title: Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology.
abstract: OBJECTIVE
  To examine the association between treatment for diabetes and Alzheimer disease (AD) neuropathology.
  
  
  METHODS
  This postmortem study matched 124 subjects with diabetes to 124 without diabetes from the Mount Sinai School of Medicine Brain Bank, on age (mean = 81.2 + 9.3), sex (57.3% F), and severity of dementia (Clinical Dementia Rating [CDR] 2.4 + 1.7). Densities of neuritic plaques (NPs) and of neurofibrillary tangles (NFTs) were assessed in several neocortical regions and in the hippocampus, entorhinal cortex, and amygdala. Diabetic subjects were classified according to their recorded lifetime antidiabetic medications: none (n = 29), insulin only (n = 49), diabetes medications other than insulin only (n = 28), or concomitant use of both insulin and any oral antidiabetic medications (n = 18). For each dependent variable, analysis of covariance controlling for age at death, sex, and CDR distinguished among the nondiabetic patients and four diabetic subgroups.
  
  
  RESULTS
  There were differences among the five groups for NP ratings in the entorhinal cortex (p = 0.003), amygdala (p = 0.009), and overall NP (p = 0.014) as well as counts of NPs in all regions examined (p values ranging from 0.009 to 0.04). NP ratings in the hippocampus (p = 0.057) and the combined neocortical measure (p = 0.052) approached significance. In each analysis, the concomitant medication group had significantly fewer NPs (approximately 20%) than any of the other groups, which were relatively similar. No significant NFT differences were found.
  
  
  CONCLUSIONS
  The results of this study suggest that the combination of insulin with other diabetes medication is associated with substantially lower neuritic plaque density consistent with the effects of both on the neurobiology of insulin.
authors.affiliation: Mount Sinai School of Medicine, Department of Psychiatry, One Gustave Levy Place, Box 1230, New York, NY 10029, USA. michal.beeri@mssm.edu
authors.forename: M S
authors.initials: MS
authors.lastname: Beeri
authors.forename: J
authors.initials: J
authors.lastname: Schmeidler
authors.forename: J M
authors.initials: JM
authors.lastname: Silverman
authors.forename: S
authors.initials: S
authors.lastname: Gandy
authors.forename: M
authors.initials: M
authors.lastname: Wysocki
authors.forename: C M
authors.initials: CM
authors.lastname: Hannigan
authors.forename: D P
authors.initials: DP
authors.lastname: Purohit
authors.forename: G
authors.initials: G
authors.lastname: Lesser
authors.forename: H T
authors.initials: HT
authors.lastname: Grossman
authors.forename: V
authors.initials: V
authors.lastname: Haroutunian