In this study there was no evidence of a long-term effect on cognitive function independently attributable to surgery or major illness. While almost a quarter of nondemented participants progressed to a CDR greater than zero during the course of the study, the risk of progression was not greater in the surgery or illness groups. This study also included people with mild dementia. As expected, there was an accelerating long-term downward course for the demented people; however, the rate of that decline was not affected by the occurrence of a surgical or medical event.
This study is different in several respects from other studies focusing on postoperative cognitive decline, most notably in its collection of pre-event data and the use of modern techniques of longitudinal data analysis, similar to those used by Selnes and colleagues.19
Without good evidence, it has been proposed that psychometric scores of surgical patients should be adjusted based on an average learning effect among a healthy, non-surgical control group, and further that POCD may be diagnosed based on a statistically defined threshold for this corrected psychometric score.1,2,10
This approach implies that the learning effect is similar in magnitude and variability in both surgical and non-surgical groups, that a smaller learning effect is evidence for cognitive decline, and that POCD is a binary outcome. Our method using participants in the ADRC avoided the pitfalls of defining POCD using arbitrary thresholds, of adjusting for a learning effect using untested assumptions, and of not assessing cognitive trends prior to the event. Remarkably, even the nondemented participants who did not have surgery or a major illness had a downward change in tests of cognitive function after a simulated event, emphasizing the danger of untested statistical assumptions.
The inclusion of demented individuals, especially those in the very mild stage of dementia, provides one potential explanation for why our conclusions differ from those of previous studies. Our results clearly demonstrate a downward longitudinal course in very mildly demented people prior to surgery or major illness comparable with that of very mildly demented people who do not experience such events. Two-thirds of these people would have been included in other studies as nondemented given that their Mini Mental Status Exam scores were not below a commonly used threshold. Because longitudinal assessments were not available for these people in other studies, their downward course could have been inappropriately attributed to surgery rather than to the existing dementia. More sensitive screening tests than the Mini Mental Status Exam, like the AD-830,31
or the recently described score for detecting subtle neurological abnormalities32
, would be more likely to detect patients with early dementia or other neurological abnormalities. Interestingly, other retrospective clinical studies that have specifically examined the impact of surgery on Alzheimer's disease have also not demonstrated an association between surgery or anesthesia and the risk of Alzheimer's disease exacerbation or the onset of dementia.33-35
Further, a retrospective, population-based, Dutch cross-sectional study also found no support for the notion that a history of an operation is a determinant or independent risk factor for accelerated age-related subtle cognitive decline.36
This study has several important limitations: (1) A limitation common to all studies of POCD is the difficulty in matching people undergoing surgery with appropriate controls.14
One of the strengths of our study is that participants in the surgery and illness groups were included in the study substantially prior to these events. Nonetheless, we cannot conclude that they were well matched with the control participants, who did not have a surgery or major illness. Further, hospital admission may be a poor surrogate for determining major illness. (2) Patients with early POCD might be more likely to die in the year following surgery2
and this could mask the detection of long-term POCD in any study. Participants who died prior to a first post-event (surgery or illness) assessment and those who did not present for follow-up owing to ill health would not have been included in our sample. Thus, we cannot comment on the possible confounding effect of early death or poor health on the detection of long-term POCD. Nonetheless, it is unlikely that the majority of people with cognitive decline die within the first year of surgery2,5
or illness, so it is improbable that exclusion of people who died early would completely mask the detection of long-term cognitive decline. (3) Cognitive decline has been found to persist for up to 3 months following non-cardiac surgery.1,2
Although this study did not demonstrate long-term cognitive decline attributable to surgery or illness, early cognitive decline with subsequent recovery could not be assessed because participants were only assessed at annual intervals and the timing of cognitive tests in relation to surgery and illness was variable. It is important to emphasize that this study could not determine how short-term changes in cognition may have impacted the general well being of older subjects. (4) The heterogeneity of surgeries and illnesses in our study presents another possible limitation; cognitive decline may only occur following certain surgeries and illnesses, thus diluting the observed effect size.13
Nevertheless, because of the inclusion of surgeries and illnesses typically experienced by a cohort of elderly people, the results of this study can be readily generalized. Moreover, the results of the study were not altered when the 41 participants who had less invasive surgeries (hand surgery, minor GI surgery, breast surgery, and other ) were excluded from the general linear mixed effects model. (5) The relatively higher education of participants in the ADRC and their presumed greater motivation level, as reflected by participation in a voluntary, longitudinal research endeavor, represents another potential limitation.
While our study did not address cognitive decline following cardiac surgery, it is notable that a recent study with long-term follow-up after open heart surgery, using a similar statistical approach and appropriate controls, was also unable to demonstrate persistent cognitive decline independently attributable to the surgery or the use of cardiopulmonary bypass.19
Although it is not known whether the patients received general or regional anesthesia, the type of anesthesia has not been shown in previous studies to influence the likelihood of postoperative cognitive decline.4,13,18
If cognitive decline following non-cardiac surgery were both common and debilitating, this would have major public health implications. It would imply that alternatives to surgery should be pursued for elderly people and that stringent efforts should be pursued to determine who is vulnerable to this complication and how it may be prevented. If cognitive decline were not common, long lasting, or severe, this would suggest that elderly people could be reassured and that surgery could proceed, based on the need for surgery and the patients' general health. In this study of subjects having a mixture of surgical procedures, long-term cognitive decline attributable to non-cardiac surgery was not evident. With mounting animal evidence implicating POCD as a real phenomenon6-9
, coupled with long term outcome studies associating POCD with increased mortality2,5
, it is now imperative to conduct properly designed and appropriately powered studies with meaningful clinical endpoints to determine whether any specific
surgery, anesthetic technique, or patient characteristic might be independently associated with long-term postoperative cognitive decline.