Discussion
Transient visual disturbances, memory, cognitive function, AD dementia
DISEASE
The present trial did not demonstrate PoCC for the efficacy of BI 425809 in improving memory, cognitive function, and activities of daily living in patients with probable AD dementia, and therefore, a suitable dose could not be defined in this patient population.No significant, non-flat dose–response relationships for any of the models used was detected for the change from baseline to week 12 in the ADAS-CogBI 425809 was generally well-tolerated with no new safety issues identified. No meaningful differences between the treatment groups or dose dependencies were observed. Transient visual disturbances and central nervous system side effects have previously been noted for GlyT1 inhibitors [There are a few potential limitations to this study. The trial was of a relatively short duration (12 weeks); it may be that this period was not long enough to reveal any statistically or clinically relevant effects of treatment. Nonetheless, in the case of a symptomatic effect, one would expect an early response; therefore, a longer trial may not necessarily have yielded different results. Additionally, patients with a broad range of disease severity (mild-to-moderate with MMSE scores ranging from 15 to 26 at screening) were recruited, and the presence or absence of background AChEIs might also impact our findings. However, findings from the numerical analysis of the mild versus moderate probable AD dementia subgroups, as well as the subgroup of patients with concomitant AChEI use, were similar to those of the overall analyses.Another potential limitation may be that some of the patients recruited for the trial were too advanced in the progression of their disease symptomatology for GlyT1 inhibition to have an effect [In 2018, the NIA-AA changed their diagnostic criteria of AD for research purposes from a clinical to biological definition, with biomarker and neuropathological findings now forming the basis of these criteria [