Around each of the slopes at each baseline HbA1c. This would permit a variety of scenarios such as high baseline HbA1c, negative slope, low standard deviation, etc. However, the trajectories that we found are empirical, reflecting the true reality of our sample, and converged to 6 trajectories, which do not cover all the spectrum of trajectories to, theoretically, enable such an examination. This is a limitation of an observational study, but, a randomized trial where patients with high initial HbA1c levels were treated/not treated to decrease it, would be unethical. We nevertheless, performed, on the full sample, secondary analyses examining the relationships of mean and standard deviation of HbA1c with the cognitive outcomes and found that higher mean and standard deviation in HbA1c measurements over time were associated with lower scores in overall cognitive score and in executive functions, consistent with the trajectories results. Brain imaging was not performed in this study, thus limiting our ability to evaluate the contribution of cerebrovascular abnormalities to the association of trends in glycemic control with cognition. This is particularly relevant both because T2D is a vascular disease, but also because trajectories of HbA1c were not associated with episodic memory, suggesting non AD-related mechanisms. Entry into the DR, rather than time of T2D diagnosis, which was not available to us, is referred to as “baseline”. Although women are slightly under-represented in the study, sex was one of the covariates in the comparison of groups. Israel has a strong family oriented culture, so a major role in grand- parenting was the primary reason of refusal by women to participate in the study. Additional strengths of this study include the large sample, validated T2D diagnosis for each subject, an average of 18 HbA1c measurements permitting investigation of trajectories of HbA1c over time, strong validity for risk factor levels and medical diagnosis, and a thorough cognitive evaluation. Fluorescent reporter proteins derived from the green fluorescent protein and its derivatives have been used to analyze a wide array of cellular processes such as gene regulation, protein localization, and protein interaction. However, GFP-based fluorescent proteins require molecular oxygen for the generation of cyclic tripeptide chromophore, which has been a major drawback in the GFP-based reporter protein applications under conditions with limited oxygen supply. Alternatively, the flavin mononucleotide -based fluorescent proteins can be employed as an in vivo reporter system. Bacterial FbFPs respond to light blue and activate stress-related signaling pathways. Among these FbFPs, Escherichia coli FbFP which consists of 137 amino acids was engineered from the photoactive LOV domain of Bacillus subtilis YtvA, which is a 261-amino acid protein consisting of two functional domains, a core LOV domain and a sulfate transporter.