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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT00850928
First received: February 24, 2009
Last updated: February 13, 2014
Last verified: February 2014
  Purpose

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.


Condition
Postoperative Cognitive Dysfunction
Mild Cognitive Impairment

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Postoperative Cognitive Decline, Inflammation, and Plasma Levels of Beta-amyloids.

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • 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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine whether major surgery induces an increase in plasma Aβ40 and Aβ42. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To determine whether the pattern of plasma inflammatory markers is different in patients with MCI compared to patients without MCI. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To determine whether the Apolipoprotein E genotype correlates with POCD. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To examine the relationship between plasma levels of Aβ40 / Aβ42 and subject performance on neurocognitive testing. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To establish a correlation between preoperative mild cognitive impaired (MCI) and post operative cognitive decline ( POCD) using neurocognitive testing. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Serum and plasma will be collected and stored at baseline, intra-operatively, and one day post-operative for analysis of markers of inflammation. Plasma will be collected and stored at baseline, three months, and six months for analysis of Beta Amyloid levels. DNA will be collected and stored at baseline for analysis of Apolipoprotein E.


Estimated Enrollment: 50
Study Start Date: December 2008
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Subjects
65 years and older scheduled for spine surgery will be undergoing serial assessments preoperatively and postoperatively over 6 time-points.

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.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

65 years and older scheduled for major spinal surgery.

Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00850928

Locations
United States, New York
NYU School of Medicine
New York City, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
Investigators
Principal Investigator: Alex Bekker, M.D., Ph.D. NYU School of Medicine
Study Director: Michael Haile, M.D. NYU School of Medicine
  More Information

No publications provided

Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT00850928     History of Changes
Other Study ID Numbers: H08-658
Study First Received: February 24, 2009
Last Updated: February 13, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
Postoperative Cognitive Dysfunction
MCI
Mild Cognitive Impairment
Aβ40
Aβ42
Apolipoprotein E
Inflammatory Markers
Inflammatory markers
Apolipoprotein E Profile
Serum Beta Amyloid Profile
Inflammatory Markers Profile

Additional relevant MeSH terms:
Inflammation
Cognition Disorders
Pathologic Processes
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on April 17, 2014