Knodt Annchen R, Burke James R, Welsh-Bohmer Kathleen A, Plassman Brenda L, Burns Daniel K, Brannan Stephen K, Kukulka Michael, Wu Jingtao, Hariri Ahmad R
Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA.
Department of Neurology, Duke University School of Medicine, Durham, NC, USA.
Alzheimers Dement (N Y). 2019 Jun 26;5:254-263. doi: 10.1016/j.trci.2019.05.004. eCollection 2019.
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.
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.
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.
Our exploratory analyses suggest that low-dose pioglitazone has measurable effects on mnemonic brain function associated with AD risk and pathophysiology.
线粒体功能障碍与阿尔茨海默病（AD）的病理生理学有关。因此，正在对有患病风险的个体进行延缓发病的临床试验，评估对线粒体功能有积极影响的药物。通过更好地理解这些药物如何影响与AD风险和病理生理学相关的大脑中间表型，可以推动此类正在进行的临床研究。
在55名健康老年志愿者中采用随机、平行组、安慰剂对照设计，我们探究了口服低剂量吡格列酮（一种具有线粒体促进作用的噻唑烷二酮类药物）对在编码新面孔-名字对期间通过功能磁共振成像测量的海马体活动的影响。
与安慰剂相比，连续14天每日服用0.6毫克吡格列酮（而非2.1毫克、3.9毫克或6.0毫克）与第7天和第14天编码新面孔-名字对时右侧海马体激活相对于基线显著增加有关。
我们的探索性分析表明，低剂量吡格列酮对与AD风险和病理生理学相关的记忆脑功能有可测量的影响。
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