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Does Cognitive Training Prevent Cognitive Decline?A Systematic Annals of Internal Medicine REVIEW Does Cognitive Training Prevent Cognitive Decline? A Systematic Review Mary Butler, PhD, MBA; Ellen McCreedy, PhD; Victoria A. Nelson, MSc; Priyanka Desai, MSPH; Edward Ratner, MD; Howard A. Fink, MD; Laura S. Hemmy, PhD; J. Riley McCarten, MD; Terry R. Barclay, PhD; Michelle Brasure, PhD, MSPH, MLIS; Heather Davila, MPA; and Robert L. Kane, MD† Background: Structured activities to stimulate brain function— group sessions. The MCI trials used attention controls more of- that is, cognitive training exercises—are promoted to slow or pre- ten than trials with healthy populations. For healthy older adults, vent cognitive decline, including dementia, but their effective- training improved cognitive performance in the domain trained ness is highly debated. but not in other domains (moderate-strength evidence). Results for populations with MCI suggested no effect of training on per- Purpose: To summarize evidence on the effects of cognitive formance (low-strength and insufficient evidence). Evidence for training on cognitive performance and incident dementia out- prevention of cognitive decline or dementia was insufficient. Ad- comes for adults with normal cognition or mild cognitive impair- verse events were not reported. ment (MCI). Limitation: Heterogeneous interventions and outcome mea- Data Sources: Ovid MEDLINE, EMBASE, the Cochrane Central sures; outcomes that mostly assessed test performance rather Register of Controlled Trials, and PsycINFO through July 2017, than global function or dementia diagnosis; potential publica- supplemented by hand-searches. tion bias. Study Selection: Trials (published in English) lasting at least 6 Conclusion: In older adults with normal cognition, training im- months that compared cognitive training with usual care, waitlist, proves cognitive performance in the domain trained. Evidence information, or attention controls in adults without dementia. regarding prevention or delay of cognitive decline or dementia Data Extraction: Single-reviewer extraction of study character- is insufficient. istics confirmed by a second reviewer; dual-reviewer risk-of-bias Primary Funding Source: Agency for Healthcare Research and assessment; consensus determination of strength of evidence. Quality. Only studies with low or medium risk of bias were analyzed. Data Synthesis: Of 11 trials with low or medium risk of bias, 6 Ann Intern Med. 2018;168:63-68. doi:10.7326/M17-1531 Annals.org enrolled healthy adults with normal cognition and 5 enrolled For author affiliations, see end of text. adults with MCI. Trainings for healthy older adults were mostly This article was published at Annals.org on 19 December 2017. computer based; those for adults with MCI were mostly held in † Deceased. ear of losing one's cognitive ability to Alzheimer dis- METHODS Fease and related dementias (ADRD) and ultimately We developed and followed a standard protocol declining to a state considered by many to be worse that was posted on the Agency for Healthcare Research than death (1) is driving a growing “brain-training” in- and Quality (AHRQ) Web site (www.effectivehealthcare dustry. Cognitive training programs, marketed to oth- .ahrq.gov). Full details of the methods, including litera- erwise healthy adults and persons with a recent diag- ture searches, findings, and evidence tables, are avail- nosis of mild cognitive impairment (MCI), make bold able in the final report (2). claims for reversing brain aging. Such claims include Data Sources and Searches the ability to boost “cognitive reserve” in midlife (with We searched Ovid MEDLINE, PsycINFO, EMBASE, cognitive reserve referring to both the mismatch be- and the Cochrane Central Register of Controlled Trials tween clinical symptoms of dementia and pathologic for relevant literature published between January 2009 brain lesion load at death and the repeatedly demon- and July 2017 (see Part A of the Supplement, available strated association between educational achievement at Annals.org, for searches) and hand-searched refer- and dementia risk). However, few studies have evalu- ence lists of selected articles. We identified studies ated the effect of cognitive training programs on cog- published before 2009 by reviewing studies included nitive decline or the onset of dementia, which is the outcome of interest for most people who buy these programs. See also: This review systematically evaluates the existing lit- erature on the effectiveness of cognitive training in pre- Related articles.......................30,39,52 venting cognitive decline and ADRD. It is part of a Editorial comment ..........................77 larger systematic review commissioned by the National Web-Only Institute on Aging to address a range of potential inter- Supplement ventions to slow cognitive decline and prevent or delay CME/MOC activity dementia. Annals.org Annals of Internal Medicine 1 Downloaded From: http://annals.org/ by August Anneberg on 12/20/2017 REVIEW Does Cognitive Training Prevent Cognitive Decline? and excluded from the 2010 AHRQ review on prevent- Role of the Funding Source ing Alzheimer disease and cognitive decline (3). The National Institute on Aging of the National In- stitutes of Health requested this report from the AHRQ Study Selection Evidence-based Practice Center Program. The funding Two investigators independently reviewed titles agencies provided comments on draft reports but had and abstracts of search results and screened the full no role in data collection, analysis, interpretation, or text of potentially eligible references. We included ran- manuscript development. domized trials of cognitive training interventions enroll- ing adults with either normal cognition or MCI if the studies followed participants for at least 6 months, pro- RESULTS vided cognitive performance or incident dementia out- comes, and were published in English. We excluded We identified 35 publications of 34 unique ran- studies that enrolled only persons diagnosed with de- domized controlled trials of cognitive training interven- mentia. The final health outcome of interest was inci- tions, 11 of which had medium or low risk of bias (5– dent ADRD. Intermediate health outcomes of interest 16). Only 1 trial was industry funded (8), whereas in 3 included performance on cognitive testing, biomarker cases, trial funding was not reported (9, 15, 16). (See protein levels, brain matter volume, and brain cell ac- the Supplement Figure and Supplement Tables C1 to tivity level. No restrictions were placed on sample size C4 for the literature flow diagram, evidence tables, and or comparator type. risk-of-bias assessments.) The Table summarizes the overall strength-of- Data Extraction and Quality Assessment evidence findings. For cognitively normal adults, One reviewer extracted study, population, inter- moderate-strength evidence suggests that cognitive vention, comparator, and setting characteristics as well training in a particular domain improves performance as the funding source from all eligible studies. Risk of in that domain compared with inactive or attention con- bias was assessed independently from full texts by 2 trol populations. These results are driven largely by the investigators using an instrument based on AHRQ guid- results from the ACTIVE (Advanced Cognitive Training ance (4). Risk of bias was individually reviewed overall for Independent and Vital Elderly) trial. Low-strength and for each outcome and time point, and was summa- evidence suggests that for persons with MCI, cognitive rized as low, medium, or high on the basis of a sum- training in a particular domain does not improve per- mary of bias risk across risk-of-bias domains and confi- formance in that domain compared with controls. The dence that results were credible given the study's MCI trials have more limitations and are less precise limitations. Outcomes and adverse events were ex- than the studies conducted with cognitively normal par- tracted from studies with low to medium risk of bias. A ticipants. Evidence is insufficient for incident MCI or second reviewer checked the quality of all data. ADRD outcomes. Data Synthesis and Analysis Studies in Cognitively Normal Populations Only studies with low or medium risk of bias Six trials with low to medium risk of bias tested were summarized, because we judged findings from training interventions in cognitively normal older adults studies with high risk of bias to lack validity, have little (5–10). Sample sizes for the selected studies ranged meaning, or be easily misinterpreted. Because studies from 40 to 2832 participants. Interventions lasted from used a highly varied set of outcome measures, neuro- 2 weeks to 6 months; follow-up ranged from 6 months psychological tests were categorized by the following to 2 years. Three of the 6 trials used only computer- specific cognitive domains to facilitate analysis: execu- based interventions (6–8), 2 used a combination of tive function, attention, and processing speed; mem- computer and noncomputer (paper-and-pencil) inter- ory; language; and visuospatial abilities (Supplement ventions (5, 9), and 1 used group-based competition Table A1). The domains of executive function, atten- to increase divergent thinking (10). Three of the tion, and processing speed were grouped together be- computer-based interventions were designed to in- cause cognitive tests frequently measure all 3 of these crease performance on a specific cognitive domain related domains. Because studies analyzed and re- (such as processing speed) (5, 6, 9), 1 used computers
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