Demographic characteristics of the study population are shown in table . Relative to controls, AD patients did not significantly differ with respect to sex, race or Hispanic ethnicity; however, they were significantly older (median age, 79 vs. 70 years; p < 0.001), less educated (median years of education, 14 vs. 16; p < 0.001) and more likely to carry one or more copies of the APOE
4 allele (APOE4 carriers, 13.7 vs. 2.5%; p < 0.001).
Demographic information of the 400 participants in the TARCC longitudinal research cohort
Median serum G-CSF levels were significantly lower in AD cases compared to controls (8.1 vs. 9.9 pg/ml, respectively; table ). G-CSF remained significantly associated with diagnostic category (β = −0.073; p = 0.008) following adjustment for age, sex, education and APOE status (table ). To test for residual confounding by the APOE4 allele, an analysis was run after stratification of the sample on APOE4 status. Serum G-CSF was not significantly associated with disease status in either the APOE4-positive or APOE4-negative group. However, the p values were marginal (0.053 and 0.077 in APOE4-negative and APOE4-positive individuals, respectively), and the trends were consistent with those observed in the unstratified sample (data not presented).
Odds ratio for disease status following adjustment for multiple factors as determined by multivariate logistic regression
Among AD participants only (n = 197), higher serum G-CSF levels were negatively associated with lower (worse) scores on the MMSE (β = −0.178; p = 0.014; table ) and positively associated with higher (worse) scores on the CDR Global (β = 0.170; p = 0.018; table ) and CDR Sum of Boxes (β = 0.153; p = 0.035; table ).
Multivariate logistic regression for MMSE scores of participants in the TARCC longitudinal cohort with a diagnosis of probable AD
Multivariate logistic regression for global CDR scores of participants in the TARCC longitudinal cohort with a diagnosis of probable AD
Multivariate logistic regression for CDR-Sum of Boxes scores of participants in the TARCC longitudinal cohort with a diagnosis of probable AD
In post-hoc analyses, serum G-CSF levels were tested for association with individual neuropsychiatric test score by multivariate logistic regression. Serum G-CSF concentration was significantly associated with only digit span among AD participants and delayed logical memory among controls (table ). In an attempt to resolve the impact of a number of key processes that have been shown to be important to AD pathology, we performed a set of stratified analyses. First, we selected proteins that were representative of inflammation (C-reactive protein; CRP), coagulation (thrombopoietin; THP) and neurotrophic factors (brain derived neurotrophic factor; BDNF). Next, we stratified the participants based upon tertiles for each of these proteins. Finally, we evaluated the association between G-CSF and diagnostic status (AD vs. NC) for participants within each group. Serum G-CSF levels were significantly associated with diagnostic status for participants in the mid-tertile for THP and BDNF. In contrast, G-CSF was associated with diagnostic status only for participants in the high-tertile for CRP (table ).
Multivariate logistic regression for association between serum G-CSF levels and neuropsychological test scores, following adjustment for age, gender, years of education and APOE4 status
Results for G-CSF from multivariate logistic regression analysis of G-CSF and MMSE scores among AD patients following stratification into tertiles on brain-derived neurotrophic factor (BDNF), C-reactive protein (CRP) and thrombopoietin