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

Brain scans of 9,772 people aged 44 to 79, who were enrolled in the UK Biobank study, have revealed that smoking, high blood pressure, high pulse pressure, diabetes, and high BMI — but not high cholesterol — were all linked to greater brain shrinkage, less

A large Chinese study involving 20,000 people has found that the longer people were exposed to air pollution, the worse their cognitive performance in verbal and math tests. The effect of air pollution on verbal tests became more pronounced with age, especially for men and the less educated.

A review of 34 longitudinal studies, involving 71,244 older adults, has concluded that depression is associated with greater cognitive decline.

A study following nearly 28,000 older men for 20 years has found that regular consumption of leafy greens, dark orange and red vegetables and berry fruits, and orange juice, was associated with a lower risk of memory loss.

Poor sleep has been associated with the development of Alzheimer's disease, and this has been thought to be in part because the protein amyloid beta increases with sleep deprivation. A new study explains more.

A small study has found that a 12-week exercise program significantly improved cognition in both older adults with

A clinical trial involving 9361 older adults (50+) with hypertension but without diabetes or history of stroke has found that intensive control of blood pressure significantly reduced the risk of developing mild cognitive impairment.

Survey data from 6,807 Danish older adults (average age 60) in the Copenhagen City Heart Study, has found that being distressed in late midlife is associated with a higher risk of dementia in later life.

Poor sleep has been associated with Alzheimer's disease risk, but a new study suggests a specific aspect of sleep is important.

Data from 1,215 older adults, of whom 173 (14%) were African-American, has found that, although brain scans showed no significant differences between black and white participants,

Pages

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