Thursday, July 31, 2008

ICAD: Marriage May Protect Against Dementia

By Todd Neale

CHICAGO, 31 july 2008-- The give and take of marriage may be enough to stave off Alzheimer's disease and other cognitive impairment, a prospective population-based study suggested. People living alone from midlife on were almost three times as likely to develop some level of cognitive impairment as those who were living with a partner (OR 2.89, P<0.001).
Krister Hakansson, of Vaxjo University in Vaxjo, Sweden, and the Karolinska Institute in Stockholm, reported at the International Conference on Alzheimer's Disease here. There were similar greater risks of mild cognitive impairment (OR 3.17, P<0.001) and Alzheimer's disease (OR 2.83, P<0.05) for those living alone.
"This study points to the beneficial effects of a married life," Hakansson said, "consistent with the general hypothesis of social stimulation as a protective factor against dementia."
It has been suggested that remaining socially active may protect against the development of dementia, and Hakansson reasoned that a partner relationship would form the most intense form of social interaction because of the necessity of dealing with another's needs or perspectives, enhanced communication, and joint problem-solving.
So he and colleagues turned to the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, which randomly selected middle-age participants from the general population of Finland. Baseline measurements were taken from 1972 to 1987.
In 1998, after a mean follow-up of 21 years, 1,432 of the participants ages 65 to 79 were evaluated for signs of cognitive impairment. At baseline, 1,147 were married or cohabitating, 111 were single, 63 were separated or divorced, and 111 were widowed.
At the end of follow-up, 139 were diagnosed with some form of cognitive impairment, including 82 with mild cognitive impairment -- which may represent a transitional phase between normal age-related memory decline and Alzheimer's disease -- and 48 with Alzheimer's.
Those who were not living with a partner at midlife were twice as likely to have some level of cognitive impairment (OR 2.09, P<0.01) or mild cognitive impairment (OR 2.14, P<0.01) later in life than those who were married or cohabitating, regardless of their late-life living status.
The association with an increased risk of Alzheimer's disease did not reach statistical significance.
Widowed participants at midlife who did not remarry had the highest increased risk of any cognitive impairment (OR 3.53, P<0.001), mild cognitive impairment (OR 3.10, P<0.01), and Alzheimer's disease (OR 7.70, P<0.001) later in life.
Having the APOE-e4 genotype -- a risk factor for Alzheimer's -- was particularly damaging for those who were widowed or divorced from midlife through late life. Those who were married and had the high-risk genotype had a 3.44-fold (P<0.05) increased risk of Alzheimer's disease, compared with a 25.55-fold (P<0.001) greater risk for those who were divorced or widowed.
This suggested, Hakansson said, that other factors beyond cohabitation were involved in the associations.
All analyses were adjusted for education, body mass index, cholesterol, blood pressure, occupation, physical activity, smoking habits, and depression at midlife, as well as APOE e4 status, age at follow-up, and gender.
Hakansson speculated that those who were widowed or divorced -- and remained so -- were at a greater risk than those who were single because the loss of a partner destabilized the psychobiological system, enhancing vulnerability to disease.
Hakansson made no disclosures.
Primary source: International Conference on Alzheimer's DiseaseSource reference:Hakansson K "Unmarried life: paving the way for dementia?" ICAD 2008; Abstract O2-07-01.
ICAD: Biomarkers May Help Identify Pre-Clinical Alzheimer's

By Todd Neale
CHICAGO, 31 july 2008-- Several biomarkers may be useful in detecting the pre-clinical stages of Alzheimer's disease or in evaluating the effectiveness of therapies in development, researchers said here.
Four studies presented at the International Conference on Alzheimer's Disease explored the usefulness of biomarkers in blood and cerebrospinal fluid and a new tracer for positron emission tomography (PET).
"There's been a focus on moving the detection threshold for this disease into earlier symptomatic phases and ultimately into asymptomatic individuals," said Ronald Petersen, M.D., Ph.D., of the Mayo Clinic in Rochester, Minn., and vice chair of the medical and scientific advisory council of the Alzheimer's Association, who moderated the session at which the results were presented.
Biomarkers are needed to do the latter, Dr. Petersen said.
"It is greatly preferable that these markers be easy to obtain, such as in samples of blood or urine, or through readily available imaging technologies, such as MRI and PET," said William Thies, Ph.D., vice president of medical and scientific relations at the association.
One such biomarker -- increased expression of the protein CD-69 in peripheral blood lymphocytes -- was identified by researchers at the University of Leipzig in Germany.
Measuring the expression of CD-69 differentiated patients who were diagnosed with Alzheimer's from patients with normal cognitive function with 88% and 82% accuracy, respectively, said Louis Kirby, M.D., chief medical officer for Provista Life Sciences, which oversees the company that licensed the assay, called the LymPro test.
It also differentiated those who were diagnosed with Alzheimer's from demented Parkinson's patients with 91% accuracy when the diagnosis was Alzheimer's and 92% accuracy when the diagnosis was Parkinson's.
A larger trial is underway to verify the results, Dr. Kirby said, and the test could be on the market in October.
Two other studies explored biomarkers in cerebrospinal fluid.
The first, presented by Anne Fagan, Ph.D., of Washington University in St. Louis, looked at beta-amyloid42, a form of the protein that is particularly likely to create plaques characteristic of Alzheimer's disease.
In an earlier small study, Dr. Fagan and her colleagues had shown that the level of beta-amyloid42 in cerebrospinal fluid was inversely associated with plaques in the brain, as measured with PET scans using Pittsburgh Compound B (11C-PIB) as a tracer. (See: Another Avenue for Detecting Early Alzheimer's)
The researchers repeated the study in a larger cohort of 132 patients (mean age 65.7) who had no to mild dementia, and found similar results.
Of 37 patients who had a large amount of plaques, 36 (97%) had low levels of beta-amyloid42.
Of 95 patients with low levels of plaques, 80 (84%) had high levels of the protein in their cerebrospinal fluid.
"Our analyses suggest that a decline in [beta-amyloid42 in cerebrospinal fluid] may effectively identify non-demented individuals who are in the preclinical stage of Alzheimer's, even before they are PIB positive," Dr. Fagan said.
The second study examined the presence of another protein, beta-secretase (BACE1), in cerebrospinal fluid.
Past studies have shown that the protein is involved in the processing of amyloid precursor protein and the production of toxic beta-amyloid, and that it is over-expressed in the brains of Alzheimer's patients.
So Harald Hampel, M.D., of Trinity College Dublin, and colleagues examined the presence of BACE1 in the cerebrospinal fluid of 47 patients with mild cognitive impairment.
After a mean of 2.3 years of follow-up, 15 of the patients had developed Alzheimer's disease.
Cox-regression analysis showed that BACE1 levels and APOE e4 genotype -- a risk factor for Alzheimer's disease -- were the strongest predictors for progression to Alzheimer's.
The technique requires further study, Dr. Hampel said, but it may eventually be used as an outcome biomarker in clinical trials of anti-amyloid therapies for Alzheimer's.
A fourth study evaluated the effectiveness of a new tracer for PET scans of amyloid plaques.
The first tracer developed, 11C-PIB, has a relatively short half-life -- 20 minutes -- making it suited mostly for larger medical centers that can produce the compound on-site.
Michael Pontecorvo, Ph.D., of Avid Radiopharmaceuticals in Philadelphia, reported that a new tracer, called 18F-AV-45, has a longer half-life -- about two hours -- and therefore, would not necessarily have to be made on-site.
The tracer was retained in the brains of patients diagnosed with Alzheimer's but not in older individuals with normal cognitive function and showed rapid uptake and steady levels in the brain from 50 to 90 minutes after administration.
The compound "has the potential to aid in the diagnosis and early detection of Alzheimer's in a community setting and may be a useful biomarker for the development and monitoring of novel amyloid reducing therapies," Dr. Pontecorvo said.
Phase II trials with the compound have been initiated, he said.
Dr. Fagan's study was supported by grants from the NIH and the National Institute on Aging and by the Dana Foundation and the Charles and Joanne Knight Alzheimer's Initiative.
Dr. Hampel made no disclosures.
Dr. Pontecorvo is an employee of Avid Radiopharmaceuticals.
Dr. Petersen has participated in previous studies with Avid.
ICAD: IV Immunoglobulin Therapy Shows Early Signs of Efficacy in Alzheimer's

By Peggy Peck
CHICAGO, 31 july2008 -- Mild-to-moderate Alzheimer's disease can be safely and effectively treated with intravenous immunoglobulin (IVIG) therapy, according to preliminary results from a trial reported here. Over nine months, patients randomized to IVIG demonstrated significant improvement on a number of cognitive measures compared with placebo, with no evidence of toxicity, said Norman Relkin, M.D., of Weill Cornell Medical College in New York, discussing an interim analysis of the first double-blind phase II trial of the therapy. "The key points," said Dr. Relkin at the International Conference on Alzheimer's Disease, "are that this was the first time that a controlled clinical trial of this treatment demonstrated benefit at what we believe to be an optimal dose."
He said an 18-month phase III trial was scheduled to begin this fall, recruiting at 35 clinical sites. IVIG is an appealing therapy option because "it is obtained from the plasma of healthy humans and, as such, it has the advantage of having an established safety record."
Moreover, it is literally loaded with antibodies, including antibodies against beta amyloid, he said. Asked how he could be sure that the benefit was the result of IVIG targeting beta amyloid and not attributable to other antibody activity, Dr. Relkin said that there was a dose-dependent decrease in both plasma and cerebrospinal fluid beta amyloid.
One drawback of the treatment is cost. Dr. Relkin said IVIG costs about $100 per gram and "we use 20 to 30 grams per treatment."
Another consideration is time and accessibility. Patients need to travel to a clinic where they receive infusion that typically takes at least two hours.
The trial randomized eight patients to placebo and 16 to IVIG at 0.4 g/kg every two weeks. All patients were in their early 70s and all had mild-to-moderate Alzheimer's disease. Five of the placebo patients and seven of the IVIG patients were women.
All patients were taking acetylcholinesterase inhibitors.
Efficacy endpoints were the Alzheimer's Disease Assessment Scale and the Clinical Global Impression of Change.
At six months, there was no significant difference on the Alzheimer's Disease Assessment Scale (P=0.054) but at nine months, IVIG patients performed significantly better than placebo patients (P=0.009), Dr. Relkin said.
On the Clinical Global Impression of Change, the benefit was significant and apparent at six months (P=0.017), and was sustained at nine months (P=0.003), he said.
The trial was funded by the National Institutes of Health and Baxter, which is developing IVIG for Alzheimer's disease. Dr. Relkin disclosed support from Baxter Bioscience, Pfizer, Eisai, Myriad, and Smart Genetics.
Primary source: International Conference on Alzheimer's DiseaseSource reference:Tsakanikas D, et al "Effects of uninterrupted intravenous immunoglobulin treatment of Alzheimer's disease for 9 months" ICAD 2008; Abstract 08-A-3147.
New Alzheimer's predictors advance earlier detection

NEW YORK, 31 july 2008 – The following news tips are based on poster and oral presentations at the Alzheimer's Association 2008 International Conference to be held in Chicago from July 26 to July 31. Each presentation is embargoed for a specific date and time.
Brain Atrophy and Biomarkers May Help Identify People at Risk for Alzheimer's Susan de Santi, Ph.D., Associate Professor, Department of Psychiatry, NYU Langone Medical Center EMBARGOED FOR RELEASE UNTIL TUESDAY, July 29, 2008 at 12:30 p.m. CT
By combining MRI brain scans and measurements of certain compounds in the cerebrospinal fluid, NYU researchers were able to distinguish individuals who would develop Alzheimer's disease over a two-year period. In a study of 23 people, they found atrophy in areas of the brain involved in learning and memory, and significantly higher CSF levels of phosphorylated tau and other compounds among individuals who would develop Alzheimer's compared to those individuals who didn't progress from mild cognitive impairment over the two-year period. This preliminary study suggests that combining these tests could help predict which individuals with mild cognitive impairment are at the highest risk for developing Alzheimer's disease.

Presentation # P3-067
Big Immune Response to Common Mouth Bacteria Linked to Alzheimer's. Angela R Kamer, D.M.D., M.S., PhD., Assistant Professor, College of Dentistry, New York University EMBARGOED FOR RELEASE UNTIL SUNDAY, July 27, 2008, at 12:30 p.m. CT
In a study investigating the link between Alzheimer's disease and a heightened inflammatory-immune response, NYU researchers found that twice as many subjects with probable Alzheimer's disease tested positive for antibodies in their plasma against a type of bacteria that is commonly found in the mouth. The pioneering study supports a growing body of evidence that associates notable immune changes with a means of predicting and classifying Alzheimer's disease. Together with other immune markers associated with Alzheimer's disease, antibodies to these periodontal bacteria could serve to better understand the causes and mechanisms of the disease, the researchers say.

Presentation # P1-348
Signs of Brain Disease among Healthy Individuals Lidia Glodzik, MD, PhD, Research Physician, Center for Brain Health at NYU Langone Medical Center EMBARGOED FOR RELEASE UNTIL TUESDAY, July 29, 2008 at 12:30 p.m. CT
NYU researchers identified signs of pathology before the clinically noticeable stages of mild cognitive impairment that normally precede Alzheimer's disease. The study involved a cognitively normal group of people ages 40 to 86. It found that higher levels of tau protein in the cerebrospinal fluid correlated with lower grey matter density in brain regions that are important for learning and memory, and are susceptible to Alzheimer's. Combining cerebrospinal fluid measurements and imaging markers to identify normal subjects who are more vulnerable to the neurodegenerative disease opens an opportunity to explore early detection in the service of prevention, the researchers report.

Presentation # PS-070
Couples Counseling Helps the Spouse Caregiver Mary S. Mittelman, Dr.P.H., Research Professor in the Department of Psychiatry at New York University School of Medicine EMBARGOED FOR RELEASE UNTIL WEDNESDAY July 30 at 2:30 p.m. CT
When the patient with Alzheimer's and their spouse caregiver are counseled separately, they are expected to go home and live together. Can couples counseling help stabilize their relationship as they grapple with the disease? Early results show that it can. In a pilot study, researchers at NYU's Silberstein Center offered six counseling sessions focused on the new needs of each member of a couple brought about by the illness. Each of the ill spouses was in the early stages of dementia and could still participate in a counseling session. The NYU researchers report that all caregivers were surprised by how much the person with dementia could communicate in the session. They also report that relationships improved as a result of the counseling, and the caregivers became less depressed.

Presentation # P4-429
Subjective Memory Complaints a Predictor of Further Cognitive Decline Barry Reisberg, MD, Professor, Department of Psychiatry at NYU Langone Medical Center EMBARGOED FOR RELEASE UNTIL TUESDAY, July 29, 2008 at 12:30 p.m. CT
An NYU study that followed 213 healthy adults over an average of 7 years found that subjects with subjective memory complaints at the first evaluation were almost 7 times more likely to experience cognitive decline to mild cognitive impairment or dementia compared to adults without initial complaints. This is the first prediction study to link subjective cognitive impairment to both mild cognitive impairment and dementia and underlines the importance in studying early, non-specific symptoms that arise before mild cognitive impairment is apparent, the researchers report. Such efforts are critical to preventing the disease. To develop preventive interventions it may be necessary to accurately identify the disease in its earliest manifestations, when symptoms are first emerging, say the NYU researchers. These subjective symptoms appear to occur as early as twenty or more years before the overt dementia of Alzheimer's appears.

Presentation # PS-043
A Decreasing Ability to Learn Among Aging Healthy Carriers of APOE 4 Nunzio Pomara, M.D., Professor in the Department of Psychiatry, NYU Langone Medical Center; Director of the Geriatric Psychiatry Program, Nathan S. Kline Institute EMBARGOED FOR RELEASE WEDNESDAY, July 30, 2008, at 1 PM CT
A new study by NYU researchers at the Nathan Kline Institute suggests that a major genetic risk factor for Alzheimer's disease, apoE 4, may exert its adverse effects long before clinical symptoms of the disease emerge. During this critical period they believe there may be a gradually decreasing ability to learn new material, and subsequently form new memories. The scientists evaluated 184 healthy adults, ages 38 to 80 (64 people carried the apoE4 allele), using standardized measures of verbal learning and memory, such as learning a list of words. At younger ages, surprisingly, those with the apoE 4 genetic risk factor significantly outperformed those without it. By ages 60 to 64 and older, however, performance in the apoE 4 group dropped below the non-apoE 4 group.

Presentation # HT-3577
Genetic Mutation Linked to a More Abundant Form of Alzheimer's Protein Allal Boutajangout, PhD, Research Assistant Professor, Department of Medicine and Psychiatry at NYU Langone Medical Center EMBARGOED FOR RELEASE UNTIL WEDNESDAY July 30, 2008 at 4:00 p.m. CT
NYU researchers found that a specific gene mutation previously associated with an increase in production of an Alzheimer's disease-causing protein, amyloid beta, also promotes the entanglement of another protein, tau, which also is associated with the neurodegenerative disease. Mice that produced human types of tau while expressing the gene mutation showed a significant increase in the harmful form of the tau protein in the brain. The research provides a new model for Alzheimer's onset and progression.

Presentation #04-01-05
Study Further Ties Digestion of Harmful Protein to Alzheimer's Disease Dun-Sheng Yang, PhD, Assistant Professor, Department of Psychiatry, NYU Langone Medical Center; Research Scientist, Center for Dementia Research, Nathan S. Kline Institute EMBARGOED FOR RELEASE UNTIL SUNDAY, July 27, 2008 at 12:30 p.m. CT
NYU researchers genetically enhanced the activity of digestive enzymes in the nerve cells of mice that were susceptible to producing an overabundant amount of amyloid beta, the abnormal protein found in the plaques littering the brains of people with Alzheimer's. The mice showed lower amounts of the protein in parts of the brain responsible for advanced thinking, learning and memory—evidence that their brain cells were more efficient at digesting and expelling the toxic, misfolded protein, the researchers report. The study shows that the failure to degrade amyloid beta in lysosomes containing the digestive enzymes is an important factor in Alzheimer's disease. Amyloid beta and another protein called tau are associated with the disease, but it hasn't yet been proven definitively that either actually causes the disease.

Presentation # P1-059
Study Suggests a Link Between Amyloid and Memory Paul M. Mathews, PhD, Assistant Professor, Department of Psychiatry, NYU Langone Medical Center; Research Scientist, Center for Dementia Research, Nathan S. Kline Institute EMBARGOED FOR RELEASE UNTIL SUNDAY, JULY 28, 2008 at 3:00 p.m. CT
By manipulating levels of the beta amyloid peptide, which accumulates in brain plaques in people with Alzheimer's disease, NYU researchers have found that the peptide not only plays a toxic role in the neurodegenerative disease but also is crucial in modulating learning and memory consolidation in the normal brain. The rat study, which controlled peptide levels in a region of the brain that is important in learning and memory, suggests that its disruption may be one of the underlying causes of nerve dysfunction during Alzheimer's disease pathogenesis.

Presentation #02-02-01
Dysfunctional Transporters in Nerves Related to Alzheimer's Seonil Kim, Ph.D student, Sackler Institute for Graduate Biomedical Sciences, NYU Langone Medical Center, Graduate Training Program in Cellular and Molecular Biology, Nathan S. Kline Institute and Ralph Nixon, M.D., Ph.D., Professor of Psychiatry and Cell Biology, NYU Langone Medical Center EMBARGOED FOR RELEASE UNTIL TUESDAY, JULY 29, 2008 at 12:30 p.m. CT
An NYU study found that membrane vesicles that are essential for the trafficking of materials across nerve cells are an important factor in the pathology of Alzheimer's disease. Mouse neurons which over-produce a precursor to the amyloid protein closely linked to Alzheimer's disease development were unable to shuttle the vesicles to their proper destinations in nerve cells, causing them instead to enlarge abnormally and accumulate. The impeded transport of these vesicles, according to the researchers, may affect communications within and between nerve cells that are critical for cognition and when disrupted can lead to the neurodegeneration of Alzheimer's disease.

Presentation # PS-410
Early Phases of Creating a Vaccine against Prion Disease Thomas Wisniewski, MD, Department of Pathology at NYU Langone Medical Center EMBARGOED FOR RELEASE UNTIL TUESDAY, July 29, 2008 at 11:30 a.m. CT
In an animal study, NYU researchers bolstered immunity against a toxic and infectious version of the prion protein, which causes a group of brain diseases, including mad cow's disease. By injecting a safe, reconfigured form of the protein into the body cavity of mice, in addition to orally delivering a neutral bacterial booster, animals could produce more antibodies against the prion protein in the mouth and blood system, preventing access of the infectious prions to the brain. The inoculated mice remained symptom free for 400 days after exposure to infectious prion, while their brains were free from the disease causing protein. The finding has the potential to safely curb prion diseases, such as chronic wasting disease and variant Creutzfeld-Jacob disease, which are thought to be spread by oral exposure to prion.

Presentation # S3-01-04
Tau Immunotherapy Prevents Cognitive Decline in an Alzheimer's Mouse Model Einar M. Sigurdsson, PhD, Assistant Professor of Psychiatry and Pathology, NYU Langone Medical Center EMBARGOED FOR RELEASE UNTIL WEDNESDAY, JULY 30, 2008 at 3:45 p.m. CT
NYU researchers have successfully prevented the cognitive decline of mice by employing a vaccine that targets tangles of tau, a type of protein associated with Alzheimer's disease. Tests confirmed that the immunotherapy helped preserve cognition as well as reduced tau protein tangles in the brain. The findings support the possibility of an immunotherapy that treats Alzheimer's disease by directly targeting toxic forms of the tau protein.

Presentation # O4-04-04
Enzyme inhibition modulates Alzheimer's pathology in mice Jose Morales-Corraliza, Ph.D, NYU Langone Medical Center and Research Scientist, Nathan S. Kline Institute EMBARGOED FOR RELEASE UNTIL SUNDAY, JULY 27, 2008 at 12:30 p.m. CT
Researchers at NYU Langone Medical Center and the Nathan Kline Institute found that the inhibition of the calpain enzyme, which is involved in various cellular processes, led to a robust decrease in amyloid deposition in mice that develop plaque pathology commonly seen in Alzheimer's disease. Modulation of neuronal calpain activity presents a potential therapeutic approach to Alzheimer's, they report. Presentation #P1-079
Partial gene-deletion improves memory dysfunction in Alzheimer's mice Masuo Ohno, Ph.D., NYU Langone Medical Center and head of the Laboratory of Molecular and Cellular Cognition, Center for Dementia Research at the Nathan Kline Institute EMBARGOED FOR RELEASE UNTIL SUNDAY, JULY 27, 2008 at 12:30 p.m. CT
An animal study by NYU researchers reveals that partially inhibiting an enzyme that initiates the release of amyloid beta led to an improvement in neuronal and cognitive deficits in mice that produced excessive amounts of the plaque forming protein. The approach poses a possibility to rescue Alzheimer's-related deficits, the researchers report.

Presentation #P1-092
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Medivation Alzheimer's drug helps -- if used early

By Julie Steenhuysen
31 july 2008--A drug for Alzheimer's disease made by Medivation Inc kept symptoms at bay for 18 months, U.S. researchers said on Wednesday, but people who got the drug after first taking a placebo fared less well, suggesting early treatment is best.
The latest results, being presented at the Alzheimer's Association's international meeting in Chicago, found Dimebon was safe and continued to benefit people who took it for a year and a half.
"The most important thing from my point of view is there were no new safety issues that emerged with longer exposure of the patients," said Dr. Jeffrey Cummings of UCLA, who helped with the study.
The results from the 183-patient study conducted in Russia found people continued to improve, with benefits seen in cognition, memory, activities of daily living and behavior.
The study also found that people who were treated with a placebo for a year and then took Dimebon stabilized across five measures of thinking ability, but were unable to catch up to the group who had taken it for the full 18 months.
"People initially treated with the placebo and then crossed over to Dimebon did not show the same level of benefit as those people who took Dimebon for the full 18 months," Cummings said in a statement.
"This emphasizes the benefit of earlier treatment and suggests the possibility that Dimebon may slow the progress of Alzheimer's," he said.
Medivation has provided frequent updates of patients in the study in Russia, where patients in the study took few if any drugs other than Dimebon.
Such a study would not be possible in Western countries, where most Alzheimer's patients take a variety of other drugs.
Some doctors think the true test of whether Dimebon represents an advance over current therapies will come from studies done in the West, where patients have ready access to other drugs that can slow progression of the disease.
These include Eisai Co Ltd's and Pfizer Inc's Aricept, Forest Laboratories Inc's Namenda, Novartis AG's Exelon and Johnson & Johnson's Razadyne.
All affect message-carrying chemicals in the brain called neurotransmitters, but lose their effect over time.
"The one issue with this trial is that no other treatments were allowed," Dr. Scott Turner, incoming director of the Memory Disorders Program at Georgetown University Medical Center in Washington, said in a telephone interview.
"Here it will be tested as an add-on, and the question is will it have any other benefit (when taken) with the current therapies," he said. "I think that is a big if."
Cummings thinks the drug has a shot.
"I think we will continue to see an effect because the signal was strong; but under the circumstances of a global trial, it will likely be not as clearly seen as it was in the Russian trial," he said in a telephone interview.

Wednesday, July 30, 2008

ICAD: Brain Atrophy Patterns May Aid Early Identification of Alzheimer's

By Todd Neale
CHICAGO, 30 july 2008 -- A pattern of Alzheimer's disease-type brain atrophy in asymptomatic patients may help diagnose incipient disease at its very earliest stages, a researcher suggested here. In 109 patients ages 60 and older with no cognitive impairment, the presence of Alzheimer's-like patterns of structural abnormality, as seen by serial MRIs, increased slowly with age, Christos Davatzikos, Ph.D., of the University of Pennsylvania, reported at the International Conference on Alzheimer's Disease here. The rate at which the Alzheimer's-like pattern was found accelerated at about age 75, he said.
"Although the clinical significance of these Alzheimer's-like patterns of brain atrophy must be further evaluated," he said, "we are very hopeful that these pattern analysis tools will provide early indicators of brain changes that resemble those seen in people with Alzheimer's, years before memory problems are recognized clinically."
Dr. Davatzikos and colleagues used MRI scans from the Alzheimer's Disease Neuroimaging Initiative for high-dimensional pattern analysis and classification to find the Alzheimer's-like patterns of structural changes.
Each patient was given a score -- called the SPARE-AD index -- on the basis of how closely their brain patterns matched negative Alzheimer's-like pattern scores, which indicated a more normal brain, and positive scores, which indicated an Alzheimer's-like pattern.
The pattern was then applied to a cohort of healthy participants in the Baltimore Longitudinal Study on Aging as well as 15 patients with mild cognitive impairment. All of the participants were followed for up to nine years.
Using the pattern, 98.7% of the cognitively normal participants were correctly classified as normal through the end of the study.
In the patients who had mild cognitive impairment, many showed progression to an Alzheimer's-like pattern of structural abnormality in the brain, and at a faster rate than the healthy participants.
Overall, participants who had a score indicating an Alzheimer's-like pattern had lower scores of cognitive function compared with those who did not have evidence of the pattern according to results of two measures on the California Verbal Learning Test (P=0.0075 and P=0.0067).
"Structural abnormality scores and their rates of change define subgroups of cognitively normal and mild cognitive impairment individuals whose cognitive scores differ significantly," Dr. Davatzikos said, "further indicating the clinical relevance of this structural biomarker."
He said that the SPARE-AD index could be used in conjunction with other imaging markers to recognize the early signs of Alzheimer's disease before they present clinically.
Dr. Davatzikos was supported in part by grants from the National Institute on Aging and by a grant from the Institute for the Study of Aging.
Primary source: International Conference on Alzheimer's DiseaseSource reference:Davatzikos C, et al "Longitudinal progression of AD-like patterns of brain atrophy in a normal elderly cohort and in MCI: a high-dimensional pattern classification study" ICAD 2008; Abstract IC-P2-090.
ICAD: Combo of Diabetes Drugs May Protect Against Alzheimer's

By Todd Neale
CHICAGO, 30 july 2008Diabetics who took both insulin and other medications for the disease had fewer plaques associated with Alzheimer's disease than other patients, researchers said here. In a postmortem study, patients on combination treatment had significantly fewer beta-amyloid plaques (P=0.014) than diabetics who were on one treatment alone or patients who did not have diabetes, Michal Schnaider Beeri, Ph.D., of Mount Sinai School of Medicine in New York, reported at the International Conference on Alzheimer's Disease.
Overall, the combination group had about 80% fewer plaques compared with the other groups combined.
However, there were no significant between-group differences in the occurrence of neurofibrillary tangles.
"These results suggest that the combination [of insulin and other diabetes medications] … may beneficially influence Alzheimer's-related brain changes," Dr. Beeri said. "This also points to biological pathways in the brain, such as insulin signaling, that might be a focus for developing new treatment strategies."
Because diabetes has been associated with a greater risk of mild cognitive impairment and Alzheimer's disease in epidemiological studies, the researchers expected to see more plaques when they examined the brains of diabetics.
In a previous study by Dr. Beeri's group, however, that wasn't the case. In fact, they found fewer plaques. Other neuropathological studies have failed to find any association between diabetes and the number of plaques or neurofibrillary tangles.
Dr. Beeri and her colleagues hypothesized that the treatments for diabetes may influence the neuropathology of Alzheimer's.
To test the hypothesis, the researchers studied 248 brains -- 124 from diabetics and 124 from non-diabetics -- from the Mount Sinai School of Medicine Brain Bank. Most of the specimens came from the Jewish Home and Hospital in Bronx, N.Y., and the two groups were matched by age, sex, and severity of dementia.
The mean age of the patients at death was 81.2 and 57.3% were female. The mean clinical dementia rating was 2.4, indicating moderate to severe dementia.
Non-diabetics had slightly lower body mass indices but the difference was not statistically significant.
Of the diabetics, 29 were not on any medication, 49 were taking insulin only, 28 were taking medications other than insulin -- like glyburide or metformin -- and 18 were taking both insulin and another diabetes medication.
The researchers examined the extent of plaques and neurofibrillary tangles in several neocortical regions and in the hippocampus, entorhinal cortex, and amygdala using the CERAD (Consortium to Establish A Registry for Alzheimer's Disease) neuropathological battery.
The group that was on combination treatment for diabetes had significantly fewer beta-amyloid plaques in the entorhinal cortex (P=0.003), amygdala (P=0.009), and overall (P=0.014) compared with the other groups, which did not differ significantly from each other.
The differences approached statistical significance in the hippocampus (P=0.057) and the combined neocortical measure (P=0.052).
When the researchers additionally controlled for APOE e4 genotype, BMI, and fasting glucose at the time of nursing home admission, there was no change in the findings.
Dr. Beeri acknowledged some limitations of the study, including the inability to determine causation and potential confounding. Nor could the survivor effect be ruled out, she said.
Nevertheless, Dr. Beeri said, the results suggest that diabetes medications may influence biological pathways involved in beta-amyloid processing.
The study was funded by the National Institute on Aging. Dr. Schnaider Beeri made no disclosures.
Primary source: International Conference on Alzheimer's DiseaseSource reference:Schnaider Beeri M, et al "Combination of insulin with other diabetes medication is associated with lower Alzheimer's neuropathology" ICAD 2008; Abstract O2-04-01.
ICAD: Mild Cognitive Impairment More Common Than Expected

By Todd Neale
CHICAGO, 30 july 2008-- The rate of new cases of mild cognitive impairment in patients over 70 is higher than previously expected, results from the Mayo Clinic Study of Aging showed. Initially healthy participants developed mild cognitive impairment at a rate of 5.3% a year (95% CI 4.3% to 6.5%), two to three times higher than the rate of new cases of dementia in the same population, Ronald Petersen, M.D., Ph.D., of the Mayo Clinic in Rochester, Minn., reported at the International Conference on Alzheimer's Disease here. "If we extrapolate Alzheimer's incidence rates to mild cognitive impairment, we would expect perhaps 1% to 2% per year," said Dr. Petersen, who is also the vice chair of the Alzheimer's Association's medical and scientific advisory council, "but our findings were substantially higher than that."
The rate increased from 3.5% (95% CI 2.4% to 5%) in participants ages 70 to 79 to 7.2% (95% CI 5.5% to 9.3%) in those ages 80 to 89.
In addition, men were nearly twice as likely as women to develop mild cognitive impairment (HR 1.92, 95% CI 1.22 to 3.02).
Although mild cognitive impairment may represent a transitional phase to various forms of dementia, it is unknown how often it occurs in a population-based setting, the researchers said.
To find out, they turned to the Mayo Clinic Study on Aging, which randomly selected participants ages 70 to 89 from Olmsted County, Minn., in 2004; 1,786 participants were available for analysis.
Each participant underwent a baseline examination that included an assessment of cognitive function and a neurological exam. In addition, the researchers interviewed a close acquaintance of each participant. Follow-up was conducted in 15-month intervals.
The rates of mild cognitive impairment in men and women were 6.2% (95% CI 4.7% to 8.1%) and 4.4% (95% CI 3.1% to 6%), respectively.
Compared with women, men were more likely to have amnestic mild cognitive impairment (HR 2.00, 95% CI 1.12 to 3.57) as well as the non-amnestic subtype (HR 1.82, 95% CI 0.87 to 3.81), although the latter comparison did not reach statistical significance.
"These results underscore the urgency of developing new and better strategies to create disease-modifying therapies for Alzheimer's," Dr. Petersen said. "In addition, for public health purposes, we need to know how many people are cognitively impaired and potentially on the road to Alzheimer's."
Ralph Nixon, M.D., Ph.D., of New York University, and a member of the medical and scientific advisory council of the Alzheimer's Association, said, "This both magnifies the urgency of the problem of Alzheimer's disease and extends it to an even larger population but also gives some hope of early intervention that would target this population at an earlier stage of the disease."
According to Dr. Petersen, the findings may not be generalizable to populations outside of the predominantly white population of northern European descent of Olmsted County.
He noted, however, that the results of worldwide studies of mild cognitive impairment were not "drastically" different from those of the current study.
The findings are particularly important considering the shifting population distribution associated with aging baby boomers, Dr. Petersen said.
The study was supported by grants from the National Institute on Aging and by the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program.
Dr. Peterson declared being a consultant for GE Healthcare and chair of the safety monitoring committee for Elan Pharmaceuticals.
His co-authors declared potential conflicts of interest with Elan Pharmaceuticals, sanofi-aventis, and Myriad.

Primary source: International Conference on Alzheimer's DiseaseSource reference:Peterson R, et al "The Mayo Clinic study of aging: incidence of mild cognitive impairment" ICAD 2008; Abstract O2-01-01.
New study finds healthy children of Alzheimer patients show early brain changes

30 july 2008--Medical College of Wisconsin researchers in Milwaukee have reported that children of Alzheimer's patients who are carriers of a genetic risk factor for Alzheimer's disease have neurological changes that are detectable long before clinical symptoms may appear.
Functional MRI brain imaging revealed that these symptomless carriers of the APOE-4 gene demonstrated significantly reduced functional brain connectivity between the hippocampus and the posterior cingulated cortex, two important brain structures for memory processing. These structures are relevant for information acquisition, filtering and sorting.
The study, conducted at Froedtert Hospital, was led by Shi Jiang Li, Ph.D., professor of biophysics, and was presented at the Alzheimer's Association International Conference on Alzheimer's disease in Chicago, July 29th
"Just as if cancer could be detected when there were only a few cells, decades before it was evident, the advantage of identifying those at great risk for having Alzheimer's would be of tremendous value in development of interventional therapies," says Dr. Li.
The researchers studied 28 neurologically-normal subjects, between ages 45 and 65. Twelve carried the APOE-4 gene and 16 did not. The two groups showed no significant difference in age, educational level, or neuropsychological performances. All subjects received fMRI scans. For each subject, functional connectivity between the two brain structures was measured in a resting state.
Results showed that functional connectivity in the non APOE-4 carriers was approximately 65 percent better than that of the carriers.
Other members of the research team were Piero Antuono, M.D., professor of neurology, and Zhilin Wu, Ph.D., Chunming Xie, Ph.D., and Jennifer L. Jones, M.S., research associates in the departments of biophysics and neurology.

Tuesday, July 29, 2008

Study: 'Pre-dementia' is rising, especially in men


29 july 2008--A milder type of mental decline that often precedes Alzheimer's disease is alarmingly more common than has been believed, and in men more than women, doctors reported Monday.
Nearly a million older Americans slide from normal memory into mild impairment each year, researchers estimate, based on a Mayo Clinic study of Minnesota residents.
That's on top of the half million Americans who develop full-blown Alzheimer's or other forms of dementia — a problem sure to grow as baby boomers age. The oldest boomers turn 62 this year.
"We're seeing that in fact there's a much larger burgeoning problem out there" of people at risk of developing dementia, said Dr. Ronald Petersen, the Mayo scientist who led the study.
Dr. Ralph Nixon, a New York University psychiatrist and scientific adviser to the Alzheimer's Association, was blunt.
"We're facing a crisis," he said.
There are no treatments now to prevent this mental slide or reverse it once it starts.
But that may be changing. Researchers on Monday reported early, somewhat encouraging results from an experimental nose spray that seemed to improve certain memory measures in a study of mildly impaired people.
The drug, for now just called AL-108, needs testing in a longer, larger study. It is being developed by Allon Therapeutics Inc., based in Vancouver, B.C.
Doctors said it shows the potential for new types of medicines that target the protein tangles that kill nerve cells, instead of targeting the sticky brain deposits that have gotten most of the attention up to now.
The studies were reported at the International Conference on Alzheimer's Disease in Chicago.
Petersen is the scientist who defined mild cognitive impairment, or MCI, as a transition phase between healthy aging and dementia. It is more than "senior moments" like forgetting where you parked the car, but not as severe as having dementia, where you forget what a car is for.
People with it have impaired memory but not other problems like confusion, inattention or trouble putting thoughts into words.
The Alzheimer's Association says more than 5 million Americans have Alzheimer's, but no estimate for this "pre-dementia" has been available until now.
Petersen's federally funded study involved roughly 1,600 people, ages 70 through 89, living in Olmstead County, which surrounds the Mayo Clinic in Rochester, Minn. All tested normal when they were enrolled in the study, but more than 5 percent had developed mild impairment when evaluated a year later.
Men were nearly twice as likely as women to develop it. That's a surprise, because some studies have found more women with Alzheimer's than men. But there may be a simple explanation:
Even though more men may be impaired, women outlive them and therefore have more time to develop full-blown dementia.
"This is a very large and important issue for our country and for the world," said Duke University psychologist Brenda Plassman. A smaller study she published earlier this year backs up the Mayo study's findings.
The mild impairment rate is two to three times larger than many researchers had expected, Petersen said.
"It's the iceberg under the tip," agreed Dr. R. Scott Turner, incoming director of the memory disorders program at Georgetown University Medical Center. A prime goal is finding drugs to treat the mild impairment before Alzheimer's develops.
The AL-108 study tried to do that. Scientists gave 144 people with mild impairment either a low or high dose of the drug or a dummy drug for 12 weeks. The study missed its main goal — a composite of various memory scores — and the low dose showed no effect. But those on the higher dose improved on some memory tasks after one month and benefits lasted a month after they stopped treatment, said the study's leader, Dr. Donald Schmechel of Duke University.
The study was sponsored by the drug maker.
In another study presented at the conference on Sunday and published on the Internet by the British medical journal The Lancet, researchers reported that dementia rates in developing countries may be considerably higher than official estimates and closer to rates in wealthy countries.
Scientists used a more liberal definition of dementia more suitable to poorer, less educated populations, where respect for family often means relatives don't regard dementia as a burden so much and may be less likely to report problems.
The study involved nearly 15,000 people in 11 sites from China, India, Cuba, Mexico and other nations. Dementia rates ranged from nearly 6 percent in rural China to nearly 12 percent in the Dominican Republic, said co-author Martin Prince of King's College in London.
The World Health Organization and the Alzheimer's Association were among the study's sponsors.
On the Net:
National Institute on Aging:
Alzheimer's Association:
Allon drug boosts memory in pre-Alzheimer patients

29 july 2008--A nasal spray by Allon Therapeutics Inc significantly improved some measures of memory in patients with mild cognitive impairment -- a precursor to Alzheimer's disease, researchers reported on Monday.
The drug, AL-108, is among the first of a new class of Alzheimer's treatments to target the fibrous tangles in the brain caused by an abnormal build-up of the protein tau.
Dr. Donald Schmechel of Duke University Medical Center in Durham, North Carolina, and colleagues studied two doses of the drug in 144 patients aged 55-85 at 16 U.S. centers. All had amnestic mild cognitive impairment, a type that is more likely to lead to Alzheimer's disease than other forms of MCI.
After 12 weeks, the group that got the high dose (15 mg twice daily) had a statistically significant improvement over those who got no treatment in a few measures of short-term memory, including visual, verbal and auditory working memory, which often worsens as Alzheimer's advances.
Four weeks after the treatment stopped, the group that got the high dose had a 62.4 percent improvement in some measures of short-term memory compared to the group that got no drug. No serious side effects were seen, the researchers told the International Conference on Alzheimer's Disease in Chicago.
There was no improvement in other measures, but Schmechel said he believed the drug is promising.
"There was a trend but it was not statistically significant," Schmechel said in an interview.
But in some tests -- notably a memory game that involved matching and another in which patients had to remember a string of numbers -- there were clear improvements.
Schmechel, who has consulted for Allon but who does not own shares in the company, said he believed the company should continue developing the drug.
Hypnosis shown to reduce symptoms of dementia

29 july 2008--A scientist at the University of Liverpool has found that hypnosis can slow down the impacts of dementia and improve quality of life for those living with the condition.
Forensic psychologist, Dr Simon Duff, investigated the effects of hypnosis on people living with dementia and compared the treatment to mainstream health-care methods. He also looked at how hypnosis compared to a type of group therapy in which participants were encouraged to discuss news and current affairs.
They found that people living with dementia who had received hypnosis therapy showed an improvement in concentration, memory and socialisation compared to the other two treatment groups. Relaxation, motivation and daily living activities also improved with the use of hypnosis.
Dr Duff said: "Over a nine month period of weekly sessions, it became clear that the participants attending the discussion group remained the same throughout. The group who received 'treatment as usual' showed a small decline over the assessment period, yet those having regular hypnosis sessions showed real improvement across all of the areas that we looked at.
"Participants who are aware of the onset of dementia may become depressed and anxious at their gradual loss of cognitive ability and so hypnosis – which is a tool for relaxation – can really help the mind concentrate on positive activity like socialisation."
Further research will now take place to establish whether hypnosis maintains its effects on dementia as the illness progresses, over longer periods of time.
Dr Dan Nightingale, co-author of the research and leading dementia consultant at the Abacus Clinic in Newark, added: "Evidence to date has shown that we can enhance the quality of life for people living with dementia through the correct use of hypnosis. We have now developed a course for clinicians who wish to incorporate hypnosis into health care plans."
Alzheimer's Linked to Thyroid-Related Hormone

By Crystal Phend
BOSTON, 29 july 2008 -- Abnormal levels of the hormone thyrotropin, which controls thyroid function, may be associated with an increased risk of Alzheimer's disease in women, researchers found.
Alzheimer's disease was more than twice as common among women with the highest and lowest levels of serum thyrotropin compared with those in the more normal range (P<0.001 and P=0.003, respectively), reported Zaldy S. Tan, M.D., M.P.H., of Harvard and Beth Israel Deaconess Medical Center, and colleagues in the July 28 issue of the Archives of Internal Medicine.
However, the associations did not extend to men for either high or low levels of the hormone in the analysis of the longitudinal Framingham Study.
Further confirmation is needed, though, before clinical conclusions could be drawn from the findings, the researchers said.
Both hypo- and hyperthyroidism have long been recognized as causes of reversible cognitive impairment such that routine screening of serum thyrotropin levels is included in evaluation of patients with suspected dementia, the researchers said.
Several epidemiologic studies have also suggested thyroid function may play a role in irreversible dementia.
So, the researchers analyzed thyrotropin levels in 1,864 men and women participating in the larger, community-based Framingham Study. None of these participants had cognitive problems when assessed for dementia at baseline from 1977 through 1979.
Overall, serum thyrotropin levels were greater than 10.0 mIU/L among 4.2% of participants and less than 0.1 mIU/L in 5% of patients.
During 12.7 years of biennial follow-up assessments, 209 patients developed Alzheimer's disease.
For women, thyrotropin levels were significantly linked to Alzheimer's disease with a 2.20-fold higher risk for both those in the lowest tertile (with levels below 1.0 mIU/L) and for those in the highest tertile, with levels above 2.1 mIU/L (multivariate adjusted P=0.003 and P=0.002, respectively).
Even among women who did not have overt thyroid dysfunction --thyrotropin levels of 0.1 to 10.0 mIU/L -- the same U-shaped relationship was seen for Alzheimer's risk.
In the fully adjusted model, women in the upper tertile were at a 2.09-times higher risk (P=0.001) and those in the lower tertile were at a 1.70-fold elevated risk (P=0.02).
The same was not true for men, however. Compared with men in the middle third for thyrotropin levels, risk of Alzheimer's disease was not elevated whether thyrotropin levels were high (hazard ratio 1.07, P=0.85) or low (HR 1.10, P=0.78).
The results were unchanged when controlling for patients taking thyroid supplements and when assessed by all-cause dementia rather than Alzheimer's disease.
Sex differences related to thyroid hormone are well known for bone density, as are higher incidences of clinical and subclinical thyroid disease in women compared with men, the researchers noted, suggesting an effect modification by sex.
Whether the effect of thyrotropin was causative could not be determined from the observational study and either direction of causality is plausible, they noted.
Neurodegeneration related to Alzheimer's disease could lead to a reduction in thyrotropin secretion or alter pituitary responsiveness, or depletion of the hormone could lead to Alzheimer's abnormalities by enhancing phosphorylation of tau proteins, they suggested.
Another possibility is that low or high thyrotropin levels could damage neurons or blood vessels, leading to cognitive problems.
The researchers cautioned that the study may have been limited by the availability of only a single thyrotropin measure without data on thyroxine levels, depression status, other illnesses that could affect thyroid levels, or the use of antithyroid medications.
And the almost exclusively Caucasian population in the study suggests that the findings need validation in more diverse populations, Dr. Tan and colleagues said.
The authors also noted that when analyses were limited to individuals with thyrotropin levels of 0.5 to 5.0 mIU/L, the U-shaped relationship between thyrotropin levels and Alzheimer's disease was attenuated.
This, they wrote "suggests that the relationship may have been accounted for by individuals with more extreme thyrotropin values in the full tertile analysis."
The study was supported by the Framingham Heart Study of the National Heart, Lung, and Blood Institute and grants from the National Institutes of Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, and the National Heart, Lung, and Blood Institute.
The researchers reported no conflicts of interest.
Primary source: Archives of Internal MedicineSource reference:Tan ZS, et al "Thyroid function and the risk of Alzheimer disease: The Framingham Study" Arch Intern Med 2008; 168: 1514-1520.
Bone Density of Hip Connected to Breast Cancer Risk After Menopause

By Crystal Phend
TUSCON, Ariz., 29 july 2008 -- Strong bones in postmenopausal women may correlate with higher breast cancer risk, researchers said.
Each unit increase in total hip bone mineral density T-score was linked to a 25% greater risk of developing breast cancer, Zhao Chen, Ph.D., M.P.H., of the University of Arizona, and colleagues, reported in the Sept. 1 issue of CANCER.
Although the traditional Gail score was a stronger predictor -- with a 35% increased breast cancer risk for postmenopausal women with a high score -- bone mineral density modestly added to the predictive value in an analysis of the prospective Women's Health Initiative study.
The Gail risk model is a well known tool that estimates the 5-year and lifetime risk of invasive breast cancer for women 35 and older. The version of the Gail score most widely used currently includes race/ethnicity, a history of atypical hyperplasia, and a history of lobular carcinoma in situ.
Women with the highest scores on both assessments showed a sharp increase in incident breast cancer (P<0.05).
Rather than suggesting a benefit of low bone mineral density, which increases fracture risk, the study supported using clinical information from osteoporosis screening to aid breast cancer risk assessment or even as an alternative to the Gail model, the researchers said.
Other studies have also supported a link between breast cancer and bone mineral density, but this was the first to add evaluation of Gail risk assessment results in the same population of women.
The analysis included 9,941 women (average age 63) who had a dual-energy X-ray absorptiometry (DEXA) scan at one of three clinical centers in the larger Women's Health Initiative study.
During more than eight years of follow-up, 327 women developed breast cancer.
Both high bone mineral density and high Gail scores were associated with breast cancer rates.
Women with a high Gail score of at least 1.67 had an age-adjusted breast cancer incidence of 47.8 per 10,000 person-years whereas for women with lower Gail scores the incidence was 33.1 per 10,000 person-years.
Likewise, age-adjusted incidence rose with total hip bone mineral density T-score. Incidence was as follows:
For women with T-scores in the normal range, 45.5 breast cancer cases per 10,000 person-years.
For women with a low bone mineral density, 29.5 cases per 10,000 person-years.
For women with T-scores in the osteoporosis range, 11.0 cases per 10,000 person-years.
Including the Gail score and hip bone mineral density T-score together in the same model across the entire population, both assessments retained significance as independent predictors with little or no change in the hazard ratios for breast cancer risk (HR 1.47 for Gail score of 1.67 or higher, P=0.001, and HR 1.26 for higher bone density, P<0.001).
Women with both very high Gail scores and bone mineral density were found to be at an exceptionally high risk for breast cancer in the current study. However, the interaction between the Gail score and bone mineral density T-score is confined to the higher-risk groups on both measures.
Adding other major risk factors for breast cancer, including body mass index, race or ethnicity, hormone use, and smoking history, only slightly attenuated the associations (HR 1.35 for high Gail score, P=0.02, and HR 1.25 for higher bone density, P<0.001).
This suggested that confounding by known breast cancer risk factors did not account for the correlations, the researchers said. "However, considering these factors may enhance the prediction."
For the women overall and those with below-average Gail scores and total hip bone density, the two tests did not interact significantly. However, breast cancer risk increased sharply for women above the median on both scores with a significant interaction (P=0.002).
The results may have limited generalizability because of the relatively small number of minority women and the potentially more health-conscious population enrolled in the study, Dr. Chen and colleagues noted.
The study was funded by Eli Lilly.
One of the researchers reported acting as a consultant for Astra-Zeneca, Novartis, and Genentech and receiving grant support from Amgen.

Primary source: CancerSource reference:Chen Z, et al "Hip bone density predicts breast cancer risk independently of Gail score -- Results from the Women's Health Initiative" Cancer 2008; 113.

Monday, July 28, 2008

Angiotensin receptor blockers are lower incidence, progression of Alzheimer's disease

Boston, MA, 28 july 2008—Researchers at Boston University School of Medicine (BUSM) have, for the first time, found that angiotensin receptor blockers (ARBs)—a particular class of anti-hypertensive medicines—are associated with a striking decrease in the occurrence and progression of dementia. Data from this study will be presented this weekend (July 27) at the 2008 International Conference on Alzheimer's disease in Chicago.
Using data from the Decision Support System Database of the U.S. Department of Health System Veterans Affairs (with information on more than 5 million people), researchers looked at records from patients using ARBs, and compared them with subjects who had a similar health status, but were taking different medications. They found patients taking ARBs had about a 35-40 percent lower chance of getting Alzheimer's disease or dementia.
The researchers also examined patients who were already suffering from Alzheimer's disease or dementia, and found those subjects had up to a 45 percent lower chance of developing delirium, being admitted to nursing homes or dying. Patients who appeared to benefit particularly well from use of ARBs were those who had experienced strokes before or during the course of their illness.
According to the researchers these results suggest that ARBs might protect against developing Alzheimer's disease and dementia. "For those who already have dementia, use of ARBs might delay deterioration of brain function and help keep patients out of nursing homes," said lead presenter Benjamin Wolozin, MD, PhD, a professor of pharmacology at BUSM. "The study is particularly interesting because we compared the effects of ARBs to other medications used for treating blood pressure or cardiovascular disease. This suggests that ARBs are more effective than other blood pressure and cardiovascular medications for preventing Alzheimer's disease or dementia," he added.
Although the researchers are unsure why ARBs might be so beneficial, they believe one possibility suggested by prior studies on animal models is that ARBs help prevent nerve cell injury from blood vessel damage or help promote nerve cell recovery after blood vessel damage. Damage to blood vessels is thought to reduce brain capacity and promote dementia, so reducing this damage might prevent the occurrence or progression of dementia.
This study was funded by the Retirement Research Foundation and from the Casten Foundation.
MRIs show promise for early Alzheimer's diagnosis

By Julie Steenhuysen
28 july 2008--Researchers have used magnetic resonance imaging scans to locate Alzheimer's-like plaques in rabbits, bringing researchers a step closer to being able to diagnose the disease using ordinary MRI equipment.
"Although some of the technology used to generate these images was designed specifically for rabbits, this preliminary discovery hints at the promise of using clinical MRI scanners to visualize plaques in people with Alzheimer's," John Ronald of Ontario's Robarts Research Institute said in a statement.
The study, unveiled at the International Conference on Alzheimer's Disease in Chicago on Sunday, was one of several showing how widely available MRI scans could be used for early diagnosis of the brain-wasting disease.
The study marks the first time researchers have been able to "see" brain plaques using conventional MRI scanners. Currently, high-powered MRI scanners have been able to spot them in animals, and PET scanners using special marker chemicals have worked as well.
Currently, an autopsy is the only sure way to confirm Alzheimer's disease, by identifying the brain lesions such as amyloid plaques that characterize the disease. Doctors typically rely on a series of tests to give them a good idea of whether someone has Alzheimer's.
Researchers in the Canadian study fed rabbits a high-cholesterol diet for two years, which caused them to form amyloid plaques in their brains. Scans of these rabbits revealed void areas or black spots in several areas including the hippocampus, an important memory center in the brain.
Autopsies found small clusters of amyloid plaques in these void areas, not found in rabbits fed a normal diet.
"This may be used for animal imaging, but potentially down the road it may be used for human imaging," Ronald told a media briefing.
Dr. Jeffrey Kaye of the Oregon Health & Science University in Portland, who moderated the briefing, said the study has promise but the jump between rabbits and humans may not be effortless. He said researchers using special high-field MRI magnets can already see amyloid plaques in mice, but so far have not been able to see them in human brains.
"I have to believe it will be solved," Kaye added.
In a separate study, researchers at the Mayo Clinic in Rochester, Minnesota, said they were able to use a computer program to analyze information on MRI scans that could distinguish between normal and Alzheimer's brains with 90 percent accuracy.
The program, known as STAND, measures the degree of atrophy in a person's brain.
The researchers compared data gathered from 101 people who had an MRI within four years of their death to data gathered after they died by a test known as Braak staging, which measures the severity of fibrous tangles in the brain.
"This study shows that information extracted from MRI scans can accurately capture the severity of Alzheimer's tangle pathology," Prashanthi Vemuri, who presented the results, said in a statement.
A third group from the University of Pennsylvania in Philadelphia, using a new computer-based image analysis technique, was able to find Alzheimer-like activity in the brains of elderly people who had normal cognitive capabilities, and in a group with mild cognitive impairment.
While more study is needed to understand the findings, they hope the tools will help in the search for early brain changes that signal the start of Alzheimer's.
"These MRI studies show that researchers are moving closer to accurate early detection of the disease, and that we may soon be able to use this technology to determine who is at greater risk," William Thies of the Alzheimer's Association said in a statement.
Most Fit Have Less Brain Atrophy From Alzheimer's

28 july 2008-- Physical fitness can help the mind, body and quality of life of people with early Alzheimer's disease and dementia, according to new research.
"These studies reinforce the need for increased awareness and education about the importance of living a brain-healthy lifestyle, including staying physically active," William Thies, vice president of medical and scientific relations for the Alzheimer's Association, said in a news release. "Growing evidence shows that physical exercise does not have to be strenuous or require a major time commitment. It is most effective when done regularly, and in combination with a brain-healthy diet, mental activity and social interaction."
The two studies were expected to be presented Sunday at the Alzheimer's Association International Conference on Alzheimer's Disease in Chicago.
In the first study, MRI brain imaging of people taking a treadmill stress test showed a connection between cardio-respiratory fitness and Alzheimer's-related brain changes in the hippocampus, an area of the brain important for memory and spatial navigation. The hippocampus is one of the first regions of the brain to suffer damage from Alzheimer's.
"We found that, in early-stage Alzheimer's, cardio-respiratory fitness is correlated with regional brain volumes in key areas affected by the disease," study researcher Robyn Honea of the University of Kansas Medical Center, in Kansas City, said in the news release. "This suggests that maintaining cardio-respiratory fitness may positively modify Alzheimer's-related brain atrophy."
In the second study, researchers from Western Medicine in Nedlands, Australia, showed that a caregiver-driven, home-based exercise program could reduce falls, improve balance and maintain the quality of life in people with dementia over a 12-month period.
The program centered on increasing good balance, which has been previously shown to have the greatest impact on reducing falls. Caregivers were taught a tailored set of exercises and were taught how to prompt their loved ones to do them by incorporating them in everyday routines.
According to the researchers, people with dementia fall up to three times more than those who have no cognitive impairment.
In the first six months, patients in the exercise program fell significantly less often than those in a control group. Those doing the exercises also improved their balance over 12 months, while the control group showed some deterioration in their balance over this time.
People in the exercise group also showed no significant increase in fear of falling over 12 months, while the usual care group became more fearful -- a key factor affecting the person's quality of life.
"As people become increasingly affected by the changes in their memory and thinking, and as the risk of falls becomes greater, quality of life can deteriorate," study researcher Megan Wraith said in a conference-issued news release. "This study is small and is just a beginning, but maintaining quality of life at the same level in the context of deteriorating cognitive abilities is an achievement. The results are sufficiently encouraging to pursue this approach and develop a caregiver focused home-based exercise program on a larger scale."
More information
The National Institute on Aging has more about caring for someone with Alzheimer's disease.
European Drug Watchdog Supports New Pill by Bayer

LONDON, 28 july 2008— Bayer’s experimental anticoagulant Xarelto, its biggest new drug hope, has been recommended for approval by the European Medicines Agency, lifting the German company’s shares.
The drug watchdog said on Friday that its Committee for Medicinal Products for Human Use had backed Xarelto for the prevention of blood clots after hip or knee surgery.
Recommendations for marketing approval by the committee are normally endorsed by the European Commission within a couple of months.
Bayer, which estimates that global sales of the drug could reach 2 billion euros ($3.14 billion) for all indications, said it was particularly pleased by the speedy positive opinion.
“We received it only nine months after the submission — very fast compared to average,” said Kemal Malik, a member of the Bayer HealthCare executive committee, responsible for product development.
Bayer shares rose 3.6 percent, to $87.50, in New York trading as investors welcomed the green light, which reinforces Bayer’s reputation for having a promising new drug pipeline.
Bayer had previously said it expected Xarelto to go on sale in Europe by the end of the year.
Citi analysts said progress with Xarelto showed Bayer was making a transition from a reorganization play — after its 17 billion euro acquisition of Schering in 2006 — to a growth story driven by a maturing pipeline of new medicines.
Outside Europe, regulatory filings for Xarelto have been submitted in more than 10 countries, including Canada and China. It is expected to be submitted for approval soon in the United States, where it will be marketed by Bayer’s partner Johnson & Johnson.
Although the initial use of Xarelto will be in preventing blood clots after hip- and knee-replacement surgery, the big commercial potential lies in using it to prevent strokes in people with atrial fibrillation, a common heart arrhythmia.
The medicine, which is also known by the generic name rivaroxaban, is taken as a single tablet, once daily.

Sunday, July 27, 2008

Antihistamine Looks Promising for Alzheimer's Patients : Dimebon Shows Improvements in Brain Function and Memory

27 july 2008--Alzheimer's disease can be heartbreaking to watch and frustrating to treat. Most medicines on the market do little more than delay the inevitable mental decline.
But a new drug called Dimebon appears to stop and perhaps even reverse the symptoms of the cruel and degenerative disease, according to a new study published in the journal Lancet today.
"I was pleasantly surprised to see the effect on cognitive function, on memory, on activities of daily living that not only were clearly significant but seemed to increase over time," said Dr. Sam Gandy, former chairman of the Alzheimer's Association Medical and Scientific Advisory Council.
Dimebon wasn't designed to treat Alzheimer's disease. Far from it. It's an antihistamine that was supposed to treat allergies.
But a study that tracked 120 mild to moderate Alzheimer's patients for a year, and found that at six months those taking Dimebon three times a day showed significant improvement in mental tests and cognitive functioning, while those placed on the placebo kept deteriorating. A year into the study, the Dimebon group was still improving, while those without the drug were declining rapidly.
What's most encouraging for researchers is that current Alzheimer's drugs lose their effectiveness after three or six months. But Dimebon still worked after at least a year and seemed to be improving with time.
For those five million Americans living with Alzheimer's disease, memories tend to be lost first and then its victims lose the ability to care for themselves.
Currently, there is no cure for Alzheimer's, so eventually, they lose their lives. Those with Alzheimer's in the moderate to severe stages often lose the ability to complete daily tasks, such as dressing themselves, walking and eating.
Karen Henes, 62, of Croton-on-Hudson, N.Y., was diagnosed with Alzheimer's just a year ago, and already complains of some such symptoms.
"I would like to just go see my grandchildren. I can't," Henes said. "I'm not responsible enough just to drive. I can't always remember what to do. It's really sad."
Her husband Michael expressed equal frustration with the disease.
"Life with Karen is so frustrating. It has already changed," he said. "She writes down all her appointments and she still doesn't remember them. On a day-to-day basis, it's a struggle."
Dimebon has been shown to improve patient memory and skills, and to help on small daily tasks like using the telephone, shopping and remembering the grocery list.
Doctors haven't yet figured out exactly how the drug works. Researchers think that the drug affects the mitochondria, or the energy powerhouses of the brain cells.
There are two major classes of Alzheimer's drugs and researchers think that Dimebon performs both functions.
Alzheimer's patients, families and doctors tend to be skeptical of new drugs because so many have fallen short over the years.
Dr. Gandy cautioned that the new study was small. Dimebon must go through more clinical tests. And even if they're a success, it will be at least two years before Dimebon is approved for treatment by the Federal Drug Administration.
"This is promising, but it's not marketed anywhere in the world right now, and it hasn't been approved in any country," said Dr. Rachelle Doody, the study's principal investigator and Effie Marie Cain chair in Alzheimer's disease research at Baylor College of Medicine.
"This is coming along," she told ABC News. "It's coming along pretty quickly relative to other agents, but this drug and all the others are not cures for the disease."
Alzheimer's patients like Henes are optimistic.
"I can't wait. I am so excited about the possibility," Henes said. "If I can stay the way I am now until a drug that comes along, I will be a lucky person."
Results From the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) Study

LONDON, 27 july 2008-- The SEAS (Simvastatin and Ezetimibe in
Aortic Stenosis) study has investigated the effects of intensive
cholesterol lowering with the combination of simvastatin (40 mg daily) and
ezetimibe (10 mg daily) in patients with aortic stenosis.
Aortic stenosis (which involves partial blockage of the aortic valve in
the heart) is a relatively common disease among older people in Western
populations. Left untreated, it can progress to death from heart failure or
cardiac arrest. Aortic valve replacement for severe symptoms is the second
most frequent type of heart surgery. Apart from surgery, there is no
medical therapy known to prevent or heal this condition. Population studies
and other scientific research indicate that a high blood level of
LDL-cholesterol (so called "bad cholesterol) is a risk factor for
developing aortic stenosis and may be involved in the pathological process.
Treatment to lower LDL-cholesterol in many other types of patient has been
shown to produce substantial reductions in the rates of heart attacks,
strokes and other adverse outcomes.
The SEAS study is the first large-scale randomised trial to assess the
effects of lowering LDL-cholesterol in patients with aortic stenosis. The
study was initiated and designed by academic researchers in Scandinavia,
and carried out at 173 clinical centres in Norway, Denmark, Sweden,
Finland, Germany, UK and Ireland. It included 1873 patients with mild to
moderate aortic stenosis without symptoms who were not considered to have a
clear indication for treatment with cholesterol-lowering drugs. Patients
were randomly assigned to receive either intensive cholesterol lowering
with the combination of simvastatin (40 mg daily) and ezetimibe (10 mg
daily) or matching placebo. The first patient was included in 2001. The
study was completed according to the study plan when the last patient
included had been followed for 4 years (March 2008). Vital status at the
end of the study was established for all patients. All data have been
checked for completeness and the data file for analysis was closed on 30
June 2008.
The scientific leadership of the study was a Steering Committee
consisting of 14 academic representatives of centres in each of the
participating countries and two members (a statistician and a coordinator)
representing the funders. The SEAS study is funded by the pharmaceutical
companies Merck Sharp & Dohme (MSD) and Schering-Plough who market the
drugs being tested. All clinical endpoint events were adjudicated by an
independent committee that was blinded to the study treatment allocation.
The study was monitored by an independent Data Safety and Monitoring Board.
Data collection was performed by MSD, and the data were analyzed by
statisticians at Ulleval University Hospital in Oslo, Norway, and at MSD.
The primary endpoint of the SEAS study was "major cardiovascular
events", which is the composite of events associated with aortic valve
disease and with atherosclerotic disease. The secondary endpoints were the
two separate components of the primary endpoint: "aortic valve disease
events" (surgical valve replacement, hospitalization because of heart
failure, and cardiovascular death); and "atherosclerotic disease events"
(non-fatal myocardial infarction, coronary artery bypass surgery or
percutaneous coronary intervention, hospitalization because of unstable
angina pectoris, non-haemorrhagic stroke and cardiovascular death).
Subsidiary outcomes included echocardiographic evidence of aortic stenosis
progression and safety.
Compared with placebo, the combination of simvastatin and ezetimibe
reduced LDL-cholesterol by an average of 61%, corresponding to a reduction
of about 2 mmol/L (76 mg/dl), and this effect was sustained throughout the
study. 688 patients had one or more primary endpoint events. No significant
difference was observed between the treatment groups for the combined
primary endpoint (333 patients with an event on LDL-lowering treatment
versus 355 on placebo; hazard ratio [HR] 0.96; 95% confidence interval [CI]
0.83 to 1.12). Nor was there a significant difference for the secondary
endpoint of aortic valve disease events alone (308 versus 326; HR 0.97; 95%
CI 0.83 to 1.14). The combination of simvastatin and ezetimibe did,
however, produce a statistically significant 22% (95% CI 3% to 37%; p=0.02)
proportional reduction in the secondary endpoint of atherosclerotic events
alone: 148 (15.7%) in the simvastatin plus ezetimibe group versus 187
(20.1%) in the placebo group.
The study therapy was generally well tolerated, with no significant
differences between the treatment groups in the proportions of patients who
stopped taking study treatment (irrespective of whether it was active or
placebo). In the subsidiary safety analyses, a total of 158 patients were
recorded with a serious adverse event attributed to cancer. More of these
events were observed among patients assigned the combination of simvastatin
and ezetimibe than among those assigned placebo (93 [9.9%] versus 65
[7.0%]; unadjusted p=0.03), and there were also slightly more cancer deaths
(39 [4.1%] versus 23 [2.5%]; unadjusted p=0.05). These apparent differences
were not related to any particular type of cancer and did not become
significantly larger with more prolonged treatment.
The observed differences in cancer in the SEAS study are based on small
numbers and could have occurred as a result of chance. In order to assess
their relevance, the SEAS data have been provided to an independent
academic group for combined analysis with data on cancer from the two other
large trials of simvastatin and ezetimibe, which are still in progress. The
SHARP (Study of Heart and Renal Protection) study is a randomized
placebo-controlled trial of simvastatin and ezetimibe in 9400 patients with
chronic kidney disease. The IMPROVE-IT (IMProved Reduction of Outcomes:
Vytorin Efficacy International Trial) study is a randomized double-blind
trial of simvastatin and ezetimibe compared to simvastatin alone which has
recruited 12,000 of a planned 18,000 patients with acute coronary disease.
In combination, the SHARP and IMPROVE-IT studies involve about 4 times
as many cancers as in the SEAS study. The analysis of SHARP and IMPROVE-IT
does not support the suggestion of an increase in cancer that was raised by
the subsidiary analyses of the relatively small numbers of cancers in the
SEAS study. Independent analysis of these data was initiated and has been
conducted and interpreted by the Clinical Trial Service Unit (CTSU) at the
University of Oxford, UK. The CTSU also designed and is conducting the
SHARP trial, which is funded by a research grant to the University of
Oxford from MSD and Schering-Plough academic. Both the SHARP study and the
analyses of cancer data have been conducted by the CTSU independently of
the pharmaceutical companies. Please, refer to the press release issued by
the CTSU today.
In conclusion, the SEAS study has found that intensive LDL-cholesterol
lowering with the combination of simvastatin and ezetimibe in patients with
mild to moderate aortic stenosis does appear to reduce the risk of coronary
artery disease events (as has been shown for many other types of patient in
previous trials) but not the rate of progression of aortic valve disease.
The use of simvastatin and ezetimibe in such patients was generally well
tolerated and safe.
Pittsburgh cancer center warns of cell phone risks

PITTSBURGH (AP) 27 july 2008— The head of a prominent cancer research institute issued an unprecedented warning to his faculty and staff Wednesday: Limit cell phone use because of the possible risk of cancer.
The warning from Dr. Ronald B. Herberman, director of the University of Pittsburgh Cancer Institute, is contrary to numerous studies that don't find a link between cancer and cell phone use, and a public lack of worry by the U.S. Food and Drug Administration.
Herberman is basing his alarm on early unpublished data. He says it takes too long to get answers from science and he believes people should take action now — especially when it comes to children.
"Really at the heart of my concern is that we shouldn't wait for a definitive study to come out, but err on the side of being safe rather than sorry later," Herberman said.
No other major academic cancer research institutions have sounded such an alarm about cell phone use. But Herberman's advice is sure to raise concern among many cell phone users and especially parents.
In the memo he sent to about 3,000 faculty and staff Wednesday, he says children should use cell phones only for emergencies because their brains are still developing.
Adults should keep the phone away from the head and use the speakerphone or a wireless headset, he says. He even warns against using cell phones in public places like a bus because it exposes others to the phone's electromagnetic fields.
The issue that concerns some scientists — though nowhere near a consensus — is electromagnetic radiation, especially its possible effects on children. It is not a major topic in conferences of brain specialists.
A 2008 University of Utah analysis looked at nine studies — including some Herberman cites — with thousands of brain tumor patients and concludes "we found no overall increased risk of brain tumors among cellular phone users. The potential elevated risk of brain tumors after long-term cellular phone use awaits confirmation by future studies."
Studies last year in France and Norway concluded the same thing.
"If there is a risk from these products — and at this point we do not know that there is — it is probably very small," the Food and Drug Administration says on an agency Web site.
Still, Herberman cites a "growing body of literature linking long-term cell phone use to possible adverse health effects including cancer."
"Although the evidence is still controversial, I am convinced that there are sufficient data to warrant issuing an advisory to share some precautionary advice on cell phone use," he wrote in his memo.
A driving force behind the memo was Devra Lee Davis, the director of the university's center for environmental oncology.
"The question is do you want to play Russian roulette with your brain," she said in an interview from her cell phone while using the hands-free speaker phone as recommended. "I don't know that cell phones are dangerous. But I don't know that they are safe."
Of concern are the still unknown effects of more than a decade of cell phone use, with some studies raising alarms, said Davis, a former health adviser in the Clinton Administration.
She said 20 different groups have endorsed the advice the Pittsburgh cancer institute gave, and authorities in England, France and India have cautioned children's use of cell phones.
Herberman and Davis point to a massive ongoing research project known as Interphone, involving scientists in 13 nations, mostly in Europe. Results already published in peer-reviewed journals from this project aren't so alarming, but Herberman is citing work not yet published.
The published research focuses on more than 5,000 cases of brain tumors. The National Research Council in the U.S., which isn't participating in the Interphone project, reported in January that the brain tumor research had "selection bias." That means it relied on people with cancer to remember how often they used cell phones. It is not considered the most accurate research approach.
The largest published study, which appeared in the Journal of the National Cancer Institute in 2006, tracked 420,000 Danish cell phone users, including thousands that had used the phones for more than 10 years. It found no increased risk of cancer among those using cell phones.
A French study based on Interphone research and published in 2007 concluded that regular cell phone users had "no significant increased risk" for three major types of nervous system tumors. It did note, however, that there was "the possibility of an increased risk among the heaviest users" for one type of brain tumor, but that needs to be verified in future research.
Earlier research also has found no connection.
Joshua E. Muscat of Penn State University, who has studied cancer and cell phones in other research projects partly funded by the cell phone industry, said there are at least a dozen studies that have found no cancer-cell phone link. He said a Swedish study cited by Herberman as support for his warning was biased and flawed.
"We certainly don't know of any mechanism by which radiofrequency exposure would cause a cancerous effect in cells. We just don't know this might possibly occur," Muscat said.
Cell phones emit radiofrequency energy, a type of radiation that is a form of electromagnetic radiation, according to the National Cancer Institute. Though studies are being done to see if there is a link between it and tumors of the brain and central nervous system, there is no definitive link between the two, the institute says on its Web site.
"By all means, if a person feels compelled that they should take precautions in reducing the amount of electromagnetic radio waves through their bodies, by all means they should do so," said Dan Catena, a spokesman for the American Cancer Society. "But at the same time, we have to remember there's no conclusive evidence that links cell phones to cancer, whether it's brain tumors or other forms of cancer."
Joe Farren, a spokesman for the CTIA-The Wireless Association, a trade group for the wireless industry, said the group believes there is a risk of misinforming the public if science isn't used as the ultimate guide on the issue.
"When you look at the overwhelming majority of studies that have been peer reviewed and published in scientific journals around the world, you'll find no relationship between wireless usage and adverse health affects," Farren said.
Frank Barnes, who chaired the January report from the National Research Council, said Wednesday that "the jury is out" on how hazardous long-term cell phone use might be.
Speaking from his cell phone, the professor of electrical and computer engineering at the University of Colorado at Boulder said he takes no special precautions in his own phone use. And he offered no specific advice to people worried about the matter.
It's up to each individual to decide what if anything to do. If people use a cell phone instead of having a land line, "that may very well be reasonable for them," he said.
Susan Juffe, a 58-year-old Pittsburgh special education teacher, heard about Herberman's cell phone advice on the radio earlier in the day.
"Now, I'm worried. It's scary," she said.
She says she'll think twice about allowing her 10-year-old daughter Jayne to use the cell phone.
"I don't want to get it (brain cancer) and I certainly don't want you to get it," she explained to her daughter.
Sara Loughran, a 24-year-old doctoral student at the University of Pittsburgh, sat in a bus stop Wednesday chatting on her cell phone with her mother. She also had heard the news earlier in the day, but was not as concerned.
"I think if they gave me specific numbers and specific information and it was scary enough, I would be concerned," Loughran said, planning to call her mother again in a matter of minutes. "Without specific numbers, it's too vague to get me worked up."
Jennifer Yates reported from Pittsburgh. Science Writer Seth Borenstein reported from Washington. Reporter Ramit Plushnick-Masti contributed from Pittsburgh and Science Writer Malcolm Ritter contributed from New York.
On the Net:
Advice from the University of Pittsburgh Cancer Institute:
Food and Drug Administration on cell phones:
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