Associations between glucose metabolism measures and amyloid and tau load on PET 14 years later: Findings from the Framingham Heart Study

Objective. Type 2 diabetes and glucose metabolism have previously been linked to Alzheimer’s disease (AD). Yet, findings on the relation of glucose metabolism with amyloid and tau pathology later in life remain unclear.

Research Design and Methods. We included 288 participants (mean age= 43.1, SD=10.7, range 20-70) without dementia from the Framingham Heart Study (FHS), who had available measures of glucose metabolism (i.e., one-time fasting plasma glucose and insulin) and PET measures of amyloid and/or tau 14 years later. We performed linear regression analyses to test associations of plasma glucose (continuously and categorically; elevated defined as >100mg/dl), plasma insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) with amyloid or tau load on PET. When significant, we explored whether age, sex, and APOE ε4 allele carriership (AD genetic risk) modified these associations.

Results. Our findings indicated that elevated plasma glucose was associated with greater tau load 14 years later (B[95%CI]=0.03 [0.01 – 0.05], p=0.024 after false discovery rate (FDR) correction) but not amyloid. APOE ε4 carriership modified this association (B[95%CI]: -0.08 [-0.12 – -0.03], p=0.001), indicating that the association was only present in APOE ε4 non-carriers (n=225). Plasma insulin and HOMA-IR were not associated with amyloid or tau load 14 years later after FDR correction.

Conclusions. Our findings suggest that glucose metabolism is associated with increased future tau but not amyloid load. This provides relevant knowledge for prevention strategies and prognostics to improve healthcare.