Alzheimer’s Disease-Related Neuropathology Among Patients with Medication Treated Type 2 Diabetes in a Community-Based Autopsy Cohort

Details

• Alternative Title:
  J Alzheimers Dis
• Personal Author:
  Barthold, Douglas ; Gibbons, Laura E. ; Marcum, Zachary A. ; Gray, Shelly L. ; Keene, C. Dirk ; Grabowski, Thomas J. ; Postupna, Nadia ; Larson, Eric B. ; Crane, Paul K.
• Description:
  Background:
  
  Diabetes is a risk factor for Alzheimer’s disease and related dementias (ADRD). Epidemiologic evidence shows an association between diabetes medications and ADRD risk; cell and mouse models show diabetes medication association with AD-related neuropathologic change (ADNC).
  
  Objective:
  
  This hypothesis-generating analysis aimed to describe autopsy-measured ADNC for individuals who used diabetes medications.
  
  Methods:
  
  Descriptive analysis of ADNC for Adult Changes in Thought (ACT) Study autopsy cohort who used diabetes medications, including sulfonylureas, insulin, and biguanides; total N= 118. ADNC included amyloid plaque distribution (Thal phasing), neurofibrillary tangle (NFT) distribution (Braak stage), and cortical neuritic plaque density (CERAD score). We also examined quantitative measures of ADNC using the means of standardized Histelide measures of cortical PHF-tau and Aβ1–42. Adjusted analyses control for age at death, sex, education, APOE genotype, and diabetes complication severity index.
  
  Results:
  
  Adjusted analyses showed no significant association between any drug class and traditional neuropathologic measures compared to nonusers of that class. In adjusted Histelide analyses, any insulin use was associated with lower mean levels of Aβ1–42 (−0.57 (CI: −1.12, −0.02)) compared to nonusers. Five years of sulfonylureas and of biguanides use was associated with lower levels of Aβ1–42 compared to nonusers (−0.15 (CI: −0.28, −0.02), −0.31 (CI: −0.54, −0.07), respectively).
  
  Conclusion:
  
  Some evidence exists that diabetes medications are associated with lower levels of Aβ1–42, but not traditional measures of neuropathology. Future studies are needed in larger samples to build understanding of the mechanisms between diabetes, its medications, and ADRD, and to potentially repurpose existing medications for prevention or delay of ADRD.
  
  
• Subjects:
  Aged Aged, 80 And Over Alzheimer Disease Amyloid Beta-Peptides Autopsy Biguanides Diabetes Mellitus, Type 2 Female Humans Hypoglycemic Agents Insulin Male Neurofibrillary Tangles Neuropathology Peptide Fragments Prospective Studies Sulfonylurea Compounds

  More +
• Source:
  J Alzheimers Dis. 83(3):1303-1312
• Pubmed ID:
  34420950
• Pubmed Central ID:
  PMC8846930
• Document Type:
  Journal Article
• Funding:
  R01 MH121424/MH/NIMH NIH HHSUnited States/ ; K76 AG059929/AG/NIA NIH HHSUnited States/ ; U01 AG006781/AG/NIA NIH HHSUnited States/ ; OT3 HL152448/HL/NHLBI NIH HHSUnited States/ ; P30 AG066509/AG/NIA NIH HHSUnited States/ ; U01 CE002967/CE/NCIPC CDC HHSUnited States/
• Volume:
  83
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:540d7ad844ef2d4bacdb360f295b641be5c0afd81841f856dc63c8cea8f89ed8
• Download URL:
  https://stacks.cdc.gov/view/cdc/114476/cdc_114476_DS1.pdf
• File Type:
  [PDF - 345.50 KB ]