Insulin-related therapies look preliminarily good in clinical trials, too. In 2007, researchers in Seattle conducted a small, randomized clinical trial in which patients with early Alzheimer's disease received daily puffs of insulin in the nose for 21 days. (The team chose this method of administration so that the insulin would move more directly to the brain without circulating throughout the body, where it might cause an unwanted drop in blood glucose.) The group, led by Suzanne Craft of the VA Puget Sound Medical Center, found that patients who received insulin were better able to pay attention to a story that was read to them and recall details 20 minutes later. Their caregivers also rated their mental functioning more highly. The team is now conducting a larger clinical trial, with results expected this fall. Craft says she is optimistic that insulin may open new doors for Alzheimer's patients. However, she shies away from dubbing the disease a "diabetes of the brain," noting that diabetes is normally diagnosed on the basis of elevated glucose levels, which do not appear to be at play here.
Other promising, early results come from the diabetes drug rosiglitazone, which has a checkered reputation. In patients with type 2 diabetes, rosiglitazone (aka Avandia) acts to increase insulin sensitivity in the body. But it may also raise the risk of heart attacks. The hope is that in some Alzheimer's patients, at least, the drug will have benefits for the brain—without the cardiovascular downside. In a small trial in 2005, Alzheimer's patients who received rosiglitazone for six months showed better attention and better recall than those who received a placebo. A more substantial, phase-two trial, published in 2006 and sponsored by GlaxoSmithKline (which makes the drug), found that patients who received rosiglitazone also fared better after 24 weeks of treatment—but only if they did not carry a particular gene variant. (This variant, called APOE-E4, is known to predispose people to the disease.)
GSK is now sponsoring several multinational phase-three trials, involving roughly 3,000 patients in 22 countries, which are expected to show more definitively whether rosiglitazone helps to improve cognition and functional capacity in patients with mild to moderate disease. Results are expected this summer. GSK researcher Michael Gold says that the Data Safety and Monitoring Board, which oversees these studies and has access to unblinded data, has not signaled a need to change or stop the studies based on safety. Still, researchers like Craft, who has served as a consultant to GSK, suggest that other drugs in the same chemical class as rosiglitazone might ultimately offer benefits to Alzheimer's patients with less cardiovascular risk.
Of course, taking intranasal insulin or a diabetes drug like rosiglitazone is not the only possible way to boost the brain's sensitivity to insulin. Another, even better option may be to do aerobic exercise, says Craft. And this seems to hold for older adults in general, including those without Alzheimer's: Better insulin signaling and glucose uptake in the brain may offer them a cognitive boost as well. One more reason, it seems, to close the medicine cabinet and work up a good sweat.
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