Midlife insulin resistance, APOE genotype, and late-life brain amyloid accumulation

: Ekblad LL, Johansson J, Helin S, Viitanen M, Laine H, Puukka P, Jula A, Rinne JO

Publisher: LIPPINCOTT WILLIAMS & WILKINS

: 2018

: Neurology

: NEUROLOGY

: 90

: 13

: E1150

: E1157

: 9

: 0028-3878

DOI: https://doi.org/10.1212/WNL.0000000000005214

: https://research.utu.fi/converis/portal/detail/Publication/34041865

ObjectiveTo examine whether midlife insulin resistance is an independent risk factor for brain amyloid accumulation in vivo after 15 years, and whether this risk is modulated by APOE epsilon 4 genotype.MethodsThis observational study examined 60 elderly volunteers without dementia (mean age at baseline 55.4 and at follow-up 70.9 years, 55.5% women) from the Finnish population-based, nationwide Health2000 study with [C-11]Pittsburgh compound B-PET imaging in 2014-2016. The participants were recruited according to their homeostatic model assessment of insulin resistance (HOMA-IR) values in the year 2000, and their APOE epsilon 4 genotype. The exposure group (IR+, n = 30) consisted of individuals with HOMA-IR > 2.17 at baseline (highest tertile of the Health2000 study population), and the control group (IR-, n = 30) consisted of individuals with HOMA-IR < 1.25 at baseline (lowest tertile). The groups were enriched for APOE epsilon 4 carriers, resulting in 50% (n = 15) APOE epsilon 4 carriers in both groups. Analyses were performed with multivariate logistic and linear regression.ResultsAn amyloid-positive PET scan was found in 33.3% of the IR-group and 60.0% of the IR+ group (odds ratio 3.0, 95% confidence interval 1.1-8.9, p = 0.04). The increased risk was seen in carriers and noncarriers of APOE epsilon 4 genotype. Higher midlife, but not late-life continuous HOMA-IR was associated with a greater brain amyloid burden at follow-up after multivariate adjustments for other cognitive and metabolic risk factors (ss = 0.11, 95% confidence interval 0.002-0.22, p = 0.04).ConclusionsThese results indicate that midlife insulin resistance is an independent risk factor for brain amyloid accumulation in elderly individuals without dementia.

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