**5. Conclusions**

There is robust and highly replicated evidence for positive association between Li treatment and gray matter volumes. There has also been a strong experimental background for biochemical underpinnings of lithium's neuroprotective effect that may have possible relevance for therapeutic action of this ion in the AD. A negative association between lithium use and dementia confirmed in most epidemiological studies, including the recent ones on lithium in drinking water, has also been quite substantial. All the same, the results of using lithium in the treatment of AD involve some methodological and clinical issues, which complicate the interpretations. One must acknowledge the heterogeneity of studies regarding of methodology, duration of intervention, dose regimen, and also outcome variables. Nonetheless, three of the four available studies meta-analyzed by Matsunaga et al. [41] suggested some benefits from lithium treatment on amnestic mild cognitive impairment or early stages of the AD, including effects on illness biomarkers.

Despite the wide range of supporting evidence, the neuroprotective effects of lithium are mostly neglected and little known outside of the mood disorders field. However, considering the current paucity of treatments for neurodegenerative disorders, we cannot afford to let the research into neuroprotective effects of lithium come to a halt. The evidence presented in this chapter would warrant further testing of lithium as a disease-modifying treatment for the AD.
