18 November 2002. By guest writer Brenda Patoine. Insulin resistance is emerging as a possible risk factor for Alzheimer’s, and data from a pilot trial presented at the 2002 Neuroscience meeting indicate that an insulin-sensitizing drug may represent a novel treatment approach. Suzanne Craft of the University of Washington, Seattle, reported preliminary results of a proof-of-concept study using rosiglitazone, a drug used to treat type II diabetes.
Evidence implicating insulin sensitivity in AD has been building for some time: Insulin has been shown to modulate levels of aggregatable Aβ, affect tau pathology, and is linked to oxidative stress and inflammatory responses. Roughly every other AD patient shows insulin resistance measured as high plasma insulin levels, low CSF insulin levels, and reduced insulin-mediated glutamate metabolism. Craft has previously shown that exogenous insulin administration improves memory in AD patients. It is not yet clear whether this is an early, pathogenic event, or reflects one of many aspects of physiologic dysregulation seen in AD.
There is interest in rosiglitazone because it mediates insulin-sensitization via PPAR-γ receptors and also has anti-inflammatory effects, Craft said. She enrolled 10 newly or recently diagnosed AD patients (mean age 71.9) and five controls, put them on four mg. of rosiglitazone or placebo for six months, and conducted cognitive and blood tests at baseline, two, and four months. Results from the four-month interval showed statistically significant improvement in tests of delayed recall (p<.05) and selective attention (p<.05) in the treatment groups. Test scores for category fluency, which measures frontal executive functioning, remained constant. Control subjects declined on all scores.
These are preliminary data, as outcome measures following a 10-week washout period-which will indicate if rosiglitazone modifies disease or merely provides symptomatic relief-are not yet available. Craft expects full results by next summer. "What’s exciting to me about this study is the convergence of these two areas of anti-inflammatory and insulin-sensitivity research; if we can understand that, we may get some insights into the pathogenesis of Alzheimer’s disease."
Brenda Patoine is a science writer in Lagrangeville, New York, who writes for BrainWork and other publications.