Department of Clinical Science, University of Bergen, Bergen, Norway.
Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.
Brain Res. 2020 Jan 1;1726:146519. doi: 10.1016/j.brainres.2019.146519. Epub 2019 Oct 22.
Metabolites involved in one-carbon metabolism (OCM) may predict cognitive prognosis in dementia. The link between OCM, apolipoprotein E (APOE), and DNA methylation creates a biologically plausible mechanism of interaction.
To assess OCM metabolites as predictors of 5-year cognitive prognosis in patients with mild dementia, and in subgroups defined by the APOEε4 allele variant.
We followed one-hundred and fifty-two patients with mild dementia (86 with Alzheimer's disease, 66 with Lewy body dementia, including 90 with at least one APOEε4 allele) for 5 years with annual Mini-Mental State Examinations (MMSE). Total homocysteine, methionine, choline, betaine, dimethylglycine, sarcosine, folate, cobalamin and pyridoxal 5'-phoshate were measured in serum at baseline. We used linear mixed models to assess metabolite-MMSE associations, including 3-way interactions between metabolites, time, and APOEε4. False-discovery rate adjusted p-values (Q-values) are reported.
Metabolite concentrations were not different in patients with dementia according to the presence of APOEε4. Overall, serum concentration of total homocysteine was inversely associated with MMSE performance, while betaine was positively associated with MMSE (Q < 0.05), but neither was associated with MMSE decline. Serum concentrations of betaine, dimethylglycine and sarcosine, however, were associated with slower MMSE decline in patients with APOEε4, but with faster MMSE decline in patients without the allele (all 3-way interactions: Q < 0.05).
Components of the choline oxidation pathway are associated with a better cognitive prognosis in APOEε4 carriers and a worse cognitive prognosis in non-carriers. Further research investigating targeted metabolic interventions according to APOE allele status is warranted.
参与一碳代谢（OCM）的代谢产物可能预测痴呆患者的认知预后。OCM、载脂蛋白 E (APOE) 和 DNA 甲基化之间的联系创造了一种具有生物学意义的相互作用机制。
评估 OCM 代谢产物作为轻度痴呆患者 5 年认知预后的预测指标，并根据 APOEε4 等位基因变体进行亚组分析。
我们对 152 名轻度痴呆患者（86 名阿尔茨海默病患者，66 名路易体痴呆患者，包括 90 名至少携带一个 APOEε4 等位基因）进行了 5 年的随访，每年进行一次简易精神状态检查（MMSE）。在基线时测量血清中的总同型半胱氨酸、蛋氨酸、胆碱、甜菜碱、二甲氨基乙醇、肌氨酸、叶酸、钴胺素和吡哆醛 5'-磷酸。我们使用线性混合模型评估代谢物与 MMSE 的关联，包括代谢物、时间和 APOEε4 之间的 3 向相互作用。报告了经假发现率调整的 p 值（Q 值）。
根据 APOEε4 的存在，痴呆患者的代谢产物浓度没有差异。总的来说，血清总同型半胱氨酸浓度与 MMSE 表现呈负相关，而甜菜碱与 MMSE 呈正相关（Q < 0.05），但两者均与 MMSE 下降无关。然而，在携带 APOEε4 的患者中，甜菜碱、二甲氨基乙醇和肌氨酸的血清浓度与 MMSE 下降较慢相关，而在不携带该等位基因的患者中，与 MMSE 下降较快相关（所有 3 向相互作用：Q < 0.05）。
胆碱氧化途径的成分与 APOEε4 携带者的认知预后较好和非携带者的认知预后较差相关。根据 APOE 等位基因状态进行靶向代谢干预的进一步研究是必要的。
