Cognitive Training and Neuroplasticity in Mild Cognitive Impairment (CogTraining)

• ClinicalTrials.gov Identifier: NCT03205709
• Recruitment Status: Active, not recruiting
• First Posted: July 2, 2017
• Last Update Posted: October 4, 2022
• Sponsor: New York State Psychiatric Institute
• Collaborators: Duke University; Queens College, The City University of New York
• Information provided by (Responsible Party): Davangere P. Devanand, New York State Psychiatric Institute

Tracking Information

• First Submitted Date: June 22, 2017
• First Posted Date: July 2, 2017
• Last Update Posted Date: October 4, 2022
• Actual Study Start Date: November 29, 2017
• Estimated Primary Completion Date: July 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 4, 2022)

Change overtime in the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) [ Time Frame: [Time Frame: Baseline, Weeks 12, 52, 78] ]

The modified ADAS-Cog is a cognitive battery that assesses learning, memory, language production, language comprehension, constructional praxis, ideational praxis, and orientation.

Original Primary Outcome Measures (submitted: June 29, 2017)

• Change overtime in the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) [ Time Frame: [Time Frame: Baseline, Weeks 12, 32 52, 78] ]
  The modified ADAS-Cog is a cognitive battery that assesses learning, memory, language production, language comprehension, constructional praxis, ideational praxis, and orientation.
• Change overtime in Pfeffer Functional Activities Questionnaire (FAQ) [ Time Frame: [Time Frame: Screen, Weeks 12, 20, 32 52, 78] ]
  FAQ is a widely used 10-item instrument that takes 3 minutes to administer and focuses on instrumental, social and cognitive functioning.

Current Secondary Outcome Measures (submitted: February 4, 2022)

• Neuropsychological Testing Composite Score [ Time Frame: [Time Frame: Baseline, Weeks 12, 52, 78] ]
  Neuropsychological Testing Composite Score is a compiled score of all neuropsychological tests administered in the protocol, i.e. Auditory Verbal Learning Test, Block Design, Verbal Fluency, Visual Reproduction, Boston Naming Task, Trails A and B
• Change overtime in Pfeffer Functional Activities Questionnaire (FAQ) [ Time Frame: [Time Frame: Screen, Weeks 12, 20, 32 52, 78] ]
  FAQ is a widely used 10-item instrument that takes 3 minutes to administer and focuses on instrumental, social and cognitive functioning.
• UPSA [ Time Frame: [Time Frame: Baseline, Weeks 32, 78] ]
  It is a performance-based measure of functional abilities that includes measures of simulated real-world activities, for example, planning a trip to the beach, remembering documents to bring to a medical appointment, and dialing a phone number.
• Change overtime in the Neurocognitive Performance Test [ Time Frame: [Time Frame: Baseline, Weeks 12, 78] ]
  NCPT is a set of assessments that test your skills using tasks independent of the Lumosity games. This test is completed online using your Lumosity login.

Original Secondary Outcome Measures (submitted: June 29, 2017)

• Change overtime in the Auditory Verbal Learning Test (AVLT) [ Time Frame: [Time Frame: Baseline, Weeks 12, 52, 78] ]
  The AVLT evaluates a wide diversity of functions short-term auditory-verbal memory, rate of learning, learning strategies, retroactive, and proactive interference, presence of confabulation of confusion in memory processes, retention of information, and differences between learning and retrieval.
• Change overtime in Digit Symbol Substitution Test (DSST). [ Time Frame: [Time Frame: Baseline, Weeks 12, 32 52, 78] ]
  The DSST requires participants to transcribe a unique geometric symbol with its corresponding Arabic number.
• Change overtime in Clinical Dementia Rating (CDR) [ Time Frame: Screen ]
  Clinical Dementia Rating (CDR) is a numeric scale used to quantify the severity of symptoms of dementia. Six areas are examined by the health professional for this scale: memory, orientation, judgment and problem-solving, community affairs, home and hobbies, and personal care.
• Change overtime in the Mail-In Cognitive Function Screening Instrument [ Time Frame: [Time Frame: Screen, Weeks 12, 20, 32 52, 78] ]
  The Mail-In Cognitive Function Instrument (MCFSI) consists of 2 similar sets of 14 questions. These sets are mailed separately to the subject and the informant, who are asked to complete them independently. The questions assess the subject's decline in function over the past year.

Current Other Pre-specified Outcome Measures (submitted: February 4, 2022)

• Geriatric Depression Scale [ Time Frame: [Time Frame: Screen, Weeks 12, 32, 52, 78) ]
  Used to assess depression
• MMSE (Mini Mental Status Exam) [ Time Frame: [Time Frame: Screen, Weeks 12, 32 52, 78] ]
  A 30-point questionnaire that is widely used in clinical research to measure cognitive impairment.
• WMS-III Logical Memory I & II [ Time Frame: [Time Frame: Screen] ]
  Used to measure logical memory function in an individual. Participant is read stories, and asked to remember the story's details at two different time points.
• Block Design [ Time Frame: [Time Frame: Baseline, Weeks 12, 52, 78] ]
  Block Design is primarily a measure of visual-spatial and organizational processing abilities, as well as nonverbal problem-solving skills.
• Verbal Fluency [ Time Frame: [Time Frame: Baseline, Weeks 12, 52, 78] ]
  Assesses phonemic fluency by requesting the participant to orally produce as many words as possible that begin with certain letters within a 60-second time period.
• Boston Naming Task [ Time Frame: [Time Frame: Baseline, Weeks 12, 52, 78] ]
  It is a confrontational word retrieval task for 60-items.
• Trails A and B [ Time Frame: [Time Frame: Baseline, Weeks 12, 52, 78] ]
  Parts A and B are composed of 25 circles. Patients are asked to scan the entire page and identify the next number or letter in a sequence.
• User engagement scale [ Time Frame: [Time Frame: Week 12, 78] ]
  This measures (version adapted for computer games) multiple aspects of engagement, usability and satisfaction on a 5-point Likert scale and comprises both negative ("I felt annoyed when on this site", "the game was confusing") and positive ("I really had fun", "It was really worthwhile") items.
• UPSIT (University of Pennsylvania Smell Identification Test) [ Time Frame: [Time Frame: Baseline, Week 78) ]
  This assesses olfactory identification deficits. Participants will be asked to scratch smells in testing booklets, and choose the selection that best corresponds to the odor that is being emitted.
• Cognitive Reserve Index [ Time Frame: [Time Frame: Screen] ]
  A brief questionnaire assessing for cognitive reserve.
• Visual Reproduction Test [ Time Frame: [Time Frame: Baseline, Weeks 12, 52, 78] ]
  A test used to assess visual memory.
• MRI Hippocampal Volume [ Time Frame: [Time Frame: Baseline, Week 78] ]
  Mean right and left hippocampal volume.
• MRI Cortical Thickness [ Time Frame: Time Frame: Baseline, Week 78] ]
  Mean right and left cortical thickness.
• fMRI Default Mode Network (DMN) [ Time Frame: [Time Frame: Baseline, Week 78] ]
  Functional MRI default mode network.

Original Other Pre-specified Outcome Measures (submitted: June 29, 2017)

• Lifestyle Experiences Questionnaire [ Time Frame: [Time Frame: Screen, Week 78] ]
• Beck Depression Inventory II [ Time Frame: [Time Frame: Screen, Weeks 12, 52, 78) ]
• MMSE [ Time Frame: [Time Frame: Screen, Weeks 12, 20, 32 52, 78] ]
• WMS-III Logical Memory I&II [ Time Frame: [Time Frame: Screen] ]
• Block Design [ Time Frame: [Time Frame: Baseline, Weeks 12, 32 52, 78] ]
• Verbal Fluency [ Time Frame: [Time Frame: Baseline, Weeks 12, 32 52, 78] ]
• Boston Naming Task [ Time Frame: [Time Frame: Baseline, Weeks 12, 32 52, 78] ]
• Trails A and B [ Time Frame: [Time Frame: Baseline, Weeks 12, 32 52, 78] ]
  Parts A and B are composed of 25 circles. Patients are asked to scan the entire page and identify the next number or letter in a sequence.
• NCPT online cognitive performance test [ Time Frame: [Time Frame: Weeks 12, 32 52, 78] ]
• User engagement scale [ Time Frame: [Time Frame: Week 78] ]
• UPSIT [ Time Frame: [Time Frame: Baseline,Week 52) ]

Descriptive Information

• Brief Title: Cognitive Training and Neuroplasticity in Mild Cognitive Impairment
• Official Title: Cognitive Training and Neuroplasticity in Mild Cognitive Impairment
• Brief Summary: The purpose of this study is to evaluate if systematic cognitive training can improve cognitive performance in participants (55 and older) with memory loss. This study will evaluate the effects of Computerized Cognitive Training (CCT) for improvement in everyday cognitive and function status, in addition to long-term changes in brain networks over an 18-month period. Although there is no distribution of medication for this study, participants are required to have an at-home computer.
• Detailed Description: In this clinical trial, investigators will evaluate if systematic cognitive training can improve cognitive performance in participants with memory loss. This study is for those who have demonstrated difficulty with memory. It will evaluate the effects of Computerized Cognitive Training (CCT) for improvement in everyday cognitive and function status, in addition to long-term changes in brain networks over an 18-month period. In this study, participants will be randomly assigned to Training Group 1 or 2; therefore, one will have a 50% chance of being assigned to CCT, and a 50% chance of being assigned to Crossword Puzzle Training (CPT). During the 18- month period, participants will be asked to come to the Memory Disorders Clinic at the New York State Psychiatric Institute (NYSPI) for a screening evaluation, and if eligible, will return for five follow-up visits at Weeks 12, 32, 52, and 78.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Treatment

Condition

• Mild Cognitive Impairment
• Memory Disorders
• Memory Impairment
• Cognitive Impairment
• Cognitive Disorder
• Cognitive Decline

Intervention

• Other: Computerized Cognitive Training
  Computerized online cognitive training will be used to target specific cognitive abilities and neural networks to potentially improve cognitive functioning through neuroplasticity.
• Other: Crossword Puzzles
  These are intended to mimic crossword puzzles in newspapers.

Study Arms

• Active Comparator: Training Group 1
  Computerized Cognitive Training
  Intervention: Other: Computerized Cognitive Training
• Placebo Comparator: Training Group 2
  Crossword puzzles
  Intervention: Other: Crossword Puzzles

• Publications *: D'Antonio J, Simon-Pearson L, Goldberg T, Sneed JR, Rushia S, Kerner N, Andrews H, Hellegers C, Tolbert S, Perea E, Petrella J, Doraiswamy PM, Devanand D. Cognitive training and neuroplasticity in mild cognitive impairment (COG-IT): protocol for a two-site, blinded, randomised, controlled treatment trial. BMJ Open. 2019 Aug 30;9(8):e028536. doi: 10.1136/bmjopen-2018-028536. Erratum In: BMJ Open. 2019 Sep 11;9(9):e028536corr1.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 3, 2022): 107
• Original Estimated Enrollment (submitted: June 29, 2017): 100
• Estimated Study Completion Date: July 31, 2023
• Estimated Primary Completion Date: July 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Males and females 55 to 95 years of age (inclusive) at the time of informed consent.
2. Subjective cognitive complaints, i.e., memory or other cognitive complaints, e.g., naming/language.
3. Meets criteria for cognitive impairment (CI) defined as scores > 1 below standardized norms on memory function as identified by the Wechsler Memory Scale (WMS) III Logical Memory immediate or delayed recall score.
4. Folstein Mini Mental State (MMSE) score ≥ 23 out of 30.
5. A family member or other individual who is in contact with the patient and consents to serve as informant during the study; this can be a telephone informant in the case of patients who do not have a live-in informant or close significant other.
6. Access to a home desktop or laptop computer at acceptable internet speed for the study duration.

Exclusion Criteria:

1. Diagnosis of dementia of any type.
2. Current clinical evidence of schizophrenia, schizoaffective disorder, major depression, psychosis, or bipolar I disorder (DSM-IV criteria).
3. Active suicidal ideation or plan.
4. Current or recent (past 6 months) alcohol or substance use disorder (DSM-5 criteria).
5. Clinical stroke with residual neurological deficits. While we will not exclude patients with cerebrovascular disease, we will not include patients who have had a stroke with residual clinical deficits because it is not clear that this type of patient is similar to the MCI (Mild Cognitive Impairment) patient generally, and clear-cut neurological impairment, e.g., hemiplegia/hemiparesis or speech impairment, may compromise the patient's ability to do the CCT or active control 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. Other patients receive medications that may be associated with cognitive impairment but are rarely considered the likely etiology, e.g., theophylline, nifedipine, beta blockers; they will not be excluded. Patients receiving other psychotropic medications not expected to have a material impact on cognition, e.g., SSRIs (Selective Serotonin Reuptake Inhibitors) and SNRIs (Serotonin-norepinephrine reuptake inhibitors) will be eligible.
7. Presence of any of the following disorders: a) Central Nervous System infection, 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; g) Mental retardation.
8. Acute, severe unstable medical illness. For cancer, acutely ill patients (including those with metastases) will be excluded, but past history of successfully treated cancer will not result in exclusion.
9. Contraindication to MRI scan: pacemaker, metal implants following surgery, any other contraindication to MRI. Eligibility for the MRI scan is a requirement for the study.
10. UPSIT (University of Pennsylvania Smell Identification Test) exclusions: current smoker > 1 pack daily, current upper respiratory infection (retested as soon as the infection clears). UPSIT scores are reduced in schizophrenia, Parkinson's disease and Parkinson's related conditions; these disorders are exclusion criteria for this study. Patients with UPSIT exclusions, e.g., current heavy smoker (less than 3% of older adults in our experience), will not receive the UPSIT but will continue to participate in all other aspects of the study.
11. Patients lacking English-speaking ability as determined by self-report and clinical evaluation.
12. Regular online brain training or regular crossword puzzle user, defined as doing these procedures at a frequency of twice weekly or greater during the year prior to screening. 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.
13. Participation in another intervention trial for cognitive impairment.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years to 95 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03205709
• Other Study ID Numbers: 7395
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Davangere P. Devanand, New York State Psychiatric Institute
• Original Responsible Party: New York State Psychiatric Institute
• Current Study Sponsor: New York State Psychiatric Institute
• Original Study Sponsor: Same as current

Collaborators

• Duke University
• Queens College, The City University of New York

Investigators

• Principal Investigator: Davangere P Devanand, MD; Columbia University
• Principal Investigator: Murali Doraiswamy, MD; Duke University
• Principal Investigator: Joel Sneed, PhD; Queens College

• PRS Account: New York State Psychiatric Institute
• Verification Date: October 2022