Pre-Diabetes, but not Type 2 Diabetes, Is Related to Brain Amyloid in Late Middle-Age

Background: Type 2 diabetes is a dementia risk factor, but its relation to Alzheimer's disease (AD), the most common cause of dementia, is unclear. Objective: Our primary objective was to examine the association of pre-diabetes and type 2 diabetes with brain amyloid-B (AB), the putative main culprit of AD. Our secondary objective was to examine the association of pre-diabetes and type 2 diabetes with neurodegeneration, cerebrovascular disease (CVD), and memory performance. Methods: We conducted a cross-sectional study of 350 late middle-aged Hispanics without dementia in New York City. We classified diabetes status as normal glucose tolerance (NGT), pre-diabetes, and type 2 diabetes following American Diabetes Association criteria. Brain AB was ascertained as global AB standardized value uptake ratio using PET with 18 F-Florbetaben. Neurodegeneration was operationalized as cortical thickness in regions affected by AD using MRI. CVD was operationalized as white matter hyperintensity volume (WMH) on MRI, and memory as performance with the selective reminding test (SRT). Results: Mean age was 64.15 +/- 3.34 years, 72.00% were women, and 35.43% were APOE 84 carriers. Pre-diabetes, but not type 2 diabetes, was associated with higher AB compared with NGT. Type 2 diabetes treatment was related to lower AB. Type 2 diabetes was related to lower cortical thickness, higher WMH, and lower SRT score. Conclusion: Pre-diabetes, but not type 2 diabetes, is associated with higher brain AB in late middle age, and this observation could be explained by the relation of diabetes treatment with lower brain AB. Whether type 2 diabetes treatment lowers brain AB requires further study.