Amyloid deposition and small vessel disease are associated with cognitive function in older adults with type 2 diabetes

Orit H. Lesman-Segev*, Sapir Golan Shekhtman, Ramit Ravona Springer, Abigail Livny, Hung Mo Lin, Ouyang Yuxia, Maya Zadok, Ithamar Ganmore, Anthony Heymann, Chen Hoffmann, Liran Domachevsky, Michal Schnaider Beeri

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Diabetes is associated with cognitive decline, but the underlying mechanisms are complex and their relationship with Alzheimer’s Disease biomarkers is not fully understood. We assessed the association of small vessel disease (SVD) and amyloid burden with cognitive functioning in 47 non-demented older adults with type-2 diabetes from the Israel Diabetes and Cognitive Decline Study (mean age 78Y, 64% females). FLAIR-MRI, Vizamyl amyloid-PET, and T1W-MRI quantified white matter hyperintensities as a measure of SVD, amyloid burden, and gray matter (GM) volume, respectively. Mean hemoglobin A1c levels and duration of type-2 diabetes were used as measures of diabetic control. Cholesterol level and blood pressure were used as measures of cardiovascular risk. A broad neuropsychological battery assessed cognition. Linear regression models revealed that both higher SVD and amyloid burden were associated with lower cognitive functioning. Additional adjustments for type-2 diabetes-related characteristics, GM volume, and cardiovascular risk did not alter the results. The association of amyloid with cognition remained unchanged after further adjustment for SVD, and the association of SVD with cognition remained unchanged after further adjustment for amyloid burden. Our findings suggest that SVD and amyloid pathology may independently contribute to lower cognitive functioning in non-demented older adults with type-2 diabetes, supporting a multimodal approach for diagnosing, preventing, and treating cognitive decline in this population.

Original languageEnglish
Article number2741
JournalScientific Reports
Volume14
Issue number1
DOIs
StatePublished - Dec 2024

Funding

FundersFunder number
National Institutes of HealthAG051545, R01AG034087, AG043878, AACSF-21-850735, P50 AG05138, AG053446
Alzheimer's Association
Office of Extramural Research, National Institutes of Health
Office of Research Infrastructure Programs, National Institutes of Health

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