This review identified 62 studies that assessed POCD after cardiac surgery and examined the adherence to the recommendations of the Consensus Statement that was published in 1995.7
We found significant variability in the neuropsychological tests and the timing of the tests used to measure POCD. Most batteries covered the domains of attention and verbal memory, while motor function was measured less frequently. Half of studies assessed anxiety or depression and a few accounted for the learning effect. Consequently, standard analytic criteria for POCD did not emerge, indicating that the Consensus Statement guidelines are not widely accepted or applied. The resultant heterogeneity in how POCD is measured and defined may limit the ability to compare POCD outcomes across studies and possibly impede progress in the field.
Studies of cardiac surgery have inherent variability because of patient factors (age, education, comorbidity), cardiac surgery factors (hypothermia, cardiopulmonary bypass, cross clamp, bleeding), physiologic factors (inflammation, microembolization, blood brain barrier function), intraoperative factors (anesthesia, cerebral oxygenation, hypotension), perioperative factors (medication, sleep, complications), and postoperative factors (rehabilitation, depression, social supports). Identifying POCD in patients becomes more difficult when variable measurement of cognitive function with different neuropsychological tests and multiple analytic criteria are utilized. Thus, confronted with two POCD studies with different results, it is difficult to know whether the differences are substantive or simply related to how POCD is measured and defined. Development of standardized criteria for neuropsychiatric conditions such as delirium17
, Alzheimer’s disease18
, and depression19
has allowed clinical and basic science research in these conditions to progress.
Ultimately, using standardized criteria creates a dichotomous definition of POCD. In this review, we found that recent studies analyze and report both a dichotomous definition and a continuous/summary measure of cognitive function. While calculation of a dichotomous definition has clinical applicability, it reduces statistical power in the study. Additionally, the mechanism of how multiple neuropsychological tests are combined into a single measure of cognitive function remains the subject of a debate because of the cognitive domain overlap of neuropsychological tests, the method of combination (e.g. mean/sum of Z-scores, confirmatory factor analysis, etc), and the impact of learning. Thus, it may be timely to utilize the wealth of evidence from recent studies to revisit measurement methods and definitions for POCD.
Importantly, the data from the studies identified in this review can play a key role in the development of a standardized battery and analytic criteria for POCD, which can address the challenges associated with POCD in several ways. First, each neuropsychological test measures more than one cognitive domain (e.g. Performance on Trailmaking requires attention as well as working memory and motor skills) and thus, the tests are highly correlated. As a result, impairment in one cognitive domain may have effects on tests that predominantly measure other cognitive domains (e.g. Impaired psychomotor skill will affect performance on Trailmaking, independent of attention or working memory). Using previous studies, a standardized cognitive battery would define the degree of contribution of a neuropsychological test to each cognitive domain and ensure adequate coverage of all appropriate cognitive domains. Second, the information about floor effects (i.e. poor initial performance which cannot decline) 20
and ceiling effects (i.e. excellent initial performance which cannot improve) can be obtained from the current literature and used to optimize selection of neuropsychological tests to detect clinically significant change.21
Third, learning effects can be measured and factored into a standardized neuropsychological battery and analytic criteria for POCD.15,22,23
The learning effect occurs because repeated administration of tests increases the knowledge of the test structure and thus, performance tends to improve with repeated administration. Fourth, a standardized battery would help define the test-retest reliability of the neuropsychological tests. Reliable neuropsychological tests are important to reduce regression to the mean, where performance at the extreme (high or low) will tend to move toward the mean on repeat testing.24
Finally, using the current literature, the contribution of individual variability vs. true change would likely be better characterized.20,21
For example, neuropsychological performance can be affected by factors not related to cognitive function (i.e. sleep the night prior, frustration of commute to testing center, or fatigue towards the end of testing). The current literature could be used to establish normative values for defining significant change. Ultimately, this change definition would need to be validated against a change in social or occupational function to demonstrate that it was clinically significant.
The development and validation of a standardized neuropsychological battery and analytic criteria could help advance POCD to the level of a clinical disorder by improving efficiency of measurement, identifying patients at high risk, and ensuring clinical meaning of the outcome. If POCD were more easily operationalized, smaller physician groups would be empowered to measure POCD to improve operative technique, anesthesia protocols, and perioperative care without requiring external funding to conduct a research study (reimbursement for cognitive testing may be necessary). A standardized battery and criteria would also be a boon to research in this area. For example, when standardized criteria for delirium were developed17
the number of research studies published on delirium increased by over 100% in the subsequent 10 years compared to the 10 years prior.
In conclusion, using the recommendations of the1995 Statement of Consensus on Assessment of Neurobehavioral Outcomes after Cardiac Surgery as a framework, the present systematic literature review identified 62 unique studies of POCD and analyzed the adherence to these recommendations. While the cognitive domains of attention and memory are included in nearly all studies, there is significant variability in the coverage of other cognitive domains and in the individual neuropsychological tests used to measure POCD. Moreover, no standard analytic criteria for POCD have emerged. This heterogeneity limits the ability to compare POCD amongst studies. A unified battery and analytic criteria would improve comparability, address measurement challenges such as learning, floor, and ceiling effects, and ultimately, advance science in this field by allowing clinicians and investigators to develop a better understanding of the causes of POCD and thereby to develop strategies for its prevention or treatment.