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Longitudinal prognostic value of serum "free" copper in patients with Alzheimer disease

From the Department of Neuroscience (R.S., E.C., F.M., M.V., P.M.R.), AFaR-Osp. Fatebenefratelli, Isola Tiberina, Rome; Neurology (R.S., F.B., M.V., F.V., P.M.R.), University Campus Biomedico, Rome; Medical Statistics & Information Technology (P.P.), AFaR-Fatebenefratelli Association for Research, Isola Tiberina, Rome; Casa di Cura San Raffaele (P.P., P.M.R.), Cassino & IRCCS San Raffaele Pisana, Rome; and IRCCS Centro S. Giovanni di Dio-FBF (C.B., R.G., G.B.), Brescia, Italy.

Address correspondence and reprint requests to Dr. Rosanna Squitti, Department of Neuroscience, AFaR-Osp. Fatebenefratelli, 00186, Rome, Italy rosanna.squitti{at}afar.it

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 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.

Abbreviations: AD = Alzheimer disease; ADL = activities of daily living; BBB = blood–brain barrier; CB = ceruloplasmin; CI = confidence interval; IADL = instrumental activities of daily living; MMSE = Mini-Mental State Examination; OR = odds ratio.

Supported by Grants of the Italian Health Department: "Tollerabilità ed efficacia del tetratiomolibdato di ammonio (TM) nella malattia di Alzheimer" [RF 2006 conv.58] and by a grant from the AFaR Foundation–Osp. Fatebenefratelli, Rome, Italy.

Disclosure: The authors report no disclosures.

Received May 9, 2008. Accepted in final form September 24, 2008.

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				Free Copper and Alzheimer Disease Journal Watch Neurology, April 28, 2009; 2009(428): 3 - 3. [Full Text]