A drug used to improve blood flow to the brain also could help improve learning and memory and reduce the risk of Alzheimer's disease, according to a recent study by investigators at TGen, Arizona State University and the Arizona Alzheimer's Consortium.

Fasudil has been used for more than 10 years to help protect the brain in stroke patients by dilating blood vessels when blood flow is curtailed.

Arizona psychologists, geneticists and neuroscientists reported in the February edition of the journal Behavioral Neuroscience that hydroxyfasudil, the active form of the parent drug Fasudil, improved spatial learning and working memory in middle-aged rats when negotiating a complicated maze.

The findings suggest that hydroxyfasudil may influence similar cognitive processes in humans involving the hippocampus, a part of the brain that has been shown to deteriorate in patients with age-related disorders.

"If Fasudil proves to be safe and effective in enhancing learning and memory, it could represent a viable new option for the prophylactic treatment of disorders with a cognitive decline component. This could include diseases like Alzheimer's as well as general age-related impairment. In short, it may be a new pharmaceutical weapon that could be used even before the occurrence of symptoms," said Dr. Matthew Huentelman, an Investigator in TGen's Neurogenomics Division.

Clinical trials are being explored in the areas of cognitive impairment and dementia, said Huentelman, the scientific paper's first author.

Although far from proving anything about human use of the drug, the findings support the scientific quest for a substance that could treat progressive cognitive impairment, cushion the impact of aging, or even enhance learning and memory throughout one's life span.

"Fasudil shows great promise as a cognitive enhancer during aging," said Dr. Heather Bimonte-Nelson, an Assistant Professor in ASU's Department of Psychology and the paper's lead author. "The effects in our aging-animal model were robust, showing enhancements in both learning and two measures of memory. The possibility that these findings may translate to benefits to human brain health and function is very exciting."

In the study, the researchers gave daily injections of hydroxyfasudil to middle-aged, 17-18 month old, male rats. Injection made it easy to give the drug to rats, but people take it in the form of a pill.

Rats were tested on a water radial-arm maze, which assessed how well they remembered which of the radiating arms had a reward, a sign of accurate spatial learning and working memory.

Fasudil is used to protect the brain by dilating blood vessels when blood flow is curtailed. In the body, Fasudil breaks down into the more potent hydroxyfasudil molecule, which the authors hypothesize may alter memory by affecting the function of a gene called KIBRA.

The authors recently demonstrated that KIBRA might play a role in memory in healthy young and late-middle-aged humans.

In September 2008, TGen investigators announced a link between the brain protein KIBRA and Alzheimer-s disease, a discovery that could lead to promising new treatments for this memory-robbing disorder. TGen researchers found that carriers of a memory-enhancing flavor of the KIBRA gene had a 25 percent lower risk of developing Alzheimer's disease. The findings were reported in the Neurobiology of Aging, a Philadelphia-based peer-review journal that generally focuses on how aging affects the nervous system.

"This research suggests that KIBRA, and possibly some of the proteins with which it interacts, may play a role in Alzheimer's disease," Huentelman, that paper's senior author, said at the time. The findings announced in September built on a previous TGen study published in 2006 in the prestigious journal Science, which showed a genetic link between KIBRA and memory in healthy adults. That pioneering study, led by collaborative teams from Arizona and Zurich, Switzerland, revealed a link between KIBRA and memory, in which healthy adults with the KIBRA T-allele performed better on memory tests than those without this gene.