Ahmanson Translational Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California Los Angeles, 200 Medical Plaza, Los Angeles, CA 90095, USA; Institute for Memory Impairments and Neurological Disorders, Department of Psychiatry and Human Behavior, Department of Neurobiology and Behavior, University of California, Irvine, 3206 Biological Sciences III, Irvine, CA 92697, USA.
Ahmanson Translational Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California Los Angeles, 200 Medical Plaza, Los Angeles, CA 90095, USA; Mahidol University, 999 Phutthamonthon Sai 4 Rd, Chang Wat Nakhon Pathom 73170, Thailand.
Exp Gerontol. 2018 Oct 1;111:118-121. doi: 10.1016/j.exger.2018.07.009. Epub 2018 Jul 10.
Caprylidene is a ketogen that, when metabolized, produces the ketones beta-hydroxybutyrate and acetoacetate, which can cross the blood brain barrier. It has been hypothesized that ketone bodies can be used as an alternate energy source by neurons with impaired glucose utilization. Caprylidene has been shown to improve cognition in patients with mild-to-moderate Alzheimer's disease (AD) who lacked an AD-predisposing allele (ɛ4) of the gene for apolipoprotein E. In this pilot study, we examined the effects of caprylidene on regional cerebral blood flow (rCBF) in patients with mild to moderate AD.
Sixteen subjects with mild-to-moderate AD, based on NINCDS-ADRDA criteria, were enrolled in a double-blinded, placebo-controlled, randomized clinical trial. Fourteen subjects received treatment with caprylidene, and 2 subjects were given placebo. Subjects received 4 O-water PET scans over the course of the study to assess rCBF: once before receiving a standard caprylidene or placebo dose and 90 min after the dose, on the first day and after 45 days of daily caprylidene or placebo consumption. The scans were examined by standardized volumes of interest (sVOI) and voxel-based statistical parametric mapping (spm) methods of analysis.
Subjects lacking an ɛ4 allele had significantly elevated rCBF in the left superior lateral temporal cortex by sVOI analysis after adopting a caprylidene diet for 45 days (p = 0.04), which was further corroborated by spm. The anterior cerebellum, left inferior temporal cortex, and hypothalamus were also found by spm to be regions of long-term increase in rCBF in these subjects. In contrast, patients who possessed the ɛ4 allele did not display these changes in rCBF.
Daily ingestion of caprylidene over 45 days was associated with increased blood flow in specific brain regions in patients lacking an apolipoprotein ɛ4 allele.
己烯醛是一种生酮剂，代谢时会产生β-羟丁酸和乙酰乙酸酮，这两种酮可以穿过血脑屏障。有假说认为，酮体可以作为葡萄糖利用受损的神经元的替代能源。己烯醛已被证明可以改善缺乏载脂蛋白 E 基因的阿尔茨海默病（AD）易感基因（ɛ4）的轻度至中度 AD 患者的认知能力。在这项初步研究中，我们研究了己烯醛对轻度至中度 AD 患者局部脑血流（rCBF）的影响。
根据 NINCDS-ADRDA 标准，16 名轻度至中度 AD 患者入组了一项双盲、安慰剂对照、随机临床试验。14 名患者接受己烯醛治疗，2 名患者接受安慰剂。在研究过程中，受试者接受了 4 次 O-水 PET 扫描以评估 rCBF：在接受标准己烯醛或安慰剂剂量之前、剂量后 90 分钟、第一天和每天接受己烯醛或安慰剂 45 天后各进行 1 次扫描。扫描结果通过标准化感兴趣区（sVOI）和基于体素的统计参数映射（spm）分析方法进行检查。
缺乏ɛ4 等位基因的患者在采用己烯醛饮食 45 天后，通过 sVOI 分析，左侧上外侧颞叶皮质的 rCBF 显著升高（p=0.04），spm 进一步证实了这一点。spm 还发现，这些患者的大脑前叶、左侧下颞叶皮质和下丘脑也是 rCBF 长期增加的区域。相比之下，携带ɛ4 等位基因的患者 rCBF 没有发生这些变化。
45 天内每天摄入己烯醛与缺乏载脂蛋白ɛ4 等位基因的患者特定脑区的血流增加有关。
