Clinical trial NCT00850928: Postoperative Cognitive Decline, Inflammation, and Plasma Levels of Beta-amyloids
Official title: Postoperative Cognitive Decline, Inflammation, and Plasma Levels of Beta-amyloids.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Postoperative Cognitive Dysfunction
Mild Cognitive Impairment
Keywords: Postoperative Cognitive Dysfunction
MCI
Mild Cognitive Impairment
Aβ40
Aβ42
Apolipoprotein E
Inflammatory Markers
Apolipoprotein E Profile
Serum Beta Amyloid Profile
Inflammatory Markers Profile
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2009-02-25
Enrollment: 41
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 65 years and older scheduled for major spinal surgery.

Brief summary: 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.

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 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)

Primary outcomes:
measure: 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
timeFrame: 2 years
Secondary outcomes:
measure: To determine whether major surgery induces an increase in plasma Aβ40 and Aβ42.
timeFrame: 2 years
measure: To determine whether the pattern of plasma inflammatory markers is different in patients with MCI compared to patients without MCI.
timeFrame: 2 years
measure: To determine whether the Apolipoprotein E genotype correlates with POCD.
timeFrame: 2 years
measure: To examine the relationship between plasma levels of Aβ40 / Aβ42 and subject performance on neurocognitive testing.
timeFrame: 2 years
measure: To establish a correlation between preoperative mild cognitive impaired (MCI) and post operative cognitive decline ( POCD) using neurocognitive testing.
timeFrame: 2 years
Other outcomes:
Locations:
city: New York City
country: United States
facility: NYU School of Medicine
state: New York
Study officials:
affiliation: NYU School of Medicine
name: Germaine Cuff, PhD
role: STUDY_DIRECTOR
References: