Relationship of insulin resistance and glucose to tau PET positivity

Abstract

AbstractBackgroundInsulin resistance (IR) and hyperglycemia have been linked to increased dementia risk. In some animal studies IR and hyperglycemia have been associated with tau hyperphosphorylation. In a sample of predominantly healthy middle‐aged and older adults, we examined whether higher IR and fasting glucose were related to increased odds of tau PET positivity assessed using [F‐18]MK‐6240 positron emission tomography (PET). We also explored whether relationships to tau PET positivity were moderated by global amyloid pathology measured using [C‐11]PiB PET.MethodParticipants were enrolled in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) and the Wisconsin Alzheimer’s Disease Research Center (ADRC) Clinical Core (Table 1). In the IR study, n=231 WRAP participants had homeostatic model assessment of insulin resistance (HOMA2‐IR) and PET. Twenty‐eight (12.1%) were tau PET positive (entorhinal MK‐6240 SUVR > 1.27; Betthauser et al., 2020) and 59 (25.5%) were amyloid PET positive (global PiB DVR > 1.19; Racine et al., 2016). In the Glucose study, n=332 participants (n=239 WRAP; n=93 Wisconsin‐ADRC) had fasting glucose and PET. Forty‐nine (14.8%) exhibited tau PET positivity and 81 (24.4%) were amyloid PET positive. Binary logistic regression tested whether HOMA2‐IR and glucose were related to odds of tau PET positivity. Global PiB DVR was explored as a moderator of HOMA2‐IR and glucose in separate logistic regressions.ResultHOMA2‐IR and glucose were not significantly related to odds of tau PET positivity (ps > .37), controlling for age, sex and global PiB DVR (Figure 1). Higher global PiB DVR (standardized using cut‐point to center) was significantly related to greater odds of tau PET positivity [IR study: Exp(2.8), p < .001, 95%CI: 1.9‐4.1; Glucose study: Exp(3.1), p <.001, 95%CI: 2.3‐4.4]. Global PiB DVR was not a significant moderator of insulin or glucose (ps > .81; Figure 2).ConclusionHOMA2‐IR and glucose may not be related to tau pathology in cognitively unimpaired adults. The low proportion of participants who were tau PET positive likely limited the detection of significant interaction effects. Additional research is needed in samples with a greater proportion of diabetic and cognitively impaired participants to determine potential pathways linking IR and glucose to dementia.