Efficacy of PPAR-γ agonist pioglitazone in mild Alzheimer disease
Abstract
To test the effects of the PPAR-γ agonist pioglitazone on cognition, regional cerebral blood flow (rCBF), and plasma levels of Aβ40 and Aβ42, we conducted a 6-month, randomized, open-controlled trial in patients with mild Alzheimer disease (AD) accompanied with type II diabetes mellitus. We randomly assigned 42 patients to either the group treated with 15-30 mg pioglitazone daily (n=21, pioglitazone group) or not (n=21, control group). The pioglitazone group improved cognition and rCBF in the parietal lobe, while the control group showed no such improvement. The plasma Aβ40/Aβ42 ratio increased in the control group, but showed no significant change in the pioglitazone group. Both groups showed good control of diabetes during the study. In addition, pioglitazone treatment resulted in a decrease in fasting plasma insulin levels, indicating enhanced insulin sensitivity. The results of this pilot study demonstrated that pioglitazone exhibited cognitive and functional improvements, and stabilization of the disease in diabetic patients with AD. Pioglitazone may offer a novel strategy for the treatment of AD.
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Thiazolidinediones tested in AD patients reestablish glucose regulation, reduce inflammation and Aβ peptide accumulation, and increase cerebral blood flow.
“Recently the insulin sensitizers thiazolidinediones (TZD), primarily developed to treat diabetes, have been tested in AD patients and reported to reestablish glucose regulation but also reduce inflammation and A β peptide accumulation as well as increase cerebral blood flow (Sato et al., 2011).”
From Inhibition of the mitochondrial pyruvate carrier in astrocytes reduces amyloid and tau accumulation in the 3xTgAD mouse model of Alzheimer's disease (2024) · cites this paper as Sato et al., 2011
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- Authors
- Sato, T., Hanyu, H., Hirao, K., Kanetaka, H., Sakurai, H., & Iwamoto, T.
- Affiliations
- Tokyo Medical University (JP)
- Corresponding author
- Sato, Tomohiko
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 32
- Issue
- 9
- Pages
- 1626-1633
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W1976619844
- Cited by
- 387
- References
- 4
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 21 · 2023: 21 · 2022: 29 · 2021: 39 · 2020: 20 · 2019: 25 · 2018: 27 · 2017: 18 · 2016: 23 · 2015: 23 · 2014: 32 · 2013: 25 · 2012: 30
- FWCI
- 12.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- pioglitazone, PPARγ agonists, mild Alzheimer disease, type 2 diabetes, regional cerebral blood flow, plasma amyloid-beta, cognitive function, insulin sensitivity, fasting insulin, parietal lobe
- MeSH terms
- Pioglitazone, Aged, Aged, 80 and over, Alzheimer Disease, Cognition Disorders, Diabetes Mellitus, Type 2, Female, Humans, Male, Pilot Projects, Thiazolidinediones, PPAR gamma
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