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

NCT ID: NCT06601933

Last Updated: 2025-10-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

240 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-17

Study Completion Date

2029-02-28

Brief Summary

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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.

Detailed Description

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This study plans to enroll 240 participants with MCI: 75 at Columbia University, 60 at Duke, 60 at University of Miami, 45 at University of Washington. Participants will be randomized 1:1:1 to 4 crossword puzzles per week (high dose arm), 1 crossword puzzle per week (low dose arm), or health education (control arm). In the crossword groups, this initial intensive 12-week phase will be followed by booster sessions that will each comprise 30-minute sessions (1 or 4 sessions depending on assignment) completed over 1 week, and occur at weeks 20, 32, 42, 52, 64, and 78. In-person assessments will occur at 0, 12, 32, 52, 78 weeks. During weeks 0, 12, 32, 52, and 78, participants in the 4/week crosswords group will complete three sessions at home and the fourth in clinic, and participants in the 1/week group will complete one session in the clinic and none at home. During weeks 20, 42, and 64, participants will complete all sessions at home. The health education group will receive in-person sessions and assessments at weeks 0, 12, 32, 52, and 78 weeks, each for 30 min (same time frame as the crossword groups), and phone calls will be made, each for 30 min, at weeks 20, 42 and 64 to match the crossword groups (each 30 min). Unique features of the design: Evaluation of home-based crossword puzzles as the primary intervention; Comparison of two dose conditions to a comparison group; Health education comparison group with readings to mimic placebo in clinical trials; Stratification of random assignment by site, age, and early MCI/late MCI; Evaluation of MRI atrophy indices and plasma biomarkers of neurodegeneration (Neurofilament Light, Nfl) and Alzheimer Disease pathology (ptau-217).

Conditions

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Mild Cognitive Impairment (MCI) Cognitive Training

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Comparison of 3 treatment arms
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Caregivers Investigators Outcome Assessors
Participants will know their treatment condition. Study investigators and clinicians and blinded research coordinator who administers outcomes assessments remain blind to treatment condition.

Study Groups

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Control

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.

Group Type PLACEBO_COMPARATOR

Cognitive Training

Intervention Type 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.

Low Dose Crossword

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.

Group Type ACTIVE_COMPARATOR

Cognitive Training

Intervention Type 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.

High Dose Crossword

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.

Group Type ACTIVE_COMPARATOR

Cognitive Training

Intervention Type 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.

Interventions

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Cognitive Training

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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Access to a home desktop or laptop computer or tablet at acceptable internet speed for the study duration.
2. Participants need to be 55 to 89 years of age (inclusive) at the time of informed consent.
3. Females need to be post-menopausal (last period more than 12 months earlier by history).
4. Subjective cognitive complaints, i.e., memory or other cognitive complaints, e.g., naming/language.
5. 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.
6. Montreal Cognitive Assessment (MoCA) score ≥ 20/30.
7. 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.
8. Must be English-speaking: Wide Range Achievement Test (WRAT3) score must indicate at least a 6th grade reading level with a score of ≥ 37.

Exclusion Criteria

1. Diagnosis of dementia of any type.
2. Current clinical diagnosis of schizophrenia, schizoaffective disorder, psychosis, or bipolar I disorder (Diagnostic and Statistical Manual of Mental Disorders (DSM-5 TR) criteria).
3. Current unstable or untreated major depression, or active suicidality based on a Suicide Severity Rating Scale (C-SSRS Screen version: positive answer to question 1 or 2 followed by item 6 positive answer leads to exclusion. Negative answer to questions 1 and 2: interview ends and the participant is not excluded for active suicidality).
4. Current or recent (past 6 months) alcohol or substance use disorder (DSM-5 TR criteria).
5. 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.
6. Use of medications known to have a negative impact on cognition: benzodiazepines in lorazepam equivalents greater than or equal to 1 mg daily, narcotics, anticholinergics (ACB Calculator level 3 medication leads to exclusion), large number of sedating medications in combination. Medications with anticholinergic/antihistaminergic properties will be reviewed, e.g., low dose quetiapine (≤ 25 mg daily) will be permitted, but daily use of diphenhydramine or equivalent will be reviewed. Current use of lecanemab or donanemab will be exclusionary.
7. 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.
8. Acute, severe unstable medical illness in the judgment of the clinician. For cancer, acutely ill participants (including those with metastases) are excluded, but history of successfully treated cancer does not result in exclusion.
9. Contraindication to MRI scan: MRI incompatible pacemakers and metal implants, any other contraindication to MRI. For participants with possible claustrophobia, they must be willing to do the MRI with adjunct lorazepam 0.5 mg to reduce anxiety. For participants who are recruited and are eligible for MRI but are unable to complete the baseline MRI, a repeat MRI for the same time-point can be attempted if the subject is willing. Baseline MRI is required for study inclusion.
10. 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.
11. Participation concurrently in another therapeutic clinical trial of a cognitive enhancing drug or device or procedure.
12. Geriatric Depression Scale (Short Form) score of ≥ 6.
Minimum Eligible Age

55 Years

Maximum Eligible Age

89 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Columbia University

OTHER

Sponsor Role lead

Responsible Party

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Devangere P. Devanand

Professor of Psychiatry

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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University of Miami Miller School of Medicine

Miami, Florida, United States

Site Status RECRUITING

Columbia University Irving Medical Center

New York, New York, United States

Site Status RECRUITING

Duke University Medical Center

Durham, North Carolina, United States

Site Status RECRUITING

University of Washington

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Lola Nedic, BA

Role: CONTACT

6467747202

Davangere P Devanand, MD, MBBS

Role: CONTACT

6467748658

Facility Contacts

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Sebastian Escarfuller

Role: primary

305-243-6489

Lola Nedic, BA

Role: primary

6467747202

Caroline Hellegers

Role: primary

919-681-3986

Kristen Gonzalez-Farris

Role: primary

206-897-6797

References

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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.

Reference Type DERIVED
PMID: 40852373 (View on PubMed)

Other Identifiers

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2R01AG052440-06A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

WCG 20240282

Identifier Type: OTHER

Identifier Source: secondary_id

AAAU9623

Identifier Type: -

Identifier Source: org_study_id

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