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Although dementia affects roughly 50 million people worldwide, its etiology is largely unknown. Recent studies have found a link between hypermagnesemia, hypomagnesemia, and increased risk of dementia. In this study, we explore the link between serum magnesium levels and the prevalence of dementia following the adoption of desalinated water (DSW) in Israel. DSW contains no magnesium, and relying on it for drinking water can lead to an increased incidence of hypomagnesia. Our objective was to analyze in a treat-control context how the switch to desalinated drinking water affected serum magnesium concentrations and the prevalence of dementia. We selected two cities which differed in terms of their access to underground aquifers but were otherwise similar. Rehovot has no underground water and uses over 90% DSW, whereas Kfar Saba relies almost entirely on its own aquifers. The cities are otherwise relatively similar in terms of their demographic composition. Using medical records for all subjects insured by the Maccabi Health Services in Rehovot (n = 23,991) and Kfar Saba (n = 20,541), we examined mean serum concentrations of Mg in the period prior to desalination (2001-2006) and post-desalination (2007-2018). Dementia prevalence is taken from 2007 to 2020 for the same coverage population. Serum magnesium levels were significantly lower in Rehovot following the switch to DSW (2.067 ± 0.21 pre-desalination and 2.059 ± 0.216 post-desalination, p < 0.01). In contrast, serum magnesium levels increased in Kfar Saba, which continued to rely on groundwater (2.008 ± 0.179 vs. 2.067 ± 0.206, p < 0.01). The prevalence of dementia was similar in the two cities (488/20,541, 2.37% in Rehovot and 613/23,991, 2.55% in Kfar Saba). In this ecological study, the adoption of DSW was associated with a significant decrease in serum magnesium concentrations. However, this change was not associated with a higher prevalence of dementia. While this association study cannot rule out some effect of hypomagnesemia on dementia morbidity, it suggests that the effect, if it exists, is relatively small.