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Mild Cognitive Impairment (MCI)Phase 2COGIT-2NCT06601933

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

A Phase 2 study testing Cognitive Training in people with Mild Cognitive Impairment (MCI) and Cognitive Training, run by Columbia University at 4 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 55 to 89 years
What is being tested?
Cognitive Training
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
240 participants
Where
4 sitesUnited States
Study dates
17 Dec 2024to 31 Aug 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 89 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Must be English-speaking: Wide Range Achievement Test (WRAT3) score must indicate at least a 6th grade reading level with a score of ≥ 37.

Who cannot join

  • 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 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).
  • 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.
  • Use of medications known to have a negative impact on cognition: benzodiazepines in lorazepam equivalents greater than or equal to 1 mg daily, narcotics, anticholinergic medications at ACB Calculator level 3), large number of sedating medications in combination. Current use of lecanemab or donanemab will be exclusionary.
Show all 12Show fewer
  • 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.
  • 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.
  • 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.
  • 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.

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Lola Nedic, BA contact

6467747202

ln2563@cumc.columbia.edu

Davangere P Devanand, MD, MBBS contact

6467748658

dpd3@cumc.columbia.edu

United States4 sites, 4 recruiting

  • Duke University Medical Center

    Durham, North Carolina, 27710

    Caroline Hellegers, 919-681-3986, Caroline.hellegers@duke.edu

    Murali Doraiswamy, MD

    Recruiting

  • University of Miami Miller School of Medicine

    Miami, Florida, 33136

    Sebastian Escarfuller, 305-243-6489, s.escarfuller@umiami.edu

    Philip D Harvey, PhD

    Recruiting

  • Columbia University Irving Medical Center

    New York, New York, 10032

    Lola Nedic, BA, 646-774-7202, ln2563@cumc.columbia.edu

    Davangere P Devanand, MD, MBBS

    Recruiting

  • University of Washington

    Seattle, Washington, 98104

    Kristen Gonzalez-Farris, 206-897-6797, kmfarris@uw.edu

    Angela Hanson, MD

    Recruiting

Other trials in United States

About this study

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.

Read the detailed description

This study plans to enroll 240 participants with MCI, estimated as 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).

Being tested
Cognitive Training
Keywords
Mild Cognitive Impairment, Cognitive Training, Crossword Puzzles, Health Education
Medical subject headings
Cognitive Dysfunction, Health Education

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cognitive TrainingOther

    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.

Study groups in NCT06601933
Study groupRoleWhat they receive
ControlPlacebo comparatorThis 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.
Receives: Other: Cognitive Training
Low Dose CrosswordActive comparatorThis 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.
Receives: Other: Cognitive Training
High Dose CrosswordActive comparatorThis 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.
Receives: Other: Cognitive Training

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline, 78 weeks

Secondary outcomes (3)

  1. Change in Functional Activities Questionnaire (FAQ) score

    The FAQ is a patient-reported measure of cognitive impairment on difficulties in activities of daily living. The total score range is 0 to 30, with a higher score indicating greater impairment.

    Measured: Baseline, 78 weeks

  2. Change in MRI hippocampal volume

    The hippocampal volume is a measurement of brain atrophy. Hippocampal volume ranges from 0 to 10 cu cm with higher values indicating large hippocampal volume. Decrease in this measure indicates hippocampal atrophy.

    Measured: Baseline, 78 weeks

  3. Change in cortical thickness

    The cortical thickness is a measurement of brain atrophy. Values range from 0 to 1 with higher values indicating greater cortical thickness.

    Measured: Baseline, 78 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2024
  2. Study start17 Dec 2024
  3. Primary completion28 Feb 2030 (estimated)
  4. Study completion31 Aug 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Comparison of 3 treatment arms
Masking
Triple blind
Who is masked
Care provider, Investigator, Outcomes assessor
Enrolment
240 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06601933
Sponsor's protocol ID
AAAU9623
Other IDs
2R01AG052440-06A1, WCG 20240282
Acronym
COGIT-2
Status last verified
Jul 2026
First submitted
16 Sep 2024
Last updated
28 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: De-identified participant data for all measures will be shared among investigators in the study.

Publications

  • Devanand DP, Goldberg TE, Qian M, Rushia SN, Sneed JR, Andrews HF, Nino I, Phillips J, Pence ST, Linares AR, Hellegers CA, Michael AM, Kerner NA, Petrella JR, Doraiswamy PM. Computerized Games versus Crosswords Training in Mild Cognitive Impairment. NEJM Evid. 2022 Dec;1(12):10.1056/evidoa2200121. doi: 10.1056/evidoa2200121. Epub 2022 Oct 27.

    PubMed 37635843

  • Motter JN, Pelton GH, D'Antonio K, Rushia SN, Pimontel MA, Petrella JR, Garcon E, Ciovacco MW, Sneed JR, Doraiswamy PM, Devanand DP. Clinical and radiological characteristics of early versus late mild cognitive impairment in patients with comorbid depressive disorder. Int J Geriatr Psychiatry. 2018 Dec;33(12):1604-1612. doi: 10.1002/gps.4955. Epub 2018 Jul 23.

    PubMed 30035339

  • Pfeffer RI, Kurosaki TT, Harrah CH Jr, Chance JM, Filos S. Measurement of functional activities in older adults in the community. J Gerontol. 1982 May;37(3):323-9. doi: 10.1093/geronj/37.3.323.

    PubMed 7069156

  • Liss JL, Seleri Assuncao S, Cummings J, Atri A, Geldmacher DS, Candela SF, Devanand DP, Fillit HM, Susman J, Mintzer J, Bittner T, Brunton SA, Kerwin DR, Jackson WC, Small GW, Grossberg GT, Clevenger CK, Cotter V, Stefanacci R, Wise-Brown A, Sabbagh MN. Practical recommendations for timely, accurate diagnosis of symptomatic Alzheimer's disease (MCI and dementia) in primary care: a review and synthesis. J Intern Med. 2021 Aug;290(2):310-334. doi: 10.1111/joim.13244. Epub 2021 Mar 31.

    PubMed 33458891

  • Segrave RA, Arnold S, Hoy K, Fitzgerald PB. Concurrent cognitive control training augments the antidepressant efficacy of tDCS: a pilot study. Brain Stimul. 2014 Mar-Apr;7(2):325-31. doi: 10.1016/j.brs.2013.12.008. Epub 2013 Dec 19.

    PubMed 24486425

  • Owens M, Koster EH, Derakshan N. Improving attention control in dysphoria through cognitive training: transfer effects on working memory capacity and filtering efficiency. Psychophysiology. 2013 Mar;50(3):297-307. doi: 10.1111/psyp.12010. Epub 2013 Jan 25.

    PubMed 23350956

  • Lohman MC, Rebok GW, Spira AP, Parisi JM, Gross AL, Kueider AM. Depressive symptoms and memory performance among older adults: results from the ACTIVE memory training intervention. J Aging Health. 2013 Dec;25(8 Suppl):209S-29S. doi: 10.1177/0898264312460573. Epub 2012 Sep 23.

    PubMed 23006426

  • Elgamal S, McKinnon MC, Ramakrishnan K, Joffe RT, MacQueen G. Successful computer-assisted cognitive remediation therapy in patients with unipolar depression: a proof of principle study. Psychol Med. 2007 Sep;37(9):1229-38. doi: 10.1017/S0033291707001110. Epub 2007 Jul 5.

    PubMed 17610766

  • Rozzini L, Costardi D, Chilovi BV, Franzoni S, Trabucchi M, Padovani A. Efficacy of cognitive rehabilitation in patients with mild cognitive impairment treated with cholinesterase inhibitors. Int J Geriatr Psychiatry. 2007 Apr;22(4):356-60. doi: 10.1002/gps.1681.

    PubMed 17117398

  • Harvey PD, Zayas-Bazan M, Tibirica L, Kallestrup P, Czaja SJ. Improvements in Cognitive Performance With Computerized Training in Older People With and Without Cognitive Impairment: Synergistic Effects of Skills-Focused and Cognitive-Focused Strategies. Am J Geriatr Psychiatry. 2022 Jun;30(6):717-726. doi: 10.1016/j.jagp.2021.11.008. Epub 2021 Nov 21.

    PubMed 34924275

  • Valenzuela MJ, Sachdev P. Brain reserve and dementia: a systematic review. Psychol Med. 2006 Apr;36(4):441-54. doi: 10.1017/S0033291705006264. Epub 2005 Oct 6.

    PubMed 16207391

  • Zissimopoulos J, Crimmins E, St Clair P. The Value of Delaying Alzheimer's Disease Onset. Forum Health Econ Policy. 2014 Nov;18(1):25-39. doi: 10.1515/fhep-2014-0013. Epub 2014 Nov 4.

    PubMed 27134606

  • Wolinsky FD, Jones MP, Dotson MM. Does Visual Speed of Processing Training Improve Health-Related Quality of Life in Assisted and Independent Living Communities?: A Randomized Controlled Trial. Innov Aging. 2020 Jul 31;4(4):igaa029. doi: 10.1093/geroni/igaa029. eCollection 2020.

    PubMed 32964141

  • 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.

    PubMed 15324362

  • 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.

    PubMed 40852373

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cognitive Training in people with Mild Cognitive Impairment (MCI) and Cognitive Training, run by Columbia University at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Lola Nedic, BA (6467747202, ln2563@cumc.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in ADASCog-14 (14-item Alzheimer's Disease Assessment Scale - Cognitive subscale) (time frame: Baseline, 78 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06601933, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2026.

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