Does Cognitive Training Prevent Cognitive Decline?

Fear of losing one's cognitive ability to Alzheimer disease and related dementias (ADRD) and ultimately declining to a state considered by many to be worse than death (1) is driving a growing brain-training industry. Cognitive training programs, marketed to otherwise healthy adults and persons with a recent diagnosis of mild cognitive impairment (MCI), make bold claims for reversing brain aging. Such claims include the ability to boost cognitive reserve in midlife (with cognitive reserve referring to both the mismatch between clinical symptoms of dementia and pathologic brain lesion load at death and the repeatedly demonstrated association between educational achievement and dementia risk). However, few studies have evaluated the effect of cognitive training programs on cognitive decline or the onset of dementia, which is the outcome of interest for most people who buy these programs. This review systematically evaluates the existing literature on the effectiveness of cognitive training in preventing cognitive decline and ADRD. It is part of a larger systematic review commissioned by the National Institute on Aging to address a range of potential interventions to slow cognitive decline and prevent or delay dementia. Methods We developed and followed a standard protocol that was posted on the Agency for Healthcare Research and Quality (AHRQ) Web site (www.effectivehealthcare.ahrq.gov). Full details of the methods, including literature searches, findings, and evidence tables, are available in the final report (2). Data Sources and Searches We searched Ovid MEDLINE, PsycINFO, EMBASE, and the Cochrane Central Register of Controlled Trials for relevant literature published between January 2009 and July 2017 (see Part A of the Supplement, for searches) and hand-searched reference lists of selected articles. We identified studies published before 2009 by reviewing studies included and excluded from the 2010 AHRQ review on preventing Alzheimer disease and cognitive decline (3). Supplement. Cognitive Training Supplement Study Selection Two investigators independently reviewed titles and abstracts of search results and screened the full text of potentially eligible references. We included randomized trials of cognitive training interventions enrolling adults with either normal cognition or MCI if the studies followed participants for at least 6 months, provided cognitive performance or incident dementia outcomes, and were published in English. We excluded studies that enrolled only persons diagnosed with dementia. The final health outcome of interest was incident ADRD. Intermediate health outcomes of interest included performance on cognitive testing, biomarker protein levels, brain matter volume, and brain cell activity level. No restrictions were placed on sample size or comparator type. Data Extraction and Quality Assessment One reviewer extracted study, population, intervention, comparator, and setting characteristics as well as the funding source from all eligible studies. Risk of bias was assessed independently from full texts by 2 investigators using an instrument based on AHRQ guidance (4). Risk of bias was individually reviewed overall and for each outcome and time point, and was summarized as low, medium, or high on the basis of a summary of bias risk across risk-of-bias domains and confidence that results were credible given the study's limitations. Outcomes and adverse events were extracted from studies with low to medium risk of bias. A second reviewer checked the quality of all data. Data Synthesis and Analysis Only studies with low or medium risk of bias were summarized, because we judged findings from studies with high risk of bias to lack validity, have little meaning, or be easily misinterpreted. Because studies used a highly varied set of outcome measures, neuropsychological tests were categorized by the following specific cognitive domains to facilitate analysis: executive function, attention, and processing speed; memory; language; and visuospatial abilities (Supplement Table A1). The domains of executive function, attention, and processing speed were grouped together because cognitive tests frequently measure all 3 of these related domains. Because studies analyzed and reported cognitive test results in many different ways, making it difficult or impossible to determine effect size or to assess whether between-group differences in scores or subscores were clinically meaningful (Supplement Table A2), we analyzed and reported cognitive test results by direction of effect and statistical significance. When we identified at least 2 studies or 1 large study (>500 participants) for a treatment comparison, 2 reviewers graded strength of evidence for each outcome on the basis of study limitations, directness, consistency, and precision; otherwise, strength of evidence was graded as insufficient. Assessments were confirmed by consensus. Role of the Funding Source The National Institute on Aging of the National Institutes of Health requested this report from the AHRQ Evidence-based Practice Center Program. The funding agencies provided comments on draft reports but had no role in data collection, analysis, interpretation, or manuscript development. Results We identified 35 publications of 34 unique randomized controlled trials of cognitive training interventions, 11 of which had medium or low risk of bias (516). Only 1 trial was industry funded (8), whereas in 3 cases, trial funding was not reported (9, 15, 16). (See the Supplement Figure and Supplement Tables C1 to C4 for the literature flow diagram, evidence tables, and risk-of-bias assessments.) The Table summarizes the overall strength-of-evidence findings. For cognitively normal adults, moderate-strength evidence suggests that cognitive training in a particular domain improves performance in that domain compared with inactive or attention control populations. These results are driven largely by the results from the ACTIVE (Advanced Cognitive Training for Independent and Vital Elderly) trial. Low-strength evidence suggests that for persons with MCI, cognitive training in a particular domain does not improve performance in that domain compared with controls. The MCI trials have more limitations and are less precise than the studies conducted with cognitively normal participants. Evidence is insufficient for incident MCI or ADRD outcomes. Table. Summary of Conclusions and Strength of Evidence for Cognitive Training in Adults With Normal Cognition or MCI* Studies in Cognitively Normal Populations Six trials with low to medium risk of bias tested training interventions in cognitively normal older adults (510). Sample sizes for the selected studies ranged from 40 to 2832 participants. Interventions lasted from 2 weeks to 6 months; follow-up ranged from 6 months to 2 years. Three of the 6 trials used only computer-based interventions (68), 2 used a combination of computer and noncomputer (paper-and-pencil) interventions (5, 9), and 1 used group-based competition to increase divergent thinking (10). Three of the computer-based interventions were designed to increase performance on a specific cognitive domain (such as processing speed) (5, 6, 9), 1 used computers for cognitive stimulation more generally (7), and 1 used a computer program designed to train several cognitive domains (8). Comparators included both inactive (5, 7, 8, 10) and attention controls (6, 9). No studies reported adverse effects. The largest trial of cognitive training, ACTIVE, randomly assigned 2832 older adults (mean age, 74 years) without clinically significant cognitive impairment to 1 of 3 training groups or a no-contact control group (5). In each training group, a different cognitive domain was targeted: memory, reasoning, or processing speed. Participants in the intervention groups received 10 trainings of 60 to 70 minutes over 6 weeks. Cognitive testing outcomes included measuring changes in domain-specific test performance. Patient-centered cognitive outcomes included measuring changes in everyday problem solving (such as the ability to identify information on medication bottles), everyday speed (such as the time required to find food items on a grocery shelf), driving, and degree of dependency in completing activities of daily living and instrumental activities of daily living. Incident MCI or ADRD was not a prespecified outcome. Although 5- and 10-year outcomes from the ACTIVE trial have been published (17, 18), only the results from the 2-year study had a medium risk of bias (5). At 2 years, ACTIVE participants showed improvement in the cognitive domains in which they were trained (for example, those who received memory training improved on memory-related tasks compared with control participants), but no statistically significant differences were found among groups with regard to other cognitive outcomes (for example, persons who received training in memory did not do better than control participants on reasoning tasks). Intervention and control groups did not differ in other patient-centered cognitive outcomes at 2-year follow-up. Modeled on the visual process and speed training group of the ACTIVE trial, IHAMS (the Iowa Healthy and Active Minds Study) (n= 681) (6) randomly assigned adults by age group (50 to 64 years vs. 65 years) to visual processing speed training at the study center, visual processing speed training on the participant's home computer, or computerized crossword puzzles (attention control group). Two-hour training sessions were held once a week for 5 weeks. Participants assigned to the intervention at the training center also received a booster training at 11 months. One year after training, both intervention groups showed statistically significant improvement in the primary outcome of the Useful Field of View test compared with the attention control group. The IHAMS participants also were administered 8 secondary cognitive tests on which they had not been tr