Effects of pioglitazone on cognitive function in patients with a recent ischaemic stroke or TIA: a report from the IRIS trial

J Neurol Neurosurg Psychiatry. 2018 Jan;89(1):21-27. doi: 10.1136/jnnp-2017-316361. Epub 2017 Sep 22.

Abstract

Introduction: Patients with cerebrovascular disease are at increased risk for cognitive dysfunction. Modification of vascular risk factors, including insulin resistance, could improve poststroke cognitive function.

Methods: In the Insulin Resistance Intervention after Stroke (IRIS) trial, patients with a recent ischaemic stroke or transient ischaemic attack (TIA) were randomised to pioglitazone (target 45 mg daily) or placebo. All patients were insulin resistant based on a Homeostasis Model Assessment-Insulin Resistance score >3.0. For this preplanned analysis of cognitive function, we examined the Modified Mini-Mental State Examination (3MS) score (maximum score, 100) during follow-up. Patients were tested at baseline and annually for up to 5 years. Longitudinal mixed model methods were used to compare changes in the 3MS over time.

Results: Of the 3876 IRIS participants, 3398 had a 3MS score at baseline and at least once during follow-up and were included in the analysis. Median 3MS score at baseline was 97 (IQR 93-99). The average overall least squared mean 3MS score increased by 0.27 in the pioglitazone group and by 0.29 in the placebo group (mean difference between treatment groups -0.02; 95% CI -0.33 to 0.28, p=0.88).

Conclusions: Among insulin-resistant patients with a recent ischaemic stroke or TIA, pioglitazone did not affect cognitive function, as measured by the 3MS, over 5 years.

Trial registration: ClinicalTrials.gov NCT00091949; Results.

Keywords: cognitive function; insulin resistance; ischemic attack; stroke; transient.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cognition / drug effects*
  • Double-Blind Method
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin Resistance
  • Ischemic Attack, Transient / drug therapy*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Pioglitazone
  • Risk Factors
  • Stroke / drug therapy*
  • Thiazolidinediones / therapeutic use*

Substances

  • Hypoglycemic Agents
  • Thiazolidinediones
  • Pioglitazone

Associated data

  • ClinicalTrials.gov/NCT00091949