Wednesday, February 27, 2008
statines hypertension
| To Print: Click your browser's PRINT button. NOTE: To view the article with Web enhancements, go to: http://www.medscape.com/viewarticle/570315 The Role of Statins in Treating Pulmonary Hypertension Fernando Torres, MDMedscape Pulmonary Medicine. 2008; ©2008 Medscape Posted 02/20/2008 Question
The Rho-kinase activation is noted in models of PH. PH develops in rats exposed to hypoxia for 2 weeks. This chronic hypoxic PH injury can then be reversed with 2 weeks of therapy with simvastatin. The expression of Rho-kinase-1 and 2 was markedly diminished in the rats treated with simvastatin. The activity of Rho-kinase increased threefold under hypoxic conditions and normalized with simvastatin treatment. Thus, the inhibition of Rho-kinase expression and activity maybe important in the statin effect seen in hypoxic PH in rats.[1] Similarly, the hypoxia-induced p38 MAP kinase activation and proliferation of pulmonary fibroblasts can be inhibited by statins.[2] Using the monocrotaline model of PH, PH develops in the male Sprague-Dawley rat. After exposure to monocrotaline, atorvastatin given daily for 4 weeks reduced the development of PH and reduced the levels of serotonin transporter protein in the pulmonary vasculature.[3] Similarly, PH develops in Wistar male rats injected with monocrotaline. Pravastatin but not atorvastatin was able to significantly reduce PH and restore endothelium-dependent relaxation. Both agents, however, are able to restore endothelial nitric oxide synthetase expression, prevent apoptosis, and improve medial wall thickening. Thus, potentially, different members of the statin family may have different effects on PH.[4] Mutations in the bone morphogenetic protein receptor II (BMPR2) have been identified in patients with familial PH. The use of simvastatin seems to induce BMPR2 expression and improve the BMP-BMPR2 signaling, enhancing endothelial differentiation and function.[5] Because of the benefits seen in animal models, an open-label observational study was performed at Stanford University Medical Center.[6] Sixteen patients who had PAH with different WHO functional class 1 through 4 were treated with simvastatin 20-80 mg/day. Individual patients demonstrated improvements in 6-minute walk and cardiac output or decreases in right ventricular systolic pressure. It was felt by the investigator that these improvements might be associated with simvastatin treatment. These observations have led physicians to believe that the use of simvastatin may be beneficial for the treatment of pulmonary arterial hypertension. During the past few years different human trials have been designed and are in the process of recruiting patients to answer that question. Results of these trials will probably be reported in the next few years. Currently, the American College of Chest Physicians and the World Health Organization have no recommendation for using statins in the treatment of PH. References
 Fernando Torres, MD, Assistant Professor of Medicine; Director, Pulmonary Hypertension Program, UT Southwestern, Dallas, Texas Disclosure: Fernando Torres, MD, has disclosed that he has received grants for clinical research from United Therapeutics, Gilead, and Actelion. Dr. Torres has also disclosed that he serves as an advisor or consultant to United Therapeutics, Gilead, Actelion, and Pfizer. |
calcium tabletten
Heartwire 2008. © 2008 Medscape
January 17, 2008 (Auckland, New Zealand) – A new study has shown that calcium supplementation might increase vascular events in elderly women [1]. The findings are somewhat unexpected, because previous trials have shown that calcium improves blood cholesterol levels, senior author Dr Ian R Reid (University of Auckland, New Zealand) told heartwire.
Dr Mark J Bolland (University of Auckland, New Zealand) and colleagues published the findings online in BMJ January 15, 2008.
"This is quite controversial, given that the worldwide calcium-supplement market is worth $3 billion a year," says Reid. "The trial was primarily looking at what calcium supplements do to bone density, but we had a secondary hypothesis right from the outset that calcium might actually prevent heart attack. What we found, to our surprise, was that we didn't see a decrease but an increase, and the findings appear to be quite robust." Reid added, however, that there have been some clues from three other recent studies, including one from Women's Health Initiative (WHI) in the US [2]: "these three did not find significant increases in the number of heart attacks [with calcium], but they have found upward trends."
Dr Erin D Michos (Johns Hopkins University, Baltimore, MD), who was not involved with this new study but cowrote an editorial accompanying the publication of the WHI study on vitamin-D/calcium supplements last year [3], told heartwire: "This is a thought-provoking study, although not definitive, but further work should be done."
Others warned that it is premature to make any treatment decisions on the basis of this new study. British Heart Foundation spokesperson Judy O'Sullivan said more rigorous research was needed before any firm conclusions could be drawn. "Anyone who has been advised by their doctor to take calcium supplements to protect their bones should not stop doing so in light of this study alone without medical advice," she said.
Findings equivocal
The New Zealand team randomized 1471 postmenopausal women (average age 74 years) to either calcium supplementation (1 g/day calcium citrate) or placebo. As well as bone density, they looked at adverse cardiovascular events over five years: death, sudden death, MI, angina, other chest pain, stroke, transient ischemic attack, and a composite end point of MI, stroke, or sudden death.
Reid says the study collected data on MIs and strokes "in a much more careful way" than any other previous studies have done. "We got cardiologists and other people involved and audited all those things and went back to patients' hospital records and so on."
MI was more commonly reported in the calcium group than in the placebo group (45 events in 31 women vs 19 events in 14 women, p=0.01), and the composite end point was also reached more often in the calcium group (101 events in 69 women vs 54 events in 42 women, p=0.008). Even after adjudication, MI remained more common in the calcium group, as did the composite end point.
biphosfanates, fosamax
Medscape Medical News 2008. © 2008 Medscape
January 8, 2008 — Temporary or permanent discontinuation of bisphosphonate therapy should be considered in patients who present with severe musculoskeletal pain, the US Food and Drug Administration (FDA) warned healthcare professionals yesterday. Overlooking bisphosphonate therapy as a causal factor may delay diagnosis, thereby prolonging pain and/or impairment and the use of analgesics. In contrast with the acute-phase response that sometimes accompanies initial exposure to bisphosphonate therapy, some patients experience severe and sometimes incapacitating bone, joint, and/or muscle pain that begins months or years later.
The incidence rate and risk factors for this reaction remain unknown, according to an alert sent from MedWatch, the FDA's safety information and adverse event reporting program. Moreover, discontinuation of therapy may not lead to complete relief — some patients have reported slow or incomplete resolution of symptoms.
Over the next 6 months, the FDA will be evaluating reports of severe musculoskeletal pain associated with bisphosphonate use. In the interim, patients reporting these symptoms should be monitored, and alternative causes for pain should be considered for those who do not experience a lessening or resolution of symptoms after bisphosphonate withdrawal.
Bisphosphonates are indicated for the prevention and treatment of osteoporosis and for treating hypercalcemia of malignancy and Paget's disease. They also are beneficial in patients with multiple myeloma and bone metastases from solid tumors.
Currently marketed oral bisphosphonates include risedronate sodium tablets (Actonel and Actonel + Ca, Proctor & Gamble Pharmaceuticals, Inc), alendronate sodium tablets (Fosamax and Fosamax + D, Merck & Company, Inc), ibandronate sodium tablets (Boniva, Roche), etidronate disodium tablets (Didronel, Proctor & Gamble), and tiludronate disodium tablets (Skelid, sanofi-aventis US, LLC).
Injectable bisphosphonates include pamidronate disodium injection (Aredia, Novartis Pharmaceuticals Corp) and zoledronic acid injection (Reclast and Zometa, Novartis).
Adverse events related to bisphosphonate use should be reported to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.
Welcome to Journal Watch. The content you requested requires sign in with a username and password.
Alternative to Warfarin Prevents Strokes but Causes Excess Bleeding
At the dose tested, idraparinux was not a safe alternative to vitamin K antagonists.
27-02-2008
Sunday, February 24, 2008
statins en A F
Cardiovascular News
Statin treatment may ward off AF
22 February 2008
MedWire News: Patients taking statins may be reducing their risk for developing atrial fibrillation (AF), indicate results of a meta-analysis.
The analysis covers six randomized controlled statin trials: three in patients who had a history of paroxysmal AF, or who underwent cardioversion due to persistent AF; two in patients undergoing cardiac surgery; and one in patients with acute coronary syndromes (ACS).
The trials included 3557 patients, 386 of whom developed recurrent or new-onset AF.
Laurent Fauchier (Centre Hospitalier Universitaire Trousseau, Tours, France) and team found that, overall, patients who received a statin had a significant 61% reduction in the relative risk for AF compared with those given placebo.
The benefits of statin therapy seemed most evident among patients with previous AF, who had a 67% reduction in the risk for a recurrence. This subgroup result was nonsignificant, however, with a confidence interval of 0.10-1.03.
Statin therapy resulted in a nonsignificant 40% reduction in the risk for new-onset AF after ACS or surgery, with a confidence interval of 0.27-1.37.
"The lower number of patients with new-onset or post-operative AF might in part explain the lack of significance for this subgroup," the team speculates in the Journal of the American College of Cardiology.
The researchers say that large, prospective, randomized trials are needed to confirm the protective effects of statins against AF in different patient populations.
However, they observe that such trials are unlikely to occur in patients with coronary heart disease because it would be considered unethical to randomize such patients to placebo.
"In contrast, but possibly very interestingly, it remains to be determined whether statins might bring some benefit in patients with AF without any type of established atherosclerotic disease or with a low risk of atherogenesis," write Fauchier and colleagues.
J Am Coll Cardiol 2008; 51: 828-835
Friday, February 22, 2008
PPI'sen NSAID's
Summary and Comment | Subscription Required
Risk for upper GI events was higher when NSAIDs or coxibs were prescribed without PPIs.
By Allan S. Brett, MD
February 21, 2008
Covering: Abraham NS et al. Am J Gastroenterol 2008 Feb 103:323
Wednesday, February 20, 2008
statins and sleep disturbance
Study Results
Groups were comparable at baseline on all variables, including both sleep measures. At 6 months, both the statin treatment groups showed the expected reductions in LDL-C compared with placebo, although reductions in total cholesterol, LDL-C, and triglycerides were greater with simvastatin than with pravastatin ( Table 4 ).
Simvastatin use was associated with worse sleep quality, and greater reported sleep problems than either pravastatin or placebo ( Table 5 ). Although the differences on the rating scale were small, subjects on pravastatin actually perceived their sleep quality as being better than average (> 15 on the rating scale) whereas those on simvastatin perceived theirs to be slightly worse. Similar results were seen for sleep problems.
These differences between simvastatin and pravastatin or placebo were significant when analyzed by t-test of mean on-treatment sleep scores across randomization groups by t-test and regression analyses adjusted for baseline values of the respective sleep assessment ( Table 6 ). Pravastatin did not differ significantly from placebo on any sleep outcome. In a subset of patients who reported much worse or better sleep in terms of sleep problems, only half of the patients on simvastatin as on placebo reported a "much better" rating, and 2.7 times as many reported that their sleep problems were much worse.
Sleep quality and problems were all found to be associated with tiredness, irritability, and cognition, with stronger relationships between sleep quality and tiredness and between sleep problems and irritability and cognitive impairment.
Comment
Dr. Golomb acknowledged the study limitations: only 1 lipophilic and 1 hydrophilic statin were investigated, dose response was not examined; and it remains unknown whether the effects are modified in groups excluded from the study, such as subjects with diabetes or heart disease. However, she suggested that the difference observed between simvastatin and pravastatin in this study may due to their respective lipophilic or hydrophilic properties, although the differences in lipid reduction or other differences may be involved in the differences in sleep disturbance.
Asked about the mechanisms that might be involved, Dr. Golomb noted that in primates cholesterol lowering, although not by statins, has been shown to reduce levels of central serotonin, a precursor of melatonin, the sleep-regulating hormone; statins have also been shown to alter the ratio of omega-3 to omega-6 fatty acids (omega-3 fatty acids are believed to be important for sleep); or, as observed by Dr. Golomb's group, in some patients statins lead to mitochondrial dysfunction, which is associated with sleep-disordered breathing.
Medscape Cardiology. 2008; ©2008 Medscape
Tuesday, February 19, 2008
aspartame pilots
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| Dr. Julian Whitaker on aspartame |
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By Dave Rietz WEBmaster  | |
| (NutraSweet) Artificial sweeteners are marketed with the promise of weight control, and the vast majority of people who consume them do so to either lose or avoid gaining weight. Folks, this is a fraud of gigantic proportions. From 1960 to l976, there was virtually no change in the number of Americans who were overweight: roughly 24 percent of the population. However, from the mid l980s to the present, this number has more than doubled to 54 percent! This coincides with the massive infusion of noncaloric chemical sweeteners and sugar-free "diet" foods that are eaten by close to three-quarters of the adult population. Although several factors contribute to these alarming statistics, I am convinced that our blind acceptance of the most popular of these artificial sweeteners, aspartame (NutraSweet, Equal, Spoonful), plays a significant role in our current weight problems. Far from helping us lose weight, aspartame has been proven to increase appetite, especially cravings for sweets. Imagine "diet" products that help you pack on extra pounds! And aspartame's downside doesn't end with weight gain: This sweetener is associated with multiple health problems. Since aspartame came on the market in l981, it has accounted for more than 75 percent of the complaints reported in the FDA's Adverse Reaction Monitoring system. The most common adverse reactions attributed to aspartame are headaches, dizziness, attention difficulties, memory loss, slurred speech and vision problems. This cluster of symptoms has become so common that it is actually referred to as "aspartame disease". Even more serious disorders have a suspected link with aspartame. Is it an accident that the incidence of brain tumors has increased by 10% since l975? John W. Olney, MD, of the Washington University Medical School in St. Louis believes there may be a link between the two. In an article published in The Journal of Neuropathology and Experimental Neurology, he notes that animal studies reveal high levels of brain tumors in aspartame-fed rats. According to Dr. Olney, recent findings show that aspartame has mutagenic (cancer-causing) potential, and the sharp rise in malignant brain tumors coincides with the increased use of aspartame. Could serious seizures and vision loss somehow be associated with the sweetener? The U.S. Navy and Air Force published articles in Navy Physiology and Flying Safety with this warning: "several researchers have found aspartame can increase the frequency of seizures, or lower the stimulation necessary to induce them. This means a pilot who drinks diet sodas is more susceptible to flicker vertigo, or to flicker-induced epileptic activity. It also means that all pilots are potential victims of sudden memory loss, dizziness during instrument flight, and gradual loss of vision." What about multiple sclerosis, chronic fatigue, rheumatoid arthritis, depression and other mood disorders? I have reviewed scores of documented cases of patients with symptoms so severe that they were mistakenly diagnosed with one of these conditions, only to have all signs of disease completely vanish after getting off aspartame. Yet the FDA has chosen to turn a deaf ear to repeated requests by scientists, physicians, and consumers to review aspartame's safety. Aspartame has spelled trouble from the get-go. The unique property of this chemical, which is 200 times sweeter than sugar, was accidently discovered in l965 by a chemist trying to develop an ulcer drug. Although the FDA rescinded its initial approval because of studies showing that it caused seizures and brain tumors in lab animals, the agency eventually capitulated to political and monetary pressure and in l981 gave aspartame the stamp of approval. In doing so, this bureaucracy overrode the 3-0 decision of a Public Board of Inquiry, which had reviewed the scientific data and had recommended delaying approval pending further studies on the sweetener's link with brain cancer. In the intervening years, safety concerns have mushroomed. Ralph G. Walton, MD, Professor of Psychiatry at Northeastern Ohio Universities College of Medicine, reviewed all the studies on aspartame and found 166 with relevance for human safety. Every one of the 74 studies funded by the aspartame industry gave it a clean bill of health, while 92 percent of those independently funded revealed safety problems. Once you understand a bit about the chemistry of aspartame, you'll see why it can cause so many problems. Aspartame is comprised of two amino acids, aspartic acid and phenylalanine. Aspartic acid acts as an "excitatory" neurotransmitter, or chemical messenger, in the brain, stimulating neurons to fire. Problems can arise when aspartic acid is out of balance with "inhibitory" amino acids that calm things down. Phenylalanine also easily enters the brain, where it is transformed into neurotransmitters that can further interfere with normal brain function. This is a likely reason why aspartame lowers the threshold for seizures, mood disorders, and other nervous system problems. This altered brain chemistry may also be responsible for the addictive nature of aspartame. Some patients report that getting off diet soda takes more willpower than giving up cigarettes! The remaining component, which makes up 10 percent of aspartame, may be the most dangerous part. It is a methyl ester that breaks down after ingestion into methanol, a nervous system toxin also known as free methyl alcohol or wood alcohol. Methanol is extremely harmful to the optic nerve. A main ingredient in "moonshine" it was notorious during Prohibition for causing blindness. Methanol is rapidly released into the bloodstream, where it is further metabolized into other harmful components, including formaldehyde (a known neurotoxin and carcinogen) and formic acid (the poison in ant stings). Is it any wonder that many of the symptoms of "aspartame disease" are neurological and visual? Drinking a diet soda or two (and I've had patients who drink at least a liter a day) delivers a powerful chemical rush with decidedly negative effects. With this kind of questionable history, who would want to consume this artificial chemical, particularly when there are natural and healthy sweeteners available? Please take the warnings in this article very seriously. Although some people are much more sensitive to aspartame's adverse effects than others, damage is likely cumulative. Aspartame is particularly harmful to children and the developing fetus. I strongly urge anyone with an aspartame "habit" to get off this harmful sweetener. For more information on the downside of aspartame, visit www.dorway.com or send a self-addressed envelope with six stamps to Betty Martini, Mission Possible International, 9270 9270 River Club Parkway, Duluth, Georgia 30097. Don't trade one bad habit for another by switching to sugar-laden drinks and sweets. Avoid most bottled or canned sodas, teas and juices altogether. If they don't contain an artificial sweetener, they're loaded with some kind of sugar. Your beverage of choice should be water. (Try perking it up with a slice of lemon.) Sparkling water, diluted fruit juice, and homemade iced tea flavored with the herbal sweetener stevia are other options. A few drops of stevia also nicely sweeten hot tea, coffee, cereal, yogurt, and other foods. Stevia is sold in health food stores or may be ordered from Amai Health (877/989-9954) or Wisdom of the Ancients (800/899-9908). We'll talk more about healthy sweeteners in next month's issue. | |
aspartame, aspataam, dizziness
- 1: Am J Otol. 1992 Sep;13(5):438-42.
Aspartame and dizziness: preliminary results of a prospective, nonblinded, prevalence and attempted cross-over study.
Department of Otolaryngology-Head and Neck Surgery, Georgetown University, Washington, DC.
Aspartame is a low-calorie food sweetener recently approved by the FDA for general human consumption. One of us (AJG) treated a patient whose symptoms of episodic vertigo and continuous unsteadiness resolved upon ceasing aspartame intake. A literature review revealed that although dizziness has been associated with aspartame intake, no systematic study of the problem exists. As an initial attempt to ascertain the prevalence of aspartame-related dizziness in an otolaryngologic clinic, we elected to study prospectively all patients entering with the complaint of vertigo by means of a standardized questionnaire. Those patients determined to consume aspartame were further studied in a nonblinded manner to see if aspartame intake could be correlated to symptomatology. A cross-over limb was also attempted, but no patient would participate. This presentation details the case history of the propositus patient and the preliminary results of the currently ongoing prospective study.
PMID: 1443079 [PubMed - indexed for MEDLINE]
Friday, February 15, 2008
dementia folium zuur
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NOTE: To view the article with Web enhancements, go to:
http://www.medscape.com/viewarticle/569976
This activity is developed and funded by Medscape.
News Author: Caroline Cassels
CME Author: Désirée Lie, MD, MSEd
Complete author affiliations and disclosures, and other CME information, are available at the end of this activity.
Release Date: February 11, 2008; Valid for credit through February 11, 2009
Credits Available
Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™ for physicians;Family Physicians - up to 0.25 AAFP Prescribed credit(s) for physicians
All other healthcare professionals completing continuing education credit for this activity will be issued a certificate of participation.
Physicians should only claim credit commensurate with the extent of their participation in the activity.
February 11, 2008 — Folate deficiency has been associated with a tripling of dementia risk in elderly people.
New research by investigators at Chonnam National University Medical School, Kwangju, Republic of Korea, found that individuals who were folate deficient at study outset were 3.5 times more likely to develop dementia. However, individuals with lower folate levels, but who were not folate deficient at baseline, were also at significant increased risk for dementia.
"Folate deficiency is clearly associated with a higher risk of dementia, but there also appears to be a significant association [between dementia and folate] across the non-deficient range," study author Robert Stewart, MD, MRCPsych, told Medscape Neurology & Neurosurgery.
The study is published online in the February 5 Early Release Article issue of the Journal of Neurology, Neurosurgery, and Psychiatry.
Inconsistent Findings
According to the study, previous research investigating a possible association between serum folate, vitamin B12, and homocysteine levels as predictors of dementia have been inconsistent.
To explore this relationship, the researchers conducted a prospective community-based study and looked at baseline concentrations of folate, vitamin B12, and homocysteine levels and changes in these factors with time and the relationship to incident dementia.
The 2-year study included 518 subjects aged 65 years or older living in 1 of 2 geographic catchment areas (1 urban, 1 rural) in Kwangju, South Korea.
At baseline, all subjects were evaluated for dementia as defined by the Mini-Mental State Examination, the Instrumental Activities of Daily Living Scale, and the Clinical Dementia Rating scale. In addition, a complete medical history was taken and full physical and neurologic examinations conducted.
Blood samples were collected at baseline and again at study follow-up. Demographic information as well as data on depression, smoking, alcohol consumption, and daily physical activity was also gathered, and subjects were assigned a summary score.
At median follow-up of 2.4 years, 45 individuals (8.7%) developed dementia. Of these, 34 (6.6%) had Alzheimer's disease, 7 (1.4%) had vascular dementia, and 4 had "other" dementia types.
The prevalence of baseline folate deficiency was 3.5%. This, said Dr. Stewart, is relatively low vs Western populations, possibly because of the high intake of green vegetables in the Korean diet.
Adjusted analyses revealed that incident dementia increased significantly across descending quintiles of baseline folate concentrations. However, incident dementia was not associated with baseline vitamin B12 or homocysteine levels.
Brain-Body Connection Sometimes Overlooked
During the follow-up period, dementia occurred more commonly in subjects with a relative decline in folate and vitamin B12 levels. The investigators also noted that declining folate levels were associated with an increase in homocysteine concentrations.
In addition, incident dementia was significantly linked to older age, lower education, more severe cognitive impairment and disability, lower physical activity, and the presence of the apolipoprotein E ε4 allele.
According to Dr. Stewart, when researchers adjusted for weight loss during the study period, the strength of all associations lessened. This finding, said Dr. Stewart, is consistent with previous research that physical changes such as weight loss occur very early in dementia, before the onset of clinical symptoms, and may, at least in part, be responsible for changes in folate, vitamin B12, and homocysteine levels.
"When a doctor sees a patient with suspected dementia, it is very important that their physical health and nutritional status are checked right at the outset. One of the problems that we have in the [United Kingdom] is that physicians tend to be less attentive to dementia patients' physical health, possibly because they view dementia purely as a problem of brain function. This is something that needs to be remedied," he said.
The study was supported by the Korea Health 21 R&D, Ministry of Health & Welfare, Republic of Korea. The study authors have disclosed no relevant financial relationships.
J Neurol Neurosurg Psychiatry. Published online February 5, 2008.
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
- Describe the predictive value of baseline plasma folate, vitamin B12, and homocysteine levels for predicting incident dementia in older adults.
- Describe the predictive value of changes in levels of folate, vitamin B12, and homocysteine for predicting incident dementia.
Clinical Context
Folate, vitamin B12, and homocysteine are all involved in 1-carbon transfer (methylation) reactions necessary for the production of monoamine neurotransmitters, phospholipids, and nucleotides. Cross-sectional studies have found correlations between folate deficiency and hyperhomocysteinemia and dementia and cognitive impairment, but results from prospective cohort studies have been controversial.
This is a 2-year community-based prospective cohort study of elderly adults without dementia at baseline to examine the association between baseline and changing folate, vitamin B12, and homocysteine levels and incident dementia.
Study Highlights
- Included were adults older than 65 years from 2 geographic catchment areas (1 rural, 1 urban) in 1 country who completed identical assessments at baseline and at follow-up.
- Participants were identified from a national registry and were seen at baseline and at 2 years.
- Examinations included the Mini-Mental Status Examination, the Clinical Dementia Rating Scale, Instrumental Activities of Daily Living Scale, history, disability (World Health Organization Disability Assessment Schedule II), and full physical and neurologic examination.
- Risk factors for dementia that were assessed and accounted for included alcohol, smoking, and physical activity.
- Apolipoprotein E ε4 allele status was determined.
- Senior investigators assigned diagnoses for dementia, Alzheimer's disease, and vascular dementia using standard criteria.
- Investigators were blinded to the blood assay status of each participant evaluated.
- Fasting morning blood samples were collected for plasma folate, vitamin B12, and homocysteine levels at baseline and at follow-up.
- At baseline, 732 of 1204 residents completed all measures, and 518 subsequently completed all follow-up evaluations.
- Mean follow-up duration was 2.4 years.
- Of this cohort, 45 participants developed incident dementia for a rate of 8.7%, with 6.6% having Alzheimer's disease, 1.4% having vascular dementia, and 0.8% having "other" dementia.
- Incident dementia was significantly predicted by older age, lower educational level, more severe cognitive impairment, disability, lower physical activity, and presence of the apolipoprotein E ε4 allele.
- Mean age was 71.6 years for those without and 74.3 years for those with dementia.
- 54.9% of those without dementia were women vs 63.8% of those with dementia.
- With time, folate levels decreased whereas vitamin B12 levels increased, which may have reflected vitamin B12 supplementation.
- Incident dementia was significantly predicted by lower baseline folate levels, with incidence increasing across quintiles of decreasing folate levels (P = .025).
- Baseline vitamin B12 and homocysteine levels did not predict incident dementia.
- Vitamin B2 level was positively associated with folate levels (P = .001), whereas homocysteine levels were inversely associated with folate levels (P < .001).
- Decreasing folate, weakly increasing vitamin B12, and increasing homocysteine levels with time were all predictive of dementia, with adjusted odds ratios (ORs) of 1.49, 1.55, and 1.21, respectively.
- Adjustment for weight loss reduced the magnitude of the associations.
- The prevalence of folate deficiency at baseline was 3.5%; vitamin B12 deficiency, 17.4%; and hyperhomocysteinemia, 19.7%.
- The adjusted ORs for incident dementia associated with deficiency conditions were 3.43, 1.53, and 1.57 for reduced folate and vitamin B12 and increased homocysteine levels, respectively.
- The authors suggested that changes in folate, vitamin B12, and homocysteine levels with older age may reflect somatic manifestations of early dementia, such as weight loss.
- The authors suggested that interventions for preventing dementia include addressing the nutrition of frail elderly adults.
Pearls for Practice
- Baseline serum folate level predicts later incident dementia.
- With time, decreasing levels of folate, weakly increasing vitamin B12 and greater increasing levels of homocysteine are associated with increased risk for incident dementia.
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Target Audience
This article is intended for primary care clinicians, geriatricians, neurologists, psychiatrists, and other specialists who care for patients at risk for or who have dementia.
Goal
The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.
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Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Medscape, LLC designates this educational activity for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity. Medscape Medical News has been reviewed and is acceptable for up to 300 Prescribed credits by the American Academy of Family Physicians. AAFP accreditation begins 09/01/07. Term of approval is for 1 year from this date. This activity is approved for 0.25 Prescribed credits. Credit may be claimed for 1 year from the date of this activity. AAFP credit is subject to change based on topic selection throughout the accreditation year.
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Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.
News Author
Caroline Cassels
is a journalist for Medscape. Caroline has been a journalist in the health field for 18 years, writing extensively for both physician and consumer audiences. She launched an awarding-winning consumer publication and edited several consumer health websites before joining thekidney.org, a nephrology site recently acquired by WebMD. She can be contacted at CCassels@medscape.net.Disclosure: Caroline Cassels has disclosed no relevant financial relationships.
CME Author
Désirée Lie, MD, MSEd
Clinical Professor, Family Medicine, University of California, Orange; Director, Division of Faculty Development, UCI Medical Center, Orange, CaliforniaDisclosure: Désirée Lie, MD, MSEd, has disclosed no relevant financial relationships.
Brande Nicole Martin
is the News CME editor for Medscape Medical News.Disclosure: Brande Nicole Martin has disclosed no relevant financial information.
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Saturday, February 09, 2008
dementia folic acid
| To Print: Click your browser's PRINT button. NOTE: To view the article with Web enhancements, go to: http://www.medscape.com/viewarticle/569920 Folate Deficiency May Triple Dementia Risk in the Elderly Caroline Cassels Medscape Medical News 2008. © 2008 Medscape
February 8, 2008 — Folate deficiency has been associated with a tripling of dementia risk in the elderly. New research by investigators at Chonnam National University Medical School, in Kwangju, Republic of Korea, found that individuals who were folate deficient at study outset were 3.5 times more likely to develop dementia. However, individuals with lower folate levels but who were not folate deficient at baseline were also at significantly increased dementia risk. "Folate deficiency is clearly associated with a higher risk of dementia, but there also appears to be a significant association [between dementia and folate] across the nondeficient range," study author Robert Stewart, MD, told Medscape Neurology & Neurosurgery. The study is published online February 5 in the Journal of Neurology Neurosurgery and Psychiatry. Inconsistent Findings According to the study, previous research investigating a possible association between serum folate, vitamin B12, and homocysteine levels as predictors of dementia have been inconsistent. To explore this relationship, the researchers conducted a prospective community-based study and looked at baseline concentrations of folate, vitamin B12, and homocysteine levels and changes in these factors over time and the relationship to incident dementia. The 2-year study included 518 subjects aged 65 years or older living in 1 of 2 geographic catchment areas — 1 urban, 1 rural — in Kwangju, South Korea. At baseline, all subjects were evaluated for dementia using the Mini-Mental State Examination (MMSE), the Instrumental Activities of Daily Living Scale, and the Clinical Dementia Rating scale. In addition, a complete medical history was taken and full physical and neurological examinations conducted. Blood samples were collected at baseline and again at study follow-up. Demographic information as well as data on depression, smoking, alcohol consumption, and daily physical activity was also gathered, and subjects were assigned a summary score. At a median follow-up of 2.4 years, 45 (8.7%) individuals developed dementia. Of these, 34 (6.6%) had Alzheimer's disease (AD), 7 (1.4%) had vascular dementia, and 4 had "other" dementia types. The prevalence of baseline folate deficiency was 3.5%. This, said Dr. Stewart, is relatively low compared with Western populations, possibly because of the high intake of green vegetables in the Korean diet. Adjusted analyses revealed incident dementia increased significantly across descending quintiles of baseline folate concentrations. However, incident dementia was not associated with baseline vitamin B12 or homocysteine levels. Brain-Body Connection Sometimes Overlooked Over the follow-up period, dementia occurred more commonly in subjects with a relative decline in folate and vitamin B12 levels. The investigators also noted declining folate levels were associated with an increase in homocysteine concentrations. In addition, incident dementia was significantly linked to older age, lower education, more severe cognitive impairment and disability, lower physical activity, and the presence of the apolipoprotein E4 allele. According to Dr. Stewart, when researchers adjusted for weight loss over the study period, the strength of all associations lessened. This finding, said Dr. Stewart, is consistent with previous research, that physical changes such as weight loss occur very early in dementia, before the onset of clinical symptoms, and may, at least in part, be responsible for changes in folate, B12, and homocysteine. "When a doctor sees a patient with suspected dementia, it is very important that their physical health and nutritional status are checked right at the outset. One of the problems that we have in the UK is that physicians tend to be less attentive to dementia patients' physical health, possibly because they view dementia purely as a problem of brain function. This is something that needs to be remedied," he said. The study was supported by the Korea Health 21 R&D, Ministry of Health & Welfare. J Neurol Neurosurg Psychiatry. Published online February 5, 2008. Abstract
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Friday, February 01, 2008
agression
adoption, and family studies all suggest a genetic influence
underlying aggression (5), with heritability estimates for dimensional
measures of aggression ranging from 44% to
72% in adults. Ametaanalysis of more than 20 twin studies
confirmed a substantial role for a genetic influence underlying
aggression (6). Although behavioral genetic studies to
date have not attempted to distinguish among aggression
subtypes, impulsive aggression appears to be quite distinct
from premeditated aggression. Overall, the recurring theme
emerging from more than 20 years of empiric research is
that ‘‘impulsive aggression’’ demonstrates the most consistent
and noteworthy findings with respect to both biological
correlates (7,8) and psychopharmacologic treatment (9,10).
Biological factors include a variety of neurotransmitter and
neuromodulator systems. Most data involve the central serotonin
(5-hydroxytryptamine or 5-HT) system, although
limited data is now emerging for a role for other central
systems involving catecholamines, steroids, neuropeptides,
and cholesterol and fatty acids. This chapter reviews the
neuropsychopharmacologic data relevant to these systems
and concludes with a discussion of the psychopharmacology
of aggression.
