Oxidative balance, homocysteine, and uric acid levels in older patients with Late Onset Alzheimer's Disease or Vascular Dementia Carlo Cervellati a, ⁎, Arianna Romani a , Davide Seripa b , Eleonora Cremonini a , Cristina Bosi c , Stefania Magon c , Angelina Passaro c , Carlo M. Bergamini a , Alberto Pilotto d , Giovanni Zuliani c a Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, 44121 Ferrara, Italy b Gerontology and Geriatric Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo 71013, Foggia, Italy c Department of Medical Science, Section of Internal Medicine, Gerontology, and Clinical Nutrition, University of Ferrara, 44100 Ferrara, Italy d Geriatrics Unit, Azienda ULSS 16 Padova, S. Antonio Hospital, 35127 Padova, Italy abstract article info Article history: Received 12 October 2013 Received in revised form 20 November 2013 Accepted 25 November 2013 Available online xxxx Keywords: Dementia Homocysteine Late Onset Alzheimer's Disease Oxidative stress Uric acid Vascular Dementia This study aimed to investigate whether Late Onset Alzheimer's Disease (LOAD) and Vascular Dementia (VAD) might be associated with a distinct profile of oxidative stress (OxS) peripheral markers. Serum levels of hydroper- oxides, homocysteine, advanced oxidation protein products, uric acid, thiols, and total and residual antioxidant power were assessed in 103 mild cognitive impairment (MCI), 89 LOAD, 54 VAD patients and 48 Controls. Compared with Controls, a similar oxidative unbalance (high hydroperoxides and low residual antioxidant power) was observed in MCI, LOAD and, although less pronounced, VAD. Moreover, individuals with simulta- neously high levels of homocysteine and uric acid, both well-known risk factors for cardiovascular disease, had a high probability to be affected by VAD (O.R.:10.50; 95% C.I.: 2.33–47.2), but not LOAD (O.R.: 3.0; 95% C.I.:0.86–10.76) compared with individuals with normal values. Our data suggest that, although they might share a common OxS-related pathogenesis, VAD and LOAD might maintain some distinctive features, with a predominance of “vascular component” in VAD compared with LOAD. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Late Onset Alzheimer's Disease (LOAD) and Vascular Dementia (VAD) represent the two most common forms of dementia in elderly populations with nearly 70% of patients belonging to LOAD and 20% to VAD [1]. Thus far, the clear cut-off diagnosis differentiating LOAD and VAD is complicated by the lack of well-recognized discriminatory parameters, in particular as regards the cognitive profile [2]. Moreover, it is acknowledged that some markers of vascular injury typical of VAD might coexist with the diagnosis of LOAD [3,4]. In parallel, amyloid β (Aβ) accumulation, one of the recognized pathological hallmarks of Alzheimer disease, has been found, at a minor extent, also in patients affected by VAD [5]. It has been proposed that oxidative stress (OxS) might play a key-role in the pathogenesis of both LOAD and VAD [4]. Indeed, free radicals, including reactive oxygen species (ROS), can react with substrates essential for the survival of neurons such as proteins, lipids, and nucleic acid, leading to neuropathological lesions and to brain damage [6,7]. Besides, brain is highly susceptible to oxidative damage, mainly because of the high level of polyunsaturated fatty acid (the main target of free radicals attack), the high oxygen requirement for its metabolic processes, and the low concentration of antioxidants contrasting ROS activity [8,9]. In LOAD, OxS might be both the cause of Aβ accumulation, by increasing Aβ precursor protein (APP), and the effect of Aβ accumulation, thus emphasizing the neurotoxicity of the amyloid [10–12]. On the other hand, the origin of OxS in VAD might be more associated to the typical vascular abnormalities observed in patients affected by this type of dementia. Indeed, vascular endothelium is able to synthesize, store, and release free radicals in response to stimuli such as injury and hypox- ia/hypoperfusion [13]. Vascular OxS is also implicated in the onset of several well-recognized risk factors for VAD (and LOAD) including diabetes, stroke, atherosclerosis, and hypertension [13]. The relationship between OxS and dementia development has been nicely characterized in animals, in vitro, and in post-mortem models, but it still awaits confirmations by studies on living human patients [14–18]. This is more evident for clinical data regarding VAD, which are substantially contrasting since both increased markers of oxidative damage and/or decrease antioxidants [19–21] or normal OxS peripheral level [22] have been reported. These discrepancies might be explained by some limitations of previous studies including small sample size, lack of control over relevant confounding factors (i.e. age, diabetes, and hypertension), and use of OxS marker detection methods with low reliability. In this study we tried to overcome some of these limitations. To address this issue, we evaluated a number of distinct serum indicators Journal of the Neurological Sciences xxx (2013) xxx–xxx ⁎ Corresponding author at: Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, Via Luigi Borsari, 46, 44121 Ferrara, Italy. Tel.: +39 3480399087; fax: +39 0532 45 44 42. E-mail address: crvcrl@unife.it (C. Cervellati). JNS-12943; No of Pages 6 0022-510X/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jns.2013.11.041 Contents lists available at ScienceDirect Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns Please cite this article as: Cervellati C, et al, Oxidative balance, homocysteine, and uric acid levels in older patients with Late Onset Alzheimer's Disease or Vascular Dementia, J Neurol Sci (2013), http://dx.doi.org/10.1016/j.jns.2013.11.041