Type 2 diabetes is associated with reduced performance in multiple cognitive domains. Despite promising findings supported by an increasing number of preclinical and clinical studies, the neuroprotective effects of antidiabetic therapy remain still controversial and the pathological pathways underlying the cognitive impairment onset to be elucidated. Real-world data contribute to drive better study design, generating real-world evidence to significantly contribute to steps towards the drug repurposing and the individualized therapy, thus reducing the burden of chronic disease, in the clinical practice.
AIM 1:
To evaluate the beneficial effects of antidiabetic therapy to individuals more prone developing CI by including patients with one prescription for anti-diabetic drugs for T2DM. Comparisons with controls will be carried out. The study population of interest will be monitored starting from the date of their first prescription (index date) and categorized into several cohorts based on the drug treatment.
Participants will be monitored for 10 years from the index date until the outcome occurred. Outcomes: 1. diagnosis of major CI defined as a hospital admission. New prescriptions for anti-dementia drugs will also be evaluated. 2. primary diagnosis of mild CI defined as hospital admission. A descriptive analysis will be conducted, including age, sex, comorbidities and concomitant drugs, laboratory test analysis. Survival analysis will be done to evaluate and compare the risk of cognitive decline among the groups.
AIM 2-AIM 3:
To shed light on bidirectional relationship between diabetes and the onset of cognitive decline and to investigate the interindividual variation in drug response based on genetic profile by evaluating the change of a set of biomarkers indicative of inflammation and of immune aging, also investigating whether poorly controlled diabetes, clinical complications, concomitant metabolic disorders (or alterations), genetic polymorphism (AIM 3)
