The key strengths of our study was the length of follow-up of our patients; the median duration of follow-up Protein Tyrosine Kinase inhibitor for mixed AD and pure AD was 28.2 and 36 months, respectively. Furthermore, our study was a naturalistic study on outcomes of cognitive enhancers in AD that aimed to describe results from treatment in patients who were treated by usual care. Naturalistic studies mirrored naturalistic outpatient settings and so served a complementary role to more structured efficacy trials and pragmatic studies of AD. The study also has several limitations: this was a retrospective study without randomization of cognitive enhancer assignment and no control for prestudy

exposure to other medications. The results were findings from a single center with the types of cognitive enhancers used representing the practice in our center. However, this practice was based on BYL719 clinical trial evidence of cognitive enhancers that were shown to delay cognitive impairment in patients with mild to moderately severe

AD, with no robust support for any one drug [14]. Patients with AD + svCVD were over-represented in our sample, which may reduce the generalizability of our findings. Hence, these findings should be MM-102 confirmed in independent samples with adequate representation of patients with ‘pure AD’ and ‘AD + svCVD’. 5 Conclusion Cholinergic dysfunction is present in both AD and mixed AD of the svCVD category. Cognitive enhancers are effective in slowing the rate of cognitive decline in patients with AD, and seemingly more so for patients with mixed AD of the svCVD

category. The finding of potential benefit of cognitive enhancer therapy for patients with AD + svCVD will need to be confirmed in randomized clinical trials. Acknowledgment The research was supported by the National Neuroscience Institute, Singapore. Author Contributions Ng Kok Pin contributed to the study design, interpretation of data, drafting/revising of the manuscript for intellectual content and gave final approval. Aloysius Ng contributed to the acquisition of data, statistical analysis, interpretation of the data, drafting/revising of the Thiamet G manuscript for intellectual content and gave final approval. Pryseley Assam contributed to the statistical analysis, interpretation of results, drafting/revising the manuscript for intellectual content and gave final approval. Esther Heng contributed to the acquisition of data, statistical analysis, interpretation of data and gave final approval. Nagaendran Kandiah contributed to the study design, statistical analysis, interpretation of the data, drafting/revising of the manuscript and gave final approval. Conflict of Interest Disclosures Ng Kok Pin reports no conflict of interest. Aloysius Ng reports no conflict of interest. Pryseley Assam reports no conflict of interest. Esther Heng reports no conflict of interest.