Kessing Lars Vedel, Gerds Thomas Alexander, Knudsen Nikoline Nygård, Jørgensen Lisbeth Flindt, Kristiansen Søren Munch, Voutchkova Denitza, Ernstsen Vibeke, Schullehner Jörg, Hansen Birgitte, Andersen Per Kragh, Ersbøll Annette Kjær
Psychiatric Center Copenhagen, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
JAMA Psychiatry. 2017 Oct 1;74(10):1005-1010. doi: 10.1001/jamapsychiatry.2017.2362.
Results from animal and human studies suggest that lithium in therapeutic doses may improve learning and memory and modify the risk of developing dementia. Additional preliminary studies suggest that subtherapeutic levels, including microlevels of lithium, may influence human cognition.
To investigate whether the incidence of dementia in the general population covaries with long-term exposure to microlevels of lithium in drinking water.
DESIGN, SETTING, AND PARTICIPANTS: This Danish nationwide, population-based, nested case-control study examined longitudinal, individual geographic data on municipality of residence and data from drinking water measurements combined with time-specific data from all patients aged 50 to 90 years with a hospital contact with a diagnosis of dementia from January 1, 1970, through December 31, 2013, and 10 age- and sex-matched control individuals from the Danish population. The mean lithium exposure in drinking water since 1986 was estimated for all study individuals. Data analysis was performed from January 1, 1995, through December 31, 2013.
A diagnosis of dementia in a hospital inpatient or outpatient contact. Diagnoses of Alzheimer disease and vascular dementia were secondary outcome measures. In primary analyses, distribution of lithium exposure was compared between patients with dementia and controls.
A total of 73 731 patients with dementia and 733 653 controls (median age, 80.3 years; interquartile range, 74.9-84.6 years; 44 760 female [60.7%] and 28 971 male [39.3%]) were included in the study. Lithium exposure was statistically significantly different between patients with a diagnosis of dementia (median, 11.5 µg/L; interquartile range, 6.5-14.9 µg/L) and controls (median, 12.2 µg/L; interquartile range, 7.3-16.0 µg/L; P < .001). A nonlinear association was observed. Compared with individuals exposed to 2.0 to 5.0 µg/L, the incidence rate ratio (IRR) of dementia was decreased in those exposed to more than 15.0 µg/L (IRR, 0.83; 95% CI, 0.81-0.85; P < .001) and 10.1 to 15.0 µg/L (IRR, 0.98; 95% CI, 0.96-1.01; P = .17) and increased with 5.1 to 10.0 µg/L (IRR, 1.22; 95% CI, 1.19-1.25; P < .001). Similar patterns were found with Alzheimer disease and vascular dementia as outcomes.
Long-term increased lithium exposure in drinking water may be associated with a lower incidence of dementia in a nonlinear way; however, confounding from other factors associated with municipality of residence cannot be excluded.
动物和人体研究结果表明，治疗剂量的锂可能改善学习和记忆，并改变患痴呆症的风险。其他初步研究表明，低于治疗水平，包括微量锂，可能会影响人类认知。
调查普通人群中痴呆症的发病率是否与长期接触饮用水中的微量锂相关。
设计、设置和参与者：这项丹麦全国性、基于人群的巢式病例对照研究，检查了居住城市的纵向个体地理数据、饮用水测量数据，并结合了1970年1月1日至2013年12月31日期间所有年龄在50至90岁、因痴呆症诊断而住院的患者以及来自丹麦人群的10名年龄和性别匹配的对照个体的特定时间数据。估算了所有研究个体自1986年以来饮用水中的平均锂暴露量。数据分析于1995年1月1日至2013年12月31日进行。
医院住院或门诊诊断为痴呆症。阿尔茨海默病和血管性痴呆的诊断为次要结局指标。在初步分析中，比较了痴呆症患者和对照者之间锂暴露的分布情况。
该研究共纳入73731例痴呆症患者和733653名对照者（中位年龄80.3岁；四分位间距74.9 - 84.6岁；女性44760名[60.7%]，男性28971名[39.3%]）。诊断为痴呆症的患者（中位值11.5μg/L；四分位间距6.5 - 14.9μg/L）和对照者（中位值12.2μg/L；四分位间距7.3 - 16.0μg/L；P <.001）之间的锂暴露在统计学上有显著差异。观察到一种非线性关联。与暴露于2.0至5.0μg/L的个体相比，暴露于超过15.0μg/L（发病率比[IRR]，0.83；95%置信区间，0.81 - 0.85；P <.001）和10.1至15.0μg/L（IRR，0.98；95%置信区间，0.96 - 1.01；P = 0.17）的个体患痴呆症的发病率比降低，而暴露于5.1至10.0μg/L（IRR，1.22；95%置信区间，1.19 - 1.25；P <.001）的个体发病率比升高。以阿尔茨海默病和血管性痴呆为结局时也发现了类似模式。
饮用水中锂暴露长期增加可能与痴呆症发病率较低呈非线性相关；然而，不能排除来自与居住城市相关的其他因素的混杂影响。
