Revisiting global cognitive and functional state 13 years after a clinical trial of lithium for mild cognitive impairment

Abstract

Objectives: To re-evaluate a sample of older adults enrolled in a randomized controlled trial of lithium for amnestic mild cognitive impairment (MCI) after 11 to 15 years, re-assessing their current (or last available) global cognitive and functional state. Methods: We recalled all former participants of the Lithium-MCI trial conducted by our group between 2009 and 2012 to perform a single-blinded, cross-sectional evaluation of their global clinical state to compare the long-term outcome of those who received lithium vs. those who received placebo. Results: Of the original sample (n=61), we were able to reach 36 participants (59% of retention), of whom 22 had previously received lithium (61% of the recall sample) and 14 (39%) had received placebo. Since 30.5% of the recalled sample was deceased, psychometric data were collected only for 69.5% of the participants. We found statistically significant differences in current mean Mini Mental State Examination score according to previous treatment group (25.5 [SD, 5.3] vs. 18.3 [SD, 10.9], p = 0.04). The lithium group also had better performance in the phonemic Verbal Fluency Test than the control group (34.4 [SD, 14.4] vs. 11.6 [SD, 10.10], p < 0.001). Differences in these measures also had large effect sizes, as shown by Cohen’s d values of 0.92 and 1.78, respectively. Conclusion: This data set suggests that older adults with amnestic MCI who had been treated with lithium during a previous randomized controlled trial had a better long-term global cognitive outcome than those from a matched sample who did not receive the intervention.

Molecular mechanisms and therapeutic potential of lithium in Alzheimer’s disease: repurposing an old class of drugs

“…Additionally, it can decrease CSF levels of P-tau and increase CSF levels of Aβ 1-42 ( Forlenza et al, 2011 ; Forlenza et al, 2019 ). A longitudinal analysis of cognitive and functional status conducted recently, 13 years after enrollment in a trial of lithium therapy, revealed that older adults with aMCI who were treated with lithium had better long-term cognitive outcomes than a matched sample without treatment ( Damiano et al, 2023 ). The study suggests that lithium treatment may provide long-term and sustained neuroprotective benefits.…”

mTORC1 Activation In Presumed Classical Monocytes: Observed Correlates With Human Size Variation and Neuropsychiatric Disease

“…Although formal biochemical analysis of aging pathways is a relatively novel academic discipline, medical modulation of nutrient sensing pathways in humans has been widespread since the approval of lithium in the United States in 1970. Lithium, a glycogen synthase kinase inhibitor, has proven efficacy not only in bipolar disorders [1] but also more recently in Alzheimer’s disease prophylaxis [2], and is known to extend Drosophila lifespan [3]. The combination of lithium with drugs that inhibit the mammalian target of rapamycin complex 1 (mTORC1) (by rapamycin) and mitogen-activated protein kinase (by trametinib) pathways, can, in Drosophila , increase lithium’s 11% lifespan extension to 48% [4].…”

Low and very low lithium levels: Thyroid effects are small but still require monitoring

“…That is an important question, because increasing evidence suggests that even very low doses might delay the onset of dementia 18–24 . If a larger study due for completion in 2024 25,26 also finds slower cognitive decline in patients with low‐dose lithium, a dramatic increase in public interest in lithium could follow 27,28 .…”

“…That is an important question, because increasing evidence suggests that even very low doses might delay the onset of dementia. [18][19][20][21][22][23][24] If a larger study due for completion in 2024 25,26 also finds slower cognitive decline in patients with low-dose lithium, a dramatic increase in public interest in lithium could follow. 27,28 Such interest could improve or even reverse lithium's reputation, if thyroid effects of low lithium doses are small, because the downside of long-term use would also be small.…”