MADRID — Thiazolidinediones may reduce the incidence of Alzheimer's disease or forestall its progression in both diabetic and nondiabetic patients, researchers reported at the 10th International Conference on Alzheimer's Disease and Related Disorders.
Diabetes is thought to increase the incidence of Alzheimer's disease through several pathways, including decreased cortical utilization of glucose, and increased oxidative stress, inflammation, and deposition of amyloid-β. Besides regulating insulin and improving glucose usage, the drugs have been shown in animal models to suppress microglial-mediated inflammation and reduce amyloid plaque formation, Donald Miller, Sc.D., and Dr. David Geldmacher said at a press conference during the meeting, which was sponsored by the Alzheimer's Association.
Dr. Miller examined the incidence of new Alzheimer's cases among a cohort of 142,328 veterans (mean age 66 years) with diabetes, who were followed for 6 years. The group included patients who received a new prescription for either a thiazolidinedione (74,525) or insulin (67,803).
After 6 years' follow-up, there were 3,191 new cases of Alzheimer's, a rate of 0.24% per year.
Patients who got a thiazolidinedione were 19% less likely to develop the disorder than were those treated with insulin, said Dr. Miller of the department of health services at Boston University School of Public Health. The results remained significant even after controlling for potential confounders including demographics, body mass index, and other medications.
Dr. Miller obtained similarly significant results favoring thiazolidinediones when he compared the drugs with metformin.
More research is necessary before any firm conclusions can be drawn, however. “It would be premature to say that these drugs prevent Alzheimer's in diabetes patients,” he said. “These are preliminary results, although they are encouraging.”
Dr. Geldmacher, director of the memory disorder program at the University of Virginia, Charlottesville, examined the effect of pioglitazone compared with placebo in nondiabetic patients with probable Alzheimer's disease. The randomized, controlled trial included 30 subjects (mean age 70 years) whose mean Mini-Mental State Examination score was 21.
All patients maintained their existing antidementia drugs during the trial; 15 also received pioglitazone (45 mg/day), while the remaining 15 received the placebo.
After 18 months, there was a nonsignificant trend toward better cognitive performance in the treated patients, Dr. Geldmacher said. “None of the measures reached statistical significance, but the effect size we saw was similar to that seen with existing antidementia drugs.”
In fact, he said, pioglitazone appeared to have a synergistic effect with existing drug therapy, doubling its cognitive impact.
Just as importantly, the drug was safe and well tolerated, he added. “We were somewhat concerned that it could cause hypoglycemia in these patients, none of whom had diabetes, but that was not the case.” The only significant adverse event observed was lower extremity edema, a side effect also seen in diabetic patients who take the drug.