DOMINO-AD protocol:donepezil and memantine in moderate to severe Alzheimer's disease - a multicentre RCT

Alzheimer's disease (AD) is the commonest cause of dementia. Cholinesterase inhibitors, such as donepezil, are the drug class with the best evidence of efficacy, licensed for mild to moderate AD, while the glutamate antagonist memantine has been widely prescribed, often in the later stages of AD. Memantine is licensed for moderate to severe dementia in AD but is not recommended by the England and Wales National Institute for Health and Clinical Excellence. However, there is little evidence to guide clinicians as to what to prescribe as AD advances; in particular, what to do as the condition progresses from moderate to severe. Options include continuing cholinesterase inhibitors irrespective of decline, adding memantine to cholinesterase inhibitors, or prescribing memantine instead of cholinesterase inhibitors. The aim of this trial is to establish the most effective drug option for people with AD who are progressing from moderate to severe dementia despite treatment with donepezil.

Comparative performances of birnessite and cryptomelane MnO as electrode material in neutral aqueous lithium salt for supercapacitor application

Na-doped Birnessite-type manganese oxide (d-MnO) has been synthesized using the chemical method and characterized through X-ray diffraction and SEM, showing the lamellar structure and high crystal structure. A comparative study of the electrochemical performances of this material with those of the commercial Cryptomelane-type MnO has then been undertaken in ten neutral aqueous electrolytes for supercapacitor applications. Aqueous electrolytes, containing a lithium salt, LiX (where X = SO , NO, CHCO , CHSO, ClO , CHCO, TFSI, Beti, BOB, or Lact), have been first prepared under neutral pH conditions to reach the salt concentration, providing the maximum in conductivity. Their transport properties are then investigated through conductivities, viscosities, and self-diffusion coefficient measurements. Second, the thermal behaviors of these electrolytic aqueous solutions are then evaluated by using a differential scanning calorimeter from (213.15 to 473.15) K in order to access their liquid range temperatures. Cyclic voltammograms (CV) in three electrode configurations are thereafter investigated using Na Birnessite and Cryptomelane as working electrode material from (-0.05 to 1.5) V versus Ag/AgCl at various sweep rates from (2 to 100) mV·s. According to anion nature/structure and manganese oxide material type, different CV responses are observed, presenting a pure capacitive profile for Beti or CH CO and an additional pseudocapacitive signal for the smallest anions, such as ClO and NO . The capacitances, energies, and efficiencies are finally calculated. These results indicate clearly that electrolytes based on a mineral lithium salt under neutral pH condition and high salt concentration (up to 5 mol·L) have better electrochemical performances than organic ones, up to 1.4 V with good material stability and capacity retention. The relationship between transport properties, electrostatic and steric hindrance considerations of hydrated ions, and their electrochemical performances is discussed in order to understand further the lithium intercalation-deintercalation processes in the lamellar or tunnel structure of investigated MnO. © 2013 American Chemical Society.