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

Обзор

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.

Подробное описание

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).

Вмешательства

• Другое 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 eit

Первичные конечные точки

• Change in ADASCog-14 (14-item Alzheimer's Disease Assessment Scale - Cognitive subscale) [Срок оценки: Baseline, 78 weeks]

Вторичные конечные точки (3)

• Change in Functional Activities Questionnaire (FAQ) score [Срок оценки: Baseline, 78 weeks]
• Change in MRI hippocampal volume [Срок оценки: Baseline, 78 weeks]
• Change in cortical thickness [Срок оценки: Baseline, 78 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 4 центра

• University of Miami Miller School of Medicine — Miami
• Columbia University Irving Medical Center — New York
• Duke University Medical Center — Durham
• University of Washington — Seattle

Публикации

• 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. PMID 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. PMID 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. PMID 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 synth PMID 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. PMID 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. PMID 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. PMID 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. PMID 17610766

Идентификаторы

NCT: NCT06601933 · AAAU9623 · 2R01AG052440-06A1 · WCG 20240282

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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