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Longitudinal prognostic value of serum "free" copper in patients with Alzheimer disease.
Neurology. 2009 Jan 06; 72(1):50-5.Neur

Abstract

BACKGROUND

Serum copper not bound to ceruloplasmin ("free") appears slightly elevated in patients with Alzheimer disease (AD). We explored whether a deregulation of the free copper pool can predict AD clinical worsening.

METHODS

We assessed levels of copper, iron, zinc, transferrin, ceruloplasmin, peroxides, total antioxidant capacity, free copper, and apolipoprotein E genotype in 81 patients with mild or moderate AD, mean age 74.4, SD = 7.4 years, clinically followed up after 1 year. The association among biologic variables under study and Mini-Mental State Examination (MMSE) (primary outcome), activities of daily living (ADL), and instrumental activities of daily living (IADL) (secondary outcomes) performed at study entry and after 1 year were analyzed by multiple regression.

RESULTS

Free copper predicted the annual change in MMSE, adjusted for the baseline MMSE by means of a linear regression model: it raised the explained variance from 2.4% (with only sex, age, and education) to 8.5% (p = 0.026). When the annual change in MMSE was divided into < 3 or > or = 3 points, free copper was the only predictor of a more severe decline (predicted probability of MMSE worsening 23%: odds ratio = 1.23; 95% confidence interval = 1.03-1.47; p = 0.022). Hyperlipidemic patients with higher levels of free copper seemed more prone to worse cognitive impairment. Free copper at baseline correlated with the ADL and IADL clinical scales scores at 1 year.

CONCLUSIONS

These results show an association between copper deregulation and unfavorable evolution of cognitive function in Alzheimer disease. Further research is needed to establish whether copper is an independent risk factor for cognitive decline.

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Authors+Show Affiliations

Squitti R
Department of Neuroscience, AFaR-Osp. Fatebenefratelli, 00186, Rome, Italy. rosanna.squitti@afar.it
Bressi F
No affiliation info available
Pasqualetti P
No affiliation info available
Bonomini C
No affiliation info available
Ghidoni R
No affiliation info available
Binetti G
No affiliation info available
Cassetta E
No affiliation info available
Moffa F
No affiliation info available
Ventriglia M
No affiliation info available
Vernieri F
No affiliation info available
Rossini PM
No affiliation info available

MeSH

AgedAged, 80 and overAlzheimer DiseaseCognition DisordersCopperDisease ProgressionFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMental Status ScheduleNeuropsychological TestsPredictive Value of TestsProbabilityPrognosisRisk FactorsStatistics as Topic

Pub Type(s)

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

Language

eng

PubMed ID

19122030

Clinical Trial Links

Trial of Novel Oral Zinc Cysteine Preparation in Alzheimer's Disease

Citation

Squitti, R, et al. "Longitudinal Prognostic Value of Serum "free" Copper in Patients With Alzheimer Disease." Neurology, vol. 72, no. 1, 2009, pp. 50-5.
Squitti R, Bressi F, Pasqualetti P, et al. Longitudinal prognostic value of serum "free" copper in patients with Alzheimer disease. Neurology. 2009;72(1):50-5.
Squitti, R., Bressi, F., Pasqualetti, P., Bonomini, C., Ghidoni, R., Binetti, G., Cassetta, E., Moffa, F., Ventriglia, M., Vernieri, F., & Rossini, P. M. (2009). Longitudinal prognostic value of serum "free" copper in patients with Alzheimer disease. Neurology, 72(1), 50-5. https://doi.org/10.1212/01.wnl.0000338568.28960.3f
Squitti R, et al. Longitudinal Prognostic Value of Serum "free" Copper in Patients With Alzheimer Disease. Neurology. 2009 Jan 6;72(1):50-5. PubMed PMID: 19122030.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Longitudinal prognostic value of serum "free" copper in patients with Alzheimer disease. AU - Squitti,R, AU - Bressi,F, AU - Pasqualetti,P, AU - Bonomini,C, AU - Ghidoni,R, AU - Binetti,G, AU - Cassetta,E, AU - Moffa,F, AU - Ventriglia,M, AU - Vernieri,F, AU - Rossini,P M, PY - 2009/1/6/entrez PY - 2009/1/6/pubmed PY - 2009/4/9/medline SP - 50 EP - 5 JF - Neurology JO - Neurology VL - 72 IS - 1 N2 - BACKGROUND: Serum copper not bound to ceruloplasmin ("free") appears slightly elevated in patients with Alzheimer disease (AD). We explored whether a deregulation of the free copper pool can predict AD clinical worsening. METHODS: We assessed levels of copper, iron, zinc, transferrin, ceruloplasmin, peroxides, total antioxidant capacity, free copper, and apolipoprotein E genotype in 81 patients with mild or moderate AD, mean age 74.4, SD = 7.4 years, clinically followed up after 1 year. The association among biologic variables under study and Mini-Mental State Examination (MMSE) (primary outcome), activities of daily living (ADL), and instrumental activities of daily living (IADL) (secondary outcomes) performed at study entry and after 1 year were analyzed by multiple regression. RESULTS: Free copper predicted the annual change in MMSE, adjusted for the baseline MMSE by means of a linear regression model: it raised the explained variance from 2.4% (with only sex, age, and education) to 8.5% (p = 0.026). When the annual change in MMSE was divided into < 3 or > or = 3 points, free copper was the only predictor of a more severe decline (predicted probability of MMSE worsening 23%: odds ratio = 1.23; 95% confidence interval = 1.03-1.47; p = 0.022). Hyperlipidemic patients with higher levels of free copper seemed more prone to worse cognitive impairment. Free copper at baseline correlated with the ADL and IADL clinical scales scores at 1 year. CONCLUSIONS: These results show an association between copper deregulation and unfavorable evolution of cognitive function in Alzheimer disease. Further research is needed to establish whether copper is an independent risk factor for cognitive decline. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/19122030/Longitudinal_prognostic_value_of_serum_"free"_copper_in_patients_with_Alzheimer_disease_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&amp;pmid=19122030 DB - PRIME DP - Unbound Medicine ER -