Cognitive Training and Neuroplasticity in Mild Cognitive Impairment: COGIT-2 Trial

NCT06601933 | Recruiting Phase 2 DMC

• 3 other identifiers: AAAU96232R01AG052440-06A1WCG 20240282
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 4

Brief Summary

Effective, clinically meaningful treatments are lacking for patients with mild cognitive impairment (MCI), which is associated with increased risk of transition to dementia. Cognitive training represents an important therapeutic strategy. In a previous study, crossword puzzles were found to be superior to computerized cognitive training on the primary cognitive outcome and function with decreased brain atrophy. Building on these findings, this study will evaluate and compare the impact of high dose crosswords (4 puzzles per week) to low dose crosswords (1 puzzle per week) and a health education control group on the cognition and function of participants.

Conditions

Mild Cognitive Impairment (MCI); Cognitive Training

Keywords

Mild Cognitive Impairment; Cognitive Training; Crossword Puzzles; Health Education

Outcome Measures

Primary Outcomes (1)

• Change in ADASCog-14 (14-item Alzheimer's Disease Assessment Scale - Cognitive subscale)

  The ADASCog-14 is a brief neuropsychological assessment used to assess the severity of cognitive symptoms of dementia. It is one of the most widely used cognitive scales in clinical trials and is considered to be the "gold standard" for assessing antidementia treatments. The total score range is 0 to 90; a higher score indicates greater cognitive impairment.

  Baseline, 78 weeks

Secondary Outcomes (3)

• Change in Functional Activities Questionnaire (FAQ) score

  Baseline, 78 weeks

• Change in MRI hippocampal volume

  Baseline, 78 weeks

• Change in cortical thickness

  Baseline, 78 weeks

Other Outcomes (3)

• Change in Preclinical Alzheimer Composite-5 (PACC5)

  Baseline, 78 weeks

• Change in Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL-PI)

  Baseline, 78 weeks

• plasma neurofilament light and ptau 217

  Baseline, 78 weeks

Study Arms (3)

Control

PLACEBO COMPARATOR

This sample will receive health education. The participant will read chapters from the book, "Living a Healthy Life with chronic conditions," 5th edition, by K Lorig, D Laurent, V Gonzalez, D Sobel, M Minor and M Gecht-Silver, and review chapters with the unblinded study coordinator.

Other: Cognitive Training

Low Dose Crossword

ACTIVE COMPARATOR

This sample will receive low dose crossword training with one crossword puzzle per week during the first 12 weeks on the Cognifit web-based platform. Subsequent booster sessions will occur at 20, 32, 42, 52, 64 and 78 weeks.

Other: Cognitive Training

High Dose Crossword

ACTIVE COMPARATOR

This sample will receive high dose crossword training. This sample will receive high dose crossword training with four crossword puzzles per week during the first 12 weeks on the Cognifit web-based platform, followed by booster sessions at 20, 32, 42, 52, 64 and 78 weeks.

Other: Cognitive Training

Interventions

Cognitive Training OTHER

Participants (n=240) will be randomized to high dose crosswords, low dose crosswords, and health education at 1:1:1 ratio, stratified by site, age (\< 70 and 70 years), and MCI status (early MCI and late MCI). In the two crossword puzzles conditions, after initial training to use the web-based platform, the participant will be assigned to do 12 weeks of crossword puzzles four times per week or 12 weeks of crossword puzzles once per week at home. After these 12 weeks, booster sessions will be either four or one 30-minute session(s) completed over 1 week. These booster sessions will occur at weeks 20, 32, 42, 52, 64, and 78. In-person assessments will occur at 0, 12, 32, 52, 78 weeks with one crossword puzzle session, which will count toward the booster session. Health education will involve reading chapters in a book on common illnesses and lifestyle, and a research staff member will review these chapters at the same assessment intervals as the crossword puzzles conditions.

Control; High Dose Crossword; Low Dose Crossword

Eligibility Criteria

• Age: 55 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Access to a home desktop or laptop computer or tablet at acceptable internet speed for the study duration.
• Participants need to be 55 to 89 years of age (inclusive) at the time of informed consent.
• Females need to be post-menopausal (last period more than 12 months earlier by history).
• Subjective cognitive complaints, i.e., memory or other cognitive complaints, e.g., naming/language.
• Meets criteria for cognitive impairment (CI), including either EMCI (early MCI) or LMCI (late MCI), defined as memory impairment documented by scoring below the education adjusted cutoff on the Logical Memory II subscale (Story A, Delayed Paragraph Recall) from the Wechsler Memory Scale - III (WMS-III) (the maximum score is 25). The criteria for MCI (includes EMCI and LMCI) and used in COGIT-2 are as follows: EMCI is defined by a WMS-III Logical memory delayed recall score of 3-6 with 0-7 years of education, score of 5-9 with 8-15 years of education, and score of 9-11 with 16 or more years of education. LMCI is defined by a WMS-III Logical Memory delayed recall score ≤ 2 with 0-7 years of education, score ≤ 4 with 8-15 years of education, and score ≤ 8 with ≥ 16 years of education.
• Montreal Cognitive Assessment (MoCA) score ≥ 20/30.
• An informant (relative, friend, other caregiver) who contacts the participant at least weekly is required to provide information about the participant's functioning. This can be a telephone informant in the case of participants who do not have a live-in informant or close significant other. If the informant drops out, an alternate informant can be designated by the participant but the new informant will need to sign the informant information sheet in person.
• Must be English-speaking: Wide Range Achievement Test (WRAT3) score must indicate at least a 6th grade reading level with a score of ≥ 37.

You may not qualify if:

• Diagnosis of dementia of any type.
• Current clinical diagnosis of schizophrenia, schizoaffective disorder, psychosis, or bipolar I disorder (Diagnostic and Statistical Manual of Mental Disorders (DSM-5 TR) criteria).
• Current or recent (past 6 months) alcohol or substance use disorder (DSM-5 TR criteria).
• Clinical stroke with residual neurological deficits. While we will not exclude participants with cerebrovascular disease or transient ischemic attacks (TIAs), we do not wish to include participants with a frank clinical stroke because it is not clear that this type of participant is similar to the MCI participant generally, and clear-cut neurological impairment, e.g., hemiplegia/hemiparesis or speech impairment, may compromise the ability to do the procedures and to complete the neuropsychological test battery.
• Presence of any of the following disorders: a) Central Nervous System Infections, with cerebrospinal fluid evidence of meningitis, encephalitis, or other infectious process; b) dementia of any type; c) Huntington's disease; d) Multiple sclerosis; e) Parkinson's disease; f) Other neurologic disorders with focal signs, e.g., amyotrophic lateral sclerosis.
• Regular use of crosswords or formal computerized cognitive training platforms averaging once per week or more than once per week in the past year. Eligible participants who join the trial are instructed not to do these procedures on their own during the trial, i.e., independent of the study.
• Participation concurrently in another therapeutic clinical trial of a cognitive enhancing drug or device or procedure.
• Geriatric Depression Scale (Short Form) score of ≥ 6.

Sponsors & Collaborators

• Columbia University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (4)

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

University of Washington

Seattle, Washington, 98104, United States

RECRUITING

Related Publications (15)

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• Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004 Sep;256(3):183-94. doi: 10.1111/j.1365-2796.2004.01388.x.

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• Wang LA, Goldberg TE, Harvey PD, Hanson AJ, Motter J, Andrews H, Qian M, Zhang R, Janis M, Doraiswamy PM, Devanand DP. Crossword puzzle training and neuroplasticity in mild cognitive impairment (COGIT-2): 78-week, multi-site, randomized controlled trial with cognitive, functional, imaging and biomarker outcomes. Int J Clin Trials. 2025 Apr-Jun;12(2):111-120. doi: 10.18203/2349-3259.ijct20251032. Epub 2025 Apr 11.

  PMID: 40852373 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Health Education

Interventions

Cognitive Training

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Adherence Interventions; Medication Adherence; Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Neurological Rehabilitation; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Central Study Contacts

Lola Nedic, BA

CONTACT

6467747202; ln2563@cumc.columbia.edu

Davangere P Devanand, MD, MBBS

CONTACT

6467748658; dpd3@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will know their treatment condition. Study investigators and clinicians and blinded research coordinator who administers outcomes assessments remain blind to treatment condition.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Model Details: Comparison of 3 treatment arms

Study Record Dates

• First Submitted: September 16, 2024
• First Posted: September 19, 2024
• Study Start: December 17, 2024
• Primary Completion (Estimated): February 28, 2029
• Study Completion (Estimated): February 28, 2029
• Last Updated: October 31, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: From October 15, 2024 until September 30, 2029

Locations

US (4)