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Query: UMLS:C0240066 (iron deficiency)
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This article examines the epidemiological data on chronic akathisia, tardive akathisia, and withdrawal akathisia. The limitations of the data are discussed--in particular, the lack of consistent definitions of the syndromes. The studies suggest that a significant proportion of patients chronically treated with neuroleptics suffer from akathisia. The prevalence may be as high as 40 percent, although a conservative estimate would be closer to 30 percent. Risk factors for the development of chronic akathisia and tardive akathisia are poorly understood, but old age, female sex, iron deficiency, negative symptoms, cognitive dysfunction, and affective disorder diagnosis need to be studied further for their potential role. While there is convincing evidence that akathisia may develop after neuroleptic cessation or reduction in dose, the prevalence and risk factors for withdrawal akathisia are not known. Reports of akathisia in children and the elderly have been few, and more systematic research is necessary. Akathisia appears to be common in individuals with mental retardation treated chronically with neuroleptics.
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PMID:The epidemiology of drug-induced akathisia: Part II. Chronic, tardive, and withdrawal akathisias. 748 75

Generalised pruritus is common in the elderly. Idiopathic 'senile pruritus' is a diagnosis of exclusion, and an underlying systemic disorder should be sought. Thyroid disease, haematological malignancy, iron deficiency, cholestasis or renal impairment may be responsible for pruritus. Rarely pruritus may occur after cerebral infarction or as a paraneoplastic phenomenon. The mechanisms of pruritus are poorly understood. In systemic disorders, correction of the underlying disorder alleviates itch. However, when this cannot be achieved, a symptomatic approach is required. Response to treatment varies enormously and an empirical approach is often required. Topical applications are available to soothe the skin and bandaging techniques may improve their efficacy. A number of more targeted treatments are available for renal and cholestatic pruritus. Novel therapies such as thalidomide, opioid antagonists, ondansetron and phototherapy with ultraviolet (UV)-B radiation are now being used. Treatment of pruritus needs to be individualised, and the elderly present a particular challenge. Adequate delivery of simple emollients may be impossible because of physical impairment The elderly are more vulnerable to the adverse effects of treatments, comorbidities may alter the pharmacokinetics of drug metabolism and polypharmacy increases the likelihood of adverse drug interactions. Cognitive impairment can lead to poor compliance with treatment. The patient's general health, the severity of symptoms and the adverse effects of treatment all need to be considered. Most treatments are of benefit only to some patients; others derive only marginal improvement. Many of the newer treatments are unlicensed for pruritus and should preferably be administered under specialist supervision. We review the literature concerning the treatment of itch associated with systemic diseases, with particular emphasis on issues relevant to the elderly. Pruritus is a difficult symptom to treat. However, it is hoped that research into the mechanisms underlying the pruritus of systemic disease will allow a better understanding so that we should be able to look forward to more specific and effective therapies in the future.
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PMID:Treatment of pruritus associated with systemic disorders in the elderly: a review of the role of new therapies. 1257

Cancer-related anemia often develops from the infiltration of marrow by malignant cells, impaired hemoglobin (Hb) production related to chemotherapy or radiation therapy, iron deficiency, or low endogenous erythropoietin levels. Patients with cancer-related anemia may experience cognitive dysfunction including decreased mental alertness, poor concentration, and memory problems. Anemia-mediated cerebral hypoxia may cause symptoms such as headache, vertigo, tinnitus, and dizziness. These symptoms often are exacerbated in the elderly patient with cancer and related to underlying low Hb concentrations. Restoring Hb levels via the administration of iron supplements, blood transfusions, or, more recently, erythropoiesis-stimulating therapy (epoetin alfa) results in significant improvement of cognitive function. The use of epoetin alfa as a treatment option for patients with chemotherapy-associated anemia and an Hb concentration less than 10 g/dL has been recommended by the American Society of Clinical Oncology and the American Society of Hematology. Erythropoiesis-stimulating therapies are a promising treatment option for cancer-related anemia that may improve cognitive function and quality of life for patients with cancer.
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PMID:Anemia in the oncology patient: cognitive function and cancer. 1502 12

Psychiatric manifestations are frequently associated with pernicious anemia including depression, mania, psychosis, dementia. We report a case of a patient with vitamin B12 deficiency, who has presented severe depression with delusion and Capgras' syndrome, delusion with lability of mood and hypomania successively, during a period of two Months. Case report - Mme V., a 64-Year-old woman, was admitted to the hospital because of confusion. She had no history of psychiatric problems. She had history of diabetes, hypertension and femoral prosthesis. The red blood count revealed a normocytosis with anemia (hemoglobin=11,4 g/dl). At admission she was uncooperative, disoriented in time and presented memory and attention impairment and sleep disorders. She seemed sad and older than her real age. Facial expression and spontaneous movements were reduced, her speech and movements were very slow. She had depressed mood, guilt complex, incurability and devaluation impressions. She had a Capgras' syndrome and delusion of persecution. Her neurologic examination, cerebral scanner and EEG were postponed because of uncooperation. Further investigations confirmed anemia (hemoglobin=11,4 g/dl) and revealed vitamin B12 deficiency (52 pmol/l) and normal folate level. Antibodies to parietal cells were positive in the serum and antibodies to intrinsic factor were negative. An iron deficiency was associated (serum iron=7 micromol/l; serum ferritin concentration=24 mg/l; serum transferrin concentration=3,16 g/l). This association explained normocytocis anemia. Thyroid function, hepatic and renal tests, glycemia, TP, TCA, VS, VDRL-TPHA were normal. Vitamin B12 replacement therapy was started with hydroxycobalamin 1 000 ng/day im for 10 days and iron replacement therapy. Her mental state improved dramatically within a few days. After one week of treatment the only remaining symptoms were lability of mood, delusion of persecution, Capgras' syndrome but disappeared totally 9 days after the beginning of the treatment. A neurologic examination was possible because of cooperation. All the tendon reflexes of inferior members were absent. The plantars were in flexion and there was a left inferior member hypoesthesia. The cerebral scan and EEG were normal. Fundic biopsy, realized by fibroscopy, revealed fundic atrophia and intestinal metaplasia compatible with Biermers' disease. The iron deficiency exploration concluded diet deficiency. Mme V. appeared euphoric, her speech was very rapid with play on words and overactivity. This hypomania state totally disappeared 3 days after. Six Months after her hospitalisation, she presented an hypothyroidism (TSH=3,780; T3=1,35; T4=1,08). A thyroid hormones replacement was started and she continued to receive Monthly B12 replacement. Discussion - This case report illustrates psychiatric manifestations of Biermers' disease. The clinical arguments in favour are: white woman, more than 60 Years old, no history of psychiatric problems, atypical symptoms (confusional state with psychiatric symptoms), fluctuation of symptoms (severe depression with confusional state, delusion of persecution and Capgras' syndrome; delusion with lability of mood and hypomania), dramatic improvement after 9 days of vitamin B12 replacement therapy. The biological arguments are: anemia, vitamin B12 deficiency, normal folate level, atrophia and fundic metaplasia, positive antibodies to parietal cells in the serum, association between Biermers' disease and autoimmune disease (Haschimoto thyroidite). Psychiatric manifestations can occur in the presence of low serum B12 levels but in the absence of the other well recognized neurological and haematological abnormalities of pernicious anemia. Mental or psychological changes may precede haematological signs by Months or Years. They can be the initial symptoms or the only ones. Verbank et al. described the case of a patient with vitamin B12 deficiency in whom hypomania, paranoia and depression had been successively presented during a period of 5 Years before anemia have been developed. The case of Mme V. is similar in the succession of severe depression with delusion of persecution and Capgras' syndrome, delusion with lability of mood and hypomania, during a period of two Months. This report seems to be the first one of a sequence of several psychiatric states with pernicious anemia during a period of two Months with normocytosis anemia. To illustrate this illness we reviewed the literature regarding psychopathology associated with B12 deficiency. The most common psychiatric symptoms were depression, mania, psychotic symptoms, cognitive impairment and obsessive compulsive disorder. The neuropsychiatric severity by vitamin B12 deficiency and the therapeutic efficacy depends on the duration of signs and symptoms. Conclusion - We recommend consideration of B12 deficiency and serum B12 determinations in all the patients with organic mental disorders, atypical psychiatric symptoms and fluctuation of symptomatology. B12 levels should be evaluated with treatment resistant depressive disorders, dementia, psychosis or risk factors for malnutrition such as alcoholism or advancing age associated with neurological symptoms, anemia, malabsorption, gastrointestinal surgery, parasite infestation or strict vegetarian diet. In first intention, B12 deficiency should be researched by serum B12 determination (normal 200-950 pg/ml). Studies of methylmalonic acid and homocysteine showed that they are very sensitive functional indicators of cobalamin status especially when other evidence of cobalamin (B12) deficiency was equivocal. Measurement of methylmalonic acid (normal 73-271 nmol/l) and homocysteine (normal 5,4-13,9 micromol/l) should not replace the measurement of serum cobalamin.
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PMID:[Psychiatric manifestations of vitamin B12 deficiency: a case report]. 1502 91

Anemia is currently defined by the World Health Organization (WHO) as a hemoglobin (Hb) level <13 g/dL in men and <12 g/dL in women. While estimates vary widely, nearly one quarter of community-based octagenerians and one half of the chronically ill elderly have Hb levels that satisfy a diagnosis of anemia according to these criteria. A growing body of evidence has linked adverse events with even "mild" anemia or low-normal Hb in the elderly. Recent studies suggest strongly that aging is associated with dysregulation of pro-inflammatory cytokines, most notably interleukin-6 (IL-6), which may negatively impact hematopoiesis, either by inhibition of erythropoietin (EPO) production or interaction with EPO receptors. Anemia in older individuals is associated with a very wide range of complications, including increased risk for mortality, cardiovascular disease, cognitive dysfunction, longer hospitalization for elective procedures and comorbid conditions, reduced bone density, and falls and fractures. Not surprisingly, anemia also has a significant effect on quality of life (QOL) in the elderly. Most anemia in older individuals results from iron deficiency, chronic inflammation, or chronic kidney disease, or it may be unexplained. Future research on anemia in the elderly should focus on the age-related physiologic changes underlying this condition and whether anemia correction can reduce anemia-associated risks, and improve QOL.
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PMID:Anemia in the elderly: current understanding and emerging concepts. 1647 93

Iron deficiency is considered to be one of most prevalent forms of malnutrition, yet there has been a lack of consensus about the nature and magnitude of the health consequences of iron deficiency in populations. This paper presents new estimates of the public health importance of iron-deficiency anemia (IDA), which were made as part of the Global Burden of Disease (GBD) 2000 project. Iron deficiency is considered to contribute to death and disability as a risk factor for maternal and perinatal mortality, and also through its direct contributions to cognitive impairment, decreased work productivity, and death from severe anemia. Based on meta-analysis of observational studies, mortality risk estimates for maternal and perinatal mortality are calculated as the decreased risk in mortality for each 1 g/dl increase in mean pregnancy hemoglobin concentration. On average, globally, 50% of the anemia is assumed to be attributable to iron deficiency. Globally, iron deficiency ranks number 9 among 26 risk factors included in the GBD 2000, and accounts for 841,000 deaths and 35,057,000 disability-adjusted life years lost. Africa and parts of Asia bear 71% of the global mortality burden and 65% of the disability-adjusted life years lost, whereas North America bears 1.4% of the global burden. There is an urgent need to develop effective and sustainable interventions to control iron-deficiency anemia. This will likely not be achieved without substantial involvement of the private sector.
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PMID:Iron deficiency: global prevalence and consequences. 1701 51

While iron deficiency is not perceived as a life threatening disorder, it is the most prevalent nutritional abnormality in the world, and a better understanding of modes and sites of action, can help devise better treatment programs for those who suffer from it. Nowhere is this more important than in infants and children that make up the bulk of iron deficiency in society. Although the effects of iron deficiency have been extensively studied in systemic organs, until very recently little attention was paid to its effects on brain function. The studies of Oski at Johns Hopkin Medical School in 1974, demonstrating the impairment of learning in young school children with iron deficiency, prompted us to study its relevance to brain biochemistry and function in an animal model of iron deficiency. Indeed, rats made iron deficient have lowered brain iron and impaired behaviours including learning. This can become irreversible especially in newborns, even after long-term iron supplementation. We have shown that in this condition it is the brain striatal dopaminergic-opiate system which becomes defective, resulting in alterations in circadian behaviours, cognitive impairment and neurochemical changes closely associated with them. More recently we have extended these studies and have established that cognitive impairment may be closely associated with neuroanatomical damage and zinc metabolism in the hippocampus due to iron deficiency, and which may result from abnormal cholinergic function. The hippocampus is the focus of many studies today, since this brain structure has high zinc concentration and is highly involved in many forms of cognitive deficits as a consequence of cholinergic deficiency and has achieved prominence because of dementia in ageing and Alzheimer's disease. Thus, it is now apparent that cognitive impairment may not be attributed to a single neurotransmitter, but rather, alterations and interactions of several systems in different brain regions. In animal models of iron deficiency it is apparent that dopaminergic interaction with the opiate system and cholinergic neurotransmission may be defective.
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PMID:Brain iron deficiency and excess; cognitive impairment and neurodegeneration with involvement of striatum and hippocampus. 1879 Jul 24

Iron is essential in the brain, yet too much iron can be toxic. Tight regulation of iron in the brain may involve intrinsic mechanisms that control internal homeostasis independent of systemic iron status. Iron abnormalities occur in various neurological disorders, usually with symptoms or neuropathology associated with movement impairment or behavioral disturbances rather than cognitive impairment or dementia. Consistent with this, polymorphisms in the HFE gene, associated with the iron overload disorder hemochromatosis, show stronger associations with the movement disorder amyotrophic lateral sclerosis (motor neuron disease) than with cognitive impairment. Such associations may arise because certain brain regions involved in movement or executive control are particularly iron-rich, notably the basal ganglia, and may be highly reliant on iron. Various mechanisms, including iron redistribution causing functional iron deficiency, lysosomal and mitochondrial abnormalities or oxidative damage, could underlie iron-related neuropathogenesis. Clarifying how iron contributes causatively to neurodegeneration may improve treatment options in a range of neurodegenerative disorders. This review considers how modern molecular genetic approaches can be applied to resolve the complex molecular systems and pathways by which brain iron homeostasis is regulated and the molecular changes that occur with iron dyshomeostasis and neuropathogenesis.
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PMID:Molecular genetic approaches to understanding the roles and regulation of iron in brain health and disease. 2034 52

Control of iron homeostasis is essential for healthy central nervous system function: iron deficiency is associated with cognitive impairment, yet iron overload is thought to promote neurodegenerative diseases. Specific genetic markers have been previously identified that influence levels of transferrin, the protein that transports iron throughout the body, in the blood and brain. Here, we discovered that transferrin levels are related to detectable differences in the macro- and microstructure of the living brain. We collected brain MRI scans from 615 healthy young adult twins and siblings, of whom 574 were also scanned with diffusion tensor imaging at 4 Tesla. Fiber integrity was assessed by using the diffusion tensor imaging-based measure of fractional anisotropy. In bivariate genetic models based on monozygotic and dizygotic twins, we discovered that partially overlapping additive genetic factors influenced transferrin levels and brain microstructure. We also examined common variants in genes associated with transferrin levels, TF and HFE, and found that a commonly carried polymorphism (H63D at rs1799945) in the hemochromatotic HFE gene was associated with white matter fiber integrity. This gene has a well documented association with iron overload. Our statistical maps reveal previously unknown influences of the same gene on brain microstructure and transferrin levels. This discovery may shed light on the neural mechanisms by which iron affects cognition, neurodevelopment, and neurodegeneration.
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PMID:Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene. 2223 60

Iron deficiency is common throughout the world and has been linked to cognitive impairments. Using neonatal piglets to model human infants, we assessed the impact of iron deficiency on spatial learning and memory. Artificially reared piglets were fed 1 of 3 liquid diets with varying concentrations of iron: control (CON), mildly deficient (MID), or severely deficient (SID; 100, 25.0, or 10.0 mg iron/kg milk solids, respectively) for 4 wk. Relative to CON, SID and MID piglets had reduced hemoglobin (P < 0.05) as well as magenta skin color (P < 0.001), which correlated with hematocrit (R(2) = 0.76; P < 0.001). SID and MID hemoglobin differed at wk 3 and 4 (P < 0.05). In a hippocampal-dependent, spatial, T-maze task, SID piglets were unable to acquire the task (post hoc contrast: first vs. last day of acquisition), while MID piglets demonstrated deficits in reversal learning (P = 0.032). Iron concentrations in the liver (P < 0.001), serum (P = 0.003), and hippocampus (P = 0.004), but not prefrontal cortex, were lower in MID and SID compared with CON piglets. The level of the transferrin receptor mRNA (TFR) was greater in the prefrontal cortex of CON piglets than in MID and SID piglets (P = 0.001) but not the hippocampus. Gene expression of several neurotrophic factors and proinflammatory cytokines, as well as whole-brain and hippocampal volume, were not affected by dietary treatment. In conclusion, neonatal iron deficiency leads to cognitive impairment, which may be due in part to a reduced iron concentration in the hippocampus.
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PMID:Early life iron deficiency impairs spatial cognition in neonatal piglets. 2351 51


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