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© 2008 American Academy of Neurology Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathologyFrom The Departments of Psychiatry (M.S.B., J.S., J.M.S., S.G., M.W., C.M.H., H.T.G., V.H.), Neurology (S.G.), and Pathology (D.P.P.), Mount Sinai School of Medicine, New York; Jewish Home and Hospital (G.L.), New York; and Bronx VA Medical Center (V.T.), NY. Address correspondence and reprint requests to Dr. Michal Schnaider Beeri, Mount Sinai School of Medicine, Department of Psychiatry, One Gustave Levy Place, Box 1230, New York, NY 10029 michal.beeri{at}mssm.edu 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 ( Conclusion: 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.
Abbreviations: AD = Alzheimer disease; ANCOVA = analysis of covariance; CDR = Clinical Dementia Rating; CERAD = Consortium to Establish a Registry for Alzheimer’s Disease; IR = insulin receptors; JHH = Jewish Home and Hospital; NFT = neurofibrillary tangle; NP = neuritic plaque.
Supported by NIA grants K01 AG023515-01A2 (Dr. Beeri), AG02219 (Dr. Haroutunian), and AG05138 (Dr. Sano) and by the Dextra Baldwin McGonagle Foundation and the Joseph E. and Norma G. Saul Foundation. Disclosure: The authors report no disclosures. Received January 17, 2008. Accepted in final form May 30, 2008. This article has been cited by other articles:
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20%) than any of the other groups, which were relatively similar. No significant NFT differences were found. 
