September 9, 2008 — One of the fastest-growing areas of pharmaceutical sales may pose a risk to patients who also suffer from age-related dementia or Alzheimer's disease. University of Virginia neuroscientist Jeremy Tuttle has received a $1.4 million grant from the National Institute on Aging to study whether certain bladder control medications might actually accelerate brain structural damage.

"The most common reason for institutionalizing a person suffering from age-related dementia or Alzheimer's disease is urinary incontinence," Tuttle said. "Many times these patients are also taking bladder control medications and there is conflicting research that certain types of these medications could worsen, or possibly benefit, these brain conditions."
 
The drugs used to treat urinary incontinence, known as antimuscarinic agents, affect the metabolism of amyloid peptide in unpredictable ways, Tuttle said. Amyloid-beta peptide is deposited as plaques in the brains of Alzheimer's disease patients and is thought to be involved in the disease. Antimuscarinic agents can affect amyloid metabolism consistently but oppositely, even if the drugs are relatively non-specific antagonists of muscarinic receptors.

There are at least five antimuscarinic drugs currently on the market and they differ in specificity and how they are distributed in the body. Testing their impact upon amyloid will suggest which of the compounds might pose less risk and if there are beneficial effects that might be examined further.
 
Tuttle said he plans to use his grant to study biochemical and mouse models that can be used to test the effects of the current medications and to have a model ready to evaluate new drugs which come into development. He is currently involved with Pfizer evaluating how Detrol affects amyloid metabolism.
 
"It is only recently that this potential danger of bladder control medications to mental status and the brain has been realized," Tuttle said.