Possible treatment for working memory decline with age

September, 2011

A study has successfully countered reduced activity in the prefrontal cortex seen in older monkeys. Clinical trials are now investigating whether the drug can improve working memory in older humans.

A study comparing activity in the dorsolateral prefrontal cortex in young, middle-aged and aged macaque monkeys as they performed a spatial working memory task has found that while neurons of the young monkeys maintained a high rate of firing during the task, neurons in older animals showed slower firing rates. The decline began in middle age.

Neuron activity was recorded in a particular area of the dorsolateral prefrontal cortex that is most important for visuospatial working memory. Some neurons only fired when the cue was presented (28 CUE cells), but most were active during the delay period as well as the cue and response periods (273 DELAY neurons). Persistent firing during the delay period is of particular interest, as it is required to maintain information in working memory. Many DELAY neurons increased their activity when the preferred spatial location was being remembered.

While the activity of the CUE cells was unaffected by age, that of DELAY cells was significantly reduced. This was true both of spontaneous activity and task-related activity. Moreover, the reduction was greatest during the cue and delay periods for the preferred direction, meaning that the effect of age was to reduce the ability to distinguish preferred and non-preferred directions.

It appeared that the aging prefrontal cortex was accumulating excessive levels of an important signaling molecule called cAMP. When cAMP was inhibited or cAMP-sensitive ion channels were blocked, firing rates rose to more youthful levels. On the other hand, when cAMP was stimulated, aged neurons reduced their activity even more.

The findings are consistent with rat research that has found two of the agents used — guanfacine and Rp-cAMPS — can improve working memory in aged rats. Guanfacine is a medication that is already approved for treating hypertension in adults and prefrontal deficits in children. A clinical trial testing guanfacine's ability to improve working memory and executive functions in elderly subjects who do not have dementia is now taking place.

Reference: 

[2349] Wang, M., Gamo N. J., Yang Y., Jin L. E., Wang X-J., Laubach M., et al.
(2011).  Neuronal basis of age-related working memory decline.
Nature. advance online publication,

Related News

Data from more than 14,265 people older adults (51+) multiple times over a decade or more through the University of Michigan Health and Retirement Study has found that people with higher “multimorbidity scores” showed much faster cognitive decline than those with lower scores, even though most o

Large study shows level of beneficial alcohol consumption much lower than thought

Data from over 5,000 individuals found that a measure of belly fat (waist:hip ratio) was associated with reduced cognitive function in older Irish adults (60+). Body mass index (BMI), however, was found to protect cognitive function.

A study involving 116 healthy older adults (65-75) has found that higher levels of several key nutrients in the blood were associated with more efficient brain connectivity and better cognitive performance.

A long-running study involving 8225 adults found that self-reported diet during midlife (mean age 50) was not significantly associated with subsequent risk for dementia.

A small study comparing 38 younger adults (average age 22) and 39 older adults (average age 68) found that the older adults were less able to recognize when they made errors.

Can computer use, crafts and games slow or prevent age-related memory loss?

Americans with a college education live longer without dementia and Alzheimer's

Socially active 60-year-olds face lower dementia risk

Stressors in middle age linked to cognitive decline in older women

Data from some 900 older adults has linked stressful life experiences among middle-aged women, but not men, to greater memory decline in later life.

Pages

Subscribe to Latest newsSubscribe to Latest newsSubscribe to Latest health newsSubscribe to Latest news