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.


[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,


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Older people find it harder to see the wood for the trees

September, 2011

A study indicates that difficulty in seeing the whole, vs elements of the whole, is associated with impairment in perceptual grouping, and this is more common with age.

A standard test of how we perceive local vs global features of visual objects uses Navon figures — large letters made up of smaller ones (see below for an example). As in the Stroop test when colors and color words disagree (RED), the viewer can focus either on the large letter or the smaller ones. When the viewer is faster at seeing the larger letter, they are said to be showing global precedence; when they’re faster at seeing the component letters, they are said to be showing local precedence. Typically, the greater the number of component letters, the easier it is to see the larger letter. This is consistent with the Gestalt principles of proximity and continuity — elements that are close together and form smooth lines will tend to be perceptually grouped together and seen as a unit (the greater the number of component letters, the closer they will be, and the smoother the line).

In previous research, older adults have often demonstrated local precedence rather than global, although the results have been inconsistent. One earlier study found that older adults performed poorly when asked to report in which direction (horizontal or vertical) dots formed smooth lines, suggesting an age-related decline in perceptual grouping. The present study therefore investigated whether this decline was behind the decrease in global precedence.

In the study 20 young men (average age 22) and 20 older men (average age 57) were shown Navon figures and asked whether the target letter formed the large letter or the smaller letters (e.g., “Is the big or the small letter an E?”). The number of component letters was systematically varied across five quantities. Under such circumstances it is expected that at a certain level of letter density everyone will switch to global precedence, but if a person is impaired at perceptual grouping, this will occur at a higher level of density.

The young men were, unsurprisingly, markedly faster than the older men in their responses. They were also significantly faster at responding when the target was the global letter, compared to when it was the local letter (i.e. they showed global precedence). The older adults, on the other hand, had equal reaction times to global and local targets. Moreover, they showed no improvement as the letter-density increased (unlike the young men).

It is noteworthy that the older men, while they failed to show global precedence, also failed to show local precedence (remember that results are based on group averages; this suggests that the group was evenly balanced between those showing local precedence and those showing global precedence). Interestingly, previous research has suggested that women are more likely to show local precedence.

The link between perceptual grouping and global precedence is further supported by individual differences — older men who were insensitive to changes in letter-density were almost exclusively the ones that showed persistent local precedence. Indeed, increases in letter-density were sometimes counter-productive for these men, leading to even slower reaction times for global targets. This may be the result of greater distractor interference, to which older adults are more vulnerable, and to which this sub-group of older men may have been especially susceptible.

Example of a Navon figure:




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Gingko biloba & Ginseng

  • The most convincing study has found no benefit of gingko biloba on cognition in older adults.
  • Previous evidence that gingko biloba can improve memory has been decidedly mixed.
  • The most promising results have occurred with multiple sclerosis patients; there is also some reason to think those with cardiovascular problems may benefit.
  • Gingko biloba is not without side-effects.
  • The quality of the supplements is also probably a factor in determining whether it will be of value.

Most studies supporting the use of gingko have been looking at its use in people suffering from dementia, Alzheimer's, multiple sclerosis etc. That is, not in healthy seniors. There is some evidence that gingko may be helpful with cardiovascular problems and, given recent research that suggests "what's good for the heart is good for the brain", perhaps this is the source of any effects gingko may have on memory and cognitive function.

Gingko can have serious side-effects - those taking other medications, or about to undergo surgery, are advised to tell their doctor if they are taking gingko. There is also some evidence that it may be a danger to unborn children. Nor is it yet clear what the correct dose might be (one study found a beneficial effect at a low dose, but no effect when a higher dose was used!) The quality of the various gingko preparations for sale is also quite variable.

Given these caveats however, some individuals may find gingko helpful - chiefly, it would appear, in terms of a slightly increased alertness. I would speculate that those who do find it helpful are those people whose memory problems are caused by certain cardiovascular risk factors, such as high cholesterol.

Older news items (pre-2010) brought over from the old website

Ginkgo biloba does not slow rate of cognitive decline

Findings from the large, long-running Ginkgo Evaluation of Memory study have sadly found no evidence for an effect of Ginkgo biloba on global cognitive change and no evidence of effect on specific cognitive domains of memory, language, attention, visuospatial abilities and executive functions. There was also no evidence for treatment effects for any particular group (i.e. by age, sex, race, education, ApoE4 status, or baseline cognitive status). The randomized, double-blind, placebo-controlled clinical trial involved 3069 seniors aged 72 to 96 years, with a median follow-up of 6.1 years. Those taking the herb took a twice-daily dose of 120-mg. Earlier results from the study found Ginkgo biloba did not reduce the incidence of dementia.

[1457] Snitz, B. E., O'Meara E. S., Carlson M. C., Arnold A. M., Ives D. G., Rapp S. R., et al.
(2009).  Ginkgo biloba for Preventing Cognitive Decline in Older Adults: A Randomized Trial.
JAMA. 302(24), 2663 - 2670.

Gingko biloba does not prevent dementia

A six-year study involving over 3000 older adults has found no reduction in the rate of dementia for those taking twice-daily 120 mg doses of Ginkgo biloba.

DeKosky, S.T. et al. 2008. Ginkgo biloba for prevention of dementia: A randomized controlled trial. JAMA, 300 (19), 2253-62.

Daily dose of ginkgo may prevent brain cell damage after a stroke

A study using genetically engineered mice has found that daily doses of ginkgo biloba can prevent or reduce brain damage after an induced stroke. More research is needed before its use in humans can be recommended, but the finding does lend support to other evidence that ginkgo biloba triggers a cascade of events that neutralizes free radicals known to cause cell death.

[1081] Saleem, S., Zhuang H., Biswal S., Christen Y., & Doré S.
(2008).  Ginkgo biloba extract neuroprotective action is dependent on heme oxygenase 1 in ischemic reperfusion brain injury.
Stroke; a Journal of Cerebral Circulation. 39(12), 3389 - 3396.

More study needed to determine if gingko biloba helps memory

A three-year study involving 118 people age 85 and older with no memory problems found no significant difference in the development of memory problems during the study between those who took ginkgo biloba extract three times a day and those who took a placebo. However, when adherence was taken into account, it was found that those who reliably took the supplement had a 68% lower risk of developing mild memory problems than those who took the placebo. But those taking ginkgo biloba were more likely to have a stroke or transient ischemic attack. Further studies are needed.

[1100] Dodge, H. H., Zitzelberger T., Oken B. S., Howieson D., & Kaye J.
(2008).  A randomized placebo-controlled trial of ginkgo biloba for the prevention of cognitive decline.
Neurology. 01.wnl.0000303814.13509.db - 01.wnl.0000303814.13509.db.

Ginkgo may improve executive function in MS patients

A study of 39 MS patients found that those receiving ginkgo biloba were about 13% faster on a Stroop test (measures a person's ability to pay attention and to sort conflicting information). Such a difference would be comparable to differences in scores between healthy people ages 30 to 39 and those ages 50 to 59. The benefit appeared to be greatest for those who had certain problems with the Stroop test.

The study was presented at the American Academy of Neurology's 57th Annual Meeting in Miami Beach, Fla.

Helping memory with "natural" supplements

Do caffeine and glucose help concentration? A recent study found that volunteers who drank a mixture containing caffeine and glucose (as well as trace levels of guarana, ginkgo and ginseng) showed clear improvements in memory and attention. Those who consumed the individual ingredients, or a placebo, did not show such improvements.
Another study by the same researchers found that high doses of lemon balm improved memory and led to greater feelings of calmness in 20 volunteers. The lemon balm was found to increase the activity of acetylcholine – an important chemical messenger which is reduced in people with Alzheimer’s disease.

Scholey, A. & Kennedy, D. 2003. Report at the British Psychological Society Annual Conference in Bournemouth 13-15 March.

Support for gingko biloba

A study of seniors with age-associated memory impairment found significant improvement in verbal recall among those who took gingko biloba for six months. PET scans revealed a correlation with better brain function in key brain memory centers, although there was no detectable changes in brain metabolism. Studies of gingko biloba have had conflicting results, and it is suggested that both length of time (most studies have looked at the effect over 3 months or less) and quality of supplement, may be important.

The research was presented at the annual meeting of the Society for Neuroscience.

Pilot study finds ginseng may improve memory in stroke dementia patients

Following mouse studies showing that ginseng increased the activities of the brain chemicals acetylcholine and choline acetyltransferase, a pilot study of 40 patients (average age 67) with mild to moderate vascular dementia was undertaken by Chinese researchers. 25 patients were randomly selected to receive ginseng extract, while 15 received the drug Duxil® (used to improve memory in elderly dementia patients). Overall, researchers found that patients who took the ginseng compound significantly improved their average memory function after 12 weeks. More research (larger samples, placebo-controls) is needed before this finding can be confirmed.

The study was reported at the American Stroke Association's 28th International Stroke Conference on February 14 in Phoenix.

No support for ginkgo as a memory enhancer

In a double-blind study of 230 healthy seniors, half of whom were given gingko biloba and half a placebo, ginkgo biloba was found to have no beneficial effect on memory and related mental functions after six weeks (the manufacturer claims beneficial effects can be noticed after four weeks).

[494] Solomon, P. R., Adams F., Silver A., Zimmer J., & DeVeaux R.
(2002).  Ginkgo for Memory Enhancement: A Randomized Controlled Trial.
JAMA. 288(7), 835 - 840.

Ginkgo biloba may slow cognitive decline in patients with mild multiple sclerosis

A six-month double-blind, placebo-controlled pilot study of 23 individuals with mild multiple sclerosis found that patients who took the herb Ginkgo biloba performed better on neuropsychological tests compared to those who took the inactive placebo.

Corey-Bloom, J., Kenney, C. & Norman, M. 2002. Paper presented at the annual meeting of the American Academy of Neurology on April 18 in Denver, Colorado.


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Post-surgery cognitive decline

Older news items (pre-2010) brought over from the old website

Cognitive decline after noncardiac surgery

Older surgical patients at greater risk for developing cognitive problems

There’s been quite a lot of research on the effects of cardiac surgery on cognitive function, but less is known about the effects of any surgery. Now a study of more than 1000 adult patients of different ages has tested memory and cognitive function before undergoing elective non-cardiac surgery, at the time of hospital discharge, and three months after surgery. It was found that many patients, regardless of age, experienced postoperative cognitive dysfunction (POCD) at the time they left the hospital (36.6% of young adults, 30.4% of the middle-aged, 41.4% of elderly). But three months later, those aged 60 and older were more than twice as likely to exhibit POCD (12.7% compared to less than 6% for both young and middle-aged). POCD was more common among those patients with lower educational level and a history of a stroke that had left no noticeable neurologic impairment. Those with POCD at both the time of hospital discharge and three months after surgery also were more likely to die within the first year after surgery. The reason for this is unclear, but it’s speculated that patients with prolonged cognitive dysfunction might be less able to take medicines correctly or may not recognize the need to seek medical care for symptoms of complications. [1]

Cognitive decline after heart bypass

More evidence bypass surgery not responsible for cognitive impairment

A 6-year study of 326 heart patients has found no differences in brain impairment between those who had on-pump coronary artery bypass surgery (152 patients), off-pump bypass surgery patients (75 patients), and those who had drugs and arterial stents to keep their blood vessels open instead of bypass surgery (99 patients). However, all of them were found to have experienced significant cognitive decline over the six-year study period on tests of verbal memory, visual memory, visuoconstruction, language, motor speed, psychomotor speed, attention, and executive function, when compared to 69 heart-healthy people who had no known risk factors for coronary artery disease. The findings provide more evidence that it is the disease and not the surgery that causes long-term cognitive problems. [2]

Long-term cognitive decline in bypass patients not due to surgery

Another study has come out supporting the view that coronary bypass patients have no greater risk of long-term cognitive decline than patients not undergoing surgery. The study involved 152 patients who had bypass surgery and 92 patients with coronary artery disease who did not have surgical intervention. Patients had memory and other cognitive tests at the beginning of the study period, and after 3, 12, 36 and 72 months. The results showed that there were no significant differences in cognitive scores between the two groups at the beginning of the study. Both groups showed modest decline in cognitive performance during the study period, but there were no significant differences in the degree of decline between the groups after six years. It was suggested that the decline in both groups was related to the presence of risk factors for vascular disease. [3]

Inflammatory system genes linked to cognitive decline after heart surgery

The finding that people with variants of two genes involved in the inflammatory system appear to be protected from suffering a decline in mental function following heart surgery raises the possibility that therapy involving drugs known to dampen the inflammatory response may be effective in preventing cognitive decline after heart surgery. The specific genes involved were those for C-reactive protein (which plays an important role in the body’s initial response to injury) and P-selectin (which helps recruit circulating white blood cells to the site of an injury). Patients with the variation of the C-reactive protein gene were 20.6% less likely to suffer mental decline, and patients with the P-selectin variant had a 15.2% risk reduction. The risk of cognitive decline for those with both gene variants was only 17% compared to 43% for patients who had neither variant. [4]

'Off-pump' CABG surgery appears to have no benefit on cognitive or cardiac outcomes at 5 years

A five-year study of 281 cardiac patients, half of whom received off-pump coronary artery bypass surgery and half on-pump surgery, has found that there was no difference in cognitive performance five years after surgery. The findings suggest that factors other than cardiopulmonary bypass may be responsible for cognitive decline, such as anesthesia and the generalized inflammatory response that is associated with major surgical procedures. [5]

Cognitive loss following coronary artery bypass surgery due to surgical technique?

A surgical strategy designed to minimize trauma to the body's largest artery – the aorta – during heart bypass surgery can significantly reduce cognitive loss that often follows the operation. The study found that at least 60% of patients showed neurological deficits following bypass surgery, but that at 6 months, 57% of patients who had traditional surgery still had deficits while only 32% of those who didn’t use the heart-lung machine during surgery, and 30% of those who had the new surgical technique still had deficits. Researchers conclude that surgical technique is the primary cause of cognitive decline following bypass surgery. [6]

Use of heart pump during bypass surgery not implicated in cognitive decline

A study involving 380 individuals has found that those patients undergoing coronary artery bypass grafting (CABG) surgery that used a cardiopulmonary heart pump had no significant differences in their mental functions compared to CABG patients whose surgery did not involve a heart pump. Patients with coronary heart disease all performed lower on cognitive tests than healthy controls, prior to surgery. By three months, both cardiac patients who had undergone surgery (with or without use of a heart pump) and those who had not, had improved cognitive function. [7]

Review finds bypass surgery free of long-term brain effects for most

A broad retrospective review of the effects of coronary artery bypass surgery on cognitive functions concludes that, although the research confirms the existence of mild deficits in the period up to three months after surgery, the procedure itself probably does not cause late or permanent neurological effects. Rather, they argue, the late cognitive declines seen in some long-term studies are for most people likely associated with progression of underlying conditions such as cerebrovascular disease. However, this is not true for all. The exceptions might include older patients and those with risk factors for cerebrovascular disease or a history of stroke. [8]

Elderly experience long-term cognitive decline after surgery

Researchers have found that two years after major non-cardiac surgery, 42% of elderly patients will have experienced a measurable cognitive decline. 59% of patients experienced cognitive decline immediately after surgery — these are the ones at greatest risk of long-term decline. Three months after surgery, 34% of patients had cognitive declines. The study involved 354 patients, with an average age of 69.5 years. [9]

Lower temperatures improve outcomes after bypass surgery

One of the possible adverse effects of cardiac bypass surgery is cognitive decline. Researchers have found that patients who were allowed an additional 10 to 12 minutes to return to normal body temperature after surgery scored almost one-third better on standard tests of cognition six weeks after surgery. (In order to protect the brain and other organs from damage while the heart is stopped during surgery, physicians cool a patient's blood as it passes through a heart-lung machine. However, toward the end of the operation, this blood needs to be rewarmed.) [10]

Cognitive decline after bypass surgery appears more transient than feared

Recent studies have found a high occurrence of cognitive problems in patients who undergo coronary artery bypass surgery, with such problems still found six weeks after surgery. In a new study comparing 140 patients who underwent bypass surgery and a second group of 92 coronary artery disease patients who did not have surgery, no differences in cognitive abilities were found when patients were re-tested at three and 12 months. This supports recent research suggesting that it is the disease itself that is the major problem, rather than the surgery. [11]

Lowered immunity puts older coronary bypass patients at higher risk for cognitive decline

Older patients with lowered immunity to certain common bacteria found in the gastrointestinal tract are more likely than younger patients to suffer cognitive decline after coronary artery bypass surgery. [12]

Cognitive impairment following bypass surgery may last longer than thought

More support for a link between cardiopulmonary bypass surgery and cognitive impairment comes from a new study. In particular, it seems, that attention may be most affected. The study also found evidence of longer-lasting cognitive decline than previously thought. Bypass patients also demonstrated poorer cognitive performance before the surgery, and it is now being suggested that it may be the disease itself that is the major problem, rather than the surgery itself. This is consistent with recent research connecting cardiovascular risk factors with risk factors for cognitive decline. [13]

Fever immediately after heart bypass surgery associated with cognitive decline

Elevated temperatures within 8-10 hours after surgery are often seen in patients who have undergone coronary bypass surgery. This has not however been regarded as anything other than a nuisance. Many bypass patients also suffer measurable cognitive decline. A new study reports on a relationship between these fevers and cognitive decline six weeks following surgery. Patients who suffered the highest post-operative temperatures also suffered the highest amount of cognitive decline. [14]

More on implications of having the Alzheimer's gene

Researchers have found an association between nerve cell changes associated with aging and the presence of a variation of the apolipoprotein gene known as apolipoprotein E4 (APOE4). This form is carried by approximately 25% of the population and has been linked to increased risk of Alzheimer's disease, cardiovascular disease and memory loss after head injury or bypass surgery. [15]

Frequency of cognitive decline after bypass surgery>

Heart bypasses are becoming increasingly common - in the U.S., more than half a million people undergo coronary-artery bypass grafting (CABG) each year. A common side-effect of the procedure is postoperative cognitive decline (frequency of occurrence estimates range from 33% to 82%, depending on the method of evaluation used). A recent study looked at the longer-term picture: in this study, cognitive decline was found in 53% of the patients at time of discharge; at 6 weeks, the rate was assessed at 36%; at 6 months, 24%. However, five years after the surgery the rate of cognitive decline was 42%. Older age, a lower level of education, a higher preoperative score for cognitive function, and the presence of cognitive decline at discharge were all predictors of cognitive decline at 5 years after CABG. Of these, the most significant predictor was a decline in cognition seen at discharge.
Note that there was no control group, so these results must be treated with caution. Note also that short-term declines in cognitive function are also reported in elderly subjects after non-cardiac surgery, and this can persist in a proportion of these patients - in fact, in 10% after 2 years. [16]

1.Monk, T.G. et al. 2008. Predictors of Cognitive Dysfunction after Major Noncardiac Surgery. Anesthesiology, 108(1), 18-30.
Price, C.C.; Garvan, C.W. & Monk, T.G. 2008. Type and Severity of Cognitive Decline in Older Adults after Noncardiac Surgery. Anesthesiology, 108(1), 8-17. Press release

2.Selnes, O.A. et al. 2009. Do Management Strategies for Coronary Artery Disease Influence 6-Year Cognitive Outcomes? Annals of Thoracic Surgery, 88, 445-454. Press release

3.Selnes, O.A. et al. 2008. Cognition 6 Years After Surgical or Medical Therapy for Coronary Artery Disease. Annals of Neurology, 63, 581-590. Press release Press release

4.Mathew, J.P. et al. 2007. Genetic Variants in P-Selectin and C-Reactive Protein Influence Susceptibility to Cognitive Decline After Cardiac Surgery. Journal of the American College of Cardiology, 49, 1934 - 1942. Press release

5.van Dijk, D. et al. 2007. Cognitive and Cardiac Outcomes 5 Years After Off-Pump vs On-Pump Coronary Artery Bypass Graft Surgery. JAMA, 297, 701-708. Press release

6.Hammon, J.W., Stump, D.A., Butterworth, J.F., Moody, D.M., Rorie, K., Deal, D.D., Kincaid, E.H., Oaks, T.E. & Kon, N.D. 2006. Single crossclamp improves 6-month cognitive outcome in high-risk coronary bypass patients: The effect of reduced aortic manipulation.The Journal of Thoracic and Cardiovascular Surgery, 131 (1), 114-121. Press release

7.McKhann, G.M., Grega, M.A., Borowicz, L.M.Jr, Bailey, M.M., Barry, S.J.E., Zeger, S.L., Baumgartner, W.A. & Selnes, O.A. 2005. Is there cognitive decline 1 year after CABG?: Comparison with surgical and nonsurgical controls. Neurology, 65, 991-999. Press release

8.Selnes, O.A. & McKhann, G.M. 2005. Neurocognitive Complications after Coronary Artery Bypass Surgery. Annals of Neurology, Published Online: April 25, 2005 (DOI: 10.1002/ana.20481) Press release

9.Monk, T. et al. 2004. Paper presented October 26 at the annual scientific sessions of the American Society of Anesthesiologists in Las Vegas. Press release

10.Grocott, H. et al. 2004. Paper presented April 26 at the annual scientific sessions of the Society of Cardiovascular Anesthesiologists. Press release

11.Selnes, O.A., Grega, M.A., Borowicz, L.M. Jr , Royall, R.M., McKhann, G.M. & Baumgartner, W.A. 2003. Cognitive changes with coronary artery disease: a prospective study of coronary artery bypass graft patients and nonsurgical controls. The Annals of Thoracic Surgery, 75 (5), 1377-1386. Press release

12.Mathew, J.P., Grocott, H.P., Phillips-Bute, B., Stafford-Smith, M., Laskowitz, D.T., Rossignol, D., Blumenthal, J.A. & Newman, M.F. 2003. Lower Endotoxin Immunity Predicts Increased Cognitive Dysfunction in Elderly Patients After Cardiac Surgery. Stroke, 34, 508. Press release

13.Keith, J.R., Puente, A.E., Malcolmson, K.L., Tartt, S., Coleman, A.E. & Marks, H.F. Jr. 2002. Assessing Postoperative Cognitive Change After Cardiopulmonary Bypass Surgery. Neuropsychology, 16(3), 411-21. Press release

14.Grocott, H.P., Mackensen, G.B., Grogore, A.M., Mathew, J., Reves, J.G., Phillips-Bute, B., Smith, P.K. & Newman, M.F. 2002. Postoperative Hyperthermia Is Associated With Cognitive Dysfunction After Coronary Artery Bypass Graft Surgery. Stroke, 33, 537-541. Press release

15.Doraiswamy, P.M. et al. 2002. Paper presented February 25 at the 15th annual meeting of the American Association for Geriatric Psychiatry in Orlando, Fla. Press release

16.Newman, M. F., Kirchner, J. L., Phillips-Bute, B., Gaver, V., Grocott, H., Jones, R. H., Mark, D. B., et al. (2001). Longitudinal Assessment of Neurocognitive Function after Coronary-Artery Bypass Surgery. N Engl J Med, 344(6), 395-402. Press release

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Older adults have better implicit memory

April, 2011

A new study further confirms the idea that a growing inability to ignore irrelevancies is behind age-related cognitive decline.

A study involving 125 younger (average age 19) and older (average age 69) adults has revealed that while younger adults showed better explicit learning, older adults were better at implicit learning. Implicit memory is our unconscious memory, which influences behavior without our awareness.

In the study, participants pressed buttons in response to the colors of words and random letter strings — only the colors were relevant, not the words themselves. They then completed word fragments. In one condition, they were told to use words from the earlier color task to complete the fragments (a test of explicit memory); in the other, this task wasn’t mentioned (a test of implicit memory).

Older adults showed better implicit than explicit memory and better implicit memory than the younger, while the reverse was true for the younger adults. However, on a further test which required younger participants to engage in a number task simultaneously with the color task, younger adults behaved like older ones.

The findings indicate that shallower and less focused processing goes on during multitasking, and (but not inevitably!) with age. The fact that younger adults behaved like older ones when distracted points to the problem, for which we now have quite a body of evidence: with age, we tend to become more easily distracted.



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Protein in the urine: A warning sign for cognitive decline

December, 2010

Two recent studies indicate that the presence of protein in the urine, even in small amounts, could be a warning sign that a patient may develop cognitive impairment with age.

A six-year study involving over 1200 older women (70+) has found that low amounts of albumin in the urine, at levels not traditionally considered clinically significant, strongly predict faster cognitive decline in older women. Participants with a urinary albumin-to-creatinine ratio of >5 mcg/mg at the start of the study experienced cognitive decline at a rate 2 to 7 times faster in all cognitive measures than that attributed to aging alone over an average 6 years of follow-up. The ability most affected was verbal fluency. Albuminuria may be an early marker of diffuse vascular disease.

Data from 19,399 individuals participating in the Renal Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, of whom 1,184 (6.1%) developed cognitive impairment over an average follow-up of 3.8 years, has found that those with albuminuria were 1.31-1.57 times more likely to develop cognitive impairment compared to individuals without albuminuria. This association was strongest for individuals with normal kidney function. Conversely, low kidney function was associated with a higher risk for developing cognitive impairment only among individuals without albuminuria. Surprisingly, individuals with albuminuria and normal kidney function had a higher probability for developing cognitive impairment as compared to individuals with moderate reductions in kidney function in the absence of albuminuria.

Both albuminuria and low kidney function are characteristics of kidney disease.


Lin, J., Grodstein, F., Kang, J.H. & Curhan, G. 2010. A Prospective Study of Albuminuria and Cognitive Decline in Women. Presented at ASN Renal Week 2010 on November 20 in Denver, CO.

Tamura, M.K. et al. 2010. Albuminuria, Kidney Function and the Incidence of Cognitive Impairment in US Adults. Presented at ASN Renal Week 2010 on November 20 in Denver, CO.




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Vascular disease underlies cognitive decline in healthy aging

December, 2010

New findings add to evidence that the key to not becoming cognitively impaired in old age is vascular health.

More evidence that vascular disease plays a crucial role in age-related cognitive impairment and Alzheimer’s comes from data from participants in the Alzheimer's Disease Neuroimaging Initiative.

The study involved more than 800 older adults (55-90), including around 200 cognitively normal individuals, around 400 people with mild cognitive impairment, and 200 people with Alzheimer's disease. The first two groups were followed for 3 years, and the Alzheimer’s patients for two. The study found that the extent of white matter hyperintensities (areas of damaged brain tissue typically caused by cardiovascular disease) was an important predictor of cognitive decline.

Participants whose white matter hyperintensities were significantly above average at the beginning of the study lost more points each year in cognitive testing than those whose white matter hyperintensities were average at baseline. Those with mild cognitive impairment or Alzheimer's disease at baseline had additional declines on their cognitive testing each year, meaning that the presence of white matter hyperintensities and MCI or Alzheimer's disease together added up to even faster and steeper cognitive decline.

The crucial point is that this was happening in the absence of major cardiovascular events such as heart attacks, indicating that it’s not enough to just reduce your cardiovascular risk factors to a moderate level — every little bit of vascular damage counts.



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More evidence that older adults become less able to ignore distraction

December, 2010

A new study adds to the evidence that our ability to focus on one thing and ignore irrelevant information gets worse with age, and that this may be a crucial factor in age-related cognitive impairment.

A study involving young (average age 22) and older adults (average age 77) showed participants pictures of overlapping faces and places (houses and buildings) and asked them to identify the gender of the person. While the young adults showed activity in the brain region for processing faces (fusiform face area) but not in the brain region for processing places (parahippocampal place area), both regions were active in the older adults. Additionally, on a surprise memory test 10 minutes later, older adults who showed greater activation in the place area were more likely to recognize what face was originally paired with what house.

These findings confirm earlier research showing that older adults become less capable of ignoring irrelevant information, and shows that this distracting information doesn’t merely interfere with what you’re trying to attend to, but is encoded in memory along with that information.



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70-year-olds smarter than they used to be

November, 2010

Findings from a large Swedish study are consistent with the hypothesis that more education and better healthcare have produced less cognitive impairment in present-day older adults.

Beginning in 1971, healthy older adults in Gothenburg, Sweden, have been participating in a longitudinal study of their cognitive health. The first H70 study started in 1971 with 381 residents of Gothenburg who were 70 years old; a new one began in 2000 with 551 residents and is still ongoing. For the first cohort (born in 1901-02), low scores on non-memory tests turned out to be a good predictor of dementia; however, these tests were not predictive for the generation born in 1930. Those from the later cohort also performed better in the intelligence tests at age 70 than their predecessors had.

It’s suggested that the higher intelligence is down to the later cohort’s better pre and postnatal care, better nutrition, higher quality education, and better treatment of high blood pressure and cholesterol. And possibly the cognitive demands of modern life.

Nevertheless, the researchers reported that the incidence of dementia at age 75 was little different (5% in the first cohort and 4.4% in the later). However, since a substantially greater proportion of the first cohort were dead by that age (15.7% compared to 4.4% of the 2nd cohort), it seems quite probable that there really was a higher incidence of dementia in the earlier cohort.

The fact that low scores on non-memory cognitive tests were predictive in the first cohort of both dementia and death by age 75 supports this argument.

The fact that low scores on non-memory cognitive tests were not predictive of dementia or death in the later cohort is in keeping with the evidence that higher levels of education help delay dementia. We will need to wait for later findings from this study to see whether that is what is happening.

The findings are not inconsistent with those from a very large U.S. national study that found older adults (70+) are now less likely to be cognitively impaired (see below). It was suggested then also that better healthcare and more education were factors behind this decline in the rate of cognitive impairment.

Previous study:

A new nationally representative study involving 11,000 people shows a downward trend in the rate of cognitive impairment among people aged 70 and older, from 12.2% to 8.7% between 1993 and 2002. It’s speculated that factors behind this decline may be that today’s older people are much likelier to have had more formal education, higher economic status, and better care for risk factors such as high blood pressure, high cholesterol and smoking that can jeopardize their brains. In fact the data suggest that about 40% of the decrease in cognitive impairment over the decade was likely due to the increase in education levels and personal wealth between the two groups of seniors studied at the two time points. The trend is consistent with a dramatic decline in chronic disability among older Americans over the past two decades.



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When estrogen helps memory, and when it doesn’t

November, 2010

Recent rodent studies confirm attention and learning is more difficult for women when estrogen is high, but estrogen therapy can help menopausal women — if given during a critical window.

Recent rodent studies add to our understanding of how estrogen affects learning and memory. A study found that adult female rats took significantly longer to learn a new association when they were in periods of their estrus cycle with high levels of estrogen, compared to their ability to learn when their estrogen level was low. The effect was not found among pre-pubertal rats. The study follows on from an earlier study using rats with their ovaries removed, whose learning was similarly affected when given high levels of estradiol.

Human females have high estrogen levels while they are ovulating. These high levels have also been shown to interfere with women's ability to pay attention.

On the other hand, it needs to be remembered that estrogen therapy has been found to help menopausal and post-menopausal women. It has also been found to be detrimental. Recent research has suggested that timing is important, and it’s been proposed that a critical period exists during which hormone therapy must be administered if it is to improve cognitive function.

This finds some support in another recent rodent study, which found that estrogen replacement increased long-term potentiation (a neural event that underlies memory formation) in young adult rats with their ovaries removed, through its effects on NMDA receptors and dendritic spine density — but only if given within 15 months of the ovariectomy. By 19 months, the same therapy couldn’t induce the changes.




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