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• W2097397301 abstract "It has been widely assumed that coronary artery bypass grafting (CABG) is associated with cognitive decline. Nevertheless, attempts to quantify these changes with neuropsychological tests have led to highly variable results. For example, the reported incidence of cognitive decline among patients evaluated shortly before hospital discharge has ranged from 14% to a high of 48% [1van Dijk D. Keizer A.M. Diephuis J.C. et al.Neurocognitive dysfunction after coronary artery bypass surgery a systematic review.J Thorac Cardiovasc Surg. 2000; 120: 632-639Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar]. Similar wide variations are reported at later follow-up time points. The source of this variability has been attributed to a variety of factors, including between-study differences in subject selection criteria, postsurgical follow-up times, and the number and sensitivity of neuropsychological tests used to measure cognitive change. A major limitation of these studies, including our own [2McKhann G.M. Goldsborough M.A. Borowicz Jr, L.M. et al.Cognitive outcome after coronary artery bypass a one-year prospective study.Ann Thorac Surg. 1997; 63: 510-515Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar], is that most did not compare the incidence of postoperative cognitive decline among CABG patients to that observed in a control group (ie, either healthy persons or those with similar degrees of cardiovascular and cerebrovascular disease). In the absence of a control group, the criterion for cognitive decline must be based on an arbitrary measure of change within the study population. In early studies, a decline of 1 standard deviation decrease from baseline in 20% of tests was commonly used [3Mahanna E.P. Blumenthal J.A. White W.D. et al.Defining neuropsychological dysfunction after coronary artery bypass grafting.Ann Thorac Surg. 1996; 61: 1342-1347Abstract Full Text PDF PubMed Scopus (238) Google Scholar]. More recently a 20% decline in 20% of neuropsychology tests has been used [4van Dijk D. Jansen E.W. Hijman R. et al.Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery a randomized trial.JAMA. 2002; 287: 1405-1412Crossref PubMed Scopus (451) Google Scholar]. Mahanna and colleagues [3Mahanna E.P. Blumenthal J.A. White W.D. et al.Defining neuropsychological dysfunction after coronary artery bypass grafting.Ann Thorac Surg. 1996; 61: 1342-1347Abstract Full Text PDF PubMed Scopus (238) Google Scholar] applied five such arbitrary criteria for decline to the same data set, and found that the incidence of cognitive decline at 6 weeks after surgery ranged from a low of 1% to a high of 34% depending on which criterion was used [3Mahanna E.P. Blumenthal J.A. White W.D. et al.Defining neuropsychological dysfunction after coronary artery bypass grafting.Ann Thorac Surg. 1996; 61: 1342-1347Abstract Full Text PDF PubMed Scopus (238) Google Scholar]. They concluded that the “large variation in the reported incidence of cognitive decline after CABG can be attributed to the different criteria used to define impairment.” Although the findings of Mahanna and colleagues [3Mahanna E.P. Blumenthal J.A. White W.D. et al.Defining neuropsychological dysfunction after coronary artery bypass grafting.Ann Thorac Surg. 1996; 61: 1342-1347Abstract Full Text PDF PubMed Scopus (238) Google Scholar] were published more than a decade ago, some contemporary studies of cognitive outcomes after CABG have continued to rely on fixed, arbitrary definitions of cognitive decline, such as 20% decline in 20% of tests [5Hammon J.W. Stump D.A. Butterworth J.F. et al.Single cross clamp improves 6-month cognitive outcome in high-risk coronary bypass patients the effect of reduced aortic manipulation.J Thorac Cardiovasc Surg. 2006; 131: 114-121Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar]. However, it is less appreciated that any estimates of the incidence of postoperative cognitive decline after CABG are essentially uninterpretable unless reference is made to a control group. A recent example is the reanalysis of data from the Octopus Study group, which originally used the 20% decline on 20% of the tests criterion in the analysis of cognitive change after conventional and off-pump CABG [4van Dijk D. Jansen E.W. Hijman R. et al.Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery a randomized trial.JAMA. 2002; 287: 1405-1412Crossref PubMed Scopus (451) Google Scholar]. Because this was a randomized trial, nonsurgical controls were not included. In their original analysis, 31% of the CABG patients were classified as having decline at 3 months. In a follow-up to this study, they recruited healthy controls not undergoing surgery and applied the same criteria for decline, and it was found that an unexpected 28% of these normal controls also met this criterion for decline [6Keizer A.M. Hijman R. Kalkman C.J. et al.The incidence of cognitive decline after (not) undergoing coronary artery bypass grafting the impact of a controlled definition.Acta Anaesthesiol Scand. 2005; 49: 1232-1235Crossref PubMed Scopus (68) Google Scholar]. Using a more conservative definition to define decline, they then compared their original CABG group with this control group and found at 3 months that 7.7 % of the CABG and 4.6% of the controls were classified as having decline. These authors conclude that their previous use of the 20% decline of 20% of test criteria had thus greatly overestimated the incidence of cognitive decline after CABG. We expand on the findings just mentioned by illustrating the effects of applying the arbitrary criterion of 20% decline on one or more tests to previously published data from our prospective study of cognitive outcomes comparing CABG and nonsurgical controls with coronary artery disease and heart-healthy controls (without risk factors for coronary artery disease) [7McKhann G.M. Grega M.A. Borowicz Jr, L.M. et al.Is there cognitive decline 1 year after CABG? Comparison with surgical and nonsurgical controls.Neurology. 2005; 65: 991-999Crossref PubMed Scopus (73) Google Scholar]. The results clearly demonstrate that there is considerable variability (both improvement and decline) in the follow-up test performance even for the control subjects without surgery. Therefore, in the absence of a control group, this normal variability associated with follow-up cognitive testing might have been incorrectly attributed to surgery-related cognitive decline. Figure 1 displays box plots of the within-subject changes in z-scores from 3 to 12 months by study group: CABG, nonsurgical control, and heart-healthy control for the cognitive domains of memory and a global domain score. Whereas there are both decliners and improvers in all study groups, previous detailed analyses of these data have shown there is little or no evidence of a disproportionate decline in cognitive performance in the CABG group relative to the controls [7McKhann G.M. Grega M.A. Borowicz Jr, L.M. et al.Is there cognitive decline 1 year after CABG? Comparison with surgical and nonsurgical controls.Neurology. 2005; 65: 991-999Crossref PubMed Scopus (73) Google Scholar]. Table 1 shows the percentage of patients in the CABG, nonsurgical control group, and heart-healthy control group who have declined or improved by more than 20% on at least 1, 2, 3, or 4 (of a total of 16) cognitive measures. Whether a participant is classified as having decline or improvement depends critically on the number of tests required to change from baseline, the amount each must change, and the total number of tests administered. As the number of tests decreases, the fraction that meets criteria for “change” increases dramatically in all of the study groups. About one-half of the participants in the CABG and nonsurgical control group meet criteria for decline if we require a 20% decrease in test performance on 2 of 16 subtests. In contrast, nearly three quarters meet criteria for improvement by this definition. This comparison emphasizes the risks of relying on one of the commonly used definitions of decline, 20% decline in 20% of tests. Even when the overall distribution of cognitive scores is unchanged with time, as it is in the present data set, this methodology identifies a substantial number of patients and controls who will be classified as having declined.Table 1Percentage of Study Participants With Decline or Improvement of 20% or Greater From 3 to 12 Months on at Least 1, 2, 3, or 4 of a Total of 16 Cognitive SubtestsNumber of TestsDeclinedImprovedCABGNSCHHCCABGNSCHHC1778459899186253493867746733128165546394151105322723CABG = coronary artery bypass grafting (n = 110); HHC = heart-healthy controls (n = 64); NSC = nonsurgical controls (n = 85). Open table in a new tab CABG = coronary artery bypass grafting (n = 110); HHC = heart-healthy controls (n = 64); NSC = nonsurgical controls (n = 85). There are several factors that may contribute to variability in follow-up neuropsychological test performance. In the context of CABG, a factor that may be expected to produce decline with time is progression of underlying cerebrovascular disease, whereas a factor that may be expected to result in improvement with time is the “practice effect,” whereby participants improve their performance as a result of repeated exposure to the same neuropsychological tests. It is likely that the degree of variability depends on the demographics and medical risk factor profile of the patient group under study, and it is therefore necessary to include a comparable group of “external” controls as a reference group. The choice of the most appropriate control group will depend on the specific research question being asked. Because both the CABG and nonsurgical controls have known risk factors for cerebrovascular disease, it is possible that the patients whose scores declined with time had progression of their underlying vascular disease. To control for this, we also included a control group that we designated as heart-healthy; these subjects had no known risk factors for vascular disease. The distribution of within subject change scores from 3 to 12 months in the heart healthy controls is remarkably similar to that of the two other groups, supporting the interpretation that the underlying mechanism is test-retest variability rather than disease-related decline. With the same longitudinal data set that is used in this report, more appropriate and powerful analyses to compare the trends in cognitive function between surgical and nonsurgical intervention groups have been discussed by Barry and colleagues [8Barry S.J. Zeger S.L. Selnes O.A. et al.Quantitative methods for tracking cognitive change 3 years after coronary artery bypass surgery.Ann Thorac Surg. 2005; 79: 1104-1109Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar]. Rather than creating a binary response of decline versus no decline for each subject, more of the available information was used by analyzing the numerical trends in the test scores themselves. Random effects regression models estimated the difference in the temporal trend between study groups, taking account of practice effect and heterogeneity among subjects in the levels and trends of their scores. In this way, all of the available information was used without discarding parts of it, as would have been the case if the individual trends had been dichotomized into decline or no decline. There are continuing reasons to monitor the association of CABG with possible postoperative cognitive change. First, the technology associated with CABG is constantly changing, and the efficacy of these changes in terms of cognitive outcomes should be determined. Second, there is increasing use of other interventions for coronary artery disease, such as “off-pump” CABG and coronary artery stenting procedures. Studies to compare the efficacy as well as comparison of the rates of adverse cognitive outcomes of these alternate approaches to coronary artery disease are needed. Finally, these cardiac interventions provide an opportunity for evaluation of possible neuroprotective agents. If changes in cognition are to be part of this outcome research, the expression of both decline and improvement in cognition should be included, as well as comparison with appropriate control groups. Without these comparisons, estimates of cognitive decline are greatly overestimated, and virtually uninterpretable. This study was supported by Grant No. 35610 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, by the Charles A. Dana Foundation, New York, NY, and the Johns Hopkins Medical Institution GCRC Grant No. RR 00052. We thank Maura Grega, Louis Borowicz, Jr, Maryanne Bailey, and Pamela Talalay for their help during the preparation of this manuscript." @default.
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• W2097397301 title "Defining Cognitive Change After CABG: Decline Versus Normal Variability" @default.
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