Efficacy of Computerized Cognitive Training in the Elderly With Mild Cognitive Impairment

Efficacy of Computerized Cognitive Training in the Elderly With Mild Cognitive Impairment: Clinical Outcomes and Magnetoencephalographic Imaging

Mild cognitive impairment (MCI) is the prodrome of the cognitive function declining before Alzheimer's disease or other dementia showed up, the impairments of language, visuospatial relationship, attention, and memory included and instrumental activities of daily living (IADL) influenced. MCI is considered as a transitional stage between normal aging and mild dementia, and the patients with MCI has differently fluctuated cognitive functions in a period of time, such as from normal cognition to MCI or developing to dementia. The annual conversion rate (ACR) of older adults with normal cognition developed to MCI is 30%, and 5% in clinical setting, and community, respectively. Not all of patients with MCI develop to Alzheimer's disease, the reversion of patients with MCI to normal cognition exists. However, MCI is a significant risk factor. The ACR of older adults with normal cognition or MCI developed to dementia is 1-2%, and 5-15%, respectively; moreover, about half of patients with MCI developed to dementia in 5 years. Cognitive training (CT) improves cognitive functions with repetitive practicing standardized cognitive tasks of specific cognitive functions, such as memory, attention, or problem solving. CT has widely defined including strategy training, in which contained cognitive exercise, strategy indicating and practicing to reducing cognitive impairments and improving performances. CT is more effective for MCI. Recently, computer-based CT (CCT) with many advantages gradually replaced the traditional paper-pencil form. Brief systematic review showed that the computer-based intervention had positive effects on behavioral symptoms, such as depression and anxiety, in patients with MCI and/or dementia. Previous studies demonstrated that computer-based intervention exhibited moderate treatment effects on overall cognitive functions in patients with MCI, and also had positive effects on learning, short-term memory, and behavioral symptoms. Older people with cognitive impairments is expected to increase by global aging. It is important for improving or maintaining cognitive functions of older adults with MCI. The efficacy of the CCT on cognitive functions, neuropsychiatric symptoms, daily functions, and brain activated imaging of the magnetoencephalography (MEG) of in older adults with MCI is worth to explore for busy clinical practice.

The study design was a prospective and single-blinded randomized controlled trial. 36 participants with MCI were recruited and demographic data (age, gender, education level /years of education, marriage status etc.) were also collected. The MCI participants underwent the comprehensive review at baseline including neuropsychological assessment and Magnetic Resonance Imaging or Computerized Tomogram. Randomization treatment assignment will be generated by the random number table and assign the patient's intervention group accordingly. Sealed opaque envelopes containing the CCT group, or the dosage-matched control group sheets will be prepared and given to the therapists. Based on the t-test effect size of index d 1.00 indicates, an estimated 17 participants in each group will be required for a power of 0.80 with a two-sided type I error of 0.05. Considering the 5% (q) drop rate, we will need to recruit 18 participants (N/1-q) for each group. The participants were randomly allocated to either the CCT group (18 participants) or the dosage-matched control group (18 participants) with individualized intervention for 30 minutes a day, 3 times a week for 4 consecutive weeks. Clinical outcome measures, and the imaging of the MEG were administered at pre- treatment, post-treatment and 1-month follow-up for further analysis. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) version 19.0. In statistical testing, two-sided p value ≤ 0.05 was considered statistically significant. The distributional properties of continuous variables were expressed by mean ± standard deviation (SD), categorical variables were presented by frequency and percentage. The differences in the distributions of continuous variables, categorical variables between the treatment and control groups were examined using two-sample t-test, Wilcoxon rank-sum test (or Mann-Whitney U test), and chi-square test. In addition, the minimum norm estimates (MNE), source-based time-frequency analysis, cross-frequency coupling, and functional connectivity were used to explore the differences of the activation of brain functions in participants between different treatment groups. The t-test was used to explore the differences of reaction time, rate of correction, and physical signals in stimulus reaction test of the MEG between in participants between different treatment groups. The correlation statistics was used to explore relationships between the scores of outcome measurements and the physical signals.

participants will be trained by the "Cookies for the brainy day", including memory, attention, calculation, executive functions, and language training.

participants will receive craft activities of occupational therapy for 30 minutes/day, 3 days/week for 4 consecutive weeks.

The Quick Mild Cognitive Impairment (Qmci) screen , a performance test, contains 6 subtests: Orientation, Registration, Clock Drawing, Delayed Recall, Verbal Fluency, and Logical Memory. The Qmci can be administered and scored in less than 5 min. The Qmci was validated with sound reliability and validity. The Qmci screen scores ranged from 0 to 100, with a higher score indicating greater cognitive function.

The Montreal Cognitive Assessment (MoCA), a performance test, is a standardized and validated tool designed to measure cognitive functions in visuospatial/executive, naming, memory, attention, language, abstraction, delayed recall, and orientation. The MoCA adds 1 score for those whose educational level ≤ 12 and scores ranged from 0 to 30, with a higher score indicating greater cognitive function.

The Contextual Memory Test is a standardized tool to measure the short-term and long-term retrospective memory and metacognition. The immediate and delayed memory is administrated by remembering 20 items related to daily context in 90 seconds. The scores of memory score, perceptual memory scores, and strategy-use scores were recorded.

The Color Trail Test has A, and B parts. Participants needs to orderly connect randomized arrangement numbers in part A, and orderly and alternately connect randomized arrangement numbers in different colors in part B. The finished time and amounts of hint, miss, color miss, and near miss were recorded.

The longest digits of forward and backward are 10 and 9, respectively. The total scores are 10 and 9, with a higher score indicating greater digit span memory.

The Cancellation Test presents 10 Arabic numerals (0-9) for 30 digits per row (8 rows) with 2 target numerals (2, 8) in 45 seconds. The amounts of correction and miss were recorded.

The Pattern Comparisons presents 30 pairs of figures for distinguishing the same or not in 30 seconds. The amounts of correction, miss and total answers were recorded.

Everyday Memory Questionnaire is a self-rated memory function questionnaire to reflect the frequency of memory miss in daily life. The frequency of memory miss, such as less than 1 time in 1-month, 2-3 times in 1-month, 1 time in 1 week, 2-6 times in 1 week, and more than 1 time in 1 day, in each situation scores ranged from 0 to 4 in 13 situations.

The Neuropsychiatric Inventory Questionnaire (NPI-Q) measures symptoms severity and caregiver distress in 12 domains, such as apathy/indifference, appetite/eating problems, disinhibition, agitation/aggression, motor disturbance, anxiety, irritability, nighttime behaviors, depression/dysphoria, delusions, elation/euphoria, and hallucinations. The symptoms severity in each domain scores ranged from 1 to 3, with a higher score indicating more severe symptoms severity. In addition, the caregiver distress in each domain scores ranged from 0 to 5, with a higher score indicating more distress for caregiver.

The Brief University of California San Diego (UCSD) Performance-based Skills Assessment (UPSA-B) contains 2 aspects: financial skills, and communication skills. The UPSA-B can be administered and scored in 10-15 min and used to measure participants how to administrate daily activities and do it how well. The UPSA-B scores ranged from 0 to 100, with a higher score indicating greater daily function.

The DAD contains 11 items of 3 domains: basic activity of daily living (dressing, hygiene, continence, eating), instrumental activity of daily living (meal preparation, telephoning, going on an outing, finance and correspondence, medications, and housework), and leisure activity (leisure). The scoring divides into 3 parts to measure about the initiation, planning and organization, and effective performance, and the scores of each part transforms to percentage for calculation. The higher percentage of each part indicates the less impairment in activities of daily living.

The 1-back working memory paradigm was used to explore the efficacy of each intervention. When one figure matches with the previous one, the participant needs to press the button for response as soon as possible. The Go-Nogo paradigm was to explore the reaction-inhibition functions. The participant needs to press the button for Go stimulus (1, 2, 4, 5, 6, 8, 9), and inhibits to press the button for Nogo stimulus (3, 7). Paired-stimulus paradigm is widely used for assessing the activation and inhibition functions of sensory cortex. The same of two stimuli (S1, S2) would show within 500 ms interval, and the magnitude of induced reaction of the second stimulus (S2) would be inhibited in normal physical condition. Calculating the S2/S1 ratio of paired-stimulus quantified the inhibition functions of sensory cortex, the much less ratio indicating the greater inhibition functions.

Inclusion Criteria: (1) were aged ≥65 years (2) amnestic type MCI was made using National Institute on Aging-Alzheimer's Association workgroups diagnostic guidelines for Alzheimer's disease with the clinical dementia rating scale (CDR) global scores of 0.5 (3) could follow command, understand the content of the assessments, and cooperate with treatment interventions through verbal communication Exclusion Criteria: (1) had the score of Geriatric Depression Scale-Short Form (GDS-SF) > 7, indicating depression status (2) had the score of Barthel Index (BI)≠100, indicating dependent basic daily living of activities (3) were diagnosed with other MCI subtypes, including frontotemporal dementia or Lewy Body those present typically different MCI syndromes (4) had other neuropsychotic diseases (5) could not administrate with MEG (6) could not participate due to severe health problem

Data are available from the Institutional Review Board of the Taipei Hospital, Ministry of Health and Welfare for researchers who meet the criteria for access to confidential data.

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