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. 2024 Sep 1;47(9):1530-1538.
doi: 10.2337/dc24-0229.

Plasma Biomarkers of Brain Injury and Their Association With Brain MRI and Cognition in Type 1 Diabetes

Amy B Karger  1 , Ilya M Nasrallah  2 , Barbara H Braffett  3 , José A Luchsinger  4 , Christopher M Ryan  5 , Ionut Bebu  3 , Valerie Arends  1 , Mohamad Habes  6 , Rose A Gubitosi-Klug  7 , Naomi Chaytor  8 , Geert J Biessels  9 , Alan M Jacobson  10 ; DCCT/EDIC Research Group
Affiliations

Plasma Biomarkers of Brain Injury and Their Association With Brain MRI and Cognition in Type 1 Diabetes

Amy B Karger et al. Diabetes Care. .

Abstract

Objective: To evaluate associations between plasma biomarkers of brain injury and MRI and cognitive measures in participants with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.

Research design and methods: Plasma amyloid-β-40, amyloid-β-42, neurofilament light chain (NfL), phosphorylated Tau-181 (pTau-181), and glial fibrillary acidic protein (GFAP) were measured in 373 adults who participated in the DCCT/EDIC study. MRI assessments included total brain and white matter hyperintensity volumes, white matter mean fractional anisotropy, and indices of Alzheimer disease (AD)-like atrophy and predicted brain age. Cognitive measures included memory and psychomotor and mental efficiency tests and assessments of cognitive impairment.

Results: Participants were 60 (range 44-74) years old with 38 (30-51) years' T1D duration. Higher NfL was associated with an increase in predicted brain age (0.51 years per 20% increase in NfL; P < 0.001) and a 19.5% increase in the odds of impaired cognition (P < 0.01). Higher NfL and pTau-181 were associated with lower psychomotor and mental efficiency (P < 0.001) but not poorer memory. Amyloid-β measures were not associated with study measures. A 1% increase in mean HbA1c was associated with a 14.6% higher NfL and 12.8% higher pTau-181 (P < 0.0001).

Conclusions: In this aging T1D cohort, biomarkers of brain injury did not demonstrate an AD-like profile. NfL emerged as a biomarker of interest in T1D because of its association with higher HbA1c, accelerated brain aging on MRI, and cognitive dysfunction. Our study suggests that early neurodegeneration in adults with T1D is likely due to non-AD/nonamyloid mechanisms.

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Conflict of interest statement

Duality of Interest. A.B.K. has received research support from Siemens Healthcare Diagnostics and Kyowa Kirin Pharmaceutical Development, has served as an external consultant for Roche Diagnostics, and has received speaker honoraria from the National Kidney Foundation, American Kidney Fund, American Society of Nephrology, and Yale University Department of Laboratory Medicine, all unrelated to this article. Industry contributors have had no role in the DCCT/EDIC study but have provided free or discounted supplies or equipment to support participants’ adherence to the study: Abbott Diabetes Care (Alameda, CA), Animas (Westchester, PA), Bayer Diabetes Care (North America Headquarters, Tarrytown, NY), Becton, Dickinson, and Company (Franklin Lakes, NJ), Eli Lilly (Indianapolis, IN), Extend Nutrition (St. Louis, MO), Insulet (Bedford, MA), Lifescan (Milpitas, CA), Medtronic Diabetes (Minneapolis, MN), Nipro Home Diagnostics (Ft. Lauderdale, FL), Nova Diabetes Care (Billerica, MA), Omron (Shelton, CT), Perrigo Diabetes Care (Allegan, MI), Roche Diabetes Care (Indianapolis, IN), and Sanofi (Bridgewater, NJ). No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
Associations of plasma biomarkers of brain injury with MRI and cognitive outcomes. Elevations of NfL were associated with increased brain age (SPARE-BA) (left), while elevations of NfL and pTau-181 were associated with decreased psychomotor and mental efficiency (middle and right).
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References

    1. Jacobson AM, Ryan CM, Braffett BH, et al.; DCCT/EDIC Research Group . Cognitive performance declines in older adults with type 1 diabetes: results from 32 years of follow-up in the DCCT and EDIC study. Lancet Diabetes Endocrinol 2021;9:436–445 - PMC - PubMed
    1. Ryan CM, van Duinkerken E, Rosano C. Neurocognitive consequences of diabetes. Am Psychol 2016;71:563–576 - PubMed
    1. Zilliox LA, Chadrasekaran K, Kwan JY, Russell JW. Diabetes and cognitive impairment. Curr Diab Rep 2016;16:87. - PMC - PubMed
    1. Gaspar JM, Baptista FI, Macedo MP, et al. Inside the diabetic brain: role of different players involved in cognitive decline. ACS Chem Neurosci 2016;7:131–142 - PubMed
    1. Biessels GJ, Nobili F, Teunissen CE, Simo R, et al. Understanding multifactorial brain changes in type 2 diabetes: a biomarker perspective. Lancet Neurol 2020;19:699–710 - PubMed

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