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

Authors

Amy B. Karger, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN.
Ilya M. Nasrallah, Department of Radiology, University of Pennsylvania, Philadelphia, PA.
Barbara H. Braffett, The Biostatistics Center, George Washington University, Rockville, MD.
José A. Luchsinger, Columbia University Irving Medical Center, New York, NY.
Christopher M. Ryan, Pitt Public Health, University of Pittsburgh, Pittsburgh, PA.
Ionut Bebu, The Biostatistics Center, George Washington University, Rockville, MD.
Valerie Arends, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN.
Mohamad Habes, Neuroimage Analytics Laboratory and Biggs Institute Neuroimaging Core, Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center San Antonio, San Antonino, TX.
Rose A. Gubitosi-Klug, Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland, OH.
Naomi Chaytor, Department of Community and Behavioral Health, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA.
Geert J. Biessels, Department of Neurology, University Medical Center Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
Alan M. Jacobson, New York University Grossman Long Island School of Medicine, New York University Langone Hospital-Long Island, Mineola, NY.

Document Type

Journal Article

Publication Date

6-11-2024

Journal

Diabetes care

DOI

10.2337/dc24-0229

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.

APA Citation

Karger, Amy B.; Nasrallah, Ilya M.; Braffett, Barbara H.; Luchsinger, José A.; Ryan, Christopher M.; Bebu, Ionut; Arends, Valerie; Habes, Mohamad; Gubitosi-Klug, Rose A.; Chaytor, Naomi; Biessels, Geert J.; and Jacobson, Alan M., "Plasma Biomarkers of Brain Injury and Their Association With Brain MRI and Cognition in Type 1 Diabetes" (2024). GW Authored Works. Paper 5118.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5118

Department

Epidemiology