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Published on: November 14, 2017
Efficacy of PPAR-γ agonist pioglitazone in mild Alzheimer disease
Tomohiko Sato1, Haruo Hanyu, Kentaro Hirao
1Department of Geriatric Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku Shinjuku-ku, Tokyo 160-0023, Japan. tomohiko@tokyo-med.ac.jp
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.
Insights
Pioglitazone improved cognition and brain blood flow in patients with mild Alzheimer disease and diabetes. This PPAR-γ agonist may offer a new Alzheimer disease treatment strategy.
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- Alzheimer disease (AD) is a neurodegenerative disorder often co-occurring with type II diabetes mellitus.
- The PPAR-γ agonist pioglitazone is known for its effects on insulin sensitivity.
- Investigating pioglitazone's impact on AD pathophysiology and cognitive function is crucial.
Purpose of the Study:
- To evaluate the effects of pioglitazone on cognitive function in patients with mild AD and type II diabetes.
- To assess the impact of pioglitazone on regional cerebral blood flow (rCBF) and plasma amyloid-beta (Aβ) levels.
- To determine pioglitazone's effect on insulin sensitivity in this patient population.
Main Methods:
- A 6-month, randomized, open-controlled trial involving 42 patients with mild AD and type II diabetes.
- Patients were assigned to receive either pioglitazone (15-30 mg daily) or no treatment (control group).
- Cognitive function, rCBF, plasma Aβ40/Aβ42 levels, and insulin sensitivity were measured.
Main Results:
- The pioglitazone group showed significant improvements in cognition and parietal lobe rCBF compared to the control group.
- Plasma Aβ40/Aβ42 ratio increased in the control group but remained stable in the pioglitazone group.
- Pioglitazone treatment enhanced insulin sensitivity, evidenced by decreased fasting plasma insulin levels, and maintained diabetes control.
Conclusions:
- Pioglitazone demonstrated potential for cognitive and functional improvement in diabetic patients with mild Alzheimer disease.
- The drug appeared to stabilize disease progression and improve cerebral blood flow.
- Pioglitazone represents a promising novel therapeutic strategy for Alzheimer disease, particularly in patients with comorbid diabetes.
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