Article

Intake of copper has no effect on cognition in patients with mild Alzheimer’s disease: a pilot phase 2 clinical trial

Journal of Neural Transmission (Impact Factor: 2.87). 08/2008; 115(8):1181-1187. DOI: 10.1007/s00702-008-0080-1
Source: PubMed

ABSTRACT Disturbed copper (Cu) homeostasis may be associated with the pathological processes in Alzheimer’s disease (AD). In the present
report, we evaluated the efficacy of oral Cu supplementation in the treatment of AD in a prospective, randomized, double-blind,
placebo-controlled phase 2 clinical trial in patients with mild AD for 12months. Sixty-eight subjects were randomized. The
treatment was well-tolerated. There were however no significant differences in primary outcome measures (Alzheimer’s Disease
Assessment Scale, Cognitive subscale, Mini Mental Status Examination) between the verum [Cu-(II)-orotate-dihydrate; 8mg Cu
daily] and the placebo group. Despite a number of findings supporting the hypothesis of environmental Cu modulating AD, our
results demonstrate that oral Cu intake has neither a detrimental nor a promoting effect on the progression of AD.

0 Bookmarks
 · 
91 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cognitive impairments are often related to aging and micronutrient deficiencies. Various essential micronutrients in the diet are involved in age-altered biological functions such as, zinc, copper, iron, and selenium that play pivotal roles either in maintaining and reinforcing the antioxidant performances or in affecting the complex network of genes (nutrigenomic approach) involved in encoding proteins for biological functions. Genomic stability is one of the leading causes of cognitive decline and deficiencies or excess in trace elements are two of the factors relating to it. In this review, we report and discuss the role of micronutrients in cognitive impairment in relation to genomic stability in an aging population. Telomere integrity will also be discussed in relation to aging and cognitive impairment, as well as, the micronutrients related to these events. This review will provide an understanding on how these three aspects can relate with each other and why it is important to keep a homeostasis of micronutrients in relation to healthy aging. Micronutrient deficiencies and aging process can lead to genomic instability.
    The Journal of Nutrition Health and Aging 01/2015; 19(1):48-57. DOI:10.1007/s12603-014-0489-1 · 2.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multiple abnormalities occur in the homeostasis of essential endogenous brain biometals in age-related neurodegenerative disorders, Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. As a result, metals both accumulate in microscopic proteinopathies, and can be deficient in cells or cellular compartments. Therefore, bulk measurement of metal content in brain tissue samples reveal only the "tip of the iceberg", with most of the important changes occurring on a microscopic and biochemical level. Each of the major proteins implicated in these disorders interacts with biological transition metals. Tau and the amyloid protein precursor have important roles in normal neuronal iron homeostasis. Changes in metal distribution, cellular deficiencies, or sequestration in proteinopathies all present abnormalities that can be corrected in animal models by small molecules. These biochemical targets are more complex than the simple excess of metals that are targeted by chelators. In this review we illustrate some of the richness in the science that has developed in the study of metals in neurodegeneration, and explore its novel pharmacology.
    Chemical Society Reviews 08/2014; 43(19). DOI:10.1039/c4cs00138a · 30.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Disbalance of zinc (Zn2+) and copper (Cu2+) ions in the central nervous system is involved in the pathogenesis of numerous neurodegenerative disorders such as multisystem atrophy, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, Wilson-Konovalov disease, Alzheimer's disease, and Parkinson's disease. Among these, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most frequent age-related neurodegenerative pathologies with disorders in Zn2+ and Cu2+ homeostasis playing a pivotal role in the mechanisms of pathogenesis. In this review we generalized and systematized current literature data concerning this problem. The interactions of Zn2+ and Cu2+ with amyloid precursor protein (APP), β-amyloid (Abeta), tau-protein, metallothioneins, and GSK3β are considered, as well as the role of these interactions in the generation of free radicals in AD and PD. Analysis of the literature suggests that the main factors of AD and PD pathogenesis (oxidative stress, structural disorders and aggregation of proteins, mitochondrial dysfunction, energy deficiency) that initiate a cascade of events resulting finally in the dysfunction of neuronal networks are mediated by the disbalance of Zn2+ and Cu2+.
    Biochemistry (Moscow) 05/2014; 79(5):391-6. DOI:10.1134/S0006297914050022 · 1.35 Impact Factor

Full-text (2 Sources)

Download
48 Downloads
Available from
Jun 1, 2014