Post-surgery cognitive decline

Data from 3,105 older adults (65+) who had either heart surgery or cardiac catheterization has found that those who had heart surgery didn’t experience much greater cognitive decline compared with those who had the much less invasive, catheter-based procedure.

Two years after the surgery, surgery participants showed a greater amount of decline equal to only 4.6 months of cognitive aging compared with those undergoing catheterization.

Unplanned hospitalizations accelerate cognitive decline in older adults

Data from the Rush Memory and Aging Project has found that emergency and urgent hospitalizations are associated with an increased rate of cognitive decline in older adults.

Non-elective hospitalizations were associated with an approximately 60% acceleration in the rate of cognitive decline from before hospitalization. Elective hospitalizations, however, were not associated with acceleration in the rate of decline at all.

Of the 930 participants (average age 81), 613 were hospitalized at least once over an average of almost five years of observation. Of those who were hospitalized, 260 (28%) had at least one elective hospital admission, and 553 (60%) had at least one non-elective hospital admission. These groups included 200 participants (22%) who had both types of hospitalizations.

The data was presented at the Alzheimer's Association International Conference in London on July 17.

Inflammation triggered by brain's own immune cells behind post-surgical decline

There is growing evidence that inflammation might be responsible for the cognitive decline seen in many older adults after surgery. Now a mouse study provides evidence that brain inflammation and cognitive decline following surgery are triggered by the brain's microglia.

When mice had their microglia temporarily depleted before surgery, they didn’t show any cognitive decline several days after surgery. They also had much lower levels of inflammatory molecules in the hippocampus. Controls — those not receiving the experimental drug to deplete microglia to around 5% of normal levels — did typically show a drop in cognitive performance.

Microglia levels returned to normal within two days after the treatment was stopped, and there was no sign of any impairment in surgical wound healing as a result of the intervention.

Delirium in older patients after surgery linked to long-term cognitive decline

A 3-year study looking at short-term and long-term cognitive decline in older patients following a surgery found that those who experienced delirium after the surgery showed significantly greater decline than those who didn’t suffer such post-surgical confusion.

The study involved 560 patients (70+), of whom 134 experienced delirium. Both groups showed a significant cognitive decline at one month, followed by a return to their previous level of cognitive function at two months and then a gradual decline for the next 34 months. However, the rate of decline over the three year follow-up was not significant for those who hadn’t experienced delirium.

Those who suffered delirium also had significantly lower cognitive function before surgery.

The odd finding that even the delirium group recovered their cognitive function at two months, before once again declining, suggests that something about the delirium triggers a cascade of events which leads to progressive, long-lasting effects.

Who’s more likely to develop delirium after surgery?

Delirium after surgery can lead to long-term cognitive decline in older adults — but not always. So what makes the difference?

A preliminary study involving 126 older adults suggests the answer lies in their cognitive function before surgery. Their global cognition score explained the most variation, with other significant factors including: IQCODE score, cognitive independent activities of daily living impairment, living alone, cerebrovascular disease, Charlson comorbidity index score, and exhaustion level. Taken together, these factors explained 32% of the variation in people’s outcome.

Delirium, an acute state of confusion, is a common condition affecting up to 50% of hospitalized older adults.

Certain leisure activities may reduce post-surgical delirium among older adults

A study of 142 older adults who underwent elective surgery found that greater participation in cognitive activities was linked with a lower incidence and lower severity of delirium.

Nearly a third of the patients (average age 71) developed post-operative delirium. Those who did had participated in fewer leisure activities before surgery compared with people who didn't experience delirium.

Out of all the activities, reading books, using email, and playing computer games reduced the risk of delirium. Playing computer games and singing were the only two activities that predicted lower severity of delirium.

The protection afforded was dose-dependent, with each additional leisure activity reducing post-operative delirium by 8%.

Because long-term cognitive decline can occur in some older adults after undergoing surgery, there has been some concern that exposure to anesthesia may be associated with increased dementia risk. It is therefore pleasing to report that data from the very large, long-running Mayo Clinic Study, the Rochester Epidemiology Project, has found that receiving general anesthesia for procedures after age 45 is not a risk factor for developing dementia.

[3409] Sprung, J., Jankowski C. J., Roberts R. O., Weingarten T. N., Aguilar A. L., Runkle K. J., et al.
(Submitted).  Anesthesia and Incident Dementia: A Population-Based, Nested, Case-Control Study.
Mayo Clinic Proceedings.

In the first mouse study, when young and old mice were conjoined, allowing blood to flow between the two, the young mice showed a decrease in neurogenesis while the old mice showed an increase. When blood plasma was then taken from old mice and injected into young mice, there was a similar decrease in neurogenesis, and impairments in memory and learning.

Analysis of the concentrations of blood proteins in the conjoined animals revealed the chemokine (a type of cytokine) whose level in the blood showed the biggest change — CCL11, or eotaxin. When this was injected into young mice, they indeed showed a decrease in neurogenesis, and this was reversed once an antibody for the chemokine was injected. Blood levels of CCL11 were found to increase with age in both mice and humans.

The chemokine was a surprise, because to date the only known role of CCL11 is that of attracting immune cells involved in allergy and asthma. It is thought that most likely it doesn’t have a direct effect on neurogenesis, but has its effect through, perhaps, triggering immune cells to produce inflammation.

Exercise is known to at least partially reverse loss of neurogenesis. Exercise has also been shown to produce chemicals that prevent inflammation. Following research showing that exercise after brain injury can help the brain repair itself, another mouse study has found that mice who exercised regularly produced interleukin-6 (a cytokine involved in immune response) in the hippocampus. When the mice were then exposed to a chemical that destroys the hippocampus, the interleukin-6 dampened the harmful inflammatory response, and prevented the loss of function that is usually observed.

One of the actions of interleukin-6 that brings about a reduction in inflammation is to inhibit tumor necrosis factor. Interestingly, I previously reported on a finding that inhibiting tumor necrosis factor in mice decreased cognitive decline that often follows surgery.

This suggests not only that exercise helps protect the brain from the damage caused by inflammation, but also that it might help protect against other damage, such as that caused by environmental toxins, injury, or post-surgical cognitive decline. The curry spice cucurmin, and green tea, are also thought to inhibit tumor necrosis factor.

A study involving 200 older adults (70+) experiencing a stay in hospital has found that at discharge nearly a third (31.5%) had previously unrecognized low cognitive function (scoring below 25 on the MMSE if high-school-educated, or below 18 if not). This impairment had disappeared a month later for more than half (58%).The findings are consistent with previous research showing a lack of comprehension of discharge instructions, often resulting in rehospitalization.

The findings demonstrate the effects of hospitalization on seniors, and point to the need for healthcare professionals and family to offer additional support. It’s suggested that patient self-management may be better taught as an outpatient following discharge rather than at the time of hospital discharge.

Sleep disruption and stress are presumed to be significant factors in why this occurs.

Major surgery often produces cognitive dysfunction, usually temporary, but for some, long-lasting. It has been suggested that the problem might have to do with the immune system's inflammatory response. A new mouse study provides more evidence for this.

The study found that giving the mice a common inhibitor of the inflammatory response (anti-tumor necrosis factor (TNF) antibody), before orthopedic surgery, decreased postoperative cognitive decline. It’s hoped human clinical testing of this approach will begin within a year.

Interestingly, the curry spice curcurmin, and catechins found in green tea, are also said to inhibit the tumor necrosis factor. Both of these have been implicated in reducing dementia and age-related cognitive impairment.

An implantable cardioverter defibrillator (ICD) is a small electronic device that monitors and regulates heartbeat, and many have been implanted in patients — an estimated 114,000 in the U.S. in 2006. Part of the implantation process involves ventricular defibrillation testing, which temporarily disrupts brain activity by causing a drop in blood pressure and blood flow to the brain. In a study involving 52 patients having cognitive tests several days before ICD surgery and again six weeks and six and 12 months afterwards, more than a third of participants had significant cognitive problems six weeks and six and 12 months after ICD surgery. Attention, short-term memory of visual words and objects, and auditory (spoken) words were most commonly affected. Although most patients regained their normal abilities by 12 months after surgery, a few (10%) first developed difficulties at that point. The results were unrelated to measurements of anxiety, depression and quality of life.

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