Lithium for Mild Cognitive Impairment

(LATTICE Trial)

Overseen By James Emanuel

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ariel Gildengers, MD

Disqualifiers: Major psychiatric, neurologic illness, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether lithium carbonate, a type of medication, can delay or slow the progression of dementia in at-risk individuals. It focuses on older adults with mild cognitive impairment, meaning they may have some memory or thinking problems but can still manage daily activities. Participants will take either lithium or a placebo for two years, with regular check-ups. Individuals aged 60 or older diagnosed with mild cognitive impairment might be suitable for this study. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for lithium carbonate?

Research has shown that lithium carbonate is generally safe in small amounts and may improve brain function and mood in individuals with mild memory issues. One study found that older adults with mild memory problems who took lithium long-term did not experience major side effects. Another study suggested that even at low doses, lithium can be safe and might enhance mental sharpness and mood in some individuals.

While these findings are promising, more research is needed to fully understand lithium's effects on dementia progression. Researchers closely monitor study participants to manage any possible side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Lithium carbonate is unique because it targets mild cognitive impairment with a fresh approach, leveraging its neuroprotective properties. While most treatments for cognitive impairments focus on managing symptoms or enhancing neurotransmitter function, lithium is believed to support brain health by promoting neuron growth and reducing inflammation. Researchers are particularly excited because lithium carbonate could offer a new way to slow down or modify the progression of cognitive decline, rather than just alleviating symptoms.

What evidence suggests that lithium might be an effective treatment for mild cognitive impairment?

Research has shown that lithium carbonate, which participants in this trial may receive, might help slow memory and thinking problems in people with mild cognitive impairment (MCI), an early stage of Alzheimer's disease. Studies have found that people who took lithium experienced a slower decline in memory and thinking skills compared to those who did not. In one study, older adults with MCI who took lithium had better thinking abilities years later than those who didn't. Another review of clinical trials found that lithium reduced the rate of cognitive decline in patients. These findings suggest lithium could be a promising option to delay or slow the progression of dementia symptoms. ^{2 6 7 8 9}

Who Is on the Research Team?

Ariel Gildengers, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for people aged 60 or older who have been diagnosed with mild cognitive impairment. It's not suitable for those with conditions that make lithium use unsafe, like kidney problems, major neurological diseases like multiple sclerosis, serious psychiatric issues, or if they can't do certain mental tests due to permanent disabilities.

Exclusion Criteria

Major psychiatric illness (mild psychiatric illness may be included)

I do not have a major neurological illness like multiple sclerosis.

I cannot take lithium due to kidney problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lithium or placebo for 2 years with quarterly monitoring

104 weeks

Quarterly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lithium Carbonate
• Placebo oral capsule

Trial Overview

The study is testing whether lithium carbonate can prevent or slow down memory loss and decline in brain function in older adults at risk of dementia compared to a placebo (a pill without medication). Participants will be randomly assigned to receive either lithium or the placebo.

How Is the Trial Designed?

Group I: Lithium carbonate Experimental Treatment 1 Intervention

Lithium carbonate will be initiated at 150 mg per day and increased based on blood levels until a steady blood level between 0.6 and 0.8 meq/L is achieved. Participants will continue at the dose achieved for 2 years with quarterly monitoring.

Group II: placebo Placebo Group 1 Intervention

Matching placebo will be initiated and increased based on pretend blood levels. Participants will take placebo for 2 years with quarterly monitoring.

Lithium Carbonate is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Lithium Carbonate for:

• Bipolar disorder

Approved in United States as Lithium Carbonate for:

• Bipolar disorder

Approved in Canada as Lithium Carbonate for:

• Bipolar disorder

Approved in Japan as Lithium Carbonate for:

• Bipolar disorder

Who Is Running the Clinical Trial?

Ariel Gildengers, MD

Lead Sponsor

Trials

1

Recruited

80+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

Lithium cholesterol sulfate (LiCS) was found to be more effective than lithium chloride (LiCl) in enhancing the phosphorylation of GSK3β, a key marker in neurodegenerative diseases, at significantly lower concentrations, suggesting it may have a better safety profile.

LiCS also effectively reduced tau phosphorylation in cell models, which is important for Alzheimer's disease, while LiCl did not show this effect, indicating that LiCS could be a promising new treatment option for Alzheimer's and Autism Spectrum Disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lithium Cholesterol Sulfate: A Novel and Potential Drug for Treating Alzheimer's Disease and Autism Spectrum Disorder. Hu, W., Zhao, M., Lian, J., et al.[2022]

Lithium ascorbate, an organic lithium salt, shows promise as a neuroprotective agent, demonstrating greater effectiveness in supporting neuronal survival under stress compared to traditional inorganic lithium salts like lithium chloride or carbonate.

With an extremely low toxicity profile (LD50 > 5000 mg/kg) and the ability to reduce brain damage and preserve myelin sheaths in models of alcohol intoxication, lithium ascorbate could be a safer alternative for neuropharmacological applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lithium Ascorbate as a Promising Neuroprotector: Fundamental and Experimental Studies of an Organic Lithium Salt. Torshin, IY., Gromova, OA., Ostrenko, KS., et al.[2023]

Lithium is considered effective for preventing relapses in bipolar disorder and reducing suicide risk, but its efficacy for treating acute episodes is not as strong as often claimed, with only a minority of patients experiencing significant benefits.

Despite its limitations, lithium remains a crucial treatment option for bipolar disorder, and its under-utilization in North America is more based on opinion than on the evidence supporting its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lithium - a continuing story in the treatment of bipolar disorder. Carney, SM., Goodwin, GM.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12030194/

An Overview of the Effects of Lithium on Alzheimer's Disease

The results demonstrated that lithium carbonate exerted a prophylactic effect in preventing further recurrences of endogenous affective ...

2.

nature.com

nature.com/articles/s41586-025-09335-x

Lithium deficiency and the onset of Alzheimer's disease

Of the metals we analysed, Li was the only one that was significantly reduced in the brain in individuals with mild cognitive impairment (MCI), ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03185208

Lithium As a Treatment to Prevent Impairment of Cognition ...

This study will examine whether lithium has anti-dementia properties in older adults who have mild cognitive impairment and are at risk of becoming demented.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9976922/

Revisiting global cognitive and functional state 13 years after ...

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- ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0165032724008723

Human brain 7Li-MRI following low-dose lithium dietary ...

Consummate with this, a recent review of three placebo controlled clinical trials concluded that lithium decreased the rate of cognitive decline ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01055392

NCT01055392 | Disease-modifying Properties of Lithium in ...

Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial. Br J ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S014976342200464X

Identifying the neuropsychiatric health effects of low-dose ...

Low-dose lithium is safe, and may improve cognition, as well as affective symptoms as an augmenter. Evidence is scant but suggests promise for low-dose lithium.

8.

journals.sagepub.com

journals.sagepub.com/doi/10.1177/02698811251371139

The effects of lithium on cognition in humans: A systematic ...

Beyond affective disorders, lithium also exhibits promise for its role in Alzheimer's disease (AD) and mild cognitive impairment (MCI; Forlenza ...

9.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8586042/

Low dose lithium treatment of behavioral complications in ...

Primary efficacy outcome was change in NPI agitation/aggression; secondary efficacy outcome was treatment response (30% reduction in NPI score for agitation/ ...