GENETIC BASIS OF COGNITIVE DECLINE AFTER SUGERY

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DESCRIPTION: Cognitive impairment occurs frequently after surgery in the approximately 400,000 patients who undergo cardiac operations each year. Cognitive impairment is most notable in the early phases after cardiac surgery, but persistence occurs in an important percentage of patients. Members of the investigators' group have found a genetic association between late-onset Alzheimer's disease and the apolipoprotein E (APOE e-4) gene. This finding triggered many recent studies which have shown an important role of APOE in the determination of neurologic injury associated with acute ischemic insults, including a markedly greater mortality and reduction in functional recovery in intracerebral hemorrhage patients who possess the APOE e-4 allele. APOE appears to code for proteins that play a significant role in determination of cellular recovery or demise after ischemic insults. The investigators propose that the biochemical products coded by this gene are not available to protect and repair the neurons of the central nervous system during cardiac surgery resulting in deficits of memory, attention, and concentration. Pilot data are reported that support the hypothesis associating APOE e-4 with cognitive impairment after cardiac surgery. The investigators will test this hypothesis with a prospective, longitudinal study evaluating the association of APOE genotype and postoperative cognitive impairment. Patients will undergo baseline (preoperative) neurologic and psychometric testing designed to evaluate memory and other cognitive functions. Neurologic evaluation will be repeated at three to five days postoperatively, with psychometric testing repeated at six weeks and one year postoperatively. A group of angioplasty patients followed longitudinally with the same testing will allow the investigators to separate the impact of surgery from potential declines in cognition associated with the e-4 allele. The central hypothesis will be tested by using change in psychometric test scores as a dependent variable in a multiple analysis of covariance model with APOE e-4 as one of several covariates. If it is found that genotype predicts loss of cognition, this will enable physicians to identify patients likely to have postoperative cognitive deficits. It is a unifying mechanism of cognitive dysfunction, that is, that neuronal damage occurs because of the lack of a normal neuronal maintenance or reparative response to the variety of ischemic insults during cardiopulmonary bypass. This new knowledge would provide future promise of gene or drug therapy to prevent this very disturbing central nervous system consequence of cardiac surgery in otherwise healthy convalescent patients.