Cognitive Decline, Cognitive Disorder, Cognitive Impairment, Memory Disorders, Memory Impairment, Mild Cognitive Impairment
Conditions
Keywords
memory, computerized training, cognition, MRI, mci, memory problems, memory complaints
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.
Interventions
OTHERComputerized Cognitive Training
Computerized online cognitive training will be used to target specific cognitive abilities and neural networks to potentially improve cognitive functioning through neuroplasticity.
OTHERCrossword Puzzles
These are intended to mimic crossword puzzles in newspapers.
Sponsors
Duke University
Queens College, The City University of New York
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
55 Years to 95 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) | [Time Frame: 78 weeks] | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change Over Time in Neuropsychological Testing Composite Score | [Time Frame: Week 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. 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. |
| Change Over Time in Functional Activities Questionnaire (FAQ) | [Time Frame: week 78] | 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. |
| Change Over Time in UCSD Performance-Based Skills Assessment (UPSA) | [Time Frame: week 78] | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Training Group 1 Computerized Cognitive Training
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. | 51 |
| Training Group 2 Crossword Puzzles
Crossword Puzzles: These are intended to mimic crossword puzzles in newspapers. | 56 |
| Total | 107 |
Baseline characteristics
| Characteristic | Total | Training Group 1 | Training Group 2 |
|---|---|---|---|
| ADAS-Cog total score | 9.6 score STANDARD_DEVIATION 3.5 | 9.5 score STANDARD_DEVIATION 3.5 | 9.6 score STANDARD_DEVIATION 3.5 |
| Age, Customized Age ≤70 yr with early MCI | 21 Participants | 10 Participants | 11 Participants |
| Age, Customized Age >70 yr with early MCI | 23 Participants | 11 Participants | 12 Participants |
| Age, Customized Age ≤70 yr with late MCI | 26 Participants | 12 Participants | 14 Participants |
| Age, Customized Age >70 yr with late MCI | 37 Participants | 18 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 103 Participants | 50 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| FAQ total score | 3.26 score STANDARD_DEVIATION 4 | 3.4 score STANDARD_DEVIATION 4.1 | 3.2 score STANDARD_DEVIATION 3.9 |
| MMSE total score | 26.97 score STANDARD_DEVIATION 1.6 | 27.1 score STANDARD_DEVIATION 1.6 | 26.8 score STANDARD_DEVIATION 1.7 |
| Neuropsychological composite z-score | 0 units on a scale STANDARD_DEVIATION 1 | -0.1 units on a scale STANDARD_DEVIATION 1 | 0.1 units on a scale STANDARD_DEVIATION 1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 11 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 81 Participants | 39 Participants | 42 Participants |
| Sex: Female, Male Female | 62 Participants | 34 Participants | 28 Participants |
| Sex: Female, Male Male | 45 Participants | 17 Participants | 28 Participants |
| UPSA total score | 81.1 score STANDARD_DEVIATION 11.1 | 80.6 score STANDARD_DEVIATION 10.9 | 81.5 score STANDARD_DEVIATION 11.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 56 |
| other Total, other adverse events | 19 / 51 | 23 / 56 |
| serious Total, serious adverse events | 12 / 51 | 9 / 56 |
Outcome results
Primary
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: [Time Frame: 78 weeks]
Population: Participants assessed at baseline and week 78, and the change over 78 weeks is the outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Training Group 1 | Change in the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) | -0.89 score | Standard Error 0.51 |
| Training Group 2 | Change in the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) | 0.55 score | Standard Error 0.48 |
Secondary
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: [Time Frame: week 78]
Population: Participants assessed at baseline and week 78, and the change over 78 weeks is the outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Training Group 1 | Change Over Time in Functional Activities Questionnaire (FAQ) | -2.00 score | Standard Error 0.34 |
| Training Group 2 | Change Over Time in Functional Activities Questionnaire (FAQ) | -0.92 score | Standard Error 0.31 |
Secondary
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: [Time Frame: Week 78]
Population: Participants assessed at baseline and week 78, and the change over 78 weeks is the outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Training Group 1 | Change Over Time in Neuropsychological Testing Composite Score | -0.24 score | Standard Error 0.08 |
| Training Group 2 | Change Over Time in Neuropsychological Testing Composite Score | -0.27 score | Standard Error 0.07 |
Secondary
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: [Time Frame: week 78]
Population: Participants assessed at baseline and week 78, and the change over 78 weeks is the outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Training Group 1 | Change Over Time in UCSD Performance-Based Skills Assessment (UPSA) | 0.55 score | Standard Error 1.23 |
| Training Group 2 | Change Over Time in UCSD Performance-Based Skills Assessment (UPSA) | -0.99 score | Standard Error 1.44 |