title: Glucose levels during life and neuropathologic findings at autopsy among people never treated for diabetes.
abstract: 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.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address: pcrane@uw.edu.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Crane
authors.affiliation: Group Health Research Institute, Seattle, WA, USA.
authors.forename: Rod L
authors.initials: RL
authors.lastname: Walker
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Sonnen
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Gibbons
authors.affiliation: VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA; Department of Psychiatry and Biobehavioral Sciences at the David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Melrose
authors.affiliation: Department of Neurology, Washington University in Saint Louis, St. Louis, MO, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Hassenstab
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: C Dirk
authors.initials: CD
authors.lastname: Keene
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: Nadia
authors.initials: N
authors.lastname: Postupna
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.affiliation: Group Health Research Institute, Seattle, WA, USA.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Larson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology; D001344:Autopsy; D001786:Blood Glucose / Q000378:metabolism*; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology; D003704:Dementia / Q000209:etiology* / Q000473:pathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology*; D014402:Tuberous Sclerosis / Q000209:etiology / Q000473:pathology
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
keywords: Glucose; Hippocampal sclerosis; Lewy bodies; Neuritic plaques; Neurofibrillary tangles; Neuropathology