Abstract：
Objective: To determine the frequency with which suspected pathogenic factors, including metals and metabolites that might contribute to Alzheimer\'s disease (AD), may be found in patients with cognitive impairment through commonly available blood tests. Methods: A variety of serum studies, including metals, ammonia, homocysteine, vitamin B12, folate, thyroid tests, metabolic products, and inflammatory markers, were measured in two cohorts: one meeting mild cognitive impairment (MCI) criteria and the other meeting mild-to-moderate dementia (DE) criteria. Medications these patients received were reviewed. Results: Metal abnormalities were detected in over half the subjects, including evidence of mercury, lead, and arsenic elevation as well as instances of excessive essential metals, iron (Fe), and copper. Some metal aberration was detected in 64% of the DE group and 66% of the MCI group. Females were more likely to have elevated copper, consistent with hormonal effects on copper excretion. Homocysteinemia was the most common abnormality, detected in 71% with DE and 67% with MCI, while methylmalonic acid was not elevated. Slight hyperammonemia was moderately common (38%) suggesting a hepatic factor in this subset. Findings of moderate insulin resistance were present in nearly half (44% DE, 52% MCI). Sixty of 65 (92%) had at least one abnormal biomarker and 60% had two or more. The most common drug taken by the total cohort was proton pump inhibitors at 22% DE and 38% MCI. Conclusions: This study suggests that both toxic metals and excessive vital metals such as copper and iron, as well as common metabolic and hepatic factors are detectable at both stages of MCI and DE. There appears to be a multiplicity of provocative factors leading to DE. Individualized interventions based on these parameters may be a means to reduce cognitive decline leading to DE. A more comprehensive prospective study of these environmental and metabolic factors with corrective early interventions appears warranted.
摘要：
目的:确定可疑致病因素的发生频率,包括可能导致阿尔茨海默病（AD）的金属和代谢物，可以通过常用的血液检查发现认知障碍患者。方法:多种血清研究,包括金属,氨,同型半胱氨酸,维生素B12，叶酸，甲状腺检查,代谢产物，和炎症标志物，在两个队列中进行测量：一个符合轻度认知障碍（MCI）标准，另一个符合轻度至中度痴呆（DE）标准。对这些患者接受的药物进行了回顾。结果：超过一半的受试者检测到金属异常，包括汞的证据，铅,和砷的升高以及过量的必需金属，铁(Fe),和铜。在DE组的64％和MCI组的66％中检测到一些金属畸变。女性更有可能有升高的铜，与激素对铜排泄的影响一致。同型半胱氨酸血症是最常见的异常，DE检测到71%，MCI检测到67%，而甲基丙二酸没有升高。轻度高氨血症是中度常见的（38％），表明该子集中存在肝脏因素。近一半的人发现中度胰岛素抵抗(44%DE，52%MCI)。65人中有60人(92%)有至少一个异常生物标志物，60%有两个或更多。整个队列中最常见的药物是质子泵抑制剂，DE为22％，MCI为38％。结论：这项研究表明，有毒金属和过量的重要金属，如铜和铁，在MCI和DE的两个阶段都可以检测到常见的代谢和肝脏因子。似乎有多种挑衅性因素导致DE。基于这些参数的个性化干预可能是减少导致DE的认知下降的手段。对这些环境和代谢因素进行更全面的前瞻性研究，并进行纠正性的早期干预似乎是有必要的。
