Optale 2010

Methods	Design: 2‐arm randomised controlled pilot trial with parallel‐group design Recruitment period: not reported No. of centres involved: 1 Unit of randomisation: individuals No. randomised: 36 Number of arms considered in this review: 2 Maximum trial duration: 6 months Funding by non‐profit organisation: Consorzio Sociale CPS gestore centro servizi “Anni Sereni” Rest‐Home, Scorzè, Venice, Italy (to Gabriele Optale). Cosimo Urgesi was supported by the Scientific Institute (IRCCS) Eugenio Medea (Ricerca Corrente 2009, Italian Ministry of Health) Funding by commercial organisation: none reported Publication status: full‐text report
Participants	Type of MCI: not applicable; diagnosis of MCI was not required Patient flow: 18 randomised, 15 described at baseline in experimental group; 18 randomised, 16 described at baseline in control group Number of females: 10 of 15 (67%) in experimental group 1; 11 of 16 (69%) in control group 1 Average age (SD): 79 (10.9) years in experimental group 1; 82 (5.0) years in control group 1 Average (SD) education: 5.3 (2.4) years in experimental group; 6 (3.5) years in control group Baseline cognitive function: measured with selection criteria on cognition overall: presence of memory deficits as documented by a corrected total score at the Verbal Story Recall (VSR) Test below the cut‐off value (15.76) Selection criteria on cognition: presence of memory deficits as documented by a corrected total score at the Verbal Story Recall (VSR) test below the cut‐off value (15.76). Corrected MMSE score ranged from 9.7 to 29.3, with 9 participants in experimental group presenting a score below the cut‐off value (23.8) and ranging from 13.1 to 29, and with 12 participants in control group presenting a score below the cut‐off value (23.8) Ethnicity: not reported APOE: number of participants positive for APOE not reported
Interventions	Type of experimental intervention: computerised CT, individualised; treatment duration 24 weeks; intervention provided as individual training, under supervision Details of experimental intervention: virtual reality memory training that involved auditory stimulation and virtual reality experiences in path finding. VR experiences are administered through a head‐mounted display V6. The VR system runs on a notebook PC Type of concomitant treatment provided: both groups participated in recreational expressive activities (reading/discussing newspapers and magazines, watching TV documentaries, participating in creative and painting workshops) and assisted‐mobility activities during training Session duration: 30 minutes in experimental group Number of treatment sessions: 60 in experimental group Treatment frequency: 3/week during first 3 months (36 sessions); 2/week in subsequent 3 months (24 sessions) in experimental group Maximum treatment duration, in weeks: 24 in experimental group Type of control intervention: other; treatment duration 24 weeks; intervention provided as individual training, under supervision Details of control intervention: "individual face‐to‐face training sessions using music therapy" Session duration: 30 minutes in control group Number of treatment sessions: 60 in control group Treatment frequency: 3/week during first 3 months (36 sessions); 2/week in subsequent 3 months (24 sessions) in control group Maximum treatment duration, in weeks: 24 in control group
Outcomes	Cognitive functioning outcomes considered Global cognitive functioning measured with Mini Mental State Examination at 3 and 6 months, on a scale from 0 to 30, with higher values indicating benefit Episodic memory measured with Verbal Story Recall at 3 and 6 months, on a scale from 0 to 28, with higher values indicating benefit Executive functioning measured with Dual Task Performance at 3 and 6 months, on a scale from not reported to not reported with higher values indicating benefit Working memory measured with Digit Span ('WAIS procedure') at 3 and 6 months, on a scale from not reported to not reported with higher values indicating benefit Verbal fluency measured with Phonemic Verbal Fluency at 3 and 6 months, on a scale from not reported to not reported with higher values indicating benefit ("The PVF requires the participant to produce in 1 minute all the words he or she can remember, starting with the letters C, P, and S") Physical functioning outcome considered Daily function measured with Activities of Daily Living – functions at 3 and 6 months, on a scale from 0 to 60, with lower values indicating benefit Quality of life outcome considered: none reported Safety outcome considered: Mortality measured at 6 months Depression outcome considered Depression measured with Geriatric Depression Scale at 3 and 6 months, on a scale from 0 to 15, with lower values indicating benefit Available cognitive functioning outcomes not considered in this review Executive functioning measured with Cognitive Estimation Test at 3 and 6 months, on a scale from not reported to not reported with higher values indicating benefit
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Judgement: method for generating random sequence is not clearly reported Quote(s): "for each replicate, half of the participants were randomly allocated to the EG, whereas the remaining participants were allocated to the CG"
Allocation concealment (selection bias)	Unclear risk	Judgement: method of allocation concealment is not reported Quote(s): "for each replicate, half of the participants were randomly allocated to the EG, whereas the remaining participants were allocated to the CG"
Blinding of participants (performance bias)	High risk	Judgement: patients were not blinded Quote(s): "a randomized controlled single‐blind procedure was used, in which the examiner administrating the clinical and neuropsychological tests remained unaware of the participants’ allocations to the EG or CG"
Blinding of physicians / personnel	High risk	Judgement: therapist supervising the training was not blinded Quote(s): "a randomized controlled single‐blind procedure was used, in which the examiner administrating the clinical and neuropsychological tests remained unaware of the participants’ allocations to the EG or CG"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Judgement: the outcome assessor was explicitly described to be blinded to the intervention assigned Quote(s): "the examiner administrating the clinical and neuropsychological tests remained unaware of the participants’ allocations to the EG or CG"
Incomplete outcome data (attrition bias) All outcomes	High risk	Judgement: 15 out of 18 (83%) randomised in experimental group were analysed, and 16 out of 18 (89%) randomised in control group were analysed. We judged high risk of bias, as the percentage randomised but not analysed exceeded 10%; a complete case analyses was performed Quote(s): "one experimental group (EG) participant and 2 control group (CG) participants died before completing the booster training. Furthermore, 2 EG participants left the rest home and went back to their families before completing the booster phase. Because we aimed to investigate the effects of both the initial and the booster training phases, the 5 participants yielding incomplete data were not included in the analyses"
Selective reporting (reporting bias)	High risk	Judgement: 1 out of 13 outcomes was not consistently performed for unclear reasons Quote(s): "the Trail Making Test was also part of the evaluation protocol but could not be administered to most participants and was not included in the final analysis"
Other bias	Unclear risk	Judgement: no other potential risks of bias detected.