EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, DECEMBER 15, 2003
To contact Richard Mayeux, M.D., M.Sc., call Annie Bayne (212) 305-3900.

STROKE MAY INCREASE RISK OF ALZHEIMER DISEASE

CHICAGO—People who have had a stroke are at an increased risk for developing Alzheimer disease (AD), especially if they also have cardiovascular disease, according to an article in the December issue of The Archives of Neurology, one of the JAMA/Archives journals.

According to information in the article, Alzheimer disease and stroke are common in the elderly population, but the relationship between these two disorders remains uncertain.

Richard Mayeux, M.D., M.Sc., of Columbia University, New York, and colleagues investigated the association between stroke and AD in 1,766 Medicare patients (older than 65 years) without dementia or AD who participated in a follow-up study from 1992 through 1999. History of stroke and presence of cardiovascular disease were noted at the beginning of the study.

The researchers found that the annual incidence for AD was 5.2 percent among patients with stroke, and 4 percent for patients without stroke. Patients with stroke were roughly 60 percent more likely to develop AD than patients who had never had a stroke.

"The results demonstrate an association between a history of stroke and AD," the authors write. "Compared with persons with no history of stroke, there was an increased risk of AD in persons with a history of stroke. The risk was highest for those with stroke who also had established vascular risk factors, such as high blood pressure, type 2 diabetes mellitus, or heart disease. Moreover, a history of stroke was associated with an earlier age at onset of dementia," the researchers write.

EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, DECEMBER 15, 2003
To contact Colin L. Masters, M.D., e-mail c.masters{at}unimelb.edu.au. To contact editorialist Roger N. Rosenberg, M.D., call Rachel Horton at (214) 648-3404.

NOVEL "METAL-CHELATION" THERAPY MAY BE HELPFUL IN PATIENTS WITH ALZHEIMER DISEASE

CHICAGO—A preliminary study suggests that a novel therapy may help improve cognitive functioning in patients with Alzheimer disease by lowering levels of a protein that is involved in the development of the disease, according to an article in the December issue of The Archives of Neurology, one of the JAMA/Archives journals.

According to the article, Alzheimer disease (AD) is thought to be caused by a buildup of "plaque" in the brain which includes the protein beta-amyloid. Scientists believe that blocking the production or accumulation of beta-amyloid in the brain could prevent or slow AD.

Colin L. Masters, M.D., of the University of Melbourne, Parkville, Victoria, Australia, and colleagues developed a study to determine whether clioquinol, a metal-protein - attenuating compound (MPAC), might help to reduce beta-amyloid levels and slow the rate of cognitive decline in patients with AD. The compound is thought to work by inhibiting zinc and copper ions from binding to beta-amyloid, thereby helping to dissolve the protein and preventing it from accumulating. Therapies that block metal ions from interacting with other molecules in the body are known as "chelation" therapies.

The researchers conducted a pilot phase 2 clinical trial of their compound in 36 patients with moderately severe AD. Eighteen patients received 125 milligrams of clioquinol twice per day for 12 weeks, then 250 milligrams twice per day for weeks 13 to 24, and 375 milligrams twice per day from weeks 25 to 36. Eighteen patients received similar doses of placebo over 36 weeks.

The patients were given tests to measure cognition at the beginning of the study and again at weeks 4, 12, 24, and 36. Levels of beta-amyloid in the blood were measured every four weeks.

The researchers found that "plasma beta-amyloid levels declined in the clioquinol group and increased in the placebo group." Patients taking clioquinol also had better scores on tests of cognitive ability.

"The findings support a proof of concept in humans that a drug targeting metal-beta-amyloid interactions can have a significant effect on beta-amyloid metabolism, and through this, a beneficial modification on the progression of AD," write the authors.

EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, DECEMBER 15, 2003
To contact Kenneth B. Gordon, M.D., call Joanne Swanson at (708) 216-2445.

ALEFACEPT EFFECTIVE IN TREATING PATIENTS WITH PSORIASIS

CHICAGO—Patients with psoriasis treated with the drug alefacept experienced a reduction in severity of their skin disease, according to an article in the December issue of The Archives of Dermatology, one of the JAMA/Archives journals.

Psoriasis is a chronic, inflammatory skin disorder. According to the article, scientific and clinical evidence suggests that T cells, specialized cells involved in the immune response, are involved in psoriasis. Skin severely affected by psoriasis has been observed to have high levels of CD4+ and CD8+ memory T cells (two types of T cells). Previous experimental studies have shown that elimination of T cells reduced the severity of psoriasis.

Kenneth B. Gordon, M.D., of Loyola University Medical Center, Maywood, Ill., and colleagues examined the effects of intravenous alefacept on the severity of psoriasis and T cell levels.

The researchers conducted a phase 3 clinical trial involving 553 patients with chronic psoriasis. The patients were randomized into one of three groups. Each group participated in a 12 week course of treatment (or placebo), followed by a twelve week period of observation without any drugs. Then, for eligible patients, there was a second 12 week course of treatment (or placebo) and another 12 weeks of observation.

• group 1 - 7.5 milligrams of intravenous alefacept each week for both courses
• group 2 - 7.5 milligrams intravenous alefacept each week in the first course, and 7.5 milligrams intravenous placebo each week for the second course
• group 3 - 7.5 milligrams intravenous placebo each week in the first course, and 7.5 milligrams intravenous alefacept each week in the second course

The researchers found that one or two courses of alefacept reduced CD4+ and CD8+ memory T cell counts. Patients who received alefacept in course 1 with the largest decrease in T cell counts experienced the greatest reduction in disease severity. The benefits of treatment lasted longest in participants who had the greatest reduction in CD4+ and CD8+ T cell counts.

EMBARGOED UNTIL 3 P.M. (CT), DECEMBER 15, 2003
To contact Jonathan Perkins, D.O., call Jennifer Seymour at (206) 987-5207.

SURGICAL TECHNIQUE MAY REDUCE PAIN AFTER TONSILLECTOMY

CHICAGO—Use of a surgical technique involving the microdissection needle—an instrument that uses less energy than the standard approach electrocautery (which controls bleeding by heating tissues)—during surgical removal of the tonsils may reduce the amount of pain experienced after tonsillectomy, according to an article in the December issue of The Archives of Otolaryngology–Head and Neck Surgery, one of the JAMA/Archives journals.

According to the article, despite the decline in the number of tonsillectomies performed in the past few decades, the procedure remains one of the most commonly performed surgeries. New technologies have evolved in surgery that shorten the surgery time, including the use of electrocautery (using a special scalpel that heats tissue as it cuts to seal wounds and prevent bleeding) also known as the "hot method". Pain after tonsillectomy is of special concern because it can interfere with eating and drinking, and researchers have observed an increase in pain associated with electrocautery.

Jonathan Perkins, D.O., of Childrens Hospital Regional Medical Center, Seattle, and Ravinder Dahiya, M.D., of Albany Medical Center, Albany, N.Y., investigated whether microdissection needle cautery (which is a type of electrocautery which uses less energy, and may therefore be less traumatic to tissues) reduced pain after surgery compared to standard electrocautery.

The researchers randomized 42 children to undergo tonsillectory into two groups: in group A, tonsillectomy was performed using standard electrocautery; in group B, tonsillectomy was performed using a lower-energy microdissection needle. The same surgeon performed all surgeries, which were identical except for the use of the instrument.

Patients were asked to rate their post-operative pain using a questionnaire based on a 10 point pain scale (10 being the worst pain). Doses of pain medication taken were also noted.

The researchers found that there was no difference in hemorrhage (bleeding) during the operations between the two groups. The operation took an average of 3.2 minutes longer for group B.

However, postoperative pain was less on days three, four and five following surgery for patients in the microdissection group than for patients in the standard electrocautery group.