LAUSR

There have been an increasing number of publications on new medications for Alzheimer’s disease (AD). Results from the first study in mild-to-moderate stages of AD using LMTM which inhibits the tau protein aggregation were recently published [1], and results from the second study in mild AD have been presented at the CTAD congress in San Diego on 8 December: although the analysis comparing low versus high doses in all participants showed no difference on cognitive and functional outcomes, there is the possibility that concurrent AD drugs interfered with the LMTM therapeutic activity. Similarly, the 5-HT6 receptor inhibitor antagonist idalopirdine which had shown encouraging results in donepezil-treated patients [2] did not show efficacy in high doses, but there is still hope for the lower doses still under testing. Thus, it appears that current trial designs where drugs are simply added on to each other do not allow to adequately measure positive (synergistic) and negative interactions. This is an important lesson as the field is planning combination therapies against various components of AD [3,4]. Results from a large-scale phase 3 study using the antiamyloid drug solanezumab in mild AD were reported on 22 November as negative for the cognitive primary outcome. This antibody against the beta42-amyloid protein had shown encouraging results in mild AD using pooled analysis from two previous phase 3 studies [5]. Results from a phase 1b study using the monoclonal antibody aducanumab demonstrated a reduction in the amount of beta-amyloid in the brain and a stabilization of clinical decline that was doserelated [6]; this has led to a large phase 3 study, still enrolling. Drugs acting by inhibition of the enzyme ß-secretase (BACE1 inhibitor) such as verubecestat are showing encouraging results [7], and there is even consideration of combining acting on the amyloid protein in different ways (antibodies and BACE1 inhibitors). This looks like a lot of medication to be used potentially in a lot of persons, and none has been demonstrated to achieve disease modification. Prevention of AD is thus clearly the current preferred alternative [8], and national plans in many countries are encouraging higher education and healthier lifestyles. The decrease in prevalence of dementia in the United States between 2000 and 2012 is attributed primarily to an increase in educational attainment [9], and other countries are reporting reductions attributed to stricter control of vascular risk factors in mid-life. An excellent overall perspective on how to defeat dementia has been written by science writer Elie Dolgin, in his feature news [10].