Finding May Explain Why Current Drugs Don't Improve Memory Function

Researchers at the University of Pittsburgh have found a new mechanism that may cause mild cognitive impairment, a forerunner to Alzheimer's disease.

The findings may explain why current drugs do not improve memory function effectively and may redirect research of the newer treatments designed to prevent memory loss, the researchers reported in the Annals of Neurology.

The brains of older people with mild cognitive impairment produce more choline acetyltransferase (ChAT), an enzyme that is linked to memory and cognitive function. Researchers speculate that this is the brain's attempt to maintain normal function as neurons linked with communication die off.

Autopsy results have backed up this theory by showing that more than 60 percent of people who had mild cognitive impairment within a year before they died already had evidence of neurodegeneration that is seen in the early stages of Alzheimer's disease.

Researchers have believed that a decrease in ChAT levels causes mild cognitive impairment and have been developing drugs that boost levels of the neurotransmitter acetylcholine, the enzyme's product.

These new findings demonstrate that the increase in ChAT in mild cognitive impairment shows the brain's ability to compensate in one area for deficits in another to try to maintain normal brain function, according to DeKosky.

As the disease progresses, the brain eventually loses the battle and ChAT levels return to normal, then decrease as the disease moves into the final stages.

"Because we thought deficits in ChAT were responsible for memory problems in patients with mild cognitive impairment, the most common treatment we use is a class of drugs called cholinesterase inhibitors that help the brain produce more," said Dr. Steven T. DeKosky, professor neurology, psychiatry, neurobiology and human genetics at the University of Pittsburgh School of Medicine.

"These results suggest that the brain increases production of ChAT on its own in people with mild cognitive impairment and that in addition to their use in early Alzheimer's disease, these drugs may be effective if used in patients who have a deficit in ChAT -- those with advanced Alzheimer's disease. These findings suggest we should spend more time researching ways to slow down or stop the early stages of neurodegeneration."

Other sources: University of Pittsburgh