 2 years (range 0.4-4.5 years).. Serum leptin levels were similar in AD patients compared to healthy controls and patients with subjective memory complaints. No correlation was observed between leptin concentrations and MMSE, annual change in MMSE during follow-up or atrophy.. Serum leptin levels are not altered in this population of relatively young AD or vascular dementia patients (mean 60) compared to healthy and clinical control groups and were not related to cognitive decline. These results suggest that peripheral leptin levels do not play a role in evolution of AD pathology.

Topics: Aged; Alzheimer Disease; Body Mass Index; Cognition Disorders; Female; Humans; Leptin; Magnetic Resonance Imaging; Male; Mental Status Schedule; Middle Aged; Sex Factors

US studies suggest that leptin, a fat-derived hormone, may be protective against the development of dementia.. To investigate the complex relationship between leptin levels and cognitive decline in elderly Italians.. We studied circulating fasting leptin levels in 809 elderly adults free from dementia who participated in the prospective Italian population-based InCHIANTI study between 1998 and 2009 (mean follow-up of 8.0 years). Global cognitive decline was defined as a reduction of ≥5 points on the Mini-Mental State Examination (MMSE). Trail-Making Tests A and B were also incorporated, with cognitive decline defined as discontinued testing or the worst 10% of change from baseline. We also investigated whether any association could be explained by midlife weight and whether cognitive decline was associated with changing leptin levels.. The multivariate adjusted relative risk ([RR]; 95% confidence interval [CI]) of cognitive decline on the MMSE was 0.84 (95% CI 0.73-0.97) in relation to baseline sex-standardized log-leptin levels. High leptin levels showed a non-significant trend toward a reduced risk of decline on the Trail-Making Tests A (RR = 0.85, 95% CI 0.71-1.02) and B (RR = 0.90, 0.79-1.02). Adjusting for midlife weight or change in weight did not alter the pattern of results, and cognitive decline was not associated with changing leptin levels.. High leptin levels were independently associated with a reduced risk of cognitive decline in elderly Italians.

Topics: Aged; Aged, 80 and over; Aging; Cognition Disorders; Female; Humans; Italy; Leptin; Longitudinal Studies; Male; Mental Status Schedule; Neuropsychological Tests; Sex Factors; Statistics as Topic

Multiple organ systems, including the brain, which undergoes changes that may increase the risk of cognitive decline, are adversely affected by diabetes mellitus (DM). Here, we demonstrate that type 2 diabetes mellitus (T2DM) db/db mice exhibited hippocampus-dependent memory impairment, which might associate with a reduction in dendritic spine density in the pyramidal neurons of brain, Aβ1-42 deposition in the prefrontal cortex (PFC) and hippocampus, and a decreased expression of neurostructural proteins including microtubule-associated protein (MAP2), a marker of dendrites, and postsynaptic density 95 (PSD95), a marker of excitatory synapses. To investigate the effects of the ZiBuPiYin recipe (ZBPYR), a traditional Chinese medicine recipe, on diabetes-related cognitive decline (DACD), db/db mice received daily administration of ZBPYR over an experimental period of 6 weeks. We then confirmed that ZBPYR rescued learning and memory performance impairments, reversed dendritic spine loss, reduced Aβ1-42 deposition and restored the expression levels of MAP2 and PSD95. The present study also revealed that ZBPYR strengthened brain leptin and insulin signaling and inhibited GSK3β overactivity, which may be the potential mechanism or underlying targets of ZBPYR. These findings conclude that ZBPYR prevents DACD, most likely by improving dendritic spine density and attenuating brain leptin and insulin signaling pathway injury. Our findings provide further evidence for the effects of ZBPYR on DACD.

Topics: Amyloid beta-Peptides; Animals; Brain; Cognition Disorders; Cytoskeletal Proteins; Dendritic Spines; Diabetes Mellitus, Experimental; Disks Large Homolog 4 Protein; Drugs, Chinese Herbal; Glucose; Glycogen Synthase Kinase 3; Guanylate Kinases; Homeostasis; Hypoglycemic Agents; Insulin; Leptin; Male; Maze Learning; Membrane Proteins; Mice, Inbred C57BL; Microtubule-Associated Proteins; Peptide Fragments; Signal Transduction; Spatial Memory

Leptin plays a critical role in neuronal development and also promotes structural and functional activities in the central nervous system. Recent studies have demonstrated that leptin could produce therapeutic effects for cognitive impairments of patients with Alzheimer's disease (AD). Post-operative cognitive dysfunction (POCD), defined as a significant dysfunction in cognitive performance for several weeks after surgery, probably has a pathogenesis similar to that of AD. Specifically, they are both characterized by cognitive impairment. In this regard, we hypothesized that leptin probably has a therapeutic benefit of alleviating symptoms of patients with POCD, and the leptin signaling pathway may be involved in the pathogenesis of POCD.

Topics: Cognition Disorders; Humans; Leptin; Postoperative Complications

Mid-life obesity and type 2 diabetes mellitus (T2DM) confer a modest, increased risk for Alzheimer's disease (AD), though the underlying mechanisms are unknown. We have created a novel mouse model that recapitulates features of T2DM and AD by crossing morbidly obese and diabetic db/db mice with APPΔNL/ΔNLx PS1P264L/P264L knock-in mice. These mice (db/AD) retain many features of the parental lines (e.g. extreme obesity, diabetes, and parenchymal deposition of β-amyloid (Aβ)). The combination of the two diseases led to additional pathologies-perhaps most striking of which was the presence of severe cerebrovascular pathology, including aneurysms and small strokes. Cortical Aβ deposition was not significantly increased in the diabetic mice, though overall expression of presenilin was elevated. Surprisingly, Aβ was not deposited in the vasculature or removed to the plasma, and there was no stimulation of activity or expression of major Aβ-clearing enzymes (neprilysin, insulin degrading enzyme, or endothelin-converting enzyme). The db/AD mice displayed marked cognitive impairment in the Morris Water Maze, compared to either db/db or APPΔNLx PS1P264L mice. We conclude that the diabetes and/or obesity in these mice leads to a destabilization of the vasculature, leading to strokes and that this, in turn, leads to a profound cognitive impairment and that this is unlikely to be directly dependent on Aβ deposition. This model of mixed or vascular dementia provides an exciting new avenue of research into the mechanisms underlying the obesity-related risk for age-related dementia, and will provide a useful tool for the future development of therapeutics.

Topics: Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Blood Pressure; Cognition Disorders; Dementia, Vascular; Diabetes Mellitus; Disease Models, Animal; Glucose Tolerance Test; Humans; Insulin; Leptin; Maze Learning; Mice; Mice, Transgenic; Mutation; Neprilysin; Obesity, Morbid; Presenilin-1; Receptors, Leptin

Topics: Aged; Aging; Alzheimer Disease; Animals; Brain; Caloric Restriction; Cognition; Cognition Disorders; Eating; Energy Intake; Humans; Leptin; Mitochondria; Nutritional Status

Neuroanatomical connections point to possible interactions between areas influencing energy homeostasis and those influencing cognition. We assessed whether serum leptin, thyroxine, and thyroid stimulating hormone (TSH) levels are associated with and interact to influence cognitive performance among US adults. Data from the National Health and Nutrition Examination Survey III (1988-1994) were used. Measures included a battery of neuropsychological tests and serum leptin, thyroxine, and TSH levels (20-59-year-old: n = 1114-2665; 60-90-year-old: n = 1365-5519). Among those 20-59-year-old, the middle tertile of leptin (vs. first tertile) was inversely related to the number of errors on the symbol digits substitution test. Increased thyroxine level was associated with a poorer performance on the serial digits test in the 20-59-year-old, but a better performance on the math test in 60-90-year-old group. TSH was associated with poor performance on various tests in the 20-59-year-old, but better performance in the 60-90-year-old group. Significant antagonistic interactions were found in both age groups between thyroxine, TSH, and leptin for a number of tests, including between leptin and thyroxine in the 60-90-year-old group in their association with word recall-correct score. We found significant associations of our main exposures with cognitive function among US adults, going in opposite directions between age groups in the cases of thyroid hormonal levels, as well as some interactive effects between exposures. It is important to conduct prospective cohort studies to provide further insight into potential interventions that would assess interactive effects of various hormonal replacement regimens.

Topics: Adult; Age Distribution; Aged; Aged, 80 and over; Aging; Biomarkers; Cognition; Cognition Disorders; Evidence-Based Medicine; Female; Health Surveys; Humans; Leptin; Male; Middle Aged; Prevalence; Thyrotropin; Thyroxine; United States; Young Adult

People with obesity and type 2 diabetes are at increased risk of cognitive impairment. We aimed to investigate the association of leptin with cognitive abilities in an elderly population with type 2 diabetes. We performed a cross-sectional study of 1057 men and women aged 60-75 years with type 2 diabetes living in Lothian (Scotland). A cognitive battery was administered. Prior intelligence was estimated from vocabulary testing and adjustment for scores on this test was used to estimate lifetime cognitive change. Relationships between fasting morning leptin levels and cognitive ability and estimated cognitive change were tested. Higher leptin levels were associated with significantly poorer estimated overall cognitive decline, and poorer performance in 2 cognitive domains assessing mental flexibility and executive function, only amongst men (p < 0.05). High morning leptin levels in elderly men with type 2 diabetes are associated with estimated age-related cognitive change.

Topics: Aged; Cognition Disorders; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Leptin; Linear Models; Male; Middle Aged; Neuropsychological Tests; Radioimmunoassay; Retrospective Studies; Verbal Learning

Weight loss is a characteristic finding of patients with Alzheimer's disease (AD). It seems that precedes cognitive impairment by some years, but the underlying causes are not fully understood. Ghrelin and leptin are involved in energy homeostasis, and may be implicated in weight losing observed in these patients.. To examine the potential relationship between ghrelin and leptin levels and weight loss in patients with AD.. The study included 27 patients (10 men and 17 women) with AD of moderate severity, and 23 controls (10 males and 13 females), matched for age and BMI. Body fat and lean mass content were assessed using a portable apparatus. Cognitive function was assessed with the Mini-Mental State Examination. Basal serum samples for the measurement of leptin, ghrelin, insulin and glucose were obtained, and serum ghrelin, insulin and glucose were measured after a 75-gr glucose load in both groups.. Patients with Alzheimer Disease (AD) have lower lean mass content compared to controls. Basal ghrelin and leptin is similar in patients with AD and controls. The area-under-the-curve for ghrelin (AUC) is lower in male patients with AD compared to control males, while no difference was observed between females AD and controls.. Male patients with AD, in contrast with female patients, fail to maintain a normal energy homeostasis even in the early stages of the disease, as shown by the decreased lean mass content in males AD compared to controls. Disruption of the normal compensatory modulation of ghrelin secretion might contribute to the metabolic changes observed in male patients with AD.

Topics: Aged; Alzheimer Disease; Area Under Curve; Body Composition; Body Fluid Compartments; Body Mass Index; Case-Control Studies; Cognition Disorders; Energy Metabolism; Female; Ghrelin; Humans; Leptin; Male; Middle Aged; Severity of Illness Index; Sex Factors; Weight Loss

Central obesity is a risk factor for cognitive decline. Leptin is secreted by adipose tissue and has been associated with better cognitive function. Aging Mexican Americans have higher levels of obesity than non-Hispanic Whites, but no investigations examined the relationship between leptin and cognitive decline among them or the role of central obesity in this association.. We analyzed 1,480 dementia-free older Mexican Americans who were followed over 10 years. Cognitive function was assessed every 12-15 months with the Modified Mini Mental State Exam (3MSE) and the Spanish and English Verbal Learning Test (SEVLT).. For females with a small waist circumference (≤35 inches), an interquartile range difference in leptin was associated with 35% less 3MSE errors and 22% less decline in the SEVLT score over 10 years. For males with a small waist circumference (≤40 inches), an interquartile range difference in leptin was associated with 44% less 3MSE errors and 30% less decline in the SEVLT score over 10 years. There was no association between leptin and cognitive decline among females or males with a large waist circumference.. Leptin interacts with central obesity in shaping cognitive decline. Our findings provide valuable information about the effects of metabolic risk factors on cognitive function.

Topics: Adipose Tissue; Aged; Aged, 80 and over; Aging; Cognition Disorders; Cohort Studies; Female; Humans; Leptin; Longitudinal Studies; Male; Mexican Americans; Middle Aged; Obesity, Abdominal; Prospective Studies; Risk Factors; Waist Circumference

We previously demonstrated that animals fed a high-fat (HF) diet for 10 weeks developed insulin resistance and behavioural inflexibility. We hypothesised that intervention with metformin would diminish the HF-feeding-evoked cognitive deficit by improving insulin sensitivity.. Rats were trained in an operant-based matching and non-matching to position task (MTP/NMTP). Animals received an HF (45% of kJ as lard; n = 24), standard chow (SC; n = 16), HF + metformin (144 mg/kg in diet; n = 20) or SC + metformin (144 mg/kg in diet; n = 16) diet for 10 weeks before retesting. Body weight and plasma glucose, insulin and leptin were measured. Protein lysates from various brain areas were analysed for alterations in intracellular signalling or production of synaptic proteins.. HF-fed animals developed insulin resistance and an impairment in switching task contingency from matching to non-matching paradigm. Metformin attenuated the insulin resistance and weight gain associated with HF feeding, but had no effect on performance in either MTP or NMTP tasks. No major alteration in proteins associated with insulin signalling or synaptic function was detected in response to HF diet in the hypothalamus, hippocampus, striatum or cortex.. Metformin prevented the metabolic but not cognitive alterations associated with HF feeding. The HF diet protocol did not change basal insulin signalling in the brain, suggesting that the brain did not develop insulin resistance. These findings indicate that HF diet has deleterious effects on neuronal function over and above those related to insulin resistance and suggest that weight loss may not be sufficient to reverse some damaging effects of poor diet.

Topics: Alzheimer Disease; Animals; Behavior, Animal; Body Weight; Brain; Cognition Disorders; Conditioning, Operant; Dietary Fats; Disease Models, Animal; Hormones; Hypoglycemic Agents; Insulin Resistance; Leptin; Male; Metformin; Nerve Tissue Proteins; Rats; Rats, Wistar; Signal Transduction; Treatment Failure

Pregnancy in the diabetic woman has long been associated with an increased risk of cognitive deficit in the offspring, which might be associated with the poor intrauterine environment for the developing fetal brain. Leptin, as an important hormone regulating the intrauterine and early extrauterine life growth and development, greatly elevated during diabetic pregnancy. The current results indicate that leptin exerts neurotrophic actions during the critical period of development of hippocampus, and acts as a cognitive enhancer. Leptin resistance was a common phenomenon in diabetic pregnancies resulting reduced leptin receptors and signaling. With sudden withdrawal of placenta-derived leptin after birth, neonatal leptin levels declined sharply. The declined leptin could not work normally with the reduced leptin receptor and thus affected the newborn's brain development, which at least partly accounted for later cognitive deficits of offspring of GDM mother. Our hypothesis provides an alternative strategy to decrease the risk of cognitive deficit of offspring of diabetic mother, by exogenously supplementing leptin after birth for some period.

Topics: Child; Cognition Disorders; Diabetes, Gestational; Female; Humans; Leptin; Pregnancy

Topics: Cognition Disorders; Humans; Leptin; Renal Dialysis

Long term consumption of a high fat diet (HFD) contributes to increased morbidity and mortality. Yet the specific effects of HFD consumption on brain aging are poorly understood. In the present study 20-month old male C57Bl/6 mice were fed either 'western diet' (41% fat), very high fat lard diet (60% fat), or corresponding control diets for 16 weeks and then assessed for changes in metabolism and brain homeostasis. Although both HFDs increased adiposity and fasting blood glucose, only the high fat lard diet increased age-related oxidative damage (protein carbonyls) and impaired retention in the behavioral test. This selective increase in oxidative damage and cognitive decline was also associated with a decline in NF-E2-related factor 2 (Nrf2) levels and Nrf2 activity, suggesting a potential role for decreased antioxidant response. Taken together, these data suggest that while adiposity and insulin resistance following HFD consumption are linked to increased morbidity, the relationship between these factors and brain homeostasis during aging is not a linear relationship. More specifically, these data implicate impaired Nrf2 signaling and increased cerebral oxidative stress as mechanisms underlying HFD-induced declines in cognitive performance in the aged brain.

Topics: Adiposity; Aging; Animals; Blood Glucose; Body Weight; Cognition Disorders; Dietary Fats; Hippocampus; Insulin; Leptin; Male; Maze Learning; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; Oxidative Stress; Protein Carbonylation; Signal Transduction

Rheumatoid arthritis (RA) is associated with enhanced pro-inflammatory cytokine levels, pain, anorexia, and cognitive changes. The enhanced production of cytokines appears before the full manifestation of the disease. So far, any experimental data on behavioral effects of early arthritis are lacking. In the present series we describe anorexia early changes in, pain hyper-sensitivity and altered cognitive behavior during the first four days of adjuvant arthritis in rats (AA), when no clinical signs are yet apparent.. AA was induced to male Lewis rats by a single injection of complete Freund's adjuvant (cFA) at the base of the tail. Plasma leptin and ghrelin were measured using specific RIA methods. Gene expressions for food-regulatory peptides, neuropeptide-Y (NPY) and interleukin-1β (IL-1β) in the hypothalamic arcuate nuclei (nARC), were quantitated by TaqMan real-time PCR. Pain sensation was measured on all four limbs and tail by the plantar test. Cognitive functions were tested in the Morris water maze (MWM).. Levels of orexigenic ghrelin as well as mRNA expression of orexigenic NPY in nucleus arcuatus (nRC)re significantly enhanced on day 2 of AA only. Reduced body weight and food intake persisted by day 4 with the most profound reduction on day 2. The mRNA for anorexigenic IL-1β in the nARC was significantly enhanced on days 2 and 4. Enhanced pain sensitivity was observed on day 2, as was the cognitive impairment given by longer time to find the hidden platform, longer time spent in thigmotaxis zone, and longer trajectory. The less effective strategy used to find the hidden platform was observed up to the day 4 of AA.. Early stage of AA brings about reduced body weight, food intake, and activation of central orexigenic pathways. The observed anorexia could be ascribed to the over-expression of anorexigenic IL-1β which dominates over the NPY orexigenic effects. On day 2 of AA higher pain sensitivity and cognitive impairment appear. All the observed change tend to recover by day 4 of the disease.

Topics: Animals; Anorexia; Arcuate Nucleus of Hypothalamus; Arthritis, Experimental; Cognition Disorders; Gene Expression; Ghrelin; Hyperalgesia; Interleukin-1beta; Leptin; Male; Neuropeptide Y; Rats; RNA, Messenger; Time Factors

Lower body weight in later life has been shown to be associated with dementia. However, abdominal fat distribution under conditions of mild cognitive impairment (MCI) and the possible involvement of leptin and adiponectin in MCI have not been fully investigated.. We analyzed 517 middle-aged-to-elderly community-dwelling persons. Abdominal subcutaneous fat and visceral fat areas were determined using computed tomography, and plasma leptin and adiponectin concentrations were measured in fasting samples. MCI was assessed using the Japanese version of the MCI screening method.. In men, the abdominal subcutaneous fat area was significantly lower in participants with MCI than in those with normal cognitive function [median (interquartile range): 107.4 (85.9, 133.1) cm² vs. 136.4 (93.1, 161.4) cm²; p = 0.002]. Logistic regression analyses with confounding factors including age and abdominal subcutaneous fat area showed that a 10 mg/l increase in plasma adiponectin had a protective effect against the development of MCI in men (odds ratio: 0.46; 95% CI: 0.20-0.97; p = 0.041). In contrast, MCI was not found to be associated with abdominal fat area or adipose-derived hormones in women.. Reduced amounts of subcutaneous fat and low levels of plasma adiponectin were found to be associated with MCI in men.

Topics: Abdominal Fat; Adipokines; Adiponectin; Adipose Tissue; Aged; Body Composition; Body Mass Index; Cognition Disorders; Cross-Sectional Studies; Female; Humans; Leptin; Logistic Models; Longitudinal Studies; Male; Middle Aged; Obesity; Risk Factors; Sex Factors; Testosterone; Tomography, X-Ray Computed

Leptin is a peptide hormone secreted by adipocytes. It has been shown to modulate production and clearance of amyloid beta (Abeta) in rodent models. We sought to determine if serum leptin was associated with cognitive decline in the elderly. We studied 2871 well-functioning elders, aged 70-79, who were enrolled in a prospective study. Serum leptin concentrations were measured at baseline and analyzed by mean+/-1S.D. Clinically significantly cognitive decline over 4 years was defined as > or =5-point drop on the Modified Mini Mental State Exam (3MS). Compared to those in the lower leptin groups, elders in the high leptin group had less cognitive decline, 20.5% versus 24.7% (OR=0.79; 95% CI 0.61-1.02, p=0.07). After adjustment for demographic and clinical variables, including body mass index and total percent body fat, those in the high leptin group had significantly less likelihood of cognitive decline, OR=0.66 (95% CI 0.48-0.91). We conclude that in elderly individuals, higher serum leptin appears to protect against cognitive decline, independent of comorbidites and body fat.

Topics: Adipose Tissue; Aged; Aging; Biomarkers; Body Mass Index; Cognition Disorders; Dementia; Disease Progression; Humans; Leptin; Metabolic Syndrome; Neuropsychological Tests; Obesity; Prospective Studies

Leptin changes brain structure, neuron excitability and synaptic plasticity. It also regulates the development and function of feeding circuits. However, the effects of leptin on neurocognitive development are unknown.. To evaluate the effect of leptin on neurocognitive development.. A 5-year-old boy with a nonconservative missense leptin gene mutation (Cys-to-Thr in codon 105) was treated with recombinant methionyl human leptin (r-metHuLeptin) at physiologic replacement doses of 0.03 mg/kg/day. Cognitive development was assessed using the Differential Ability Scales (DAS), a measure of general verbal and nonverbal functioning; and selected subtests from the NEPSY, a measure of neuropsychological functioning in children.. Prior to treatment, the patient was morbidly obese, hypertensive, dyslipidemic, and hyperinsulinemic. Baseline neurocognitive tests revealed slower than expected rates of development (developmental age lower than chronological age) in a majority of the areas assessed. After two years, substantial increases in the rates of development in most neurocognitive domains were apparent, with some skills at or exceeding expectations based on chronological age. We also observed marked weight loss and resolution of hypertension, dyslipidemia and hyperinsulinemia.. We concluded that replacement with r-metHuLeptin is associated with weight loss and changes in rates of development in many neurocognitive domains, which lends support to the hypothesis that, in addition to its role in metabolism, leptin may have a cognitive enhancing role in the developing central nervous system.. ClinicalTrials.gov NCT00659828.

Topics: Abnormalities, Multiple; Child; Cognition; Cognition Disorders; Hormone Replacement Therapy; Humans; Leptin; Male; Mutation, Missense; Obesity, Morbid

The main objective of this study was to investigate the association between human CSF leptin levels and neuropsychological (NP) performance in the setting of HIV infection. We hypothesized that human CSF leptin levels positively correlate with NP performance.. Leptin is an adipocyte-derived hormone that influences brain development and function, particularly learning and memory, in the mouse model. The extent to which leptin contributes to neurocognitive functioning in humans is less clear.. A cross-sectional evaluation of CSF leptin and NP performance was performed. Leptin levels in CSF and serum samples from 59 HIV-positive men were measured by ELISA. Comprehensive, standardized NP testing was used to determine impairment status in global and specific domains.. Lower CSF leptin levels and reduced leptin uptake into the central nervous system (CNS) correlated with impaired learning and memory performance in both univariate and multivariate analyses. In multivariate analyses, lower CSF leptin levels and reduced CNS leptin uptake were associated with worse NP performance in learning and memory, adjusting for CD4 nadir, antiretroviral treatment exposure, and HIV RNA levels in CSF.. Low CSF leptin levels are associated with poorer performance in learning and memory among HIV-infected men adjusting for usual predictors of HIV-associated neurocognitive impairment. This association is consistent with prior in vitro and animal data suggesting leptin has a trophic or facilitatory role in the hippocampus, above and beyond its role in hypothalamic regulation.

Topics: Adult; Cognition Disorders; Cross-Sectional Studies; Down-Regulation; HIV Infections; Humans; Learning; Leptin; Male; Memory; Middle Aged; Psychomotor Performance

To assess the relationships between circulating levels of proinflammatory cytokines and adrenocortical hormones and leptin early after stroke.. Blood samples were collected four times daily the first two days after stroke, twice daily the next 4 days and four times at day 7. Cognitive function and functional outcome was measured at admittance and at day 7.. Consecutive inclusion of patients admitted to the stroke unit at Umeâ University Hospital.. Eight men and 4 women with acute stroke and 10 healthy volunteers.. Levels and diurnal variations of plasma proinflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), serum adrenocortical hormones (cortisol and DHEA) and leptin, and MMSE, SSS, and ADL scores.. A significant correlation was present between IL-6 and cortisol levels the first two days after stroke (P < 0.05). In patients with a disturbed diurnal rhythm of cortisol, cortisol and leptin levels were increased (68% and 81% increase, respectively), whilst DHEA levels were unaltered. Half of the patients displayed an abnormal diurnal rhythmicity of leptin at the end of the week. Median TNF-alpha levels for the first two days after stroke also correlated to median leptin levels at the end of the week (P < 0.05). Median IL-6 levels correlated to severity of paresis on days 1 and 7 and to MMSE scores on day 7 (P < 0.05).. Neuroendocrine disturbances are common and often profound early after stroke. Cytokines seem to be important modulators of these disturbances, including diurnal rhythmicity of cortisol and leptin.

Topics: Adrenocorticotropic Hormone; Aged; Aged, 80 and over; Body Mass Index; Case-Control Studies; Circadian Rhythm; Cognition Disorders; Dehydroepiandrosterone; Female; Humans; Hydrocortisone; Interleukin-6; Leptin; Linear Models; Male; Middle Aged; Multivariate Analysis; Paresis; Stroke; Tumor Necrosis Factor-alpha