Quality Performance Measures Should Include Hypoglycemia Assessments

MedicalResearch.com Interview with:

Victor M. Montori, MD Mayo Clinic

Dr. Victor Montori

Victor M. Montori, MD MSc
Knowledge and Evaluation Research Unit in Endocrinology
Mayo Clinic, Rochester, Minnesota

MedicalResearch.com: What is the background for this study?

Response: Hypoglycemia can acutely disrupt patients’ lives through symptoms ranging from bothersome to life-threatening; worsen quality of life; and hinder medication adherence and glycemic control. Hypoglycemia is now known to increase risk of mortality, cognitive impairment, and cardiovascular events. In order to improve the quality of diabetes care, healthcare organizations use publicly reported performance measures for quality measurement and improvement, and pay-for-performance initiatives. The degree to which existing performance measures are aligned with guidelines, particularly in regard to hypoglycemia avoidance, is uncertain.

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COPD and Risk of Mild Cognitive Impairment

Michelle M. Mielke, Ph.D. Associate Professor Department of Health Sciences Research, Division of Epidemiology Department of Neurology Mayo Clinic Rochester, MN 55905MedicalResearch.com Interview with:
Michelle M. Mielke, Ph.D.
Associate Professor
Department of Health Sciences Research, Division of Epidemiology
Department of Neurology
Mayo Clinic Rochester, MN 55905

MedicalResearch.com: What are the main findings of the study?

Dr. Mielke: Using a population-based sample of cognitively normal individuals, aged 70-89 at baseline, we found that a medical-record confirmed diagnosis of COPD was associated with an increased risk of mild cognitive impairment, specifically non-amnestic mild cognitive impairment.  The risk of mild cognitive impairment increased with a longer duration of COPD such that individuals who had COPD for more than 5 years had a 2.5-fold increased risk of developing non-amnestic mild cognitive impairment.
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Bipolar Disorder: Genome-Wide Association Study

MedicalResearch.com Interview with:
Prof. Dr. Sven Cichon, PhD
Director, Division of Medical Genetics
University Hospital Basel
Human Genomics Research Group
Department of Biomedicine
University of Basel Basel, Switzerland

MedicalResearch.com: What were the main findings of the study?

Answer: We have identified two new gene regions that represent pieces of the jigsaw puzzle of genetic and non-genetic factors that lead to the development of bipolar disorder. One is the gene ADCY2 (Adenylate Cyclase 2) which is involved in signal transmission within nerve cells. The other region comprises two genes, both presumably playing a role in neurodevelopmental processes (MIR2113 and POU3F2). Importantly, these results come out of the largest of these kinds of studies so far, involving altogether more than 24,000 people.
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Should Dental Extractions Be Done Prior to Heart Surgery?

Dr. Kendra J. Grim Department of Anesthesiology Mayo Clinic, Rochester, MN 55905MedicalResearch.com Interview with:
Dr. Kendra J. Grim
Department of Anesthesiology
Mayo Clinic, Rochester, MN 55905

: What are the main findings of the study?

Dr. Grim: “The current guidelines say that if possible, treating the dental problems that patients have before heart surgery is best, to try to prevent both early and late heart infections. But the data is very unclear, because it’s very difficult to study. We found in our study that their risk of serious complications after having teeth removed may be higher than we thought. We were primarily looking at stroke, heart attack, renal failure and death. We found that actually the incidence of having one of those major morbidities was 8 percent.  Of that 8 percent, we had six patients, or 3 percent, of the total group who died between their dental surgery and scheduled heart surgery, so these patients never made it to their heart surgery. An additional 3 percent of patients died after heart surgery. “

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Hypothyroidism and Mild Cognitive Impairment Risk?

Ajay K Parsaik, MD, MS Department of Psychiatry and Behavior Sciences The University of Texas Medical School, Houston Department of Neurology and Mayo Alzheimer’s Disease Research Center, Mayo Clinic, Rochester, MinnesotaMedicalResearch.com Interview with:
Ajay K Parsaik, MD, MS
Department of Psychiatry and Behavior Sciences
The University of Texas Medical School, Houston
Department of Neurology and Mayo Alzheimer’s Disease Research Center, Mayo Clinic, Rochester, Minnesota

MedicalResearch.com: What are the main findings of the study?

Dr. Parsaik: Main findings of our study are that clinical and subclinical hypothyroidism is not associated with mild cognitive impairment in an elderly population after accounting for possible confounding factors and interactions.
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Mild Cognitive Impairment: Progression to Dementia Risk

Dr. Ronald C. Petersen M.D., Ph.D. Division of Epidemiology Department of Health Sciences Research; Department of Neurology Mayo Clinic, Rochester, MNMedicalResearch.com Interview with:
Dr. Ronald C. Petersen M.D., Ph.D.
Division of Epidemiology
Department of Health Sciences Research; Department of Neurology
Mayo Clinic, Rochester, MN

MedicalResearch.com: What are the main findings of the study?

Dr. Petersen: The diagnosis of mild cognitive impairment increases the likelihood of developing dementia.
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Sugar-Sweetened Beverages and Endometrial Cancer

Maki Inoue-Choi, PhD, MS, RD Division of Cancer Epidemiology and Genetics, National Cancer Institute National Institute on Minority Health and Health Disparities, NIH Rockville, MD 20850MedicalResearch.com Interview with:
Maki Inoue-Choi, PhD, MS, RD
Division of Cancer Epidemiology and Genetics, National Cancer Institute
National Institute on Minority Health and Health Disparities, NIH
Rockville, MD 20850

MedicalResearch.com: What are the main findings of the study?

Answer: In our study, postmenopausal women who reported higher consumption of sugar-sweetened beverages were more likely to develop estrogen-dependent type I endometrial cancer, the most common type of this cancer.
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Rheumatoid Arthritis and Increased Risk of Heart Disease

Eric Matteson, M.D. Rheumatology Chair Mayo Clinic in Rochester, Minn.MedicalResearch.com Interview with:
Eric Matteson, M.D.
Rheumatology Chair
Mayo Clinic in Rochester, Minn.

MedicalResearch.com:   What are the main findings of the studies?

Dr. Matteson: “The main finding is that patients with severe rheumatoid arthritis have a higher risk of heart disease.  Further, women who experience early menopause also have a higher risk of heart disease.”
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Parkinson’s Disease: Cognitive Impairment and Plasma Ceramides

Michelle M. Mielke, Ph.D. Associate Professor Department of Health Sciences Research Division of Epidemiology Mayo Clinic 200 First Street SW Rochester, MN 55905MedicalResearch.com: Interview with:

Michelle M. Mielke, Ph.D.
Associate Professor
Department of Health Sciences Research
Division of Epidemiology
Mayo Clinic 200 First Street SW
Rochester, MN 55905

MedicalResearch.com: What are the main findings of the study?

Dr. Mielke: Among Parkinson’s disease (PD) patients, plasma levels of ceramides and monohexylceramides were higher in patients with cognitive impairment or dementia compared to patients who were cognitively normal.  Levels of these lipids were also higher in the combined group of PD patients compared to non-PD controls but the number of controls were small.

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Dementia: Lewy Body vs Parkinson’s Disease

Rodolfo Savica, MD, MSc Department of Neurology, College of Medicine Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, MinnesotaMedicalResearch.com Interview with:
Rodolfo Savica, MD, MSc
Department of Neurology, College of Medicine
Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota


MedicalResearch.com: What are the main findings of this study?

Dr. Savica: This study is the first in North America to explore the incidence of DLB and PDD in a population based sample. We found that the overall incidence of dementia with Lewy bodies (DLB), considered the second leading cause of neurodegenerative dementia after Alzheimer`s disease, is lower than that of Parkinson`s disease (PD), increases steeply with age, and is markedly higher in men than in women.
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Mitral Valve Regurgitation from Flail Leaflets: Early Surgical Intervention May be Warranted

MedicalResearch.com Interview with: Rakesh M. Suri MD, D.Phil.
Mayo Clinic College of Medicine, Rochester, Minnesota

MedicalResearch.com: What might clinicians “take home” from this study?


a. The contemporary outcomes of surgical correction of mitral regurgitation are excellent based upon results observed in this large multinational, multi-institutional study, Mitral valve surgery now has a low peri-operative risk of death or complications, and a very high likelihood of saving a patient’s own heart valve (>90% – repair); thereby avoiding the need for replacement with an artificial valve substitute.

b. All patients with severe degenerative mitral regurgitation are at risk for heart failure and/or death when surgical correction is delayed.  A safe period of “watchful waiting” in those with severe mitral regurgitation due to flail leaflets, even in the absence of traditional Class I triggers for surgery (symptoms or left ventricular dilation/dysfunction) does not exist.

c. Prompt mitral valve surgery within months following the diagnosis of severe degenerative mitral regurgitation, even in those without symptoms, is associated with important and sustained long term benefits including a 40% decrease in death and 60% less heart failure risk, sustained many years following surgical intervention

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Controlling Health Care Costs : US Physicians Views

Jon C. Tilburt, MD, MPH Division of General Internal Medicine, Mayo Clinic, Rochester, Minnesota Biomedical Ethics Program, Mayo Clinic Knowledge & Evaluation Research Unit, Mayo Clinic Healthcare Delivery Research Program, Center for the Science of Healthcare Delivery Division of Health Care Policy and Research, Mayo ClinicMedicalResearch.com Interview with:
Jon C. Tilburt, MD, MPH

Division of General Internal Medicine, Mayo Clinic, Rochester, Minnesota
Biomedical Ethics Program, Mayo Clinic
Knowledge & Evaluation Research Unit, Mayo Clinic

Healthcare Delivery Research Program, Center for the Science of Healthcare Delivery
Division of Health Care Policy and Research, Mayo Clinic

What did you set out to find, what was your objective in this study?

  • We wanted to know physicians perceived roles and responsibilities in addressing health care costs as well as their enthusiasm for proposed strategies to contain health care spending.

Who did you study and what did you look at?

  • Practicing US physicians under age 65, we randomly selected 3900 physicians representing all specialties and mailed them an 8-page survey entitled “Physicians, Health Care Costs, and  Society.” We received 2,556 completed surveys (65% response rate).
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Study finds Current Medical Practices often Not Re-Evaluated, Many offer little Net Benefit

MedicalResearch.com Interview with Dr. Vinay Prasad, MD
Medical Oncology Branch, National Cancer Institute
National Institutes of Health, 10 Center Dr 10/12N226, Bethesda, MD20892.

MedicalResearch.com: What are the main findings of the study?

Dr. Prasad: We reviewed all original articles in the New England Journal of Medicine over ten years.  1344 articles tested some medical practice– which is a screening or diagnostic test, medication, procedure or surgery.  Only 27% or 363 articles tested current medical practice.  And of these articles 146 (40%) contradicted current standard of care, constituting a medical reversal.

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Dual energy CT accurately identifies ACL tears in emergency department

MedicalResearch.com:  Katrina N. Glazebrook, MB, ChB
Department of Radiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905

MedicalResearch.com:  Why did you do the study?

Dr. Glazebrook: We felt CT was being underutilized for evaluation of knee injuries. The utility of CT has been well documented in the assessment of fractures, but little attention has been made on soft tissue evaluation.

CT now has high spatial resolution with very thin reconstructions in any desirable plane, and we have previously noted that this allowed injured soft tissue structures such as cruciate ligaments to be well visualized [presented at Society of Skeletal Radiology meeting March 2013]. We had determined in that prior study that the best reconstruction plane to evaluate both normal and torn anterior cruciate ligaments was the oblique sagittal plane parallel to the lateral femoral condyle as routinely used in MRI imaging of the knee The soft tissue window, single energy bone removal and Dual energy bone removal were the best reconstructions to determine the presence or absence of ACL disruption The bone removal techniques removed the distracting bone so the soft tissue structures were more apparent.
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Newly approved device to treat gastroesophageal reflux disease (GERD)

Newswise — April 11 2012— Mayo Clinic in Florida will be one of the first health care institutions in the United States to offer a newly approved device to treat gastroesophageal reflux disease (GERD). The condition, also known as acid reflux disease, can lead to serious health problems.

The U.S. Food and Drug Administration (FDA) approved the device and treatment procedure on March 22 for patients with GERD who continue to have chronic reflux symptoms despite taking medication.

Mayo Clinic in Florida expects to offer the new treatment immediately, says C. Daniel Smith, M.D., chair of the Surgery Department at Mayo Clinic in Florida, and an internationally recognized expert on the treatment of GERD.

Dr. Smith is experienced in using the system because Mayo Clinic in Florida was one of only 14 centers nationally that participated in a clinical trial that led to the FDA’s approval of the device.

“Mayo has been a leader in the treatment of esophageal diseases, especially GERD, and we are pleased to be offering this new treatment to our patients immediately,” he says.

GERD is a condition in which liquid, or food, in the stomach flows back up into the esophagus due to the inability of a ring of muscle between the lower esophagus and the top of the stomach to close properly.

If drugs aimed at neutralizing the acid in the stomach fails to prevent GERD, an operation designed to correct the mechanical defect is considered. But between 1.5 million and 2 million patients of those patients could benefit from treatment that is much less complex than current surgical options, Dr. Smith says.

“The new system will offer a long-needed treatment option for a large group of underserved patients,” he says.

The results of the clinical study that led to approval of the device have not yet been published. But “the data presented to the FDA revealed striking results when compared to other GERD treatments that have been investigated over the past 20 years,” Dr. Smith says. “The system offers effective control of GERD with limited side effects and thus far an excellent safety record.”

The implanted device is a ring of tiny magnetic titanium beads that is wrapped around the junction between the stomach and esophagus, serving as a mechanical augmentation of the lower esophageal sphincter (the ring of muscle). The magnetic attraction between the beads is strong enough to keep the sphincter closed to refluxing acid, but weak enough so that food can pass through it into the stomach, Dr. Smith says. The device can be implanted using minimally invasive surgery methods.

Dr. Smith performs about 200 GERD-related surgeries a year and has been involved with many new treatments over the past several decades. “I expect this device to be a game changer for the treatment of GERD in select patients who have failed management with drugs,” says Dr. Smith.

Ken DeVault, M.D., chair of the Department of Internal Medicine at Mayo Clinic in Florida, also participated in these studies. “I have many patients who are searching for something more than medication for their reflux, but have been hesitant to undergo a traditional reflux surgery,” he says. “I think this procedure may well be a very attractive option for that group.”

Mayo Clinic physicians and scientists collaborated with Torax Medical in the development of this technology and Mayo Clinic licensed related technology to the company in exchange for equity. Drs. DeVault and Smith are paid consultants to Torax Medical.

Obese patients with HER2-positive breast cancer may have worse outcomes

SAN ANTONIO — Obese patients with early-stage HER2-positive breast cancer may have worse outcomes than patients who are normal weight or overweight, Mayo Clinic researchers found in a study presented today at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium. HER2-positive breast cancer gets its name from a protein called human epidermal growth factor receptor 2 that promotes cancer cell growth.

“Not only did obese women have poorer outcomes given several different therapies tested to treat HER2-positive breast cancer, but we know that obese patients in our study had larger tumors and were more likely to have had cancer detected in their lymph nodes, compared to patients who were not obese,” says the study’s lead author, Jennifer Crozier, M.D., a medical resident.

“While other studies have looked at the effect of body weight on treatment outcome for estrogen receptor-positive breast cancer, no one has examined this variable in the HER2-positive subtype, which accounts for about one-third of all breast cancers,” says Dr. Crozier.

Researchers used data from the North Central Cancer Treatment Group N9831 study for their analysis. This phase III randomized clinical trial tested three different options for treatment of early stage HER2-positive breast cancer: chemotherapy alone (Arm A); chemotherapy followed by Herceptin for a year (Arm B); and chemotherapy plus Herceptin, followed by Herceptin for a year (Arm C).

In a review of data from 3,017 patients, researchers found that, considering all three treatment arms together, obese patients — those with a body mass index (BMI) of 30 or more — had worse outcomes than patients with a BMI less than 30, although these trends were not statistically significant.

Researchers then calculated disease-free survival for each study arm for normal weight, overweight and obese patients, and found that patients fared best in Arm C. In this arm, the difference between BMI and outcome was not statistically significant, Dr. Crozier says. Herceptin was powerful enough to provide an equal benefit in patients with vastly varying body weights, she says.

“We are continually searching for approaches that will help our patients have the best outcome possible after their diagnosis of breast cancer, and this study suggests that excess body weight may make a difference,” says senior investigator Edith Perez, M.D., director of Mayo Clinic’s breast program in Florida.


The study was funded by the National Institutes of Health, Genentech, Bayer, and the Breast Cancer Research Foundation.

Source: Eurekalert December 8 2011

Study finds estrogen may prevent younger menopausal women from strokes

ROCHESTER, Minn. – Estrogen may prevent strokes in premature or early menopausal women, Mayo Clinic researchers say. Their findings challenge the conventional wisdom that estrogen is a risk factor for stroke at all ages. The study was published in the journal Menopause.

Researchers combined the results from a recent Mayo Clinic study with six other studies from across the world and found that estrogen is protective for stroke before age 50. That is roughly the average age when women go through menopause.

“We were very surprised because these results were unexpected,” says study author Walter Rocca, M.D., an epidemiologist and neurologist at Mayo Clinic. “The old idea that estrogen is always a problem in the brain has to be corrected.” Estrogen can be a problem in older women, he explains, but in younger women, estrogen may be important to protect the brain from strokes.

The study has implications for women who experience premature (before age 40) or early menopause (before age 45) from natural causes or from ovary removal. Women in these groups should consider taking estrogen up to approximately age 50 to prevent stroke, Dr. Rocca says.

Ischemic stroke occurs as a result of an obstruction within a blood vessel supplying blood to the brain. According to the American Stroke Association, these types of strokes account for 87 percent of all stroke cases.


Co-authors of the study include: Brandon Grossardt, M.S.; Virginia Miller, Ph.D.; Lynne Shuster, M.D.; Robert Brown, Jr., M.D.

Women exposed to diethylstilbestrol in the womb face increased cancer risk

A large study of the daughters of women who had been given DES, the first synthetic form of estrogen, during pregnancy has found that exposure to the drug while in the womb (in utero) is associated with many reproductive problems and an increased risk of certain cancers and pre-cancerous conditions. The results of this analysis, conducted by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, and collaborators across the country, were published Oct. 6, 2011, in the New England Journal of Medicine.

Beginning in 1940, diethylstilbestrol, known as DES, was used clinically to prevent certain complications of pregnancy. In the 1950s, clinical studies showed DES was ineffective for this purpose. In the late 1960s, an unusual occurrence of a rare cancer of the vagina among young women, called clear cell adenocarcinoma (CCA), was observed and subsequently linked to their exposure to DES while in the womb.

In 1971, the U.S. Food and Drug Administration notified physicians that DES should not be prescribed to pregnant women. However, between 5 million and 10 million pregnant women and babies had been exposed to the drug. It was manufactured under many different product names, and came in various forms, including pills, creams and vaginal suppositories.

“Our study carefully documents elevated risk for DES-exposed daughters for a host of medical problems — many of them also quite common in the general population,” said study author Robert N. Hoover, M.D., director of the Epidemiology and Biostatistics Program in NCI’s Division of Cancer Epidemiology and Genetics. “Without the sentinel finding of a very rare cancer in young women, and without the sustained follow-up of those who were exposed, we would not know the full extent of harm caused by DES exposure in the womb.”

In this study, which included over 6,500 women (4,600 exposed and 1,900 unexposed), the researchers found that the daughters with exposure to DES while in the womb had an increased risk of 12 medical conditions, including a twofold higher risk of infertility and a fivefold increased risk of having a preterm delivery. (See table below for complete list of increased risks.)

This study is also the first to estimate the cumulative proportion of all DES-exposed women who developed these conditions because of their exposure. Of all DES-exposed women, 1 in 5 will experience some level of infertility because of their exposure. And of all those exposed women who are successful in having at least one birth, 1 in 3 will have a preterm delivery due to DES.

Although DES-exposed daughters have about 40 times the risk of developing CCA than unexposed women, CCA is still a rare disease, occurring in 1 in 1,000 DES-exposed daughters. While the first women diagnosed with this condition in the late 1960s were adolescents and young adults at the time of their diagnosis, the research now shows that the risk for DES-exposed daughters continues through at least age 40. In addition, these women are more than twice as likely to develop pre-cancerous cells in the cervix or vagina (called cervical intraepithelial neoplasia) and have an 80 percent higher chance of developing breast cancer after age 40. According to the results of this study, by age 55, 1 in 25 DES-exposed daughters will develop abnormal cellular changes in the cervix or vagina, and 1 in 50 will develop breast cancer due to their DES exposure.

This study was the first to assess risk based on the presence of vaginal epithelial changes as a biomarker of timing and dose of DES exposure. Exposed daughters with higher total dose of DES and younger age of the embryo at first exposure had evidence of these changes in the lining of the vagina. Women with these changes were at even greater risk for 9 of the 12 conditions compared to exposed women who did not have the biomarker.

This study did not evaluate sons with DES exposure in the womb, but previous reports have indicated an increased risk for certain testicular abnormalities, including undescended testicles or the development of cysts in the epididymis, tightly coiled tubes connected to the testicles. As DES-exposed sons grow older, more data will be available to assess their cancer risk. So far, research has shown no decreased fertility for these men, even with testicular abnormalities.

The women in this study were followed as part of the NCI’s DES Follow-up Study, which began in 1992. NCI researchers will continue to study DES-exposed daughters as they move into menopausal years. The cancer risks for exposed daughters, as well as sons, are continually being studied to determine if they differ from an unexposed population. In addition, researchers are studying possible health effects on the grandchildren of mothers who took DES during pregnancy, because some of the genetic changes caused by DES exposure in the womb may be inherited.


The other research centers involved in this work are Boston University Slone Epidemiology Center, Boston; Cedars-Sinai Medical Center DES Project, Los Angeles; University of Chicago Department of Obstetrics and Gynecology; Dartmouth-Hitchcock Medical Center, Lebanon, N.H.; The Mayo Clinic DES Project, Rochester, Minn.; The Methodist Hospital-Research Institute Department of Obstetrics and Gynecology, Houston; and Tufts Medical Center, Boston.

For more information about DES exposure and cancer risk, please go to http://www.cancer.gov/cancertopics/factsheet/Risk/DES.

Blood Tests May Hold Clues to Pace of Alzheimer’s Disease Progression

Release Date: 10/03/2011

Johns Hopkins-led research suggests levels of certain fats in blood might predict rate of cognitive decline.

A team of scientists, led by Johns Hopkins researchers, say they may have found a way to predict how quickly patients with Alzheimer’s disease (AD) will lose cognitive function by looking at ratios of two fatty compounds in their blood. The finding, they say, could provide useful information to families and caregivers, and might also suggest treatment targets for this heartbreaking and incurable neurodegenerative disorder.

Past research has shown that cognitive function declines at different rates in AD patients, with roughly one-third not declining at all in five years, one-third declining at a moderate rate, and the other third declining quickly. Accurately predicting the pace of cognitive decline would help patients and caregivers better prepare and, if treatments are developed, help doctors aggressively target those whose descent into dementia is likely to be accelerated. Currently there are no predictably effective treatments that prevent, slow or stop AD, though the researchers caution that more studies need to be done before their blood fat test proves its value.

“We’re confident there’s a relationship between these lipids and AD progression, but this work is not yet ready to be used clinically,” according to Michelle Mielke, Ph.D., adjunct assistant professor of psychiatry at the Johns Hopkins University School of Medicine and lead author of an article about the work published in the Journal of Alzheimer’s Disease.

Mielke’s team analyzed data from 120 probable Alzheimer’s patients at the Alzheimer’s Disease and Memory Disorders Center at Baylor College of Medicine in Texas, measuring a variety of fats found in the patients’ blood, as well as conducting cognitive assessments during an average of 4.2 visits over 2.3 years. The researchers found that the higher the level of plasma sphingomyelins and the lower the level of ceramide — two types of fat found in cells throughout the body — the slower the progression of the dementia of Alzheimer’s disease.

Although the researchers emphasize that the link between the fats and AD is not well understood, ceramides are involved in inflammation and cell death. If there are fewer of these cell-killing ceramides circulating — which in turn may be killing off fewer important brain cells — the result may be slower disease progression, Mielke says. Meanwhile, a previous study by Mielke and her team showed that higher ceramide levels were associated with greater shrinkage of the brain’s memory center over one year in patients with mild cognitive impairment. Basic science data has also linked ceramide levels and levels of the protein amyloid beta, the accumulation of which has been tied to Alzheimer’s disease.

If the blood fat ratios do turn out to be important, Mielke says there may be ways to use this discovery to slow cognitive decline. For example, an enzyme known as sphingomyelinase metabolizes sphingomyelins into ceramides. It is possible, she says, that if a sphingomyelinase inhibitor were used to slow down the process of breaking down sphingomyelins into ceramides, the progression of the disease could be interrupted.

Though much research has been done to find ways to halt Alzheimer’s, so far the only approved therapy treats symptoms of cognitive decline in some patients for a short period of time. It does nothing to alter the course of the disease.

“And none of the other compounds in clinical trials to date are showing any benefits,” says Mielke, who is also an associate consultant in the division of epidemiology at the Mayo Clinic. “Perhaps we need to shift our focus. The answers could be in these lipids, which can be measured in the blood.”

Other Hopkins researchers contributing to this work include Norman J. Haughey, Ph.D.; Vera Venkata Ratnam Bandaru, Ph.D.; and Constantine G. Lyketsos, M.D.

A gene for Lou Gehrig’s disease and frontotemporal dementia identified

Frontotemporal dementia and amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease — two fatal neurodegenerative disease with distinct symptoms — are triggered by a common mutation in many cases, according to researchers who say they have identified the mutated gene.

In the study, reported in the September 21 online issue of Neuron, the scientists described the discovery of a genetic mutation that is accountable for almost 12 percent of familial FTD and more than 22 percent of familial ALS samples studied.

They also report that the defect is the strongest genetic risk factor found to date for the more common, non-inherited, sporadic forms of these diseases. It was found in 3 percent of sporadic FTD and 4 percent of sporadic ALS samples in the largest clinical patient series.

The study was led by scientists at the Mayo Clinic in Florida, in collaboration with researchers at UCSF, the University of British Columbia and UCLA. The finding emerged from the identification and study of a family stricken by both ALS and FTD, reported last year. In that study, led by the UCSF scientists and published in the Journal of Neurology, Neurosurgery and Psychiatry, the researchers honed in on the region in which the gene was located.

“Both clinically and at the molecular level this discovery is going to significantly improve our understanding of these diseases,” said co-author Adam Boxer, MD, PhD, of the UCSF Memory and Aging Center, the lead author on the 2010 paper. The discovery makes it possible to develop a diagnostic test for the mutation, as well as to create animal models that may be used to help unravel the molecular mysteries connecting the mutation to the diseases, he said.

In the current study, a detailed molecular genetic characterization of the family that Boxer described was done in the laboratory of senior author Rosa Rademakers, PhD, from the Mayo Clinic. She and colleagues identified the gene and the specific mutation within it.

The mutation consists of from hundreds to thousands of extra copies of a six-letter DNA sequence GGGGCC strung end to end within a region of human chromosome nine. The mutation occurs within a gene of unknown function called C9ORF72.

After identifying the mutation, the Mayo researchers searched for it in DNA from other patients with both familial and sporadic forms of the diseases, where they found the strong associations.

FTD is characterized by disturbances in decision making, language skills, behavior and emotional expression, and is as common as Alzheimer’s disease in people younger than 65, according to Boxer. ALS is a neuromuscular disease, leading to muscle paralysis and respiratory failure, often within three to five years. However, it is not unusual for patients diagnosed with one of the two diseases to exhibit symptoms of the other.

Since 2006, six separate groups have reported evidence for a genetic link between the disorders and the same chromosomal region. In the study led by Boxer last year, the researchers described clinical aspects of the disease within the family, and homed in more closely to the gene than others had.

The pattern of protein deposition in the brains of family members in the study may eventually shed light on common aspects of the neurodegenerative process that occurs in both diseases, Boxer said.

There is only one standard medical treatment for ALS, riluzole, which extend life for about six months, he said.

There is no known effective treatment to slow FTD. However, neurologists have generally become much better at recognizing the degenerative disorder, according to Boxer.

Boxer and Bruce Miller, MD, the director of the UCSF Memory and Aging Center and a co-author of both studies, are leaders in FTD research, diagnosis and patient care.

“Ten years ago some neurologists did not acknowledge the existence of FTD,” Boxer says. “Today we are much better at diagnosing the disease, although sometimes it still takes an expert to distinguish it from Alzheimer’s or from psychiatric disorders.

“We’re actively trying to develop treatments for FTD, and we believe this discovery will pave the way for major advances in these efforts.”

The researchers used a technique called linkage analysis to narrow the search for the gene by comparing affected and unaffected family members. Another group of scientists — reporting in the same online edition of Neuron on the same gene — found that C9ORF72 emerged as being significantly associated with FTD and ALS in a genome-wide scan of patients in Finland.


The Mayo portion of the study was funded by the National Institutes of Health and the ALS association (ALSA). The UCSF portion was funded by the NIH, the John Douglas French Foundation; the Hellman Family Foundation and the Tau Research Consortium and the Larry Hillblom Foundation and the state of California.

Aerobic exercise may reduce the risk of dementia

ROCHESTER, Minn. – Any exercise that gets the heart pumping may reduce the risk of dementia and slow the condition’s progression once it starts, reported a Mayo Clinic study published this month in Mayo Clinic Proceedings. Researchers examined the role of aerobic exercise in preserving cognitive abilities and concluded that it should not be overlooked as an important therapy against dementia.

The researchers broadly defined exercise as enough aerobic physical activity to raise the heart rate and increase the body’s need for oxygen. Examples include walking, gym workouts and activities at home such as shoveling snow or raking leaves.

“We culled through all the scientific literature we could find on the subject of exercise and cognition, including animal studies and observational studies, reviewing over 1,600 papers, with 130 bearing directly on this issue. We attempted to put together a balanced view of the subject,” says J. Eric Ahlskog, M.D., Ph.D., a neurologist at Mayo Clinic. “We concluded that you can make a very compelling argument for exercise as a disease-modifying strategy to prevent dementia and mild cognitive impairment, and for favorably modifying these processes once they have developed.” The researchers note that brain imaging studies have consistently revealed objective evidence of favorable effects of exercise on human brain integrity. Also, they note, animal research has shown that exercise generates trophic factors that improve brain functioning, plus exercise facilitates brain connections (neuroplasticity).

More research is needed on the relationship between exercise and cognitive function, the study’s authors say, but they encourage exercise, in general, especially for those with or worried about cognitive issues.

“Whether addressing our patients in primary care or neurology clinics, we should continue to encourage exercise for not only general health, but also cognitive health,” Dr. Ahlskog says.


Co-authors include Yonas Geda, M.D.; Neill Graff-Radford, M.D.; and Ronald Petersen, Ph.D., M.D.