The Present State of Lithium for the Prevention of Dementia Related to Alzheimer’s Dementia in Clinical and Epidemiological Studies: A Critical Review

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.

Transcranial direct current stimulation of the occipital lobes with adjunct lithium attenuates the progression of cognitive impairment in patients with first episode schizophrenia

“…The present finding of lithium treatment-induced enhancement of whole-brain functional connectivity is consistent with previous studies reporting that lithium can improve the cognitive impairment in patients diagnosed with mild cognitive impairment or dementia (34,35). Implicated mechanisms for these lithium benefits include inhibition of glycogen synthase kinase-3 and reduction of beta-amyloid and hyper-phosphorylated tau (34,35). Our data, from a large-scale imaging perspective, provide evidence suggesting that lithium can improve cognitive impairments by enhancing functional connectivity on a whole-brain level.…”

Chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway

“…The dosages of chronic lithium treatment were based on previous studies ( Hopkins & Gelenberg, 2000 ; Ishii et al, 2021 ; Katz et al, 2022 ; Shvartsur et al, 2022 ) indicating safe and therapeutic lithium plasma levels (≥0.4 mEq/L). According to our previous study ( Gao et al, 2021 ), plasma analysis showed a lithium plasma level of 0.0484±0.0022 mEq/L in the control group and 0.5523±0.1615 mEq/L in the lithium-treated group, maintained within the patient therapeutic range, i.e., 0.4 mEq/L to 1.0 mEq/L ( Ishii et al, 2021 ). Therapeutic lithium levels in plasma can be maintained at ≥0.5 mEq/L for >2 h after a single administration lithium or chronic lithium treatment in rodents ( Morrison et al, 1971 ).…”

On the role of glycogen synthase kinases in the molecular mechanisms of stress conditions and prospects for the use of lithium ascorbate

“…Соли лития способны усиливать аутофагию при многих нейродегенеративных заболеваниях путем удаления токсичных белковых агрегатов и улучшения состояния митохондрий, также способствуя нейрогенезу гиппокампа. Терапевтические концентрации лития значительно снижают уровни нерастворимого τ-белка и блокируют продукцию β-амилоидных пептидов про болезни Альцгеймера за счет ингибирования GSK-3β [46].…”