Importance of Treatment Status in Links Between Type 2 Diabetes and Alzheimer’s Disease

Abstract

OBJECTIVE To investigate relationships among type 2 diabetes treatment, Alzheimer’s disease(AD) biomarkers, and risk for dementia. RESEARCH DESIGN AND METHODS Participants were from the Alzheimer's Disease Neuroimaging Initiative (N = 1,289) and were dementia-free at baseline and underwent health assessment, cognitive testing, and MRI. A subset (n = 900) obtained a lumbar puncture to determine cerebrospinal fluid (CSF) phosphorylated tau (p-tau), total tau (t-tau), and β-amyloid 1-42 (Aβ1-42). Participants were grouped by fasting blood glucose and medication history: euglycemia (EU), prediabetes (PD), untreated diabetes (UD), and treated diabetes (TD). Relationships were investigated between treatment status and CSF biomarkers and risk for dementia. RESULTS The UD group displayed greater p-tau, t-tau, and p-tau/Aβ1-42 levels than the EU, PD, and TD groups (P values <0.05) and higher t-tau/Aβ1-42 than the EU and PD groups (P values <0.05). The UD group progressed to dementia at higher rates than the EU group (hazard ratio 1.602 [95% CI 1.057–2.429]; P = 0.026). CONCLUSIONS Treatment status may alter the relationship between type 2 diabetes and both AD biomarker profile and risk for dementia. UD is associated with elevated tau pathology and risk for dementia, whereas TD is not. Although this study is observational and therefore causality cannot be inferred, findings support the potential importance of treatment status in AD risk associated with type 2 diabetes.