Quantitative methods for tracking cognitive change 3 years after coronary artery bypass surgery: a comparison of on-pump CABG and non-surgical controls

The analysis and interpretation of change in cognitive function test scores after coronary artery bypass grafting (CABG) present considerable statistical challenges. Application of hierarchical linear statistical models can estimate the effects of a surgical intervention on the time course of multiple biomarkers. We use an "analyze then summarize" approach whereby we estimate the intervention effects separately for each cognitive test and then pool them, taking appropriate account of their statistical correlations. The model accounts for dropouts at follow-up, the chance of which may be related to past cognitive score, by implicitly imputing the missing data from individuals' past scores and group patterns. We apply this approach to a study of the effects of CABG on the time course of cognitive function as measured by 16 separate neuropsychological test scores, clustered into 8 cognitive domains. The study includes measurements on 140 CABG patients and 92 nonsurgical controls at baseline, and at 3, 12, and 36 months. Our "analyze then summarize" method allows us to identify differences between the treatment groups in individual tests as well as in aggregate measures. It takes into account the correlation structure of the data and thereby produces more precise results than summarizing before analyzing. The methods used have application to a wide range of intervention studies in which multiple biomarkers are followed over time to quantify health effects. Software to implement the methods in the R statistical package is available from the authors at http://www.biostat.jhsph.edu/sbarry/software/ATSrcode.pdf

Self-reported memory symptoms with coronary artery disease: a prospective study of CABG patients and nonsurgical controls

<p>Objective: Subjective memory complaints are common after coronary artery bypass grafting (CABG), but previous studies have concluded that such symptoms are more closely associated with depressed mood than objective cognitive dysfunction. We compared the incidence of self-reported memory symptoms at 3 and 12 months after CABG with that of a control group of patients with comparable risk factors for coronary artery disease but without surgery.</p> <p>Methods: Patients undergoing CABG (n = 140) and a demographically similar nonsurgical control group with coronary artery disease (n = 92) were followed prospectively at 3 and 12 months. At each follow-up time, participants were asked about changes since the previous evaluation in areas of memory, calculations, reading, and personality. A Functional Status Questionnaire (FSQ) and self-report measure of symptoms of depression (CES-D) were also completed.</p> <p>Results: The frequency of self-reported changes in memory, personality, and reading at 3 months was significantly higher among CABG patients than among nonsurgical controls. By contrast, there were no differences in the frequency of self-reported symptoms relating to calculations or overall rating of functional status. After adjustment for a measure of depression (CES-D rating score), the risk for self-reported memory changes remained nearly 5 times higher among the CABG patients than among control subjects. The relative risk of developing new self-reported memory symptoms between 3 and 12 months was 2.5 times higher among CABG patients than among nonsurgical controls (CI 1.24-5.02), and the overall prevalence of memory symptoms at 12 months was also higher among CABG patients (39%) than controls (14%).</p> <p>Conclusions: The frequency of self-reported memory symptoms 3 and 12 months after baseline is significantly higher among CABG patients than control patients with comparable risk factors for coronary and cerebrovascular disease. These differences could not be accounted for by symptoms of depression. The self-reported cognitive symptoms appear to be relatively specific for memory and may reflect aspects of memory functioning that are not captured by traditional measures of new verbal learning and memory. The etiology of these self-reported memory symptoms remains unclear, but our findings, as well as those of others, may implicate factors other than cardiopulmonary bypass itself.</p&gt

Alzheimer's disease severity, objectively determined and measured

AbstractIntroductionWith expansion of clinical trials to individuals across the spectrum of Alzheimer disease (AD) from preclinical to symptomatic phases, it is increasingly important to quantify AD severity using methods that capture underlying pathophysiology.MethodsWe derived an AD severity measure based on biomarkers from brain imaging, neuropathology, and cognitive testing using latent variable modeling. We used data from ADNI-1 (N = 822) and applied findings to BIOCARD study (N = 349). We evaluated criterion validity for distinguishing diagnostic groups and construct validity by evaluating rates of change in AD severity.ResultsThe AD severity factor cross-sectionally distinguishes cognitively normal participants from MCI (AUC = 0.87) and AD dementia (AUC = 0.94). Among ADNI MCI subjects, worsening scores predict faster progression to AD dementia (HR = 1.17; 95% CI, 1.13–1.22). In ADNI and BIOCARD, the pace of change in AD severity is steepest among progressors, with persisting differences by baseline diagnosis.DiscussionOur content-valid latent variable measurement model is a reasonable approach for grading AD severity across a broad spectrum beginning at preclinical stages of AD

Cognitive outcomes 3 years after Coronary Artery Bypass Surgery: a comparison of on-pump CABG and non-surgical controls

<b>Background</b> <br>Coronary artery bypass grafting has been associated with both early and late postoperative cognitive decline, but interpretation of previous studies has been limited by lack of appropriate control groups. We compared changes in cognitive performance from baseline to 3 years in patients undergoing coronary artery bypass grafting with those of a control group of patients with known risk factors for coronary artery disease but without surgery.</br> <br><b>Methods</b></br> <br>Patients undergoing coronary artery bypass grafting (n = 140) and a demographically similar nonsurgical control group with coronary artery disease (n = 92) completed baseline neuropsychological assessment and were followed up prospectively at 3, 12, and 36 months. Cognitive performance was assessed with a battery of neuropsychological tests, measuring the cognitive domains of attention, language, verbal and visual memory, visuospatial, executive function, and psychomotor and motor speed. The statistical analyses were performed in two ways: using data from all tested individuals, and using a model imputing missing observations for individuals lost to follow-up.</br> <br><b>Results</b></br> <br>Both the coronary artery bypass grafting and nonsurgical control groups improved from baseline to 1 year, with additional improvement between 1 and 3 years for some cognitive tests. The coronary artery bypass grafting group had statistically significantly greater improvement than the nonsurgical controls for some subtests, and had a comparable longitudinal course for the remainder of the subtests. Both study groups had a trend toward nonsignificant decline at 3 years on some measures, but the overall differences between groups over time were not statistically significant.</br> <br><b>Conclusions</b></br> <br>Prospective longitudinal neuropsychological performance of patients with coronary artery bypass grafting did not differ from that of a comparable nonsurgical control group of patients with coronary artery disease at 1 or 3 years after baseline examination. This finding suggests that previously reported late cognitive decline after coronary artery bypass grafting may not be specific to the use of cardiopulmonary bypass, but may also occur in patients with similar risk factors for cardiovascular and cerebrovascular disease.</br&gt

Is there cognitive decline 1 year after CABG? Comparison with surgical and nonsurgical controls

<p><b>Background:</b> It is widely assumed that decline in cognition after coronary artery bypass grafting (CABG) is related to use of the cardiopulmonary bypass pump. Because most studies have not included comparable control groups, it remains unclear whether postoperative cognitive changes are specific to cardiopulmonary bypass, general aspects of surgery, or vascular pathologies of the aging brain.</p> <p><b>Methods:</b> This nonrandomized study included four groups: CABG patients (n = 140); off-pump coronary surgery (n = 72); nonsurgical cardiac controls (NSCC) with diagnosed coronary artery disease but no surgery (n = 99); and heart healthy controls (HHC) with no cardiac risk factors (n = 69). Subjects were evaluated at baseline (preoperatively), 3 months, and 12 months. Eight cognitive domains and a global cognitive score, as well as depressive and subjective symptoms were analyzed.</p> <p><b>Results:</b> At baseline, patients with coronary artery disease (CABG, off-pump, and NSCC) had lower performance than the HHC group in several cognitive domains. By 3 months, all groups had improved. From 3 to 12 months, there were minimal intrasubject changes for all groups. No consistent differences between the CABG and off-pump patients were observed.</p> <p><b>Conclusions:</b> Compared with heart healthy controls (HHC), the groups with coronary artery disease had lower cognitive test scores at baseline. There was no evidence that the cognitive test performance of coronary artery bypass grafting (CABG) patients differed from that of control groups with coronary artery disease over a 1-year period. This study emphasizes the need for appropriate control groups for interpreting longitudinal changes in cognitive performance after CABG.</p&gt

Motor nerve terminal degeneration provides a potential mechanism for rapid recovery in acute motor axonal neuropathy after <i>Campylobacter</i> infection

We investigated the possible mechanisms of paralysis and recovery in a patient with the acute motor axonal neuropathy (AMAN) pattern of the Guillain-Barré syndrome. The AMAN pattern of GBS is characterized clinically by acute paralysis without sensory involvement and electrodiagnostically by low compound motor action potential amplitudes, suggesting axonal damage, without evidence of demyelination. Many AMAN patients have serologic or culture evidence of recent Campylobacter jejuni infection. Pathologically, the most severe cases are characterized by wallerian-like degeneration of motor axons affecting the ventral roots as well as peripheral nerves, but some fatal cases have only minor changes in the roots and peripheral nerves, and some paralyzed patients with the characteristic electrodiagnostic findings of AMAN recover rapidly. The mechanism of paralysis and recovery in such cases has been uncertain. A 64-year-old woman with culture-proven Campylobacter upsaliensis diarrhea developed typical features of AMAN. She improved quickly following plasmapheresis. Her serum contained IgG anti-GM1 antibodies. The lipopolysaccharide of the organism bound peanut agglutinin. This binding was blocked by cholera toxin, suggesting that the organism contained the Gal(beta1-3)GalNAc epitope of GM1 in its lipopolysaccharide. Motor-point biopsy showed denervated neuromuscular junctions and reduced fiber numbers in intramuscular nerves. In contrast, the sural nerve biopsy was normal and skin biopsy showed normal dermal and epidermal innervation. In AMAN the paralysis may reflect degeneration of motor nerve terminals and intramuscular axons. In addition, the anti-GM1 antibodies, which can bind at nodes of Ranvier, might produce failure of conduction. These processes are potentially reversible and likely to underlie the capacity for rapid recovery that characterizes some cases of AMAN

<i>Campylobacter jejuni</i> lipopolysaccharides in Guillain-Barré syndrome: molecular mimicry and host susceptibility

&lt;p&gt;&lt;b&gt;Objective:&lt;/b&gt; This study was designed to determine if the presence of specific ganglioside-like moieties in &lt;i&gt;Campylobacter&lt;/i&gt; lipopolysaccharides(LPSs) is related to the development of Guillain-Barré syndrome (GBS), and to discover how frequently such moieties, including GM1, are present in these LPSs.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We studied &lt;i&gt;Campylobacter&lt;/i&gt; isolates and sera from seven patients with GBS (five acute motor axonal neuropathy, one acute inflammatory demyelinating polyneuropathy, and one Fisher's syndrome), and compared them with similar specimens from patients with &lt;i&gt;Campylobacter&lt;/i&gt; enteritis alone.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; All GBS patients had antiganglioside antibodies. Anti-GM1 and anti-GD1a titers were significantly elevated in post-&lt;i&gt;Campylobacter&lt;/i&gt; GBS, both axonal and demyelinating, compared with normal control subjects or those with uncomplicated Campylobacter diarrhea. &lt;i&gt;Campylobacter&lt;/i&gt; isolated from patients with GBS and with enteritis alone had similar ganglioside-like moieties.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; These results indicate that patients who develop GBS respond differently to the ganglioside-like epitopes on Campylobacter than do non-GBS diarrhea patients. Our findings support a role for host susceptibility as a determinant for the outcome following &lt;i&gt;Campylobacter&lt;/i&gt; infection. These findings have important implications for the development of vaccines against &lt;i&gt;Campylobacter jejuni&lt;/i&gt;.&lt;/p&gt