Meditation for Adults with Mild Cognitive Impairment: A Pilot Randomized Trial

Abstract

To the Editor: High levels of chronic stress are associated with an increased incidence of mild cognitive impairment (MCI) and Alzheimer's disease (AD)1, 2 and negatively affect the hippocampus, a critical brain region in AD. Mindfulness-based stress reduction (MBSR), a standardized mindfulness meditation and yoga intervention, may decrease stress and cortisol levels, improve well-being, and increase hippocampal gray matter density in healthy adults.3, 4 Studies also demonstrate that meditation selectively activates the hippocampus,5 and experienced meditators have been found to have larger hippocampal volumes and gray matter than controls.6 Within this context, the objectives of the current study were to test the safety and feasibility of MBSR in adults with MCI and explore the effects of MBSR on cognition and well-being through standardized instruments, neuropsychological evaluations, and interviews. Fourteen subjects were recruited from 2010 to 2011 from the Beth Israel Deaconess Medical Center Cognitive Neurology Unit with the human subjects review board's approval. The study was registered with the National Institutes of Health clinical trials database (Clinicaltrials.gov, NCT01605448). Entry criteria were based on the Alzheimer's Disease Neuroimaging Initiative7 and the MCI research operational definition.8 Adults aged 55 to 90 with MCI determined by a neurologist through history, physical examination, and neuropsychological testing (including Wechsler Memory scale IV, Mini-Mental State Examination, Clinical Dementia Rating) were included. Individuals who were actively practicing meditation or yoga or had any history of brain lesions or major head trauma were excluded. Participants were randomized 2:1 to MBSR or usual care using permuted block randomization with randomly varying block size. The MBSR class met for eight 2-hour weekly sessions plus one mindfulness retreat day. Mindfulness, defined as nonjudgmental moment-to-moment awareness, was cultivated through sitting and walking meditation, body scan, and mindful movement (yoga). Home practice (30 min/d) was encouraged, with standard guided audio recordings. To assess safety and feasibility, information was systematically collected on class attendance, home practice logs, and adverse events. At baseline and 8 weeks, all participants underwent an exploratory battery of neuropsychological measures by a blinded neuropsychologist, including the Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-cog), and standardized quality-of-life (QOL) and well-being questionnaires (Table 1). Semistructured interviews were also conducted in the MBSR group. Functional magnetic resonance imaging was used to assess measures of brain function and structure; results will be reported elsewhere. Descriptive statistics were used to analyze adherence and baseline characteristics. The neuropsychological tests and well-being measures were assessed by analyzing change in scores from baseline to 8 weeks using the Wilcoxon rank sum test to compare the MBSR and control groups. All analyses were blinded and performed on an intention-to-treat basis. SAS v. 9.2 was used for quantitative analyses (SAS Institute, Inc., Cary, NC). Transcribed qualitative interviews were coded using an emergent themes inductive approach informed by grounded theory.9 The two groups (MBSR and control) did not differ in age (73 ± 8 vs 75 ± 7) or MMSE score (27 ± 2 for both groups). There were no adverse events reported related to the study protocol, mean class attendance was 7.9 out of 9, and mean daily home practice was 26 ± 20 minutes. Interview themes included improved mindfulness skills, well-being, interpersonal skills, acceptance and awareness of MCI, decreased stress reactivity, group benefit, and overall course enjoyment. There were no significant differences detected between MBSR and control in ADAS-cog change from baseline (Table 1), but individual data reflected trends of improvement for the MBSR group and worsening for the control group. Control subjects unexpectedly performed better than the MBSR group on the Trail-Making Test Parts A and B, potentially because of order of testing and fatigue effects. Otherwise, there were no significant differences between the two groups on other measures of cognition (Table 1). Nonsignificant trends that suggested improvement with MBSR were detected for the Resilience Scale, Perceived Stress Scale, QOL—Alzheimer's Disease, Herth Hope Index, and Life Orientation Test—Revised (Table 1). This proof-of-concept clinical trial found that adults with MCI can safely participate in and adhere to a MBSR program. The qualitative interviews revealed that most enjoyed the program and described improved mindfulness skills, well-being, interpersonal skills, and acceptance and awareness of MCI and decreased stress reactivity. Most data suggest a trend toward improvement for measures of cognition and well-being. Despite the principal limitation of small sample size, this study is a valuable preliminary assessment of a promising approach for individuals with MCI because it suggests that MBSR is a safe, feasible, well-accepted intervention that may positively affect QOL and well-being. For individuals who have few other options for improvement and may live in fear of progression to dementia, psychological well-being and QOL are crucial yet often forgotten factors to address and treat. Further studies with larger sample sizes are needed. We gratefully acknowledge the assistance of Drs. Peter Wayne, Maulik Purohit, Reisa Sperling, and David Eisenberg for their support and help in completing this project. We gratefully acknowledge Beth Israel Deaconess Medical Center and Harvard Medical School, the institutions at which this research was conducted. This study was supported by the Harvard Medical School Osher Research Center, the Division of General Medicine and Primary Care at Beth Israel Deaconess Medical Center, and the National Institutes of Health (NIH) National Center for Complementary and Alternative Medicine (NCCAM) (K24 AT004095). In addition, this work was conducted with support from Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH Award 8UL1TR000170–05 and financial contributions from Harvard University and its affiliated academic healthcare centers). Dr. Rebecca Wells and Dr. Michelle Dossett received support from institutional National Research Service Award T32AT000051, Ted Kaptchuk was supported by Mid-Career Investigator Award K24 AT004095, Dr. Russell Phillips was supported by Mid-Career Investigator Award K24AT000589, and Dr. Catherine Kerr was supported by K01 AT003459, all from NCCAM. Dr. Kong was supported by KO1AT003883 (NCCAM), R21AT004497 (NCCAM), R03AT218317 (National Institute on Drug Abuse), R01AT006364 (NCCAM). Dr. Davis received support from the Harvard Clinical and Translational Center (NIH Award UL1 RR 02758) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or NIH. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Dr. Wells, R.E.: design and conceptualization of study; acquisition, analysis, and interpretation of data; obtaining funding; drafting and revising the manuscript. Dr. Kerr, C.E.: design and conceptualization of study, analysis and interpretation of data, revising the manuscript. Dr. Wolkin, J.: design and conceptualization of study; acquisition, analysis, and interpretation of data. Dr. Dossett, M.: design of study, analysis and interpretation of data, revising the manuscript. Dr. Davis, R.B.: design and conceptualization of study, analysis and interpretation of data. Walsh, J.: acquisition of data, revising manuscript. Dr. Wall, B.: conceptualization of study, revising manuscript, conducting intervention. Dr. Kong, J.: design and conceptualization of study, analysis and interpretation of data, obtaining funding, drafting and revising manuscript, supervising study. Kaptchuk, T. and Dr. Phillips, R.S.: design and conceptualization of study, obtaining funding, study supervision, revising manuscript. Dr. Press, D. and Dr. Yeh, G.: design and conceptualization of study, analysis and interpretation of data, revising manuscript, supervising study. Sponsor's Role: None.

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