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February 15, 2023Research Article

Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke

View ORCID ProfileJunghee Ha, Dong Woo Choi, Kim, View ORCID ProfileKeun You Kim, Chung Mo Nam, View ORCID ProfileEosu Kim
First published February 15, 2023, DOI: https://doi.org/10.1212/WNL.0000000000207069
Junghee Ha
1Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • ORCID record for Junghee Ha
Dong Woo Choi
2Cancer Big Data Center, National Cancer Control Institute, National Cancer Center, Gyeonggi-do, Republic of Korea
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Kim
3Division of Geriatrics, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
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Keun You Kim
1Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
4Department of Psychiatry, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea
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Chung Mo Nam
5Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
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Eosu Kim
1Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
6Graduate School of Medical Science, Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • ORCID record for Eosu Kim
  • For correspondence: kimeosu@yuhs.ac
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Citation
Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke
Junghee Ha, Dong Woo Choi, Kim, Keun You Kim, Chung Mo Nam, Eosu Kim
Neurology Feb 2023, 10.1212/WNL.0000000000207069; DOI: 10.1212/WNL.0000000000207069

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Abstract

Background and objectives: Previous studies have reported the protective effect of pioglitazone on dementia in type 2 diabetic mellitus (DM) patients. Recent studies have shown that pioglitazone also lowers the risk of primary and recurrent stroke. Understanding the characteristics of patients particularly associated with the benefits of pioglitazone would facilitate its personalized use by specifying subpopulations during routine clinical care. The aim of this study was to examine the effects of pioglitazone use on dementia in consideration of stroke occurrence.

Methods: Using nationwide longitudinal data of DM patients from the Korean National Health Insurance Service DM cohort (2002–2017), we investigated the association of pioglitazone use with incident dementia in patients with new-onset type 2 DM. The heterogeneity of the treatment effect was examined using exploratory analyses. Using a multi-state model, we assessed the extent to which incident stroke affects the association between pioglitazone use and dementia.

Results: Pioglitazone use was associated with a reduced risk of dementia, compared with non-use (adjusted hazard ratio (HR) = 0.84, 95% CI, 0.75-0.95); the risk reduction in dementia was greater among patients with a history of ischemic heart disease or stroke before DM onset (adjusted HR = 0.46, 95% CI, 0.24-0.90, adjust HR = 0.57, 95% CI, 0.38-0.86, respectively). The incidence of stroke was also reduced by pioglitazone use (adjusted HR = 0.81, 95% CI, 0.66-1.00). However, when the stroke developed during the observation period of pioglitazone use, such lowered risk of dementia was not observed (adjusted HR = 1.27, 95% CI, 0.80-2.04).

Discussion: Pioglitazone use is associated with a lower risk of dementia in DM patients, particularly in those with a history of stroke or ischemic heart disease, suggesting the possibility of applying a personalized approach when choosing pioglitazone to suppress dementia in DM patients.

  • Received August 1, 2022.
  • Accepted in final form January 3, 2023.
  • © 2023 American Academy of Neurology

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Letters: Rapid online correspondence

  • Author Response: Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke
    • Eosu Kim, Physician, Yonsei University College of Medicine
    Submitted March 07, 2023
  • Reader Response: Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke
    • Qian Feng, neurological physician, Department of Neurology ,Suzhou Hospital Affiliated to Nanjing Medical University ,Suzhou,China
    Submitted February 24, 2023
  • Reader Response:Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke
    • Undurti Das, Physician/Scientist, UND Life Sciences
    Submitted February 17, 2023
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