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Rosiglitazone May Improve Function in Patients With Mild Alzheimer’s Disease

A number of recent studies suggest a link between insulin resistance and Alzheimer’s disease. The theory has been reinforced by results of a small, placebo-controlled pilot study of the insulin-sensitizing drug rosiglitazone in patients with mild cognitive impairment or mild Alzheimer’s disease, which was presented at the 9th International Conference on Alzheimer’s Disease and Related Disorders.

In the study, patients treated with rosiglitazone performed better on two standard memory tests than patients treated with placebo.
Suzanne Craft, PhD, professor of Psychiatry and Behavioral Sciences at the University of Washington and associate director of the Geriatric Research, Education, and Clinical Center at the Veterans Affairs Puget Sound Health Care System, is the senior author of the study and she presented the results at the meeting. Patients treated with 4 mg of rosiglitazone for 24 weeks improved more on “both the Stroop Test and the 12-item Buschke Memory Test” compared with patients receiving placebo. The subjects underwent memory testing at baseline and at two-month intervals.

“The improvement was apparent at four months and was greater at six months,” Dr. Craft said, “and while we didn’t conduct symptom assessments, at the end of the study a number of patients and informants (patient proxies) requested to be continued on the rosiglitazone, which we facilitated through the patients’ primary care physicians.”

“Insulin resistance is a common condition among Alzheimer’s disease patients,” Dr. Craft noted. “It is especially interesting that the improvement correlated with a change in insulin levels.”

Insulin is known to promote release of amyloid beta-protein, the protein that can accumulate in the brain and aggregate as plaques, which are a hallmark of the brain abnormality seen in patients with Alzheimer’s disease.

Dr. Craft theorized that the benefit of rosiglitazone might be associated with the action of insulin degrading enzyme. Both insulin and amyloid-beta compete for insulin degrading enzyme, thus reducing plasma insulin levels, which may free up the enzyme to attack beta-amyloid. In theory, this process would prevent the formation of amyloid plaque.

Rosiglitazone may reduce inflammation, which is also considered a factor in Alzheimer’s disease, Dr. Craft said.

The study enrolled 30 patients with either mild cognitive impairment or mild Alzheimer’s disease. Patients were randomized to 4 mg of rosiglitazone daily (n = 20) or placebo (n = 10).
9th ICADRD: Poster P3-012. Presented July 20, 2004

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FACT: Children and adolescents who consistently watch television for 2 hours or more a day are at an increased risk of being overweight, to smoke, and to have high cholesterol concentrations in early adulthood—substantial risk factors for longterm health problems in later life—conclude authors of a study from New Zealand in this week’s issue of THE LANCET. Lancet 2004; 364: 226, 257-62