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Introduction Dementia is one of the greatest health challenges the world will face in the coming decades, as it is one of the principal causes of disability and dependency among older people. Economic modelling is used widely across many health conditions to inform decisions on health and social care policy and practice. The aim of this literature review is to systematically identify, review and critically evaluate existing health economics models in dementia. We included the full spectrum of dementia, including Alzheimer's disease (AD), from preclinical stages through to severe dementia and end of life. This review forms part of the Real world Outcomes across the Alzheimer's Disease spectrum for better care: multimodal data Access Platform (ROADMAP) project. Methods and analysis Electronic searches were conducted in Medical Literature Analysis and Retrieval System Online, Excerpta Medica dataBASE, Economic Literature Database, NHS Economic Evaluation Database, Cochrane Central Register of Controlled Trials, Cost-Effectiveness Analysis Registry, Research Papers in Economics, Database of Abstracts of Reviews of Effectiveness, Science Citation Index, Turning Research Into Practice and Open Grey for studies published between January 2000 and the end of June 2017. Two reviewers will independently assess each study against predefined eligibility criteria. A third reviewer will resolve any disagreement. Data will be extracted using a predefined data extraction form following best practice. Study quality will be assessed using the Phillips checklist for decision analytic modelling. A narrative synthesis will be used. Ethics and dissemination The results will be made available in a scientific peer-reviewed journal paper, will be presented at relevant conferences and will also be made available through the ROADMAP project. PROSPERO registration number CRD42017073874. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) induces oxidative stress that ultimately defines cell fate and pathology. Mitochondria are the main energy-producing organelles in mammalian cells, but they also have a central role in formation of reactive oxygen species, cell injury, and death signaling. As the kidney is the major target in Cd toxicity, the roles of oxidative signature and mitochondrial function and biogenesis in Cd-related stress outcomes were investigated in vitro in cultured rat kidney proximal tubule cells (PTCs) (WKPT-0293 Cl.2) for acute Cd toxicity (1-30 µM, 24 h) and in vivo in Fischer 344 rats for sub-chronic Cd toxicity (1 mg/kg CdCl subcutaneously, 13 days). Whereas 30 µM Cd caused ~50 % decrease in cell viability, apoptosis peaked at 10 µM Cd in PTCs. A steep, dose-dependent decline in reduced glutathione (GSH) content occurred after acute exposure and an increase of the oxidized glutathione (GSSG)/GSH ratio. Quantitative PCR analyses evidenced increased antioxidative enzymes (Sod1, Gclc, Gclm), proapoptotic Bax, metallothioneins 1A/2A, and decreased antiapoptotic proteins (Bcl-xL, Bcl-w). The positive regulator of mitochondrial biogenesis Pparγ and mitochondrial DNA was increased, and cellular ATP was unaffected with Cd (1-10 µM). In vivo, active caspase-3, and hence apoptosis, was detected by FLIVO injection in the kidney cortex of Cd-treated rats together with an increase in Bax mRNA. However, antiapoptotic genes (Bcl-2, Bcl-xL, Bcl-w) were also upregulated. Both GSSG and GSH increased with chronic Cd exposure with no change in GSSG/GSH ratio and augmented expression of antioxidative enzymes (Gpx4, Prdx2). Mitochondrial DNA, mitofusin 2, and Pparα were increased indicating enhanced mitochondrial biogenesis and fusion. Hence, these results demonstrate a clear involvement of higher mitochondria copy numbers or mass and mitochondrial function in acute defense against oxidative stress induced by Cd in renal PTCs as well as in adaptive processes associated with chronic renal Cd toxicity. [ABSTRACT FROM AUTHOR]

Research on addiction suggests that emotional alterations play an essential role in the development, maintenance, relapse and treatment outcome of substance abuse disorders. Although many neuroimaging studies focussed on the neural response to conditioned stimuli, much less is known about the neural response to natural affective stimuli in this pathological population. Previous research has demonstrated an altered emotional experience and autonomic response to emotional stimuli using the International Affective Picture System (IAPS) in drug abusers. Here we aimed, using functional magnetic resonance imaging (fMRI), to study the alterations in the neural responsitivity to pleasant (erotic), unpleasant and neutral IAPS stimuli in cocaine addiction. Thirty-two cocaine-dependent subjects and 26 matched controls completed an fMRI session during the presentation of a set of IAPS pictures as background, while performing a letter discrimination task. Consistent with previous studies, emotional pictures activated an emotional network including amygdala, medial prefrontal cortex, orbitofrontal cortex and occipito-temporal areas in both groups. However, compared with controls, the cocaine group showed a significant hypoactivation of the dorsal and ventral striatum (including the nucleus accumbens), thalamus, parietal cortex and dorso-medial prefrontal cortex (dmPFC) when processing pleasant pictures. The analysis of pleasant versus unpleasant stimuli suggested that between-group differences in the dmPFC and striatal activation may be attributed to arousal processing rather than valence. These results could reflect the neural basis for the reduced ability of cocaine-dependent subjects to experience pleasure by daily natural reinforcers, suggesting that these alterations in the emotion processing may play an important role in drug dependence, treatment and relapse. [ABSTRACT FROM AUTHOR]