Insulin resistance is related to cognitive decline but not change in CSF biomarkers of Alzheimer's disease in non-demented adults.

Abstract

INTRODUCTION:

We investigated whether insulin resistance (IR) was associated with longitudinal age-related change in cognition and biomarkers of Alzheimer's disease (AD) pathology and neurodegeneration in middle-aged and older adults who were non-demented at baseline.

METHODS:

IR was measured with homeostatic model assessment of insulin resistance (HOMA2-IR). Core AD-related cerebrospinal fluid (CSF) biomarkers and cognition were assessed, respectively, on n = 212 (1 to 5 visits) and n = 1299 (1 to 6 visits). Linear mixed models tested whether HOMA2-IR moderated age-related change in CSF biomarkers and cognition. Linear regressions tested whether HOMA2-IR x apolipoprotein E ε4 allele (APOE ε4) carrier status predicted amyloid beta [Aβ] chronicity (estimated duration of amyloid positron emission tomography [PET] positivity) (n = 253).

RESULTS:

Higher HOMA2-IR was associated with greater cognitive decline but not with changes in CSF biomarkers. HOMA2-IR x APOE4 was not related to Aβ chronicity but was significantly associated with CSF phosphorylated tau (P-tau)181/Aβ42 level.

DISCUSSION:

In non-demented adults IR may not be directly associated with age-related change in AD biomarkers. Additional research is needed to determine mechanisms linking IR to cognitive decline.

• Authors: Gilda E Ennis, Rebecca L Koscik, Yue Ma, Erin M Jonaitis, Carol A Van Hulle, Tobey J Betthauser, Allison M Randall, Nathaniel Chin, Corinne D Engelman, Rozalyn Anderson, Ivonne Suridjan, Gwendlyn Kollmorgen, Bradley T Christian, Cynthia M Carlsson, Sanjay Asthana, Sterling C Johnson, Henrik Zetterberg, Kaj Blennow, Barbara B Bendlin
• Journal: Alzheimer's & dementia (Amsterdam, Netherlands) (Alzheimers Dement (Amst)) Vol. 13 Issue 1 Pg. e12220 ( 2021) ISSN: 2352-8729 [Print] United States
• PMID: 34337133 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.