Lithium As a Treatment to Prevent Impairment of Cognition in Elders

NCT03185208 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: PRO17030527R01AG055389-01
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

Alzheimer's disease (AD) is the most common cause of dementia in adults 65 years and older. AD leads to a complete loss of memory and independent function, and presently there is no cure. Many studies suggest that lithium treatment may delay dementia onset or slow its progression. However, more research is needed to understand the extent of its anti-dementia properties if it will be deployed broadly in the general population. 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.

Conditions

Mild Cognitive Impairment

Keywords

Lithium; Mild Cognitive Impairment; MCI; Dementia; Alzheimer; Alzheimer's Disease; Cognition; Memory; Thinking; Prevention; amyloid; imaging; MRI; PET; tau; plaques; tangles

Outcome Measures

Primary Outcomes (7)

• California Verbal Learning Test II

  California Verbal Learning Test II. Long-delay free recall. Scores range from 0 - 16; higher means better.

  Year 1 and Year 2

• Brief Visuospatial Memory Test - Revised

  Brief Visuospatial Memory Test - Revised. Delayed Recall. Scores range from 0 - 12; higher means better.

  Year 1 and Year 2

• Preclinical Alzheimer Cognitive Composite Composed of Memory and Other Cognitive Tests

  Cognitive testing measures with a composite of memory, executive function, processing speed, activities of daily living, and general cognition tests. Values are Z-scores. Higher values mean better cognition. A Z-score of 0 represents the population mean, while Z-scores of ±1 capture approximately 68% of the data around the mean and Z-scores of ±2 capture approximately 95% of the data in a normal distribution.

  Year 1 and Year 2

• Glycogen Synthase Kinase-3 Beta (GSK-3β) Activity

  Values of blood-based biomarkers

  Year 1 and Year 2

• Brain-derived Neurotrophic Factor

  Brain-Derived Neurotrophic Factor (BDNF) supports neuron survival and growth; reduced levels linked to neurodegeneration. Nucleic Acid-Linked Immuno-Sorbent Assay (NULISA) measures BDNF using nucleic acid-tagged antibody pairs recognizing different BDNF epitopes. Sequential capture/purification via polyA/biotin tails, then ligation and next-generation sequencing quantification achieves attomolar sensitivity alongside hundreds of other proteins.

  Year 1 and Year 2

• Cerebral Cortical Gray Matter Volume

  Cerebral cortical gray matter volume as measured by structural imaging (7T MRI) corrected for age, sex, and intracranial volume

  Year 1 and Year 2

• Hippocampal Volume

  Hippocampal volume values as measured by structural imaging (7T MRI) corrected for age, sex, and intracranial volume

  Year 1 and Year 2

Secondary Outcomes (1)

• Cerebrospinal Fluid Phospho Tau Level (CSF)

  Year 1 and Year 2

Other Outcomes (1)

• Brain Integrity as Measured by Structural Imaging (7T MRI)

  Year 1 and Year 2

Study Arms (2)

Lithium carbonate

EXPERIMENTAL

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.

Drug: Lithium Carbonate

placebo

PLACEBO COMPARATOR

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

Drug: Placebo oral capsule

Interventions

Lithium Carbonate DRUG

See lithium carbonate arm

Lithium carbonate

Placebo oral capsule DRUG

See placebo arm

placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• Diagnosis of Mild Cognitive Impairment

You may not qualify if:

• Major psychiatric illness (mild psychiatric illness may be included)
• Major neurologic illness (e.g., multiple sclerosis)
• Contraindication to lithium (e.g., renal insufficiency)
• Unable to complete neuropsychological testing due to non-remediable impairment (e.g., blindness)

Sponsors & Collaborators

• Ariel Gildengers, MD: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Gildengers AG, Ibrahim TS, Zeng X, Aizenstein HJ, Alkhateeb SK, Anderson SJ, Chu C, Diaz JL, Emanuel JE, Karikari TK, Li J, Lopez OL, Lopresti BJ, Royse SK, Sajewski AN, Santini T, Weinstein AM, Wu M, Butters MA. The LATTICE Study: Design of a pilot feasibility randomized controlled trial of lithium to delay cognitive decline in mild cognitive impairment. Alzheimers Dement (N Y). 2025 Jun 11;11(2):e70112. doi: 10.1002/trc2.70112. eCollection 2025 Apr-Jun.

  PMID: 40501510 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Dementia; Alzheimer Disease; Pick Disease of the Brain; Plaque, Amyloid

Interventions

Lithium Carbonate

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Limitations and Caveats

The results presented are preliminary.

Results Point of Contact

• Title: Ariel Gildengers, M.D.
• Organization: University of Pittsburgh

ariel.gildengers@pitt.edu

412-246-6002

Study Officials

• Ariel Gildengers, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, investigators (who will also be prescribers/care providers), and both clinical and cognitive raters will be blind to treatment. A non-blind physician not providing care or ratings will receive real and generate false blood levels to communicate to other investigators for the purpose of titration of the lithium/placebo. Measures for emergency unblinding will be available as well for safety.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Model Details: Longitudinal, randomized, double-blind, placebo-controlled experimental trial

Study Record Dates

• First Submitted: April 24, 2017
• First Posted: June 14, 2017
• Study Start: February 2, 2018
• Primary Completion: August 6, 2024
• Study Completion: August 6, 2024
• Last Updated: September 11, 2025
• Results First Posted: September 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)