Glucose levels during life and neuropathologic findings at autopsy among people never treated for diabetes

We evaluated associations between glucose and dementia-related neuropathologic findings among people without diabetes treatment history to elucidate mechanisms of glucose's potential effect on dementia. We used glucose and hemoglobin A1c values to characterize glucose exposures over 5 years before death (primary) and age bands from 55-59 through 80-84 (secondary). Autopsy evaluations included Braak stage for neurofibrillary tangles, Consortium to Establish a Registry for Alzheimer's Disease grade for neuritic plaques, macroscopic infarcts including lacunar infarcts, Lewy bodies, cerebral microinfarcts, and hippocampal sclerosis. Of 529 who came to autopsy, we included 430 with no history of diabetes treatment. We found no associations between glucose levels and Braak stage or Consortium to Establish a Registry for Alzheimer's Disease grade. There was a suggestion of a relationship between glucose and hippocampal sclerosis, although this was inconsistent across analyses. There was higher risk of Lewy bodies in substantia nigra and locus ceruleus with higher glucose levels in age band analyses. We did not find interactions between glucose levels, neuropathologic findings, and dementia. The mechanism by which glucose may impact dementia risk is still unknown.