Cognitive Training and Neuroplasticity in Mild Cognitive Impairment (CogTraining)

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Impairment; Mild Cognitive Impairment; Cognitive Decline; Memory Disorders; Memory Impairment; Cognitive Disorder
• Intervention / Treatment: Other: Computerized Cognitive Training; Other: Crossword Puzzles

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
• Enrollment (Actual): 107
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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 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 Re-uptake Inhibitors) and SNRIs (Serotonin-norepinephrine re-uptake 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Training Group 1; Computerized Cognitive Training	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.
Placebo Comparator: Training Group 2; Crossword puzzles	Other: Crossword Puzzles; These are intended to mimic crossword puzzles in newspapers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog)	The modified ADAS-Cog is a cognitive battery that assesses learning, memory, language production, language comprehension, constructional praxis, ideational praxis, and orientation. Value range: 0-70. A higher score indicates worse cognition.	[Time Frame: 78 weeks]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change Over Time in Neuropsychological Testing Composite Score	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. The composite neuropsychological test battery is derived by computing the baseline z-score for each individual test and then averaging the resulting z scores. The range will be -5 to +5. z score of 0 represents the sample mean and higher z score indicates better performance.	[Time Frame: Week 78]
Change Over Time in Functional Activities Questionnaire (FAQ)	FAQ: Functional Activities Questionnaire (FAQ) measures instrumental activities of daily living (IADLs), such as preparing balanced meals and managing personal finances. The score ranges from 0-30. A higher score indicates a greater level of impairment in the instrumental activities of daily living.	[Time Frame: week 78]
Change Over Time in UCSD Performance-Based Skills Assessment (UPSA)	UPSA: UCSD Performance-Based Skills Assessment. The UPSA 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. A higher score indicates greater cognitive function. For the UPSA the z score at baseline is computed (based on the mean and SD of the raw scores). The expected range is -5 to +5 with z score of 0 representing the sample mean and higher z score indicating better performance.	[Time Frame: week 78]

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geriatric Depression Scale	Used to assess depression	[Time Frame: Screen, Weeks 12, 32, 52, 78)
MMSE (Mini Mental Status Exam)	A 30-point questionnaire that is widely used in clinical research to measure cognitive impairment.	[Time Frame: Screen, Weeks 12, 32 52, 78]
WMS-III Logical Memory I & II	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.	[Time Frame: Screen]
Block Design	Block Design is primarily a measure of visual-spatial and organizational processing abilities, as well as nonverbal problem-solving skills.	[Time Frame: Baseline, Weeks 12, 52, 78]
Verbal Fluency	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.	[Time Frame: Baseline, Weeks 12, 52, 78]
Boston Naming Task	It is a confrontational word retrieval task for 60-items.	[Time Frame: Baseline, Weeks 12, 52, 78]
Trails A and B	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.	[Time Frame: Baseline, Weeks 12, 52, 78]
User engagement scale	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.	[Time Frame: Week 12, 78]
UPSIT (University of Pennsylvania Smell Identification Test)	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.	[Time Frame: Baseline, Week 78)
Cognitive Reserve Index	A brief questionnaire assessing for cognitive reserve.	[Time Frame: Screen]
Visual Reproduction Test	A test used to assess visual memory.	[Time Frame: Baseline, Weeks 12, 52, 78]
MRI Hippocampal Volume	Mean right and left hippocampal volume.	[Time Frame: Baseline, Week 78]
MRI Cortical Thickness	Mean right and left cortical thickness.	Time Frame: Baseline, Week 78]
fMRI Default Mode Network (DMN)	Functional MRI default mode network.	[Time Frame: Baseline, Week 78]

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• 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

Publications and helpful links

General 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. doi: 10.1136/bmjopen-2018-028536corr1.

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2017
• Primary Completion (Actual): September 30, 2021
• Study Completion (Actual): December 27, 2021

Study Registration Dates

• First Submitted: June 22, 2017
• First Submitted That Met QC Criteria: June 29, 2017
• First Posted (Actual): July 2, 2017

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: April 29, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: MRI; memory; cognition; memory problems; computerized training; mci; memory complaints
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Cognitive Dysfunction; Cognition Disorders; Memory Disorders
• Other Study ID Numbers: 7395

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No