Comparative Efficacy of Multicomponent Behavioral Interventions for Mild Cognitive Impairment: Effects on Patient-Selected Outcomes

With the world’s older population rapidly growing, the number of older adults with mild cognitive impairment (MCI) is on the rise. Mild cognitive impairment is considered a prodromal phase of dementia and is highly predictive of subsequent conversion, with an estimated annual conversion rate of roughly 5% in community samples. Identification of effective strategies for reducing risk of conversion to dementia is of paramount importance. A number of behavioral interventions have shown promise in clinical trials, including physical exercise, memory training, and mind-body interventions. However, the comparative efficacy of these interventions is unknown.

Chandler et al¹ tackled this question in their multisite, multicomponent comparative effectiveness cluster randomized trial, conducted with older adults with MCI at 4 outpatient academic medical centers. The study was funded by the Patient-Centered Outcomes Research Institute, whose mission is to support research that better informs patients’ and caregivers’ health care decision making. The study intervention was modeled after the Mayo Clinic Healthy Action to Benefit Independence and Thinking (HABIT) program, a 50-hour group intervention administered over 2 weeks and including 5 components: memory compensation training, computerized cognitive training, yoga, patient and caregiver support groups, and wellness education. Patient groups were randomly assigned to a program using 4 of 5 components, with 1 component withheld to estimate comparative efficacy. This novel, subtractive approach ensured all participants received substantial intervention while still permitting comparison of treatments. Outcome measures were determined by the preference rankings of previous participants in the program and included quality of life (QOL), mood, self-efficacy, and memory-related activities of daily living (mADLs). This patient-centered approach is consistent with existing clinical approaches to managing MCI, while also focusing on outcomes of the highest importance to patients and their families.

Although no significant between-group differences were observed with respect to QOL, differences were found in 2 other patient-selected outcomes. Specifically, patients who participated in yoga demonstrated significantly greater improvement in mADLs at 12 months compared with those who participated in support groups. Furthermore, those who had wellness education experienced better mood than those who had computerized cognitive training. Chandler et al¹ note that prior participants of the program ranked yoga and wellness education as the 2 least important of the 5 components, raising questions as to whether patients recognize the potential value of these interventions. Chandler et al¹ also note that while they accurately predicted a minimal effect of cognitive training on the outcomes of interest, the relatively superior effect of wellness education on mood was unexpected. However, this result is consistent with previous research demonstrating significant mood benefits of health education² and no significant difference in the effect of cognitive training vs health education on mood in older adults with MCI.³

The study by Chandler et al¹ also addresses the question of whether cognitive exercises or compensatory memory strategies are more effective for older adults with MCI. A meta-analysis of 10 studies⁴ reported that cognitive exercises were associated with greater improvements on memory-related outcomes compared with memory strategies. In contrast, a 2017 randomized clinical trial (RCT) of older adults with MCI⁵ found that those assigned to learn compensatory memory strategies demonstrated significant improvement in mADLs compared with controls, whereas the cognitive computer training group did not. The results of the study by Chandler et al¹ are consistent with this finding, as cognitive training had little to no effect on the outcomes of interest.

The results of the study by Chandler et al¹ are also consistent with those of a 12-month RCT comparing cognitive training with physical activity (resistance training) in older adults with MCI.⁶ In that study, resistance training was found to significantly improve global cognition, executive function, and verbal memory; however, the benefits of cognitive training were limited to the domain of memory. Furthermore, whereas effects on global cognition and executive function were maintained 12 months after cessation of resistance training, effects of cognitive training were observable during the active training period only. Each of these findings suggests that cognitive training programs may be of limited value and are often outperformed by physical activity programs for improving memory-related outcomes in MCI.

As Chandler et al¹ note, their trial does not provide data on the efficacy of yoga compared with other forms of physical activity. Aerobic exercise as a whole is known to improve global cognitive ability and memory among older adults with MCI.⁷ However, a 2018 review article⁸ concluded that mind-body interventions, such as yoga, may outperform conventional exercise for older adults on outcomes such as QOL and mood. For example, a meta-analysis of 18 RCTs⁹ found that yoga was significantly more effective than conventional exercise for both mental health–related and physical health–related QOL.⁹ Our previous RCT of older adults with MCI¹⁰ found that Kundalini yoga was similarly effective as memory training for improving memory performance and more effective than memory training on mood, resilience, and executive function outcomes.

In summary, the data from Chandler et al¹ support the notion that different MCI-related outcomes can be optimized by specific combinations of behavioral interventions. In particular, yoga and wellness education may be most effective for improving mADLs and mood, outcomes ranked among the most important by patients with MCI and their caregivers. This study offers a new understanding of the comparative efficacy of behavioral interventions for MCI that is easily translatable into real-world clinical practice and sets the stage for future comparative effectiveness studies aiming to prevent cognitive decline and improve QOL in older adults.

Published: May 17, 2019. doi:10.1001/jamanetworkopen.2019.3047

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Laird KT et al. JAMA Network Open.

Corresponding Author: Helen Lavretsky, MD, MS, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095 (hlavretsky@mednet.ucla.edu).

Conflict of Interest Disclosures: Dr Lavretsky reported receiving grants from Allergan/Forest Laboratories, the National Institutes of Health, Patient-Centered Outcomes Research Institute, and Alzheimer’s Research and Prevention Foundation outside the submitted work; and receiving royalties from Oxford University Press and Johns Hopkins University Press. No other disclosures were reported.