Premium
Insulin resistance is related to cognitive decline but not biomarkers of Alzheimer’s pathology in adults without dementia
Author(s) -
Ennis Gilda E,
Koscik Rebecca L,
Ma Yue,
Betthauser Tobey J,
Jonaitis Erin M,
Van Hulle Carol A,
Bouges Shenikqua,
Chin Nathaniel A,
Engelman Corinne D,
Anderson Rozalyn,
Batrla Richard,
Kollmorgen Gwendlyn,
Carlsson Cynthia M,
Asthana Sanjay,
Johnson Sterling C,
Zetterberg Henrik,
Blennow Kaj,
Bendlin Barbara B
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.047022
Subject(s) - insulin resistance , homeostatic model assessment , medicine , biomarker , dementia , cerebrospinal fluid , cognitive decline , apolipoprotein e , amyloid (mycology) , alzheimer's disease , oncology , psychology , insulin , endocrinology , disease , pathology , chemistry , biochemistry
Background Insulin resistance (IR) has been related to increased risk for Alzheimer’s clinical syndrome. While some cross‐sectional studies have linked IR to Alzheimer’s disease (AD) pathology, others have been negative. We examined the relationship of IR to longitudinal cerebrospinal fluid (CSF) biomarkers of AD pathology, cerebral amyloid chronicity, and cognitive decline. Method Participants (Table 1) were enrolled in the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a longitudinal observational study of non‐demented adults. We utilized data from biennial visits and CSF and positron emission tomography (PET) sub‐studies. For our first study, participants (n=148) had CSF biomarker data (Aβ 42 : Aβ 40 ratio, p‐tau 181 , t‐tau, and neurogranin) from 1‐5 CSF samples collected every 2‐8 years and fasting insulin and glucose (collected during 1‐5 visits before first CSF) for calculating homeostatic model assessment of insulin resistance (HOMA‐IR). CSF was assayed using the Roche NeuroToolKit on the Elecsys ® platform. Linear mixed effects models tested HOMA‐IR as a moderator of aging‐related change in CSF biomarkers. In study 2, participants (n=253) had [C11]PiB PET imaging and 3‐6 HOMA‐IR values for calculating a within‐person HOMA‐IR mean and SD (i.e., fluctuation). Amyloid chronicity was calculated by subtracting estimated age at PiB positivity (i.e., estimated age when PiB DVR ≥ 1.2) (Koscik & Betthauser, et al., 2020) from age at last HOMA‐IR. Hierarchical regression tested whether HOMA‐IR and an HOMA‐IR x APOE 4 interaction predicted amyloid chronicity. In study 3 (n=1,298), linear mixed effects tested if baseline HOMA‐IR moderated age‐related decline in longitudinal measures of the preclinical Alzheimer’s cognitive composite (PACC). Age, APOE 4, sex, education, and systolic blood pressure (SBP) were controlled in all study models. Result HOMA‐IR was not a significant moderator of aging‐related change in any CSF biomarker (Figure 1 & 2). HOMA‐IR mean and SD and the HOMA‐IR x APOE 4 interaction were not significant predictors of amyloid chronicity. Increased HOMA‐IR predicted greater age‐related decline in PACC (Figure 3). Conclusion HOMA‐IR was related to cognitive decline but not cerebral amyloid chronicity or age‐related change in CSF biomarkers of AD pathology and neurodegeneration. IR may not be directly related to preclinical AD pathology. Pathways linking IR to dementia require further investigation.