Small but continuous progress in the research of preoperative and postoperative cognitive dysfunction

Abstract

This Invited Commentary accompanies the following articles: • Hudetz JA, Patterson KM, Pagel PS. Comparison of pre-existing cognitive impairment, amnesic mild cognitive impairment, and multiple domain mild cognitive impairment in men scheduled for coronary artery surgery. Eur J Anaesthesiol 2012; 29:320–325. • Erdogan MA, Demirbilek S, Erdil F, et al. The effects of cognitive impairment on anaesthetic requirement in the elderly. Eur J Anaesthesiol 2012; 33:326–331. • Kamer AR, Galoyan SM, Haile M, et al. Meloxicam improves object recognition memory and modulates glial activation after splenectomy in mice. Eur J Anaesthesiol 2012; 29:332–337. Postoperative cognitive dysfunction (POCD) is an important complication which affects more than 10% of patients over the age of 60 years1 and contributes to postoperative mortality and premature unemployment.2 In cardiac surgery, preoperative factors such as advanced age, lower levels of education, previous cerebral disease, severe atherosclerotic disease and other co-morbid diseases, intraoperative factors such as number of emboli, duration of low arterial pressure, temperature and stress response, and postoperative factors such as temperature and arrhythmias all increase vulnerability to POCD.3 In noncardiac surgery, increasing age, lower levels of higher education, previous cerebrovascular injury, duration of anaesthesia, postoperative respiratory complications and infections, and multiple operations all increase the risk of POCD.1,4 Researchers are currently investigating several neuroprotective drugs, but consistent benefits for the prevention and treatment of POCD have yet to be demonstrated. To date, age is the most robust and consistent risk factor associated with higher cognitive decline in the postoperative period.5,6 Surgery appears to trigger brain atrophy in patients with mild cognitive impairment.7,8 Thus, older patients who show mild preoperative cognitive impairment not only have a high prevalence of undergoing surgery but also have more difficulties in recovering after anaesthesia.9 Erdogan et al.10 found similar results, in that mild cognitive preoperative impairment was associated with impaired postoperative cognitive outcome. Moreover, they suggested that, in this specific population, the simplified electroencephalogram monitoring technique of bispectral index (BIS) was not helpful when using traditional cut-off criteria to estimate the ‘depth’ of general anaesthesia and that potential drug overdosing with longer postoperative eye-opening time can be observed even when using this monitor. The authors assessed POCD with the Mini Mental State Examination (MMSE), a traditional instrument in clinical medicine. However, the MMSE is limited in the assessment of cognitive functioning. It is a screening instrument used to separate patients with cognitive impairment from those without, but it does not differentiate between different cognitive domains well enough to identify which cognitive processes are impaired and to what extent. Furthermore, the instrument relies heavily on verbal responses, reading and writing. Consequently, patients with auditory problems, visual problems, communication problems or low socio-economic status may perform poorly on the MMSE even if they are cognitively intact. Although many of the studies on POCD have used the MMSE (it is economical to administer), this is insufficient for research purposes. A fuller neuropsychological evaluation will be much more effective in parsing out diverse and related domains of cognitive functioning (e.g. language and memory), identifying areas of cognition which are influenced by hypnotic medication or opioid agonists administered intraoperatively and enabling recognition of certain confounding variables, such as the influence of hypnotics on processing speed (which, in turn, affects a variety of other cognitive functions). Therefore, results of studies that use the MMSE as the only instrument to measure cognitive functioning have to be interpreted with caution. Hudetz et al.11 investigated different classifications for clinically relevant preoperative cognitive dysfunction. Unsurprisingly, they observed that different classifications (i.e. composites) for cognitive dysfunction resulted in different predictors of cognitive dysfunction. Newman et al.12 found similar results in their systematic review of POCD after noncardiac surgery in that the diagnosis (POCD or not) changed in accordance with the definitions of the diagnosis (e.g. different composite scores). Clinicians may find these definitions confusing and unsatisfying, but they underline the need for further research to find an agreement on the definition of a common outcome such as POCD. A minimal set of preoperative and postoperative neuropsychological measures should be defined which assess overall cognitive ability, verbal and nonverbal (e.g. visual) short-term and long-term memory, working memory and executive function (e.g. verbal fluency), ideally with clearly identified cut-off scores for tests which are included in the battery. Hudetz et al.11 were able to observe neuropsychological differences between patients scheduled for coronary artery bypass grafts and those who were not, particularly in immediate and delayed story recall, which are forms of verbal declarative memory. This finding may offer a different view to those of previous investigations, which found verbal memory to be particularly sensitive in detecting postoperative cognitive dysfunction.13 Interestingly, only mild cognitive impairment with amnesia was associated with depression, in consistent with the existing literature which suggests that depression is an important variable when investigating general cognitive function. Recent studies show that depression consistently predicts cerebrovascular disease if untreated. Selective serotonin reuptake inhibitors (SSRIs) help to diminish this correlation even if the SSRI does not directly influence the person's depression. However, antidepressants are known to affect cognitive function, especially processing speed.14,15 These results underline the necessity and the importance of the inclusion of the psychiatric and medical history of the patient. It may be clinically relevant to further investigate different cognitive domains (e.g. memory, executive function) along with the patient's history (e.g. depression). Although composite scores can be useful, an explanation of the reasoning behind the specific composite would be necessary to understand and interpret the results. Recent animal studies have shown that splenectomy16 and orbital surgery17 induce neuroinflammation with direct effects on the cognition of the animal. Kamer et al.18 reported improvement in object memory recognition after surgery following administration of the nonsteroidal anti-inflammatory drug meloxicam to mice. A high dose of meloxicam administered 24 h after surgery avoided delayed POCD and preserved object recognition, possibly by inhibiting surgery-induced glial activation. This is an interesting finding because it raises the question of whether this cyclo-oxygenase-2 inhibitor could also prevent at least object recognition difficulties after surgery in humans. It will be important to determine whether this drug improves performance in other cognitive domains. Many elderly patients benefit from anaesthesia, and the proportion will increase in the coming years as the population ages. Therefore, research into POCD is important, for instance to identify patients at risk preoperatively. Clinicians could identify patients with decreased cognitive reserve via screening instruments, and specialists would then utilise standardised and validated instruments with appropriate cut-offs to determine the presence or absence of cognitive dysfunction. Optimal preparation for the perioperative course of these older patients at risk might involve, potentially, less invasive surgery, less hypnotics and less opioids, and the use of anti-inflammatory drugs. Each of the three studies published in this issue of the Journal provides us with interesting results to help the reduction of POCD and each emphasises the importance of neuropsychological assessment. Acknowledgements B.W. received support from the Swiss National Foundation (SNF; K-23K1–122264/1), Swiss Accident Company and the Bangerter-Rhyner Foundation. The funding agencies had no role in the preparation, review or approval of the manuscript. The authors have no conflict of interest. This article was checked and accepted by the Editors, but was not sent for external peer-review.