Disorder Of Cholesterol Metabolism Research Articles

Computational model for monitoring cholesterol metabolism

A non-deterministic finite automaton is designed to observe the cholesterol metabolism with the states of acceptance and rejection. The acceptance state of the automaton depicts the normal level of metabolism and production of good cholesterol as an end product. The rejection state of this machine shows the inhibition of enzymatic activity in cholesterol synthesis and removal of free fatty acids. The deficiency in human cholesterol metabolism pathway results in abnormal accumulation of cholesterol in plasma, arterial tissues leading to diseases such as hypercholesterolemia, atherosclerosis respectively and formation of gallstones. The designed machine can be used to monitor the cholesterol metabolism at molecular level through regulation of enzymes involved in the biosynthesis and metabolism of cholesterol for the treatment of diseases incident due to the respective metabolic disorder. In addition, an algorithm for this machine has been developed to compare the programmed string with the given string. This study demonstrates the construction of a machine that is used for the development of molecular targeted therapy for the disorders in cholesterol metabolism.

Visualization of cholesterol deposits in lysosomes of Niemann-Pick type C fibroblasts using recombinant perfringolysin O.

BackgroundNiemann-Pick disease type C (NPC) is caused by defects in cholesterol efflux from lysosomes due to mutations of genes coding for NPC1 and NPC2 proteins. As a result, massive accumulation of unesterified cholesterol in late endosomes/lysosomes is observed. At the level of the organism these cholesterol metabolism disorders are manifested by progressive neurodegeneration and hepatosplenomegaly. Until now filipin staining of cholesterol deposits in cells has been widely used for NPC diagnostics. In this report we present an alternative method for cholesterol visualization and estimation using a cholesterol-binding bacterial toxin, perfringolysin O.MethodsTo detect cholesterol deposits, a recombinant probe, perfringolysin O fused with glutathione S-transferase (GST-PFO) was prepared. GST-PFO followed by labeled antibodies or streptavidin was applied for immunofluorescence and immunoelectron microscopy to analyze cholesterol distribution in cells derived from NPC patients. The identity of GST-PFO–positive structures was revealed by a quantitative analysis of their colocalization with several organelle markers. Cellular ELISA using GST-PFO was developed to estimate the level of unesterified cholesterol in NPC cells.ResultsGST-PFO recognized cholesterol with high sensitivity and selectivity, as demonstrated by a protein/lipid overlay assay and surface plasmon resonance analysis. When applied to stain NPC cells, GST-PFO decorated abundant deposits of cholesterol in intracellular vesicles that colocalized with filipin-positive structures. These cholesterol deposits were resistant to 0.05%-0.2% Triton X-100 used for cells permeabilization in the staining procedure. GST-PFO-stained organelles were identified as late endosomes/lysosomes based on their colocalization with LAMP-1 and lysobisphosphatidic acid. On the other hand, GST-PFO did not colocalize with markers of the Golgi apparatus, endoplasmic reticulum, peroxisomes or with actin filaments. Only negligible GST-PFO staining was seen in fibroblasts of healthy individuals. When applied to cellular ELISA, GST-PFO followed by anti-GST-peroxidase allowed a semiquantitative analysis of cholesterol level in cells of NPC patients. Binding of GST-PFO to NPC cells was nearly abolished after extraction of cholesterol with methyl-β-cyclodextrin.ConclusionsOur data indicate that a recombinant protein GST-PFO can be used to detect cholesterol accumulated in NPC cells by immunofluorescence and cellular ELISA. GST-PFO can be a convenient and reliable probe for revealing cholesterol deposits in cells and can be useful in diagnostics of NPC disease.

The Effect of Insulin Receptor Substrates 1 and 2 Knockdown on Porcine Hepatic Glucolipid Metabolism

Objective: Through efficient shRNA interference to knockdown simultaneously IRS1 and IRS2 in porcine liver cells,and verify its effects on genes expression related to glucolipid metabolism,which may lay a solid foundation for producing the type2 diabetes mellitus model pigs. Method: First of all,cloning porcine IRS1 gene and the partial 3-untranslated region sequence of IRS2 gene by Overlap PCR and 3' RACE respectively. Then screening the most effective interference shRNA fragments of IRS1 and IRS2 by Real-time PCR. Finally, the glucolipid metabolism related genes experssion were detected in the porcine liver cells of both knocking down IRS1 and IRS2. Result: The knockdown of both IRS1 and IRS2 resulted in significant upregulation of gluconeogenic enzymes PEPCK and F-1,6-BP,as well as a decrease in Gck expression,at the same time,also led to the upregulation of lipogenic enzymes SREBP-1,Abcg8 and CYP7a1. Conclusion: The knockdown of both IRS1 and IRS2 may lead to an increasing level of blood glucose and also can cause a disorder of cholesterol metabolism. Therefore,IRS1 and IRS2 have important roles in the regulation of hepatic glucolipid metabolism.

Reactivities and Products of Free Radical Oxidation of Cholestadienols

7-Dehydrocholesterol (7-DHC) is the most oxidizable lipid molecule reported to date, with a propagation rate constant for free radical peroxidation that is 200 times that of cholesterol. To better understand the high reactivity of 7-DHC and elucidate the reaction mechanism, we synthesized conjugated and skipped nonconjugated cholestadienols that would give one of the two putative pentadienyl-radical intermediates formed in 7-DHC peroxidation. The additional dienols include 6,8(9)-dienol, 5,8(14)-dienol, 6,8(14)-dienol, and the biologically important 8-dehydrocholesterol (8-DHC; 5,8(9)-dienol). We found that all of the dienols are significantly (at least 40 times) more reactive than cholesterol. Among them, dienols leading to the formation of the pentadienyl radical in ring B (termed endo-B) of the sterol are more reactive than those leading to the pentadienyl radical spanning rings B and C (termed exo-B). By comparing the oxysterol profile formed from 7-DHC and those formed from 8-DHC and 5,8(14)-dienol, products formed from abstraction of the hydrogen atoms at C-9 and C-14 (H-9 or H-14 mechanism) were clearly differentiated. When the oxidation was carried out in the presence of the good hydrogen atom donor α-tocopherol, the oxysterol profile of 7-DHC peroxidation differed distinctly from the profile observed in the absence of the antioxidant and resembles more closely the profile observed in biological systems. This study suggests that oxidative stress and the accumulation of oxysterols should be considered as two key factors in cholesterol biosynthesis or metabolism disorders, where dienyl sterol intermediates are accumulated.

Hereditary spastic paraplegia type 5: a potentially treatable disorder of cholesterol metabolism

Spastic paraplegia type 5 (SPG5) is an autosomal, recessive, hereditary spastic paraparesis (HSP) caused by mutations in CYP7B1, which is responsible for a key step in the alternative pathway of bile acid synthesis [1]. Both pure and complicated clinical forms are possible, and brain magnetic resonance imaging (MRI) might show periventricular and subcortical white matter involvement [2]. Electrophysiology reveals abnormal conduction along the central pathways and peripheral nervous system sparing [3]. SPG5 patients have increased levels of 27-hydroxycholesterol (27OHC) in plasma and cerebrospinal fluid (CSF) [4]. Cerebral accumulation of 27OHC may be an important pathogenetic event in SPG5, with relevant therapeutic implications: indeed, since the substrate availability is a limiting factor for CYP27A1 activity [5], HMG CoA reductase inhibitors might reduce 27OHC, thus preventing neurological impairment. Here we describe two SPG5 patients and report the preliminary follow-up data including evaluation of response to statin therapy in one. Patient 1 was a 29-year-old woman with a 2-year history of gait disturbances, whereas her 24-year-old brother referred walking difficulties and lower limb stiffness since he was age 20. Past medical history revealed prolonged neonatal jaundice in both siblings. Neurological examination disclosed a pure clinical phenotype with spastic paraplegia rating scale (SPRS) [6] values of 15/52 and 10/52 in patients 1 and 2, respectively. Neuropsychological assessment did not detect cognitive impairment. Brain MRI showed slight FLAIR hyper-intense signal in the periventricular and centrum ovale white matter, and spectroscopy (1H MRS) on those areas showed a mild reduction of the relative ratio N-acetyl aspartate/creatine and the presence of a small lipid peak in both patients (Fig. 1a, b). Spinal cord MRI was normal. A motor evoked potentials (MEPs) study uncovered abnormal central motor conduction times (CMCTs) from both upper and lower limbs, and electromyography was normal. Gene analysis detected two compound heterozygous mutations (c.333_334delTC and c.806delA) in CYP7B1. Serum 27OHC levels were elevated 5.5 times in patient 1 (88 lg/ dl) and 10 times in patient 2 (159 lg/dl), respectively (normal 16 ± 3 lg/dl). Both patients underwent clinical, biochemical, and instrumental follow-up over a period of 9 months. Patient 1 was put on oral simvastatin (20 mg/day at months 0–3, 40 mg/day at months 4–6, and 60 mg/day at months 7–9), whereas her younger brother manifested cramps and marked hyperCKemia and discontinued simvastatin 3 days after introduction. When compared to baseline levels, serum 27OHC values were decreased at months 3, 6, and 9 (10, 34, and 33 %, respectively) in patient 1, and A. Mignarri A. Malandrini F. Ginanneschi A. Federico M. T. Dotti (&) Unit of Neurology and Neurometabolic Disorders, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy e-mail: dotti@unisi.it

High-Dose, High-Potency Statins Reduced Dementia Risk in the Elderly

High-Dose, High-Potency Statins Reduced Dementia Risk in the Elderly

Disorder of cholesterol and electrolytes metabolism in hypertension

Hypertension is an asymptomatic, important disease regarded as a multifactorial disorder of modern life. The frequency of hypertension range from 6-32%. People with hypertension have lipid abnormality and electrolyte abnormalities when compared to individual with normotensive. There is positive association between sodium chloride (Nacl) intake and blood pressure. In present study we are going to evaluate serum cholesterol and electrolyte level in hypertensive and in normotensive. The present study was carried out on total 200 subjects, which were divided into two groups. First group of experimental group consists of 100 subjects with known hypertensive patient (B.P>140/90mm of Hg). Another group is control group consists of 100 subjects who were healthy normotensive (B.P<140/90 mm of Hg) with no past or present history of hypertension.12 hours overnight fasting venous blood sample was collected from both the subject group in plane vacutainer and the sample was centrifuged for the estimation of fasting cholesterol level and electrolytes i.e. sodium (Na + ), Potassium (K + ). The study was carried out on two group of population, one group was subject group i.e. hypertensive group, consisting of 65 male and 35 females (total population =100) and another group is the control group i.e normotensive, consisting of 60 male and 40 females (total population = 100). The total cholesterol level significantly elevated in subject group compared to control group (p<0.001). The sodium level is statistically elevated in subject group when compared to control group (P<0.001). The potassium level significantly decreased in subject group when compared to control group (P<0.001). It has been noticed that the serum cholesterol level, serum sodium level were stastically elevated in hypertensive subjects, while serum potassium level is significantly reduced in hypertensive subject when compared to normotensive subjects.

Effect of Plant Compound Curcumin on the Expression of SR-BI and ABCA1 in Hippocampal Neurons of APPswe/PS1dE9 Double Transgenic Mice

Disorder of cholesterol metabolism plays important roles in pathogenesis of Alzheimer’s disease (AD). Plant compound curcumin has been reported to decrease Aβ deposition and cholesterol in serum, while the detailed mechanism is still unknown. To investigate the effect of curcumin on the cholesterol metabolism in Alzheimer’s disease, APPswe/PS1dE9 double transgenic mice were fed with 500ppm of curcumin every day for six months. Immunohistochemistryresults showed that the expression of ATP-binding cassette transporter A1 (ABCA1) in hippocampal neurons was increased significantly, whereas the expression of scavenger receptor class B type I (SR-BI) was not detected. These findings suggest that curcumin may promote cholesterol efflux via ABCA1 transmembrane-transport system rather than SR-BI in neurons of AD.

Corpus Callosum Measurements Correlate With Developmental Delay in Smith-Lemli-Opitz Syndrome

Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation, neurodevelopmental disorder of cholesterol metabolism caused by mutations in 7-dehydrocholesterol reductase. Corpus callosum (CC) malformations and developmental delay are common, but the relation between the two has not been evaluated. This study hypothesizes shorter callosal length and smaller area correlate with higher serum 7-dehydrocholesterol and increased severity of neurodevelopmental delay in SLOS. Thirty-six individuals with SLOS (18M/18F) between 0.20 and 12.5 years (mean = 3.9, SD = 3.6) and 36 typically developing controls (18 boys and 18 girls) between 0.12 and 12.8 years (mean = 4.0, SD = 3.6) were each imaged once on a 1.5T scanner. One midsagittal image per study was selected for manual CC measurement. Gross motor, fine motor, and language developmental quotients; anatomical severity score; and serum sterol levels were assessed. Shorter CC length and smaller area correlated with a lower developmental quotient in gross motor and language domains. Furthermore, length and area negatively correlated with a serum sterol precursors and severity score, and positively correlated with total cholesterol. Degree of developmental delay ranged from mild to severe, involving all domains. For individuals with SLOS, smaller callosal area and length are associated with higher 7-dehydrocholesterol, severity scores, and developmental delay. The relationship between callosal development and biochemical abnormalities in this cohort may lead to further studies supporting imaging biomarkers.

MiR-26 controls LXR-dependent cholesterol efflux by targeting ABCA1 and ARL7

Cellular cholesterol levels are tightly regulated and represent a balance of cholesterol uptake, endogenous synthesis and efflux. Although the classic transcriptional regulations of cholesterol metabolism by liver X receptors (LXRs) have been well studied, the potential effects of LXR-responsive microRNAs (miRNAs) still need to be unveiled. Here, we describe that miR-26, an LXR-suppressed miRNA, inhibits the expression of the ATP-binding cassette transporter A1 (ABCA1) and ADP-ribosylation factor-like 7 (ARL7), two LXR target genes which play critical roles in cholesterol efflux. These findings have not only figured out an alternative mechanism for LXR regulation, but also provided a potential therapeutic target for cholesterol metabolic disorders.

Abnormal barrier function in the pathogenesis of ichthyosis: Therapeutic implications for lipid metabolic disorders

Ichthyoses, including inherited disorders of lipid metabolism, display a permeability barrier abnormality in which the severity of the clinical phenotype parallels the prominence of the barrier defect. The pathogenesis of the cutaneous phenotype represents the consequences of the mutation for epidermal function, coupled with a “best attempt” by affected epidermis to generate a competent barrier in a terrestrial environment. A compromised barrier in normal epidermis triggers a vigorous set of metabolic responses that rapidly normalizes function, but ichthyotic epidermis, which is inherently compromised, only partially succeeds in this effort. Unraveling mechanisms that account for barrier dysfunction in the ichthyoses has identified multiple, subcellular, and biochemical processes that contribute to the clinical phenotype. Current treatment of the ichthyoses remains largely symptomatic: directed toward reducing scale or corrective gene therapy. Reducing scale is often minimally effective. Gene therapy is impeded by multiple pitfalls, including difficulties in transcutaneous drug delivery, high costs, and discomfort of injections. We have begun to use information about disease pathogenesis to identify novel, pathogenesis-based therapeutic strategies for the ichthyoses. The clinical phenotype often reflects not only a deficiency of pathway end product due to reduced-function mutations in key synthetic enzymes but often also accumulation of proximal, potentially toxic metabolites. As a result, depending upon the identified pathomechanism(s) for each disorder, the accompanying ichthyosis can be treated by topical provision of pathway product (eg, cholesterol), with or without a proximal enzyme inhibitor (eg, simvastatin), to block metabolite production. Among the disorders of distal cholesterol metabolism, the cutaneous phenotype in Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects (CHILD syndrome) and X-linked ichthyosis reflect metabolite accumulation and deficiency of pathway product (ie, cholesterol). We validated this therapeutic approach in two CHILD syndrome patients who failed to improve with topical cholesterol alone, but cleared with dual treatment with cholesterol plus lovastatin. In theory, the ichthyoses in other inherited lipid metabolic disorders could be treated analogously. This pathogenesis (pathway)-driven approach possesses several inherent advantages: (1) it is mechanism-specific for each disorder; (2) it is inherently safe, because natural lipids and/or approved drugs often are utilized; and (3) it should be inexpensive, and therefore it could be used widely in the developing world.

The orphan nuclear receptor Nur77 regulates hepatic cholesterol metabolism through the suppression of LDLR and HMGCR expression

Disorders in cholesterol metabolism are critical in development of atherosclerosis and are related to acute myocardial infarction (AMI). The liver is one of the most important organs that balances cholesterol metabolism. In order to investigate whether Nur77 is capable of regulating cholesterol metabolism in HepG2 cells and to demonstrate the underlying mechanism, the downregulation and upregulation of Nur77 expression in HepG2 cells was achieved by the transfection of siRNA specific to Nur77 and the transfection of the recombinant plasmid, pcDNA3.1-Nur77, respectively. Following the downregulation and upregulation of Nur77 expression, changes in the total cholesterol (TCHO) levels in HepG2 cells were observed based on lipid overloading. Thereafter, changes in a series of key gene expressions related to hepatic cholesterol metabolism were measured at the mRNA and protein levels by RT-PCR and western blot analysis, respectively. The TCHO levels in the HepG2 cells were found to increase following the downregulation of Nur77 expression and to decrease following the upregulation of Nur77 expression; these results were confirmed by oil red O staining of the cells. As for the hepatic cholesterol metabolism genes, low-density lipoprotein receptor (LDLR) and HMGCoA reductase (HMGCR) levels increased following the downregulation of Nur77 expression and decreased following the upregulation of Nur77 expression. However, liver X receptor α (LXRα) expression did not change markedly along with that of Nur77. According to these findings, we conclude that Nur77 is capable of reducing hepatic cholesterol based on lipid overloading, and that this may be due to the decrease in LDLR and HMGCR levels.

Peripheral cholesterol metabolic disorders and Alzheimer s disease

Strong correlations have been made between high levels of blood cholesterol and the risk to suffer Alzheimer's disease (AD). The question arises on how a peripheral event contributes to a disease that so severely affects the integrity and function of the Central Nervous System. Hypercholesterolemia has been also associated to peripheral metabolic disorders like diabetes, obesity or atherosclerosis that, in turn, predispose to AD. Here we review data, which point to alterations in blood cholesterol levels as a link between these metabolic disorders and AD. We describe and discuss common, cholesterol-related, molecular mechanisms and strategies to fight these conditions that, altogether, constitute a major cause of death in our societies.

Pathogenesis-Based Therapy Reverses Cutaneous Abnormalities in an Inherited Disorder of Distal Cholesterol Metabolism

Identification of the underlying genetic, cellular, and biochemical basis of lipid metabolic disorders provides an opportunity to deploy corrective, mechanism-targeted, topical therapy. We assessed this therapeutic approach in two patients with Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects (CHILD) syndrome, an X-linked dominant disorder of distal cholesterol metabolism. Based upon the putative pathogenic role of both pathway-product deficiency of cholesterol and accumulation of toxic metabolic intermediates, we assessed the efficacy of combined therapy with lovastatin and cholesterol. We also evaluated the basis for the poorly understood, unique lateralization of the cutaneous and bone malformations of CHILD syndrome by analyzing gene activation in abnormal and unaffected skin. Ultrastructural analysis of affected skin showed evidence of both cholesterol depletion and toxic metabolic accumulation. Topical treatment with lovastatin/cholesterol (but not cholesterol alone) virtually cleared skin lesions by 3 months, accompanied by histologic and ultrastructural normalization of epidermal structure and lipid secretion. The unusual lateralization of abnormalities in CHILD syndrome reflects selective clearance of keratinocytes and fibroblasts that express the mutant allele from the unaffected side. These findings validate pathogenesis-based therapy that provides the deficient end-product and prevents accumulation of toxic metabolites, an approach of potential utility for other syndromic lipid metabolic disorders.

Research progression of &lt;I&gt;LDLR&lt;/I&gt; mutations in Chinese Familial hyper-cholesterolemia

Familial hypercholesterolemia (FH), one monogenic autosomal dominant disease, mainly results from genetic defects in the low-density lipoprotein receptor (LDLR) gene, which leads to the reduction or absence of cell surface LDLR, disorder of cholesterol metabolism, and cholesterol deposition in different tissues and organs. FH is a common metabolic disease clinically characterized by the presence of xanthomas and premature coronary heart disease. To date, about 1 741 variants have been identified in gene LDLR, among which 108 variants were identified in Chinese FH patients. To better understand the features of LDLR gene mutations and help to FH diagnosis and therapy, this review provides a comprehensive overview of LDLR gene mutations in Chinese FH patients.

Pathogenesis of the cutaneous phenotype in inherited disorders of cholesterol metabolism

Molecular geneticists tend to conceptualize disease pathogenesis from the mutated gene outward, an approach that does not take into account the impact of barrier requirements in determining disease phenotype. An ‘outside-to-inside’ perspective has provided quite different explanations for the ichthyoses, including several of the disorders of distal cholesterol metabolism. Elucidation of responsible pathogenic mechanisms also is pointing to appropriate, pathogenesis (pathway)-based therapeutic strategies. In the case of the lipid metabolic disorders, it takes full advantage of new molecular, genetic and cellular pathogenesis information to correct or bypass the metabolic abnormality. This approach fully exploits the unique accessibility of the skin to a topical approach. Moreover, since it will utilize topical lipids and lipid-soluble, and often generic, lipid-soluble drugs, these treatments should be readily transported across the stratum corneum. If successful, this approach could initiate an entirely new departure for the therapy of the ichthyoses. Finally, because these agents are relatively safe and inexpensive, this form of treatment has the potential to be widely-deployed, even in the developing world.

Effect of high-fat diet on gene expression related cholesterol metabolism in ApoE knockout mice

To investigate the effect on gene expression related cholesterol metabolism in ApoE-/- mice with high-fat-induced insulin resistance(IR). In high-fat fed mice, FBG, FFA, TC, TG, LDL-C, HDL-C, and fasting plasma insulin were significantly higher than those of controls(P＜0.01). The INSIG2 and SCAP mRNA expressions in liver were significantly increased in high-fat fed mice compared with controls(P＜0. 05 or P＜0.01), and INSIG2 protein levels also increased(P＜0. 05). But SREBP1 mRNA expression in liver of high-fat fed mice was significantly reduced(P＜0. 05). These changes might contribute to IR and disorder of cholesterol metabolism in high-fat fed ApoE-/- mice. Key words: ApoE gene knockout; insulin resistance; Cholesterol metabolism; Related gene

Proteinuria in early childhood due to familial LCAT deficiency caused by loss of a disulfide bond in lecithin:cholesterol acyl transferase

IntroductionFamilial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare recessive disorder of cholesterol metabolism characterized by the absence of high density lipoprotein (HDL) and the triad of corneal opacification, hemolytic anemia and glomerulopathy. PatientsWe here report on FLD in three siblings of a kindred of Moroccan descent with HDL deficiency. In all cases (17, 12 and 3 years of age) corneal opacification and proteinuria were observed. In the 17-year-old female proband, anemia with target cells was observed. ResultsHomozygosity for a mutation in LCAT resulted in the exchange of cysteine to tyrosine at position 337, disrupting the second disulfide bond in LCAT. LCAT protein and activity were undetectable in the patients’ plasma and in media of COS7 cells transfected with an expression vector with mutant LCAT cDNA. Upon treatment with an ACE inhibitor and a thiazide diuretic, proteinuria in the proband decreased from 6g to 2g/24h. ConclusionThis is the first report that FLD can cause nephropathy at a very early age.

Liver transplantation as a treatment option for three siblings with homozygous familial hypercholesterolemia

FH is a hereditary inherited disorder of cholesterol metabolism. Homozygous form of the disease associates severe form of atherosclerotic disease. Clinicians have been tried to inhibit the progression of the homozygous FH with medical and surgical treatment. We here present three siblings with homozygous FH who were successfully treated with liver transplantation.

Utilisation of atypical antipsychotic drugs in institutionalised elderly persons and prevalence of metabolic alterations

ObjectivesDescribe and evaluate the use of atypical antipsychotics on the institutionalized elderly population of the Valencian Community and prevalence of associated metabolic disorders. Material and methodsMulticentre transversal descriptive study on drug use and case-control of the prevalence of disorders of glycaemia, cholesterol and triglycerides. The statistical analysis of metabolic disorders is performed on the difference in prevalence and its statistical significance between control and study groups. ResultsSix hundred eighty-one patients were included (study group: 344; control group: 337) from 20 social-health-care centres. 18.5% of the institutionalized patients are being treated with atypical antipsychotics. The most frequent diagnoses are: behavioural disorders associated with dementia (63.6%) and schizophrenia (18.4%). Risperidone is the most frequently used antipsychotic (66.0%). For all the drugs in general the doses used adjusted to those recommended for the elderly patients. The prevalence of disorders in glucose, cholesterol and triglyceride metabolism in the group under study is 23.96%, 34.83%, and 26.29%, respectively, with no statistically significant differences from the control group. The analysis by type of drug did not show significant differences. ConclusionsThe results obtained show that use of atypical antipsychotics in elderly patients complies with the established general recommendations. The doses used in elderly patients with behavioural disorders associated with dementia, mostly treated with risperidone, do not have a significant impact on the prevalence of metabolic disorders.