Table. Selected Randomized Controlled Trials of Interventions for MCI.
| Source | Patients | Mean Patient Age | Intervention | Trial Length | Primary Outcomes |
|---|---|---|---|---|---|
| Pharmacologic Treatments | |||||
| Cholinesterase inhibitors | |||||
| Salloway et al,82 2004 | N=270 adults with MCI. | 72 years | Donepezil 10 mg daily vs. placebo | 24 weeks | No significant differences between treatment groups in the two primary outcomes, New York University Paragraph Delayed Recall test and the ADCS-CGIC-MCI. |
| Petersen et al, 200583 | N=769 adults with amnestic MCI. | 73 years | Donepezil 10 mg daily vs. 2000 IU of vitamin E daily vs. placebo | 3 years | As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer's disease in the vitamin E group (hazard ratio, 1.02; 95 percent confidence interval, 0.74 to 1.41; P=0.91) or the donepezil group (hazard ratio, 0.80; 95 percent confidence interval, 0.57 to 1.13; P=0.42). |
| Doody et al,84 2009 | N=821 adults with amnestic MCI. | 70 years | Donepezil 10 mg daily vs. placebo | 48 weeks | The dual primary efficacy endpoint was not reached. At 48 weeks, there was a small, significant decrease in modified ADAS-cog (-0.90, SE, 0.37) favoring donepezil (P=0.01). Changes in CDR-SB scores were minimal and not significantly different between treatment groups. |
| Koontz et al,85 2005 | N=19 men with MCI. | 71 years | Galantamine 12 mg twice daily vs. placebo | 16 weeks | The primary outcome was the CANTAB. At 16 weeks, only one of the 6 sub-tests of the CANTAB (stockings of Cambridge) differed significantly between galantamine and placebo groups (8.3 ± 1.9 vs. 7.0 ± 1.4; P=0.023). |
| Behavioral Interventions | |||||
| Cognitive intervention | |||||
| Buschert et al,86 2011 | N=39 adults with MCI or mild AD. | 73 years | Group-based multi-component cognitive intervention vs. active control | 6 months | There were significant improvements in the ADAS-cog (P=0.02) and non-significant improvements in the MMSE (P=0.07) favoring the intervention MCI group. |
| Barnes et al,87 2009 | N=37 adults with MCI. | 74 years | Intensive, computer-based cognitive training vs. passive computer activities | 6 weeks | The primary outcome, Repeatable Battery for Assessment of Neuropsychological Status total scores, improved 0.36 standard deviations (SD) in the intervention group (P=0.097) compared with 0.03 SD in the control group (P=0.88) and the between-group difference was 0.33 SD (P=0.26). |
| Barnes et al,63 2013 | N=126 adults with memory complaints. | 73 years | 2 × 2 factorial design 4 groups: mental activity intervention (MA-I; intensive computer)/exercise intervention (EX-I; aerobic), MA-I/exercise control (EX-C; stretching and toning), mental activity control (MA-C; educational DVDs)/EX-1, MA-C/EX-C. | 12 weeks | Global cognitive scores improved significantly over time (mean, 0.16 SD; P < .001) but did not differ between groups in the comparison between the mental activity groups (P =0.17), the exercise groups (P =0.74), or across all 4 randomization groups (P=0.26). |
| Physical activity | |||||
| Lautenschlager et al,88 2008 | N=170 adults with memory complaints, 60% of whom had MCI. | 69 years | Home-based physical activity program vs. education and usual care | 24 weeks | At 18 months: 0.73-Point improvement on the ADAS-cog among patients in the intervention group vs. a 0.04-point improvement for those receiving placebo (0.69-point treatment difference, P=0.04); At 6 months: 0.26-Point improvement on the ADAS-cog among patients in the intervention group vs. a 1.04-point decrease for those receiving placebo (1.3-point treatment difference, P<0.001). Results were similar in sub-group of patients with MCI. The intervention group also showed modest improvements in word list delayed recall (verbal memory) and CDR sum of boxes (functional impairment due to cognition). |
| Baker et al,89 2010 | 33 adults with amnestic MCI. | 70 years | High-intensity aerobic exercise vs. stretching control group | 6 months | Compared with stretching, high-intensity aerobic exercise significantly improved performance on tests of executive function with stronger effects for women than men. |
| Suzuki et al,90 2012 | N=50 adults with amnestic MCI. | 75 years | Multi-component exercise program vs. educational control | 12 months | Patients in the exercise group showed superior improvements of cognitive function at treatment end for the Mini-Mental State Examination (group-by-time interaction P=0.04), the logical memory subtest of the Wechsler memory scale-revised (group-by-time interaction P=0.03), and the letter verbal fluency test (group-by-time interaction P=0.02). |
| Nagamatsu et al,91 2012 | N=86 women with subjective memory complaints. | 75 years | Resistant training twice-weekly, aerobic training twice-weekly, or balanceand tone training twice-weekly (control group) | 26 weeks | Compared with the balance and tone training (control) group, the resistance training group significantly improved performance on the Stroop Test of executive function (mean change 1.4 seconds vs. 9.1 seconds, P=0.04). Changes in Stroop test performance did not differ significantly between the aerobic training and balance and tone training groups (mean change 1.4 seconds vs. 8.8 seconds, P-value not given). |
| Barnes et al,63 2013 | N=126 adults with memory complaints. | 73 years | 2 × 2 factorial design 4 groups: mental activity intervention (MA-I; intensive computer)/exercise intervention (EX-I; aerobic), MA-I/exercise control (EX-C; stretching and toning), mental activity control (MA-C; educational DVDs)/EX-1, MA-C/EX-C. | 12 weeks | Global cognitive scores improved significantly over time (mean, 0.16 SD; P < .001) but did not differ between groups in the comparison between the mental activity groups (P =0.17), the exercise groups (P =0.74), or across all 4 randomization groups (P=0.26). |
| Multi-disciplinary care | |||||
| Woolfs et al,92 2008 | N=235adults with a suspected diagnosis of dementia or a cognitive disorder, >15% of whom had MCI. | 78 years | Integrated multidisciplinary diagnostic clinic vs. usual care | 52 weeks | At 12 months, no significant difference between groupson change in mean score on the visual analogue scale of the EuroQd measure EQ–5D (5.2 points; 95%CI, -0.58 to 10.94 points). |
| Psychotherapeutic interventions | |||||
| Joosten-WeynBanningh et al,66 2011 | N=93adults with MCI. | 70 years | Group cognitive behavioral therapy for patients vs. assignment to waiting list (control group) | 10 weeks | Primary outcome for patients: Acceptance assessed using a subscale of the Illness Cognition Questionnaire increased more in the intervention group compared to the waiting-list period (P=0.03) with an estimated between group difference of 3.49 (95%CI, –6.21 to –0.73; P=0.01). |
| Joosten-WeynBanningh et al,67 2013 | N=88 significant others of adults with MCI. | 69 years | Group cognitive behavioral therapy for significant others vs. assignment to waiting list (control group) | 10 weeks | Primary outcome for significant others: Sense of competence assessed with the Sense of Competence Questionnaire was not significantly different between the waiting list period and the interventionperiod (P=0.59), |
Abbreviations: ADAS-cog, 11-item (70-point) Alzheimer Disease Assessment Scale-cognitive subscale (higher scores indicating greater severity of cognitive impairment). ADCS-CGIC-MCI, Alzheimer Disease Cooperative Study Clinician's Global Impression of Change for MCI.CDR-SB. Clinical Dementia Rating Sum of Boxes. CANTAB, Cambridge Automated Neuropsychiatric Test Assessment Battery.