Memory Enhancing Drugs May Worsen Working Memory
New Haven, Conn. -- A new study cautions that while drugs being designed to enhance memory in the elderly seem to be effective for some types of memory, they may actually worsen working memory, according to a study by Yale researchers published Thursday in the journal Neuron.
Working memory is the cognitive ability that intelligently regulates our thoughts, actions and feelings, letting us plan and organize for the future. It is governed by the prefrontal cortex. This type of memory is constantly updated and is known to be impaired by the normal aging process.
The ability to lay down long-term memories depends upon another region of the brain, the hippocampus.
The study by Amy Arnsten, associate professor and director of graduate studies in neurobiology at Yale School of Medicine, shows that the prefrontal cortex and hippocampus have different chemical needs, and that medications being developed to enhance long-term memory actually worsen working memory in aged animals.
Biotech companies are focusing on the activating protein kinase A, an enzyme in hippocampal cells which strengthens long-term memory formation. Arnsten and colleagues found that activation of protein kinase A in prefrontal cortex worsened working memory, while inhibiting this enzyme in prefrontal cortex improved working memory in aged rats. In collaboration with Ronald Duman's laboratory, they found that aged rats with naturally occurring working memory impairment had signs of overactive protein kinase A in their prefrontal cortex.
"Because PKA is over-activated in the aged prefrontal cortex, PKA stimulation actually makes the situation worse by further impairing working memory," Arnsten said.
The study was funded by the National Institute on Aging (NIA) of the National Institute on Health (NIH). "This important study tells us that one size may not fit all when developing treatment strategies for cognitive deficits," says Molly Wagster, program director for neuropsychology of aging research at the NIA. "The differing effects of PKA activity in the hippocampus and the prefrontal cortex suggest that distinct neurochemical needs of different regions of the brain must be addressed for the development of effective ways to enhance cognition."
Co-authors included Brian Ramos, Shari Birnbaum, Isabelle Lindenmayer, Samuel Newton and Ronald Duman.
Most drugs are really imprecise tools for modifying metabolism because they typically work on more than one site with more than one effect. It is therefore not surprising that a drug aimed to have one desired effect on the hippocampus has an undesired effect on the prefrontal cortex. Drugs that attempt to reverse or slow down aging are going to be tough to develop because the most effective treatments would reverse the damage that accumulates in aging. Attempts to simply suppress or up-regulate some activity are unlikely to reverse most forms accumulated damage. It may well be possible to develop drugs that work reverse some subset of all the types of accumulated damage. But theoretically more powerful approaches such as gene therapy and cell therapy will likely prove more efficacious in the long run.
"Prefrontal cortex functions are essential to the information age and they naturally decrease with normal aging, so it's particularly important to see what this cortex needs and to give it back to this part of the brain," says study author Amy F.T. Arnsten, an associate professor and director of graduate studies in neurobiology at Yale University School of Medicine. "There's some deterioration in the hippocampus with normal aging, but what really erodes the hippocampus is Alzheimer's."
|Share |||Randall Parker, 2003 November 10 11:37 AM Brain Enhancement|