As a major outcome, two novel DOAC hits, namely the 1-(pyridin-4-yl)- (1) and 1-amidino- (23) isonipecotanilide derivatives, which proved to inhibit contemporarily thr/AChE and fXa/BChE, respectively, with inhibition constants in the low nanomolar range, deserve investigation in further ex vivo and in vivo animal models of AD and related cognitive impairments. This evidence concerns the gene ACHE and Cognitive impairment.