The hits if you do the search for "lithium dementia" are enormous, and there are lots of "high quality" Pubmed studies cited. This is an overview of many other studies, results, and is fairly recent, also. So...don't say I never gave you anything!;->
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345730/
The Present State of Lithium for the Prevention of Dementia Related to Alzheimer’s Dementia in Clinical and Epidemiological Studies: A Critical Review
Nobuyoshi Ishii, Takeshi Terao,* and Hirofumi Hirakawa
Maria OrquÃdia Teixeira Neves, Academic Editor and José Manuel Marques, Academic Editor
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Abstract
Despite the unavailability of essential anti-dementia drugs, lithium may inhibit glycogen synthase kinase-3 (GSK-3) and decrease beta-amyloid and hyper-phosphorylated tau. In this review, we hypothesized that trace to standard levels of lithium (i.e., corresponding to the therapeutic levels for bipolar disorder) may be effective for dementia prevention. Excluding three insufficient level studies, we obtained two and one excellent clinical studies on standard and trace lithium levels, respectively, all of which supported the effects of lithium for dementia prevention. In addition, we identified good clinical and epidemiological studies (four each) on standard lithium levels, of which six studies supported the effects of lithium. Moreover, of three good epidemiological studies on trace lithium levels, two supported the aforementioned effects of lithium. The number of studies were substantially small, particularly those on trace lithium levels. Moreover, studies on standard lithium levels were insufficient to establish the efficacy of lithium for dementia prevention. This necessitates accumulating good or excellent clinical evidence for the effects of trace to standard lithium levels on dementia prevention.
Keywords: review, lithium, standard levels, trace levels, dementia, dementia prevention
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1. Introduction
Lithium therapy is generally accepted as the first-line treatment for bipolar disorder. The standard therapeutic levels range from around 0.4 mEq/L to 1.0 mEq/L whereas such mood-stabilizing effects of lithium disappear less than 0.4 mEq/L in most patients with bipolar disorder. However, the effects of lithium on suicide prevention may be observed from trace to standard levels. A meta-analysis demonstrated an inverse association between trace lithium levels in drinking water and the total and female suicide mortality rates in epidemiological studies [1]. In clinical studies, for example, Kanehisa et al. [2] reported that mean lithium levels in the control group and those in the suicide-attempt group were higher than those in suicide attempters (0.00089 ± 0.00060 mEq/L, 0.00090 ± 0.00046 vs. 0.00068 ± 0.00045 mEq/L) with significant tendency. Multivariate logistic regression analysis with adjustment for age and gender revealed that patients with suicide attempts had significantly lower log-transformed lithium levels than control patients (p = 0.032, odds ratio 0.228, 95% CI 0.059–0.883). Moreover, Kurosawa et al. [3] reconfirmed the findings by adjusting for relevant factors, including eicosapentanoic acid and docosahexanoic acid. That is, multivariate logistic regression analysis with adjustment for age, gender, EPA, DHA, arachidonic acid and log-transformed lithium levels revealed that the negative associations with EPA levels (adjusted OR 0.972, 95% CI 0.947–0.997, p = 0.031) and log-transformed lithium levels (adjusted OR 0.156, 95% CI 0.038–0.644, p = 0.01) and the positive association with DHA levels (adjusted OR 1.026, 95% CI 1.010–1.043, p = 0.002) were significant in patients with suicide attempts than in control patients. With regard to standard levels of lithium on suicide, Smith and Cipriani [4] showed evidence for lithium treatment on rates of suicide in patients with mood disorder. Therefore, trace to standard levels of lithium may be effective for suicide prevention.
Dementia is characterized by a deterioration in memory, thinking, behavior, and the quality of life. It develops because of a variety of diseases and injuries that directly and/or indirectly affect the brain. In particular, Alzheimer’s disease (AD) is the most common form of dementia, characterized by the accumulation of beta-amyloid outside neurons and hyper-phosphorylated tau inside neurons. Despite the current unavailability of essential anti-dementia drugs, lithium may decrease beta-amyloid and hyper-phosphorylated tau by inhibiting glycogen synthase kinase-3 (GSK-3) α and β [5,6].
In this review, we hypothesized that trace to standard levels of lithium (i.e., corresponding to the therapeutic levels for bipolar disorder) may be effective for AD prevention.
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