Association of Dipeptidyl Peptidase-4 Inhibitor Use and Amyloid Burden in Diabetic Patients With AD-Related Cognitive Impairment

Objectives:To investigate whether dipeptidyl peptidase-4 inhibitors (DPP-4i) have beneficial effects on amyloid aggregation and longitudinal cognitive outcome in diabetic Alzheimer’s disease-related cognitive impairment (ADCI).Methods:We retrospectively reviewed 282 patients with ADCI who had positive scan of 18F-florbetaben amyloid PET images were classified into three groups according to a prior diagnosis of diabetes and DPP-4i use: diabetic patients being treated with (ADCI-DPP-4i+, n=70) or without DPP-4i (ADCI-DPP-4i-, n=71), and non-diabetic patients (n=141). Multiple linear regression analyses were performed to determine inter-group differences in global and regional amyloid retention using standardized uptake value ratios calculated from cortical areas. We assessed the longitudinal changes in Mini-Mental State Examination (MMSE) score using a linear mixed model.Results:The ADCI-DPP-4i+ group had lower global amyloid burden than the ADCI-DPP-4i− group (β = 0.075, SE = 0.024, p = 0.002) and the non-diabetic ADCI group (β = 0.054, SE = 0.021, p = 0.010) after adjusting for age, sex, education, cognitive status, and APOE ε4 carrier status. Additionally, the ADCI-DPP-4i+ group had lower regional amyloid burden in temporo-parietal areas than either the ADCI-DPP-4i− group or the non-diabetic ADCI group. The ADCI-DPP-4i+ group showed a slower longitudinal decrease in MMSE score (β = 0.772, SE = 0.272, p = 0.005) and memory recall sub-score (β = 0.291, SE = 0.116, p = 0.012) than the ADCI-DPP-4i− group.Conclusions:These findings suggest that DPP-4i use is associated with low amyloid burden and favorable long-term cognitive outcome in diabetic patients with ADCI.