Relationships between memory decline and the use of metformin or DPP4 inhibitors in people with type 2 diabetes with normal cognition or Alzheimer's disease, and the role APOE carrier status

Alzheimers Dement. 2020 Dec;16(12):1663-1673. doi: 10.1002/alz.12161. Epub 2020 Aug 16.

Abstract

Introduction: Few studies have examined memory decline among patients with type 2 diabetes using different oral hypoglycemic drugs.

Methods: Participants with normal cognition (NC) or Alzheimer's disease (AD) dementia using a hypoglycemic medication (2005 to 2019) were identified from the National Alzheimer's Coordinating Center database. Delayed memory was assessed using the Wechsler Memory Scale Revised-Logical Memory test. Associations between oral drug classes and memory over time were examined using mixed-effects models with inverse probability treatment weights.

Results: In NC (n = 1192), metformin use was associated with better memory performance over time, whereas in AD (n = 807), dipeptidyl peptidase-4 (DPP4) inhibitor use was associated with a slower rate of memory decline. Interaction effects suggested greater benefit associated with DPP4 inhibitor use among APOE ε4 carriers.

Discussion: Associations between different oral hypoglycemic drugs and memory change were not consistent between cognitively normal elderly and those with AD dementia. APOE ε4 genotype modified some relationships.

Keywords: Alzheimer's disease (AD); apolipoprotein E (APOE); diabetes; dipeptidyl peptidase-4 inhibitor (DPP4 inhibitor); memory; metformin; sulfonylurea; thiazolidinedione.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / physiology
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4 / genetics
  • Apolipoproteins E / genetics*
  • Cognition / drug effects*
  • Cognitive Dysfunction / genetics
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Female
  • Genotype
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Metformin / therapeutic use*
  • Neuropsychological Tests / statistics & numerical data

Substances

  • Apolipoprotein E4
  • Apolipoproteins E
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Metformin