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Value of serum nonceruloplasmin copper for prediction of mild cognitive impairment conversion to Alzheimer disease.
Ann Neurol 2014; 75(4):574-80AN

Abstract

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 >1.6 μmol/l had a hazard conversion rate (50% of conversion in 4 years) that was ~3× higher than those with values ≤1.6 μmol/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.

INTERPRETATION

Non-Cp copper appears to predict conversion from MCI to AD. These results encourage healthy life style choices and dietary intervention to modify this risk.

Authors+Show Affiliations

Department of Neuroscience, Fatebenefratelli Foundation, AFaR Division, Fatebenefratelli Hospital, Isola Tiberina, Rome; Laboratory of Neurodegeneration, IRCCS "San Raffaele Pisana", Rome.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24623259

Citation

Squitti, Rosanna, et al. "Value of Serum Nonceruloplasmin Copper for Prediction of Mild Cognitive Impairment Conversion to Alzheimer Disease." Annals of Neurology, vol. 75, no. 4, 2014, pp. 574-80.
Squitti R, Ghidoni R, Siotto M, et al. Value of serum nonceruloplasmin copper for prediction of mild cognitive impairment conversion to Alzheimer disease. Ann Neurol. 2014;75(4):574-80.
Squitti, R., Ghidoni, R., Siotto, M., Ventriglia, M., Benussi, L., Paterlini, A., ... Pasqualetti, P. (2014). Value of serum nonceruloplasmin copper for prediction of mild cognitive impairment conversion to Alzheimer disease. Annals of Neurology, 75(4), pp. 574-80. doi:10.1002/ana.24136.
Squitti R, et al. Value of Serum Nonceruloplasmin Copper for Prediction of Mild Cognitive Impairment Conversion to Alzheimer Disease. Ann Neurol. 2014;75(4):574-80. PubMed PMID: 24623259.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Value of serum nonceruloplasmin copper for prediction of mild cognitive impairment conversion to Alzheimer disease. AU - Squitti,Rosanna, AU - Ghidoni,Roberta, AU - Siotto,Mariacristina, AU - Ventriglia,Mariacarla, AU - Benussi,Luisa, AU - Paterlini,Anna, AU - Magri,Mariachiara, AU - Binetti,Giuliano, AU - Cassetta,Emanuele, AU - Caprara,Deborah, AU - Vernieri,Fabrizio, AU - Rossini,Paolo M, AU - Pasqualetti,Patrizio, Y1 - 2014/04/14/ PY - 2013/12/10/received PY - 2014/03/11/revised PY - 2014/03/11/accepted PY - 2014/3/14/entrez PY - 2014/3/14/pubmed PY - 2014/6/18/medline SP - 574 EP - 80 JF - Annals of neurology JO - Ann. Neurol. VL - 75 IS - 4 N2 - 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 >1.6 μmol/l had a hazard conversion rate (50% of conversion in 4 years) that was ~3× higher than those with values ≤1.6 μmol/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. INTERPRETATION: Non-Cp copper appears to predict conversion from MCI to AD. These results encourage healthy life style choices and dietary intervention to modify this risk. SN - 1531-8249 UR - https://www.unboundmedicine.com/medline/citation/24623259/Value_of_serum_nonceruloplasmin_copper_for_prediction_of_mild_cognitive_impairment_conversion_to_Alzheimer_disease_ L2 - https://doi.org/10.1002/ana.24136 DB - PRIME DP - Unbound Medicine ER -