title: Glucose intolerance, insulin resistance, and pathological features of Alzheimer disease in the Baltimore Longitudinal Study of Aging.
abstract: OBJECTIVE
  Peripheral glucose homeostasis has been implicated in the pathogenesis of Alzheimer disease (AD). The relationship among diabetes mellitus, insulin, and AD is an important area of investigation. However, whether cognitive impairment seen in those with diabetes is mediated by excess pathological features of AD or other related abnormalities, such as vascular disease, remains unclear.
  
  
  OBJECTIVE
  To investigate the association between serial measures of glucose intolerance and insulin resistance and in vivo brain β-amyloid burden, measured with carbon 11–labeled Pittsburgh Compound B (11C-PiB), and AD pathology at autopsy.
  
  
  METHODS
  Scores calculated from the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) and Braak criteria were correlated with measures of hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance in 197 participants who underwent autopsy after death and who had undergone 2 or more oral glucose tolerance tests (OGTT) using grouped analyses and a continuous mixed-models analysis. The same measures of glucose intolerance and insulin resistance were also correlated with brain 11C-PiB retention in an additional 53 living subjects from the Baltimore Longitudinal Study of Aging neuroimaging study.
  
  
  METHODS
  Prospective, serially assessed cohort of community-dwelling subjects.
  
  
  METHODS
  Cohort 1 consisted of 197 participants enrolled in the Baltimore Longitudinal Study of Aging who had 2 or more OGTTs during life and a complete brain autopsy after death. Cohort 2 consisted of 53 living subjects who had 2 or more OGTTs and underwent brain 11C-PiB positron emission tomography.
  
  
  METHODS
  Autopsy and 11C-PiB positron emission tomography.
  
  
  METHODS
  The correlation of brain markers of AD, including CERAD score, Braak score, and 11C-PiB retention, with serum markers of glucose homeostasis using grouped and continuous mixed-models analyses.
  
  
  RESULTS
  We found no significant correlations between measures of brain AD pathology or 11C-PiB β-amyloid load and glucose intolerance or insulin resistance in subjects who had a mean (SD) of 6.4 (3.2) OGTTs during 22.1 (8.0) years of follow-up. Thirty subjects with frank diabetes mellitus who received medications also had AD pathology scores that were similar to those of the cohort as a whole.
  
  
  CONCLUSIONS
  In this prospective cohort with multiple assessments of glucose intolerance and insulin resistance, measures of glucose and insulin homeostasis are not associated with AD pathology and likely play little role in AD pathogenesis. Long-term therapeutic trials are important to elucidate this issue.
authors.forename: Madhav
authors.initials: M
authors.lastname: Thambisetty
authors.forename: E
authors.initials: E
authors.lastname: Jeffrey Metter
authors.forename: An
authors.initials: A
authors.lastname: Yang
authors.forename: Hillary
authors.initials: H
authors.lastname: Dolan
authors.forename: Christopher
authors.initials: C
authors.lastname: Marano
authors.forename: Alan B
authors.initials: AB
authors.lastname: Zonderman
authors.forename: Juan C
authors.initials: JC
authors.lastname: Troncoso
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Josephine
authors.initials: J
authors.lastname: Egan
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Brien
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D000814:Aniline Compounds; D015142:Baltimore; D052160:Benzothiazoles; D003072:Cognition Disorders / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D005260:Female; D018149:Glucose Intolerance / Q000473:pathology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D011877:Radionuclide Imaging; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D052160:Benzothiazoles; D013844:Thiazoles
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