Abstract: In alternative embodiments the invention provides compositions and methods for ameliorating diseases and conditions having a beta-amyloid component, including Alzheimer's disease (AD), Vascular Dementia (VD), dementia, pre-dementia, Cognitive Dysfunction Syndrome (CDS) and loss of cognition in humans and in non-human animal. In alternative embodiment the invention provides analogs of AB-007 and its acid form E64c (loxistatin), their preparation, and pharmaceutical compositions thereof and methods of making and using same. In alternative embodiments compositions of the invention are deuterated analogs of AB-007 (or E64d) and E64c (or loxistatin). In alternative embodiments compositions of the invention are metabolically blocked forms as compared to AB-007 and loxistatin. In alternative embodiments compositions of the invention are used to ameliorate (including treat, slow, reverse or prevent) a disease or condition which can be ameliorated by partial or complete inhibition of a cysteine protease, e.g.