Effect of computerized cognitive training on mood, cognition, and serum brain-derived neurotrophic factor level in late-life depression — a pilot randomized controlled trial

Background The aim of this pilot randomized controlled trial was to test the feasibility of a computerized cognitive training targeting executive dysfunction in late-life depression and to investigate its impact on mood, cognition, and brain-derived neurotrophic factor (BDNF) levels. Methods A total of 28 community-living Chinese individuals aged 55–75 with moderate-to-severe depression and cognitive symptoms (but without mild cognitive impairment or dementia) were recruited from a community centre in Hong Kong. Participants were randomly allocated to either the experimental (receiving computerized cognitive training) or the control group (receiving computer-based health education). Both programs lasted for one hour and were conducted twice a week for 6 weeks at the community centre. We assessed mood using the Hamilton Rating Scale for Depression (HAM-D) and Patient Health Questionaire-9 (PHQ-9), cognition using the Montreal Cognitive Assessment (MoCA), and serum BDNF levels at baseline and follow-up. We performed repeated measures analysis of variance to compare the differences in outcome changes between groups and correlation analysis to test if changes in mood and cognition correlated with changes in BDNF level. Results Our sample had a mean age of 66.8 (SD = 5.3) years, a mean HAM-D score of 19.4 (SD = 7.5), and a mean PHQ-9 score of 18.0 (SD = 6.3). No adverse effects were reported. Significant differences were observed between the experimental and control groups in changes in HAM-D (-8.4 vs. -2.9; group difference = -5.5; p = 0.01), PHQ-9 (-6.6 vs. -0.6; -6.0; p < 0.001), MoCA (1.4 vs. -1.3; 2.7; p = 0.001), and serum BDNF levels (in pg/ml; 2088.3 vs. -3277.4; 5365.6; p = 0.02). Additionally, changes in HAM-D, PHQ-9, and MoCA scores correlated significantly with changes in BDNF level. Conclusion With computerized cognitive training improving mood and cognition and increasing serum BDNF levels in 6 weeks, it may serve as a safe and effective evidence-based alternative or adjuvant treatment for late-life depression. Clinical trial registration https://www.chictr.org.cn/indexEN.html, identifier ChiCTR1900027029.


Complex Attention Training
The paradigm has 4 types of cue (no, center, double, and spatial cues; Figure 1a) and 3 types of flanker (neutral, congruent and incongruent; Figure 1b).In a given trial, a central cross-fixation point presents for 400-1600 milliseconds (ms) (random), followed by one of the 4 cues for 100 ms (Figure 1c).The target, which is an arrow at the centre with 2 flankers on each side, will then appear above or below the cross-fixation.The participant is instructed to indicate the direction of the target by pressing the right or left arrow button.Each trial lasts no more than 3 seconds, each block has 48 trials, and each session has 4 blocks.The attention task involves 3 components (alerting, orienting and executive control), and each outcome can be quantified by subtracting reaction time (RT) between one condition and the reference condition

Internal Switch Training (IST)
This executive control training follows a block design, with 4 blocks in total and each block varying between 18 and 22 trials.In each block, a random number of pictures (18-22) is shown on the screen; participant has to press the button before the next picture is shown.He/she has to decide the category of each picture (e.g., food vs household) and make a silent count on the number of pictures he/she sees in each category.Participant reports his/her count at the end of the block (Figure 2).
The delay between the presentation of picture and pressing of the button is recorded automatically as RT.Trials followed by a successive picture of the same category are known as the "no switch" trials; those followed by a picture from the other category represent the "switch" trials.The "Switching cost" is the extra RT needed to process the switch trials.

Balloon Analogue Risk Training (BART)
BART is a computerized training of risk-related constructs (impulsivity and sensation seeking) and risk-taking behaviours.In each block, a simulated balloon appears on the screen, and participant is asked to pump it up by pressing a button.Each press incrementally inflates the balloon until it explodes at a certain threshold.Participants are not informed about the threshold prior to each block; this facilitates testing their initial responses to the task and changes in response as they gain experience with the task contingencies.At any point before the balloon explodes, participant has the choice to end the trial and earn simulated money based on the size of the balloon, with larger size conferring more money, but no money will be earned for that block once the balloon explodes.As such, each pump is associated with both greater risk and greater potential reward.Each block starts with a new balloon and has 30 trials.Participant can see the amount of money potentially earned in the current block and the accumulated amount earned from previous blocks (Figure 3).

Picture Matching
In this visual working memory training, a series of pictures are shown on screen, one at a time, in which the participants are instructed to memorize them.Another series of pictures are then shown, which are a mix of old and new ones, and participants are asked to identify the ones that they have seen.
Different components of computerized cognitive training: a) Training on complex attention is based on computer-based attention training composed of stimulus cues and flanker task, in which the efficiency of different components of attention can be trained, with outcomes quantified by accuracy and reaction time (RT).b) Training on executive control is based on the Internal Switch Training (IST) and the Balloon Analogue Risk Training (BART).IST targets on cognitive flexibility by training one's ability to shift attention internally between alternative mental representations.BART, which is implicated in risk taking, trains one's ability to balance the potential for reward and loss.c) Training on working memory is based on the Picture Matching training.

Figure 2 .
Figure 2. Flow of the Internal Switching