Barnes 2013

Methods	Design: 4‐arm RCT with factorial design Recruitment period: 2008 to 2009 No. of centres involved: 1 Unit of randomisation: individuals No. randomised: 126 Number of arms considered in this review: 4 Maximum trial duration: 3 months Funding by non‐profit organisation: this study was funded through a Career Development Award from the National Institute on Aging (grant K01‐AG024069), the Alzheimer’s Association (grant IIRG‐06‐27306), the University of California School of Medicine, and the Institutes of Health/National Center for Research Resources/University of California, San Francisco–Clinical and Translational Science Institute (grant KL2 RR024130) Funding by commercial organisation: none reported Publication status: full‐text report
Participants	Type of MCI: participants with self‐reported cognitive complaints at baseline Patient flow: 31 randomised, 31 described at baseline in experimental group; 32 randomised, 32 described at baseline in experimental group 2, 31 randomised, 31 described at baseline in experimental group 3; 32 randomised, 32 described at baseline in control group Number of females: 18 of 31 (58%) in experimental group 1; 20 of 32 (63%) in experimental group 2; 21 of 31 (68%) in experimental group 3; 20 of 32 (63%) in control group 1 Average age (SD): 74 (5.7) years in experimental group 1; 75 (6.1) years in experimental group 2; 71 (5.5) years in experimental group 3; 74 (6.3) years in control group 1 Average (SD) education: 16.8 (2.3) years in experimental group 1; 16.7 (2.2) years in experimental group 2; 15.6 (2.8) years in experimental group 3; 16.3 (2.1) years in control group 1 Baseline cognitive function: instrument to measure baseline cognitive function not reported Selection criteria on cognition overall: mean modified Mini Mental State examination score: 94.4; experimental group 1: global cognition (3MS) score, mean (SD): 94.4 (3.9); experimental group 2: global cognition (3MS) score, mean (SD): 94 (5.2); experimental group 3: global cognition (3MS) score, mean (SD): 94.6 (5.6); control group 1: global cognition (3MS) score, mean (SD): 94.8 (4.7) Ethnicity: experimental group 1: 0 white, 0 Indian, 0 Asian, 22 black, 0 other, 9 unclear; experimental group 2: 0 white, 0 Indian, 0 Asian, 21 black, 0 other, 11 unclear; experimental group 3: 0 white, 0 Indian, 0 Asian, 17 black, 0 other, 14 unclear; control group 1: 0 white, 0 Indian, 0 Asian, 22 black, 0 other, 10 unclear APOE: number of participants positive for APOE not reported
Interventions	Type of experimental intervention 1: computerised CT and sham exercise (stretching) Details of experimental intervention: intervention provided as individual training, without supervision. Games designed to enhance the speed and accuracy of visual and auditory processing (Posit Science). For the first 6 weeks, games focused on visual tasks, and for the second 6 weeks, games focused on auditory tasks Type of experimental intervention 2: computerised CT and aerobic exercise Details of experimental intervention 2: computerised CT as in experimental arm 1 but with concomitant aerobic exercise Type of experimental intervention 3: other Details of experimental intervention 3: DVDs of educational lectures on art, history, and science and aerobic exercise Type of control intervention: other Details of control intervention: DVDs of educational lectures on art, history, and science and sham exercise (stretching) Session duration: 60 minutes in all groups Number of treatment sessions: 36 in all groups Treatment frequency: 3/week in all groups Maximum treatment duration: 12 weeks in all groups
Outcomes	Cognitive functioning outcomes considered Global cognitive functioning measured with composite score change at 3 months, on a scale from not reported to not reported with higher values indicating benefit Episodic memory measured with RAVLT, no. of words learned at 3 months, on a scale from not reported to not reported with higher values indicating benefit Executive functioning measured with Trails B at 3 months, on a scale from not reported to not reported with lower values indicating benefit Speed of processing measured with Trails A at 3 months, on a scale from not reported to not reported with lower values indicating benefit Verbal fluency measured with no. of words by letter at 3 months, on a scale from not reported to not reported with higher values indicating benefit Physical functioning outcome considered: none reported Quality of life outcome considered: none reported Safety outcome considered: none reported Depression outcome considered: none reported Available cognitive functioning outcomes not considered in this review Episodic memory measured with RAVLT No. of words recalled at 3 months, on a scale from not reported to not reported with higher values indicating benefit Executive functioning measured with EFT Congruent reaction time at 3 months, on a scale from not reported to not reported with higher values indicating benefit Executive functioning measured with EFT Incongruent reaction time at 3 months, on a scale from not reported to not reported with higher values indicating benefit Speed of processing measured with DSST, No. correct at 3 months, on a scale from not reported to not reported with higher values indicating benefit Speed of processing measured with Useful Field of View (UFOV) Processing speed at 3 months, on a scale from not reported to not reported with higher values indicating benefit Verbal fluency measured with No. of words, by category at 3 months, on a scale from not reported to not reported with higher values indicating benefit Visuospatial function (UFOV) on a scale from not reported to not reported with higher values indicating benefit
Notes	Experimental trial arm 1 includes participants who received mental activity intervention and group exercise control (stretching and relaxation) Control arm 1 includes participants who received mental activity control and group exercise control (stretching and relaxation); Experimental trial arm 2 includes participants who received mental activity intervention as experimental trial arm 1 in combination with group exercise intervention (aerobic exercise and strength training) Experimental trial arm 3 includes participants who received mental activity control (same as control arm 1) in combination with group exercise intervention (aerobic exercise and strength training)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Judgement: random sequence adequately generated Quote(s): "participants were randomized in blocks of 4. The randomization sequence was prepared in advance by using a random‐number generator on a computer"
Allocation concealment (selection bias)	Unclear risk	Judgement: study authors state that allocation was concealed, although the method of allocation concealment is not reported Quote(s): "research staff involved with enrolment and outcome assessment were unaware of the randomization sequence and blinded to group assignment"
Blinding of participants (performance bias)	High risk	Judgement: patients were not blinded to the type of intervention Quote(s): "study participants were unaware of study hypotheses and were told that the goal of the study was to compare the effects of different physical and mental activity programs"
Blinding of physicians / personnel	Low risk	Judgement: therapists were blinded to study treatment Quote(s): "research staff involved with enrolment and outcome assessment were unaware of the randomization sequence and blinded to group assignment"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Judgement: therapists were blinded to study treatment Quote(s): "research staff involved with enrolment and outcome assessment were unaware of the randomization sequence and blinded to group assignment"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Judgement: 32 out of 32 (100%) randomised to the experimental group were analysed, and 31 out of 31 (100%) randomised to the control group were randomised; the statistical analyses were reported to be done according to the intent‐to‐treat principle; 9/32 in experimental and 3/31 in control withdrew from study but were included in the final analysis Quote(s): "all analyses were performed using intent‐to‐treat principles"
Selective reporting (reporting bias)	Low risk	Judgement: all outcomes mentioned in the methods section are reported in the results section
Other bias	Low risk	Judgement: no other sources of bias are apparent