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.
- insulin resistance
- ischemic attack
- cognitive function
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Contributors KLF, CMV, PDG and WNK contributed to the design of the data analyses and interpretation of the results and were involved in the writing and revision of the report. CMV and PDG performed the statistical analyses. KLF, CMV, MG, GAF, LHY, SEI, AML, DT and WNK participated in data acquisition. KLF drafted the report. All authors contributed to revisions of the manuscript.
Funding The IRIS trial was funded by grant (U01NS044876) from the US National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health. Active drug and placebo tablets were provided by Takeda Pharmaceuticals International, Inc.
Competing interests All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: CMV reports personal fees from Takeda Pharmaceuticals, outside the submitted work; SEI reports personal fees from Boehringer Ingelheim, personal fees from Astra Zeneca, non-financial support from Takeda, personal fees from Merck, Janssen, Novo Nordisk, Intarcia, Sanofi/Lexicon, outside the submitted work; GAF reports grants and personal fees from Medtronic and Pfizer, personal fees and non-financial support from Astra Zeneca and Boehringer Ingelheim, other from Bayer, personal fees from Athersys, Cerevast, Lundbeck, Daiichi Sankyo, outside the submitted work; no other relationships or activities that could appear to have influenced the submitted work.
Ethics approval Yale University HIC and local ethics committees at each participating site.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The IRIS trial was funded by grant (U01NS044876) from the US National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health. Active drug and placebo tablets were provided by Takeda Pharmaceuticals International.
Collaborators US Food and Drug Administration IND: 64,622; EudraCT#2008-005546-23.
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