Abstract
BACKGROUND: Endogenous Granulocyte Macrophage Colony Stimulating Factor (GMCSF) is released in rheumatoid arthritis patients, who are largely protected from Alzheimer's disease (AD). Introducing exogenous GMCSF into an AD mouse model reduced amyloid deposition by 55% and restored normal cognition. No published studies have examined exogenous GMCSF and cognitive functioning in humans. OBJECTIVES/DESIGN: The goal of the current study was to examine the association between receipt of GMCSF and cognitive functioning in patients receiving colony stimulating factors as part of routine supportive care for hematopoietic cell transplantation (HCT). SETTING AND PARTICIPANTS: Archived neuropsychological data were examined from a longitudinal study of cognitive functioning in 95 patients receiving HCT at the Moffitt Cancer Center. INTERVENTION: Receipt of GMCSF and/or Granulocyte Colony Stimulating Factor (GCSF) was ascertained through patient billing records. MEASUREMENTS: Patients were assessed with a battery of neuropsychological tests prior to transplant and 6 and 12 months post-transplant. RESULTS: Patients treated with GMCSF and GCSF (n=19) showed significantly greater improvement in total neuropsychological functioning (TNP) at 6 months than patients treated with GCSF only (n=76) (p=.04). There was no group difference in TNP at 12 months (p=.24). Improvement in TNP from baseline to 6 months post-HCT was significant in the GMCSF+GCSF group (p=.01) but not the GCSF only group (p=.33). Improvement in TNP from baseline to 12 months post-HCT was significant in both groups (ps<.01). CONCLUSION: Preliminary data from this study of humans receiving colony stimulating factors suggest that receipt of GMCSF+GCSF was associated with greater cognitive improvement than GCSF alone. Randomized controlled trials of the effects of GMCSF on cognitive functioning in humans are warranted and underway to confirm these findings.
Highlights
Cognitive decline is a major societal concern due to the aging population of many industrialized nations
Patients treated with Granulocyte Macrophage Colony Stimulating Factor (GMCSF) and Granulocyte Colony Stimulating Factor (GCSF) (n=19) showed significantly greater improvement in total neuropsychological functioning (TNP) at 6 months than patients treated with GCSF only (n=76) (p=.04)
Improvement in TNP from baseline to 6 months post-hematopoietic cell transplantation (HCT) was significant in the GMCSF+GCSF group (p=.01) but not the GCSF only group (p=.33)
Summary
Cognitive decline is a major societal concern due to the aging population of many industrialized nations. Cognitive decline results from the aging process itself, and neurodegenerative diseases such as Alzheimer’s disease (AD) and some treatments for other common age-related diseases, such as cancer [1,2,3]. One potentially promising treatment is granulocyte macrophage colony stimulating factor (GMCSF). Clinical interest in GMCSF developed out of the observation that patients with Rheumatoid Arthritis (RA) are at 8-fold reduced risk of developing AD. This finding was originally hypothesized to result from patients’ use of Non-Steroidal Anti-inflammatory Drugs (NSAIDs) [4]. Endogenous Granulocyte Macrophage Colony Stimulating Factor (GMCSF) is released in rheumatoid arthritis patients, who are largely protected from Alzheimer’s disease (AD). No published studies have examined exogenous GMCSF and cognitive functioning in humans
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