Postoperative Cognitive Decline, Inflammation, and Plasma Levels of Beta-amyloids

Overview

Postoperative cognitive dysfunction (POCD) can be a serious complication. The development of therapeutic strategies for the prevention and treatment of this condition requires the identification of subgroup of patients with the greatest incidence of POCD. Several retrospective analyses have raised the possibility that surgery is a risk factor for the accelerated progression of Alzheimer's disease (AD). Moreover, there is increasing evidence that inflammatory mechanisms are involved in the pathogenesis of AD. Major surgery can be associated with a profound systemic inflammatory response. Consequently, it is reasonable to suggest that there is a link between major surgery and the postoperative development of AD in patients who are already at high risk for this complication, e.g. the elderly with mild cognitive impairment. In addition, there are several laboratory investigations that suggest that anesthetic agents increase amyloid peptide levels as well as enhance oligomerization of these proteins. The significance of these findings, however, is unknown. This clinical study seeks to correlate perioperative inflammatory responses, perioperative changes in amyloid-beta protein levels (markers of AD) with neurocognitive and functional outcome in the elderly who are at risk for POCD. This knowledge does not exist, but is essential in the effort to plan perioperative care that can reduce the incidence of POCD as well as improve functional recovery.

We will recruit 50 patients 65 years and older scheduled for spine surgery. The design utilizes prospective serial assessments. The enrolled 50 surgical subjects will be evaluated preoperatively and postoperatively over 6 time-points (preoperatively, inta-op, post op day 1, post op day 7, three months and six months) using a widely accepted set of neurocognitive tests, multiple indices of functional recovery, as well as blood tests for plasma biomarkers of inflammation and β-amyloids. Enrollees will be divided in 2 groups: 25 patients with mild cognitive impairment (diagnosed by clinical assessment) and 25 normal elderly patients. The definition of normal elderly includes: 1). Global Deterioration Scale (GDS) \< 3 and Mini-Mental Exam Score (MMSE) \>27; 2). Performance on neurocognitive testing (including memory) that is within 1.5 Standard Deviation (SD) of the age matched normative data; 3). The informant interview confirming no functional impairment in the subject. The definition of MCI includes: self-reported memory and functional complains, a history of memory decline with functional changes that are corroborated by a knowledgeable informant, and a clinical interview resulting in a GDS=3 or higher and MMSE=26 or lower.