Value of serum nonceruloplasmin copper for prediction of mild cognitive impairment conversion to Alzheimer disease

Objective Meta‐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 co...

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Published in:Annals of neurology 2014-04, Vol.75 (4), p.574-580
Main Authors: Squitti, Rosanna, Ghidoni, Roberta, Siotto, Mariacristina, Ventriglia, Mariacarla, Benussi, Luisa, Paterlini, Anna, Magri, Mariachiara, Binetti, Giuliano, Cassetta, Emanuele, Caprara, Deborah, Vernieri, Fabrizio, Rossini, Paolo M., Pasqualetti, Patrizio
Format: Article
Language:English
Subjects:
Alzheimer Disease - blood
Alzheimer Disease - genetics
Apolipoprotein E4 - genetics
Ceruloplasmin - metabolism
Cognition Disorders - blood
Cognition Disorders - genetics
Confidence intervals
Copper
Copper - blood
Disease Progression
Female
Humans
Longitudinal Studies
Male
Neuropsychological Tests
Older people
Predictive Value of Tests
Probability
Risk Factors
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Summary:Objective Meta‐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. Methods The 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 analysis—with age, sex, baseline Mini‐Mental State Examination, APOE4, iron, non‐Cp copper, transferrin, ferritin, hypercholesterolemia, and hypertension as covariates—was applied to predict the conversion from MCI to AD. Results Among 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 (μmol/l) of non‐Cp copper, the hazard increased by ∼20%. Subjects with non‐Cp copper levels >1.6μmol/l had a hazard conversion rate (50% of conversion in 4 years) that was ∼3× higher than those with values ≤1.6μmol/l (
ISSN:0364-5134
1531-8249
DOI:10.1002/ana.24136