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

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

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Cognitive Dysfunction; Mild Cognitive Impairment

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 41

Contacts and Locations

Study Locations

• United States
  • New York
    • New York City, New York, United States, 10016
      • NYU School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

65 years and older scheduled for major spinal surgery.

Description

Inclusion Criteria:

1. Patients age 65 and older scheduled to undergo spine surgery.
2. Subjects who are able to read and understand English

Exclusion Criteria:

1. Emergent nature of the procedure which might preclude the conduct of preoperative cognitive examination
2. Participation in any other investigational intervention or clinical study
3. History of psychiatric illnesses (except depression)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Subjects; 65 years and older scheduled for spine surgery will be undergoing serial assessments preoperatively and postoperatively over 6 time-points.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To examine the effect of surgery on the progression of AD in a population at high risk for this disease through measures of Amyloid Beta levels (AB40 and AB42). levels	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine whether major surgery induces an increase in plasma Aβ40 and Aβ42.	2 years
To determine whether the pattern of plasma inflammatory markers is different in patients with MCI compared to patients without MCI.	2 years
To determine whether the Apolipoprotein E genotype correlates with POCD.	2 years
To examine the relationship between plasma levels of Aβ40 / Aβ42 and subject performance on neurocognitive testing.	2 years
To establish a correlation between preoperative mild cognitive impaired (MCI) and post operative cognitive decline ( POCD) using neurocognitive testing.	2 years

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Study Director: Germaine Cuff, PhD, NYU School of Medicine

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: February 24, 2009
• First Submitted That Met QC Criteria: February 24, 2009
• First Posted (Estimate): February 25, 2009

Study Record Updates

• Last Update Posted (Estimate): March 17, 2016
• Last Update Submitted That Met QC Criteria: March 15, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Mild Cognitive Impairment; MCI; Apolipoprotein E; Inflammatory Markers; Postoperative Cognitive Dysfunction; Aβ40; Aβ42; Apolipoprotein E Profile; Serum Beta Amyloid Profile; Inflammatory Markers Profile
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Postoperative Complications; Neurocognitive Disorders; Cognition Disorders; Inflammation; Cognitive Dysfunction; Postoperative Cognitive Complications
• Other Study ID Numbers: H08-658

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO