Patients with Alzheimer's Disease Have Increased Levels of Insulin-like Growth Factor-I in Serum but not in Cerebrospinal Fluid

Background: Insulin-like growth factor-I (IGF-I) is important for amyloid-beta (A beta) metabolism, and also interacts with the brain vasculature. In previous IGF-I studies, it has not been evaluated whether Alzheimer's disease (AD) patients had vascular comorbidities. Objective and Methods: A cross-sectional study of 40 consecutive non-diabetic AD patients and 36 healthy controls. We measured IGF-I in serum and cerebrospinal fluid (CSF) and also serum insulin. Mixed forms of AD and vascular dementia were excluded. Results: After adjustment for covariates including age, serum IGF-I level was higher in the AD group than in the controls, whereas CSF IGF-I and serum insulin were unchanged. Binary logistic regression confirmed that high serum IGF-I was associated with increased prevalence of AD [adjusted Odds Ratio (OR) =1.83, 95% confidence interval (CI): 1.005-3.32 per standard deviation (SD) increase in serum IGF-I]. This association was more robust after exclusion of patients receiving treatment with acetylcholinesterase inhibitors or N-methyl D-aspartate (NMDA) receptor antagonists (OR = 2.23, 95 % CI: 1.10-4.48). In the total study population (n = 76) as well in the AD group (n = 40), serum IGF-I correlated negatively with CSF A beta(1-42), and CSF IGF-I correlated positively with CSF/serum albumin ratio, CSF total tau, and CSF phosphorylated tau. Conclusion: In AD patients without major brain vascular comorbidities, serum but not CSF levels of IGF-I were increased after correction for covariates. This association was strengthened by exclusion of patients receiving medical treatment. Overall, the results support the notion of IGF-I resistance in mild AD dementia.