Effects of pioglitazone on mnemonic hippocampal function: A blood oxygen level–dependent functional magnetic resonance imaging study in elderly adults
Abstract Introduction Mitochondrial dysfunction is implicated in the pathophysiology of Alzheimer's disease (AD). Accordingly, drugs that positively influence mitochondrial function are being evaluated in delay‐of‐onset clinical trials with at‐risk individuals. Such ongoing clinical research ca...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
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| Online Access: | https://doi.org/10.1016/j.trci.2019.05.004 |
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| author | Annchen R. Knodt James R. Burke Kathleen A. Welsh‐Bohmer Brenda L. Plassman Daniel K. Burns Stephen K. Brannan Michael Kukulka Jingtao Wu Ahmad R. Hariri |
| author_facet | Annchen R. Knodt James R. Burke Kathleen A. Welsh‐Bohmer Brenda L. Plassman Daniel K. Burns Stephen K. Brannan Michael Kukulka Jingtao Wu Ahmad R. Hariri |
| author_sort | Annchen R. Knodt |
| collection | DOAJ |
| description | Abstract Introduction Mitochondrial dysfunction is implicated in the pathophysiology of Alzheimer's disease (AD). Accordingly, drugs that positively influence mitochondrial function are being evaluated in delay‐of‐onset clinical trials with at‐risk individuals. Such ongoing clinical research can be advanced by developing a better understanding of how these drugs affect intermediate brain phenotypes associated with both AD risk and pathophysiology. Methods Using a randomized, parallel‐group, placebo‐controlled design in 55 healthy elderly volunteers, we explored the effects of oral, low‐dose pioglitazone, a thiazolidinedione with promitochondrial effects, on hippocampal activity measured with functional magnetic resonance imaging during the encoding of novel face–name pairs. Results Compared with placebo, 0.6 mg of pioglitazone (but not 2.1 mg, 3.9 mg, or 6.0 mg) administered daily for 14 days was associated with significant increases in right hippocampal activation during encoding of novel face–name pairs at day 7 and day 14, relative to baseline. Discussion Our exploratory analyses suggest that low‐dose pioglitazone has measurable effects on mnemonic brain function associated with AD risk and pathophysiology. |
| format | Article |
| id | doaj-art-7dace41e59d045eba75375ea225eb1b3 |
| institution | OA Journals |
| issn | 2352-8737 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj-art-7dace41e59d045eba75375ea225eb1b32025-08-20T02:09:55ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372019-01-015125426310.1016/j.trci.2019.05.004Effects of pioglitazone on mnemonic hippocampal function: A blood oxygen level–dependent functional magnetic resonance imaging study in elderly adultsAnnchen R. Knodt0James R. Burke1Kathleen A. Welsh‐Bohmer2Brenda L. Plassman3Daniel K. Burns4Stephen K. Brannan5Michael Kukulka6Jingtao Wu7Ahmad R. Hariri8Laboratory of NeuroGeneticsDepartment of Psychology & NeuroscienceDuke UniversityDurhamNCUSADepartment of NeurologyDuke University School of MedicineDurhamNCUSADepartment of NeurologyDuke University School of MedicineDurhamNCUSADepartment of NeurologyDuke University School of MedicineDurhamNCUSAZinfandel Pharmaceuticals, Inc.DurhamNCUSATakeda Development Center Americas, Inc.DeerfieldILUSATakeda Development Center Americas, Inc.DeerfieldILUSATakeda Development Center Americas, Inc.DeerfieldILUSALaboratory of NeuroGeneticsDepartment of Psychology & NeuroscienceDuke UniversityDurhamNCUSAAbstract Introduction Mitochondrial dysfunction is implicated in the pathophysiology of Alzheimer's disease (AD). Accordingly, drugs that positively influence mitochondrial function are being evaluated in delay‐of‐onset clinical trials with at‐risk individuals. Such ongoing clinical research can be advanced by developing a better understanding of how these drugs affect intermediate brain phenotypes associated with both AD risk and pathophysiology. Methods Using a randomized, parallel‐group, placebo‐controlled design in 55 healthy elderly volunteers, we explored the effects of oral, low‐dose pioglitazone, a thiazolidinedione with promitochondrial effects, on hippocampal activity measured with functional magnetic resonance imaging during the encoding of novel face–name pairs. Results Compared with placebo, 0.6 mg of pioglitazone (but not 2.1 mg, 3.9 mg, or 6.0 mg) administered daily for 14 days was associated with significant increases in right hippocampal activation during encoding of novel face–name pairs at day 7 and day 14, relative to baseline. Discussion Our exploratory analyses suggest that low‐dose pioglitazone has measurable effects on mnemonic brain function associated with AD risk and pathophysiology.https://doi.org/10.1016/j.trci.2019.05.004Alzheimer's diseaseBlood oxygen level–dependent functional magnetic resonance imagingMnemonic hippocampal activityPioglitazoneThiazolidinediones |
| spellingShingle | Annchen R. Knodt James R. Burke Kathleen A. Welsh‐Bohmer Brenda L. Plassman Daniel K. Burns Stephen K. Brannan Michael Kukulka Jingtao Wu Ahmad R. Hariri Effects of pioglitazone on mnemonic hippocampal function: A blood oxygen level–dependent functional magnetic resonance imaging study in elderly adults Alzheimer’s & Dementia: Translational Research & Clinical Interventions Alzheimer's disease Blood oxygen level–dependent functional magnetic resonance imaging Mnemonic hippocampal activity Pioglitazone Thiazolidinediones |
| title | Effects of pioglitazone on mnemonic hippocampal function: A blood oxygen level–dependent functional magnetic resonance imaging study in elderly adults |
| title_full | Effects of pioglitazone on mnemonic hippocampal function: A blood oxygen level–dependent functional magnetic resonance imaging study in elderly adults |
| title_fullStr | Effects of pioglitazone on mnemonic hippocampal function: A blood oxygen level–dependent functional magnetic resonance imaging study in elderly adults |
| title_full_unstemmed | Effects of pioglitazone on mnemonic hippocampal function: A blood oxygen level–dependent functional magnetic resonance imaging study in elderly adults |
| title_short | Effects of pioglitazone on mnemonic hippocampal function: A blood oxygen level–dependent functional magnetic resonance imaging study in elderly adults |
| title_sort | effects of pioglitazone on mnemonic hippocampal function a blood oxygen level dependent functional magnetic resonance imaging study in elderly adults |
| topic | Alzheimer's disease Blood oxygen level–dependent functional magnetic resonance imaging Mnemonic hippocampal activity Pioglitazone Thiazolidinediones |
| url | https://doi.org/10.1016/j.trci.2019.05.004 |
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