Value of Serum Nonceruloplasmin Copper for Prediction of Mild Cognitive Impairment Conversion to Alzheimer Disease

ObjectiveMeta-analyses show that nonbound ceruloplasmin (non-Cp) copper (also known as free or labile copper) in serum is higher in patients with Alzheimer disease (AD). It differentiates subjects with mild cognitive impairment (MCI) from healthy controls. However, a longitudinal study on an MCI cohort has not yet been performed to assess the accuracy of non-Cp copper for the prediction of conversion from MCI to AD during a long-term follow-up. MethodsThe study included 42 MCI converters and 99 stable MCI subjects. We assessed levels of copper, ceruloplasmin, non-Cp copper, iron, transferrin, ferritin, and APOE genotype. A multiple Cox regression analysiswith age, sex, baseline Mini-Mental State Examination, APOE4, iron, non-Cp copper, transferrin, ferritin, hypercholesterolemia, and hypertension as covariateswas applied to predict the conversion from MCI to AD. ResultsAmong the evaluated parameters, the only significant predictor of conversion to AD was non-Cp copper (hazard ratio=1.23, 95% confidence interval=1.03-1.47, p=0.022); for each additional micromole per liter unit (mol/l) of non-Cp copper, the hazard increased by approximate to 20%. Subjects with non-Cp copper levels >1.6mol/l had a hazard conversion rate (50% of conversion in 4 years) that was approximate to 3x higher than those with values 1.6mol/l (<20% in 4 years). The rate of conversion was similar between APOE4 carriers and noncarriers (p=0.321), indicating that the non-Cp copper association was independent of APOE4. InterpretationNon-Cp copper appears to predict conversion from MCI to AD. These results encourage healthy life style choices and dietary intervention to modify this risk. ANN NEUROL 2014;75:574-580