Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sleep apnea syndrome (SAS), which is defined by more than 5 apneas or hypopneas per hour of sleep (9), is quite a frequent affection which concerns 1.4 to 10% of general population (1.7). The major daytime complaints of the SAS are daytime sleepiness, memory and attention disorders, headaches and asthenia especially in the morning, and sexual impotence (9). The nocturnal manifestations are dominated by sonorous and generally long standing snoring, increased by dorsal decubitus and intake of alcohol, with repeated interruptions by respiratory arrests. These manifestations are always noted but rarely spontaneously reported. The sleep, non refreshing, is agitated and perturbed by numerous awakenings. The findings of the clinical examination are poor: obesity is found in 2/3 of the cases and arterial hypertension in 1/2 of the cases (20). Polygraphic recording during sleep only permits an absolute diagnosis. This frequent affection is a real problem of public health because of its numerous complications (3, 10, 12, 13, 18, 21). Symptoms of depression are often found when a patient with a SAS is examined and conversely, symptoms which evoke a SAS can be found in the clinical examination of depressed patients. We decided so to study the thymic and anxious status of 24 patients investigated for a SAS and submitted to a polygraphic recording during sleep. Four clinical parameters were studied: DSM III-R diagnosis criteria, Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HARS) and thymasthenia rating scale of Lecrubier, Payan and Puech. We also reported Total Sleep Time (TST = 6.5 +/- 1.5), Apnea Hypopnea Index (AHI = 26.7 +/- 21.6), number (2.1 +/- 2.8/h) and duration (174.2 +/- 150.8 s/h) of hypoxic events. Results showed that among 24 patients, 8 were depressed according to DSM III-R diagnosis criteria and had MADRS > 25, 22 were anxious, 11 had a major anxiety (HARS > 15) and 15 presented thymasthenia (SET > 15). Significative correlations existed between anxiety and depression (r = 0.82; p < 0.0001), depression and thymasthenia (r = 0.77; p < 0.0001) and thymasthenia and anxiety (r = 0.75; p < 0.0001). Among the 8 depressed patients a correlation existed between AHI and depression (r = 0.72; p = 0.04), but no correlation was found between depression and hypoxic events. These results were comparable to those of Guilleminault (10), Reynolds (21), Kales (12), Bliwise (3), Klonoff (13) and Millman (18) who studied relations between SAS and depression. The evaluation of thymasthenia gave a more precise typology of the depressive state associated to SAS: the type of the mood disorder is more "blunted" and "anhedonic" than "sorrowful", particularly characterised by asthenia, lack of energy, reduction of interests (leisures, libido, work), loss of initiative, difficulties to organise tasks, fall of performances and reduction of pleasure usually felt in pleasant events (15). The physic symptomatology dominated the psychic one. The sleep disorganization, more than metabolic consequences of apneas, could be involved in this associated depressive state. Other neuropsychiatric troubles can be associated to the SAS. In fact, cognitive troubles (2, 8, 14, 16, 19, 22, 24) and personality disorders (12, 18) have been described. Our data confirm previous observations suggesting a frequent association between SAS, depression, fatigue and anxiety. Clinicians should consequently be aware that a depression with severe complaints of fatigue should deserve an investigation oriented towards SAS. Conversely, when a SAS is diagnosed, it is necessary to look for a possible depression in order to set up the most appropriate treatment. The frequency of SAS, like depression's one, increases with age. Prescription and consummation of sedative psychotropic drugs increase too with age. Since respiratory depressant effects of these drugs have been clearly demonstrated, it is important to evoke SAS when depressive and/or anxious states are diagnosed and not to aggravate it. An efficacious treatment of SAS can also cure the associated depressive state, but this one can persist. It is necessary, in this case, to select a non sedative antidepressant.
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PMID:[Depressive symptomatology and sleep apnea syndrome]. 1240 78

Cognitive deficits and hippocampal atrophy, features that are shared with aging and dementia, have been described in type 2 diabetes mellitus (T2DM). T2DM is associated with obesity, hypertension, dyslipidemia, hypothalamic pituitary adrenocortical (HPA) axis abnormalities and inflammation, all of which have been shown to negatively impact the brain. However, since most reports in T2DM focused on glycemic control, the relative contribution of these modifying factors to the impairments observed in T2DM remains unclear. We contrasted 41 middle-aged dementia-free volunteers with T2DM (on average 7 years since diagnosis) with 47 age-, education-, and gender-matched non-insulin resistant controls on cognition and brain volumes. HPA axis activity and other modifiers that accompany T2DM were assessed to determine their impact on brain and cognition. Individuals with T2DM had specific verbal declarative memory deficits, reduced hippocampal and prefrontal volumes, and impaired HPA axis feedback control. Diminished cortisol suppression after dexamethasone and dyslipidemia were associated with decreased cognitive performance, whereas obesity was negatively related to hippocampal volume. Moreover, prefrontal volume was influenced by worse glycemic control. Thus, obesity and altered cortisol levels may contribute to the impact of T2DM on the hippocampal formation, resulting in decreased verbal declarative memory performance.
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PMID:Modifiers of cognitive function and brain structure in middle-aged and elderly individuals with type 2 diabetes mellitus. 1946 94

Obesity is the single greatest risk factor for the development of Type 2 diabetes mellitus (T2DM), with the prevalence of both dramatically increasing in recent years. These conditions are associated with medical complications such as hypertension, neuropathy and cardiovascular disease. Recent evidence also suggests a greater risk of developing dementia including Alzheimer's disease. The molecular mechanisms governing these changes remain obscure, although epidemiological evidence suggests that reduced insulin sensitivity (a characteristic of T2DM) is an independent risk factor for Alzheimer's disease. Here we examine the effects of diet-induced insulin resistance on cognitive ability in an animal model not predisposed to develop Alzheimer's pathology. Following 12 weeks on a high fat diet (45% of calories as crude fat) male Wistar rats were overweight and insulin resistant but not frankly diabetic. High fat fed animals were consistently poorer in all aspects of an operant based delayed matching to position task, yet were not impaired in spatial working memory as judged by the open field watermaze test. The cognitive deficit of the HF fed animals was most apparent when the task was switched from matching to non-matching to position, suggestive of an inability to change contingency. Performance in this task was negatively correlated with whole body insulin sensitivity but not weight gain. In conclusion this study has shown that insulin resistant animals exhibit impairments in an operant measure of behavioural flexibility which precede the development of diabetes.
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PMID:High fat feeding promotes simultaneous decline in insulin sensitivity and cognitive performance in a delayed matching and non-matching to position task. 2097 95

Vascular dementia (VAD), the second most common form of dementia after Alzheimer's disease (AD) is characterized by a cognitive deficit of cerebrovascular origin. As for AD, the main proposed treatment is based on cholinesterase inhibitors. However, randomized clinical trials (RCTs) with cholinesterase inhibitors in VAD reported modest - though sometimes statistically significant - clinical efficacy. Non-cholinergic drugs with diverse rationales and mechanisms of action have also been tested in a few RCTs for VAD; the outcomes measured are variable and the evidence of efficacy is weak. The limitations of pharmacological treatment for VAD have prompted a different strategy, i.e. primary prevention aimed at reducing vascular risk factors. Several epidemiological studies reported associations of hypertension, type 2 diabetes, obesity, and inflammation with VAD and in some cases, AD. These all coincide with those of stroke, which in turn is an established factor for cognitive decline and VAD. Here too, only a few RCTs have looked at prevention of these factors, except hypertension. Some pharmacological classes are particularly promising from the clinical and experimental viewpoints: Ca2+ channel blockers and drugs affecting the renin-angiotensin system may act independently of the effects on blood pressure. Despite some conflicting results and the need for further work, the control of risk factors might prevent cognitive decline and VAD in the elderly. The benefit of tackling vascular factors is probably larger when also considering the prevention of stroke. The objective of this review is to analyze the pharmacological treatment and prevention of VAD and their outcome. The literature on Pubmed from 1980 to 2009 was examined.
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PMID:Pharmacotherapy and prevention of vascular dementia. 2129 2

The conditions of chronic obesity and overweight status are risk factors for lower cognitive performance, cognitive decline, cognitive deficit, and dementia. But lower cognitive performance early in life itself may be a risk factor for an increase in body weight over time. With this in mind, we review important papers in the literature that advance our knowledge of relations between weight and cognitive functioning, with an emphasis on papers that illustrate methodological and theoretical issues of importance. We describe the evolution in research on weight and cognition with respect to two major features: (a) the move backward in time from the diagnosis of dementia to the pre-clinical period of dementia in order to better identify risk factors; and (b) the evolution of studies from an earlier emphasis on obesity-related cardiovascular risk factors as major mediators of relations between obesity and cognition to a more recent emphasis on metabolic variables, lifestyle variables, genotype, and other mechanisms that explain relations among weight change, obesity, and cognition. We conclude that: 1) a complete understanding of the causal links between weight and cognitive functioning requires a lifespan perspective; 2) practically speaking, lifespan research may need to amalgamate and integrate research at different segments of the lifespan until such time that we can include the entire life cycle within a single study of weight and cognition; and 3) we need more studies that examine reciprocal relations between weight and cognition, especially early in life.
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PMID:Obesity, cognitive functioning and dementia: back to the future. 2205 26

Cognitive impairment is common in severe obesity. Lack of physical activity is a likely contributor to impairment in this population, as many obese persons are inactive and physical activity has been positively and independently associated with cognitive function in healthy and medically-ill samples. This study investigated whether physical activity, measured by self-report of aerobic physical activity in 85 bariatric surgery candidates, was associated with cognitive function. A subset of 31 participants also completed objective activity monitoring. Steps/d and high-cadence min/week, representative of ambulatory moderate to vigorous physical activity (MVPA), were calculated. Approximately one quarter of participants self-reported at least 30 min/d of aerobic MVPA, at least 5 d/week. Median steps/d was 7949 (IQR = 4572) and median MVPA min/week was 105 (IQR = 123). Cognitive deficits were found in 32% of participants (29% memory, 10% executive function, 13% language, 10% attention). Controlling for demographic and medical factors, self-reported aerobic physical activity was weakly correlated with lower attention (r = -0.21, p = 0.04) and executive function (r = -0.27, p < 0.01) and both self-reported aerobic physical activity and objectively-determined MVPA min/week were negatively correlated with memory (r = -0.20, p = 0.04; r = -0.46; p = 0.02, respectively). No other correlations between physical activity measures and cognitive function were significant. Contrary to expectations, greater levels of physical activity were not associated with better cognitive functioning. Such findings encourage future studies to clarify the association among cognitive function and physical activity in obese persons.
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PMID:Physical activity and cognitive function in bariatric surgery candidates. 2454 36

Activation of the immune system can impair cognitive function, particularly on hippocampus dependent tasks. Several factors such as normal aging and prenatal experiences can modify the severity of these cognitive deficits. One additional factor that may modulate the behavioral response to immune activation is obesity. Prior work has shown that obesity alters the activity of the immune system. Whether diet-induced obesity (DIO) influences the cognitive deficits associated with inflammation is currently unknown. The present study explored whether DIO alters the behavioral response to the bacterial endotoxin, lipopolysaccharide (LPS). Female C57BL/6J mice were fed a high-fat (60% fat) or control diet (10% fat) for a total of five months. After consuming their respective diets for four months, mice received an LPS or saline injection and were assessed for alterations in spatial learning. One month later, mice received a second injection of LPS or saline and tissue samples were collected to assess the inflammatory response within the periphery and central nervous system. Results showed that LPS administration impaired spatial learning in the control diet mice, but had no effect in DIO mice. This lack of a cognitive deficit in the DIO female mice is likely due to a blunted inflammatory response within the brain. While cytokine production within the periphery (i.e., plasma, adipose, and spleen) was similar between the DIO and control mice, the DIO mice failed to show an increase in IL-6 and CD74 in the brain following LPS administration. Collectively, these data indicate that DIO can reduce aspects of the neuroinflammatory response as well as blunt the behavioral reaction to an immune challenge.
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PMID:Diet-induced obesity attenuates endotoxin-induced cognitive deficits. 2554 78

Obesity is a major public health problem affecting overall physical and emotional well-being. Despite compelling data suggesting an association between obesity and cognitive dysfunction, this phenomenon has received relatively little attention. Neuroimaging studies in obese humans report reduced size of brain regions involved in cognition, but few studies have investigated the cellular processes underlying cognitive decline in obesity or the influence of obesity on cognition in the absence of obesity-related illnesses. Here, a rat model of diet-induced obesity was used to explore changes in brain regions important for cognition. Obese rats showed deficits on cognitive tasks requiring the prefrontal and perirhinal cortex. Cognitive deficits were accompanied by decreased dendritic spine density and synaptic marker expression in both brain regions. Microglial morphology was also changed in the prefrontal cortex. Detrimental changes in the prefrontal cortex and perirhinal cortex occurred before metabolic syndrome or diabetes, suggesting that these brain regions may be particularly vulnerable to early stage obesity.
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PMID:Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function. 2672 34

Epidemiological studies have shown strong correlations between high fat diets, diet-induced obesity and cognitive impairment, primarily focusing on cognitive defects after the onset of obesity. A remaining question is whether cognitive impairment precedes obesity in individuals metabolically prone to diet-induced obesity. The inbred diet-induced obesity sensitive (DIO) and resistant (DR) strains of Sprague-Dawley rats serve as models for human polygenic obesity. DIO rats become overweight on a standard rat chow and have metabolic symptoms similar to overweight humans. We hypothesized that cognitive impairment pre-exists in adult male DIO rats prior to exposure to high fat diet. Male DIO and DR rats were fed a standard rat chow diet from 4 through 20 weeks of age and subjected to the Morris water maze at 12 weeks of age. At 5 and 20 weeks of age, brains of DIO and DR males were examined for indices of inflammation, lipid peroxidation and neuroproliferation. DIO rats showed significant memory impairment on water maze and increased indices of hippocampal inflammation at 20 weeks of age compared to DR rats. At 5 weeks of age, DIO rats exhibited significantly less neural progenitor cell (NPCs) proliferation in the dentate gyrus and increased hippocampal lipid peroxidation compared to DR rats. Therefore, we conclude that DIO rats exhibit early post-weaning indices of hippocampal inflammation, lipid peroxidation and decreased NPC proliferation, as well as impaired hippocampal dependent memory by early adulthood suggesting that inherent metabolic differences predispose the DIO strain to cognitive deficit prior to exposure to high fat diet and/or obesity.
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PMID:Cognitive differences between Sprague-Dawley rats selectively bred for sensitivity or resistance to diet induced obesity. 2717 31

Fragile X syndrome (FXS) is the most common monogenetic cause of intellectual disability. The cognitive deficits in the mouse model for this disorder, the Fragile X Mental Retardation 1 (Fmr1) knockout (KO) mouse, have been restored by different pharmacological approaches, among those the blockade of cannabinoid type 1 (CB1) receptor. In this regard, our previous study showed that the CB1 receptor antagonist/inverse agonist rimonabant normalized a number of core features in the Fmr1 knockout mouse. Rimonabant was commercialized at high doses for its anti-obesity properties, and withdrawn from the market on the bases of mood-related adverse effects. In this study we show, by using electrophysiological approaches, that low dosages of rimonabant (0.1 mg/kg) manage to normalize metabotropic glutamate receptor dependent long-term depression (mGluR-LTD). In addition, low doses of rimonabant (from 0.01 mg/kg) equally normalized the cognitive deficit in the mouse model of FXS. These doses of rimonabant were from 30 to 300 times lower than those required to reduce body weight in rodents and to presumably produce adverse effects in humans. Furthermore, NESS0327, a CB1 receptor neutral antagonist, was also effective in preventing the novel object-recognition memory deficit in Fmr1 KO mice. These data further support targeting CB1 receptors as a relevant therapy for FXS.
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PMID:Possible Therapeutic Doses of Cannabinoid Type 1 Receptor Antagonist Reverses Key Alterations in Fragile X Syndrome Mouse Model. 2758 6


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