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Open Access 01-12-2023 | Insulins | Research

The relationship of insulin resistance and diabetes to tau PET SUVR in middle-aged to older adults

Authors: Gilda E. Ennis, Tobey J. Betthauser, Rebecca Langhough Koscik, Nathaniel A. Chin, Bradley T. Christian, Sanjay Asthana, Sterling C. Johnson, Barbara B. Bendlin

Published in: Alzheimer's Research & Therapy | Issue 1/2023

Abstract

Background

Insulin resistance (IR) and type 2 diabetes have been found to increase the risk for Alzheimer’s clinical syndrome in epidemiologic studies but have not been associated with tau tangles in neuropathological research and have been inconsistently associated with cerebrospinal fluid P-tau181. IR and type 2 diabetes are well-recognized vascular risk factors. Some studies suggest that cardiovascular risk may act synergistically with cortical amyloid to increase tau measured using tau PET. Utilizing data from largely nondemented middle-aged and older adult cohorts enriched for AD risk, we investigated the association of IR and diabetes to tau PET and whether amyloid moderated those relationships.

Methods

Participants were enrolled in either the Wisconsin Registry for Alzheimer’s Prevention (WRAP) or Wisconsin Alzheimer’s Disease Research Center (WI-ADRC) Clinical Core. Two partially overlapping samples were studied: a sample characterized using HOMA-IR (n=280 WRAP participants) and a sample characterized on diabetic status (n=285 WRAP and n=109 WI-ADRC). IR was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). Tau PET employing the radioligand ¹⁸F-MK-6240 was used to detect AD-specific aggregated tau. Linear regression tested the relationship of IR and diabetic status to tau PET standardized uptake value ratio (SUVR) within the entorhinal cortex and whether relationships were moderated by amyloid assessed by amyloid PET distribution volume ratio (DVR) and amyloid PET positivity status.

Results

Neither HOMA-IR nor diabetic status was significantly associated with tau PET SUVR. The relationship between IR and tau PET SUVR was not moderated by amyloid PET DVR or positivity status. The association between diabetic status and tau PET SUVR was not significantly moderated by amyloid PET DVR but was significantly moderated by amyloid PET positivity status. Among the amyloid PET-positive participants, the estimated marginal tau PET SUVR mean was higher in the diabetic (n=6) relative to the nondiabetic group (n=88).

Conclusion

Findings indicate that IR may not be related to tau in generally healthy middle-aged and older adults who are in the early stages of the AD clinicopathologic continuum but suggest the need for additional research to investigate whether a synergistic relationship between type 2 diabetes and amyloid is associated with increased tau levels.

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Title: The relationship of insulin resistance and diabetes to tau PET SUVR in middle-aged to older adults
Authors: Gilda E. Ennis
Tobey J. Betthauser
Rebecca Langhough Koscik
Nathaniel A. Chin
Bradley T. Christian
Sanjay Asthana
Sterling C. Johnson
Barbara B. Bendlin
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Insulins
Alzheimer's Disease
Positron Emission Tomography
Alzheimer's Disease
Insulins
Type 2 Diabetes
Published in: Alzheimer's Research & Therapy / Issue 1/2023
Electronic ISSN: 1758-9193
DOI: https://doi.org/10.1186/s13195-023-01180-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The relationship of insulin resistance and diabetes to tau PET SUVR in middle-aged to older adults

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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