Your incompetent? doctor already has protocols on uses of lithium for your stroke or TBI, and Alzheimers'prevention, right? Oh no, you DON'T have a functioning stroke doctor, do you?
Can Lithium Protect the Aging Brain?
Glimmer of hope emerges in pilot trial of people with mild cognitive impairment
Key Takeaways
- Lithium carbonate might have slowed decline in verbal memory in a pilot study.
- However, the treatment did not meet a prespecified threshold for the trial's primary outcomes.
- Earlier research suggested lithium may offer neuroprotective benefits in Alzheimer's and dementia.
Daily lithium carbonate showed a promising signal in the pilot LATTICE trial of older adults with mild cognitive impairment, but failed to meet a prespecified significance threshold for any of six coprimary outcomes compared with placebo.
Verbal memory scores showed the largest effect size, declining by a difference of 0.69 points per year (95% CI 0.01-1.37, P=0.05), which did not meet the prespecified threshold of P<0.01, reported Ariel Gildengers, MD, of the University of Pittsburgh School of Medicine, and co-authors in JAMA Neurology.
Hippocampal and cortical volumes declined in both groups, but no significant differences emerged.
Serious adverse events occurred in 29% of the lithium group and 23% of the placebo group; none were treatment-related. Common adverse events included increased creatinine levels (29% with lithium vs 31% with placebo), diarrhea (29% vs 15%), tiredness (29% vs 15%), and tremor (24% vs 15%).
"In a prior study, we observed that older adults with bipolar disorder who take lithium long‑term tend to show markers of better brain integrity," Gildengers said in a statement. "The new question was whether those apparent neuroprotective effects might extend beyond mood disorders, and whether we could test that rigorously in a prospective clinical trial."
The results, along with other data, support further work to assess lithium's potential neuroprotective properties, the researchers said. Earlier trials suggested that lithium decreased cognitive decline, and observational data correlated lithium in drinking water with lower dementia rates in Denmark.
LATTICE studied 80 older adults with mild cognitive impairment: 41 in the lithium group and 39 in the placebo group. Approximately 26% had a positive amyloid-beta status.
"The trial was limited by the small sample number and heterogeneity with the inclusion of many amyloid-negative participants, limiting statistical power," said Bruce Yankner, MD, PhD, of Harvard Medical School in Boston, who wasn't involved with the study.
"Nonetheless, the data suggest that lithium carbonate might have slowed decline in verbal episodic memory with a trend towards reduced hippocampal atrophy, especially in amyloid-positive individuals," Yankner told MedPage Today. "At the doses used in this study, the burden of side effects was acceptable and only modestly higher than placebo, certainly milder than standard psychiatric lithium dosing."
In 2025, an analysis led by Yankner showed significantly reduced levels of lithium in the prefrontal cortex of people with amnestic mild cognitive impairment and Alzheimer's disease. In mouse models, amyloid appeared to draw in lithium from surrounding tissue and sequester it. Replacement therapy experiments showed that amyloid plaques trapped standard lithium carbonate, but a novel lithium orotate compound avoided capture and restored memory in mice.
"Lithium carbonate was the least active of all the lithium salts tested, whereas lithium orotate was the most potent," Yankner pointed out.
The LATTICE trial used lithium carbonate at an elemental lithium dose of 30 to 60 mg per day, he noted. "Although this was considered a low dose relative to standard psychiatric lithium dosing, it is approximately 100- to 200-fold higher than the weight-equivalent dose of lithium orotate that was effective in the mouse model studies," he said. "The anticipated clinical trials of lithium orotate will therefore be of substantial interest."
LATTICE was a feasibility study conducted at the University of Pittsburgh from February 2018 to August 2024. All participants had mild cognitive impairment and were free of major psychiatric or neurologic illness at baseline. Most (83% in the lithium group and 72% in the placebo group) had amnestic mild cognitive impairment.
Participants received either a 150-mg or 300-mg dose of lithium carbonate or placebo for 2 years. The mean age was 73 in the lithium group and 71 in the placebo group. Just over half (56%) of participants were women.
Verbal memory was assessed with the California Verbal Learning Test-II (CVLT-II). Other coprimary outcomes included scores on the Brief Visuospatial Memory Test-Revised and the Preclinical Alzheimer Cognitive Composite, plus hippocampal volume, cortical gray matter volume, and plasma brain-derived neurotrophic factor.
Mean CVLT-II baseline scores were 7.95 for the lithium group and 7.90 for the placebo group. Annual scores declined by 0.73 points and 1.42 points in each group, respectively.
Exploratory analyses indicated that Hedges g effect sizes in amyloid-positive participants were 0.74 for verbal memory, 0.82 for hippocampal volume, and 0.81 for hippocampal percentage change. Amyloid-negative participants had Hedges g values of 0.32, 0.09, and 0.12, respectively.
Alzheimer's blood tests were not available when the trial was launched and participants were enrolled based on clinical symptoms. The researchers now seek support for a more definitive clinical trial using plasma biomarkers and a larger sample size.
No comments:
Post a Comment