There’s currently no known way to prevent older adults with mild cognitive impairment (MCI) from developing Alzheimer’s disease.
But there may be a safe and feasible non-pharmacological treatment that may help patients living with MCI, according to a small pilot study in the current issue of the Journal of Alzheimer’s Disease led by a neurologist and researcher with Wake Forest Baptist Health.
“Until treatment options that can prevent the progression to Alzheimer’s are found, mindfulness meditation may help patients living with MCI,” said Rebecca Erwin Wells, M.D., M.P.H., associate professor of neurology at Wake Forest School of Medicine, a practicing neurologist at Wake Forest Baptist Medical Center and associate director of clinical research for its Center for Integrative Medicine.
“Our study showed promising evidence that adults with MCI can learn to practice mindfulness meditation, and by doing so may boost their cognitive reserve.”
Mindfulness means maintaining a moment-by-moment, non-judgemental awareness of thoughts, feelings, bodily sensations, and surrounding environment.
“While the concept of mindfulness meditation is simple, the practice itself requires complex cognitive processes, discipline and commitment,” Wells explained.
“This study suggests that the cognitive impairment in MCI is not prohibitive of what is required to learn this new skill.”
Research has demonstrated that high levels of chronic stress negatively impact the hippocampus, a part of the brain involved in memory and learning, and are associated with increased incidence of MCI and Alzheimer’s.
Other studies have indicated that non-drug interventions such as aerobic exercise can have positive effects on cognition, stress levels and the brain.
To test whether a mindfulness-based stress-reduction (MBSR) program could benefit adults with MCI, the study team enlisted 14 men and women between the ages of 55 and 90 with clinically diagnosed MCI and randomized them to either an eight-week course involving mindfulness meditation and yoga or a “waiting list” control group.
The researchers previously reported that the nine participants who completed the MBSR program showed trends toward improvements on measures of cognition and well-being and indications of positive impacts on the hippocampus as well as other areas of the brain associated with cognitive decline.
The newly published study adds context to those quantitative findings with a qualitative analysis of the MBSR participants’ responses in interviews conducted at the end of the eight-week course.
“While the MBSR course was not developed or structured to directly address MCI, the qualitative interviews revealed new and important findings specific to MCI,” Wells said.
“The participants’ comments and ratings showed that most of them were able to learn the key tenets of mindfulness, demonstrating that the memory impairment of MCI does not preclude learning such skills.”
Those participants who practiced at least 20 minutes a day were most likely to have understood the underlying concepts of mindfulness, Wells noted. The image is in the public domain.
Those participants who practiced at least 20 minutes a day were most likely to have understood the underlying concepts of mindfulness, Wells noted.
The limitations of the study include the small sample size and that the results may not generalize to all patients with MCI, as two-thirds of the participants in this study had a college education or more. Additional research is needed to further test the preliminary hypotheses contained in this study.
The research was originally conducted at Beth Israel Deaconess Medical Center in Boston and Harvard Medical School.
Funding: The 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 Center for Complementary and Integrative Health of the National Institutes of Health (award T32AT000051 and grants K24 AT004095, K24 AT000589, K24 AT004965, K01 AT003459, K23 AT008406, K23 AT009218 and K01 AT008219).
According to the World Health Organization, 47.5 million people worldwide have dementia with an annual incidence of 7.7 million new cases every year.
This number is projected to increase to 75.6 million people by 2030 and to 135.5 million people by 2050 (WHO, 2016). Notwithstanding the impact of dementia on the families and caregivers of persons with dementia, the economic burden of dementia was estimated to be US$604 billion in 2010, equivalent to 1% of the worldwide gross domestic product (WHO, 2016).
Although dementia is not a natural phase of normal aging, the majority of people with dementia are older people (AIHW, 2015).
It has been estimated to be the developed world’s third largest burden of disease after depression and ischemic heart disease by the year 2030 (Mathers and Loncar, 2006).
Alzheimer’s disease (AD) is the most common form of dementia and comprises 60–70% of cases (WHO, 2016).
Mild cognitive impairment (MCI) refers to the transitional state of cognitive changes between normal aging and AD (Petersen et al., 2001).
The clinical and cognitive criteria for MCI evaluate negative changes in the individual’s cognition compared to his/her previous level.
These include objective evidence of impairment in one or more cognitive domains (Albert et al., 2011).
One of the most commonly implicated cognitive domains is episodic memory–that is, “conscious recall of events and verbal/visual materials, measured by the ability to recall lists of words or recognize faces both immediately and after a delay” (Henry et al., 2011).
Preservation of independence in functional abilities and non-diagnosis of dementia are also important for a diagnosis for MCI (Albert et al., 2011).
The MCI sub-clinical population is therefore possibly in “a transitional zone between normal cognition function and clinically probable AD” (Winblad et al., 2004), and should be identified and targeted for early therapeutic intervention.
The risk factors for dementia are essentially the same as those for heart disease (Chen et al., 2014).
Preventive approaches are important particularly in light of the fact that while several drugs are used for treating AD, there is currently no effective pharmacological treatment approved for MCI.
Studies on pharmacological treatments using cholinesterase inhibitors that are approved by the United States Food and Drug Administration (FDA) and the Australian Therapeutic Goods Administration (TGA), such as donepezil (Aricept®), rivastigmine (Exelon®) and galantamine (Razadyne®, Galantyl®, Reminyl®), on MCI patients to provide short-term benefits for mild to moderately severe AD, have produced mixed evidence with inconclusive results on cognitive improvement or progression from MCI to AD (Vega and Newhouse, 2014).
One other factor contributing to the risk of MCI and AD is poor sleep (Tsapanou et al., 2015).
Not only has this been associated with a higher risk of AD but also poorer clearance of beta-amyloid from the brain at night (Mander et al., 2015; Sprecher et al., 2015). Mindfulness training has been found to improve sleep in older adults, suggesting another possible link between mindfulness, MCI and AD (Winbush et al., 2007; Black et al., 2015).
Cognitive training is one of the interventions used in the management of MCI (Henry et al., 2011).
However, one Cochrane review concluded that due to the inadequate quality of evidence, the limited effects of performance gains derived from cognitive interventions could not be attributed to specific training effects as these improvements did not exceed those in active control conditions (Martin et al., 2011).
Another Cochrane review simply found no significant gains from cognitive training (Bahar-Fuchs et al., 2013).
More importantly, the few individual studies that found preliminary evidence of potential benefits derived from cognitive training have not established whether the effects were generalized to the daily functioning of persons with MCI
In light of this, there is a need for therapeutic interventions that specifically target risk factors that could be transferrable to activities of daily living (ADL) for persons with MCI.
Mindfulness can be described as a way of training attention and fostering awareness.
This can be done through formal attentional training (mindfulness meditation) or informal practice and applications by being more attentive and engaged in daily life.
When unmindful, distracted and inattentive, the brain switches into default mode which has been associated with poor mental health (Brewer et al., 2011) as well as higher amyloid-beta deposition (Simic et al., 2014).
Mindfulness training has been found to switch off default mode (Brewer et al., 2011).
Studies have also shown a positive association between amount of meditation practice and meta-cognitive awareness (Garland et al., 2009), attentional performance and cognitive flexibility (Moore and Malinowski, 2009).
Early intervention with mindfulness training is therefore a feasible and efficacious non-pharmacological therapeutic intervention option that may improve the cognitive function of persons with MCI and prevent progression to AD.
Indeed, there is already growing evidence to suggest that meditation may be a potentially useful and affordable treatment approach for enhancing cognition and memory in patients with neurodegenerative diseases (Newberg et al., 2014).
The positive effects of meditation on cognition and dementia risk reduction may be achieved holistically through multiple pathways such as producing neuroprotective effects from less stress-induced cortisol secretion with higher brain-derived neurotrophic factor (BDNF) levels; enhancing lipid profiles and reducing oxidative stress, thereby reducing risk for cerebrovascular/age-related neurodegenerative diseases; and reinforcing neuronal circuits and boosting cognitive reserve (Xiong and Doraiswamy, 2009).
Moreover, “studies have demonstrated the effects of mindfulness on enlarging gray matter volume (Pagnoni and Cekic, 2007; Luders et al., 2009), increasing gray matter concentration (Hölzel et al., 2008; Vestergaard-Poulsen et al., 2009; Hölzel et al., 2011; Singleton et al., 2014), strengthening brain functional connectivity (Brewer et al., 2011; Jang et al., 2011; Hasenkamp and Barsalou, 2012; Taylor et al., 2013; Wells et al., 2013b), and enhancing psychological well-being (Singleton et al., 2014), thus suggesting the potential benefits of mindfulness on MCI” (Wong et al., 2015). Mindfulness can thus prevent the “tissue volume loss in the hippocampus and posterior cingulate/precuneus (Buckner et al., 2005; Beason-Held, 2011; Fotuhi et al., 2012; Wang et al., 2013), gradual loss of gray matter (Thompson et al., 2003), reduced functional connectivity in the default mode network (Sorg et al., 2007; Gili et al., 2011; Hafkemeijer et al., 2012; Wang et al., 2013), and high chronic psychological distress (Wilson et al., 2007) that are all implicated in the memory and cognitive decline observed in MCI and AD” (Wong et al., 2015).
Two small pilot clinical studies have been conducted on persons with MCI and dementia using the Mindfulness-Based Stress Reduction (MBSR) course. In the first study, a preliminary assessment of the feasibility of eight 2-h weekly MBSR sessions and one mindfulness retreat day that was conducted using a pilot randomized trial with a small sample of 14 MCI adults, found a non-statistically significant trend toward improvement of cognition and well-being (Wells et al., 2013a).
The second pilot study involving 12 persons with dementia and 8 carers again found non-statistically significant improvements in mental well-being after attending eight 2.5-h weekly MBSR course but a non-significant decrease in well-being between post-intervention and 3-month follow-up.
Even so, qualitative analyses from course observations and interviews showed that some participants with dementia were able to learn mindfulness and experienced subjective improvements in several quality of life dimensions (Leader et al., 2013).
A key methodological limitation in these studies may be that the generic content of the MBSR course was not customized to the specific needs of the participants with cognitive impairment.
There is a lack of longer-term monitoring of the longitudinal effects of mindfulness practice on persons with MCI. Another limitation is the failure to achieve statistical significance because of the small sample sizes in these studies.
Finally, the main focus of the MBSR course is on formal mindfulness practice (meditation) and may have insufficiently emphasized the informal mindfulness practice in daily living activities, for example (e.g.,) by incorporating informal mindfulness practice into everyday activities and daily experiences.
Such informal mindfulness practice can be tied in with existing ADL (e.g., by encouraging people to eat, travel and communicate mindfully) to promote sustained mindfulness outside of meditation sessions. It would also enhance engagement with ADL, significantly increasing cognitive stimulation throughout the day, which could be assumed to be beneficial for persons with MCI.
There is preliminary evidence for this, such as Landau et al.’s study which reported increased cognitive activity such as reading, writing and playing games particularly in early- and middle-life, may directly reduce the beta-amyloid before the onset of AD, as shown that older individuals with high cognitive activity had beta-amyloid comparable to the young controls, while those with low cognitive activity had similar beta-amyloid as the AD patients (Landau et al., 2012).
Overall, the above studies suggest that a longitudinal study into a mindfulness training program that incorporates both the formal (mindfulness meditation) and informal (application in daily living activities) practices of mindfulness, and that is customized to the needs, health outcomes and level of understanding of persons with MCI, is warranted. The proposed study will meet this need.
This study adopts a non-randomized pre-/post-intervention design. Persons with a clinical diagnosis of MCI from treating health professionals will receive an 8-week group-based mindfulness training program which is customized to their needs, health outcomes and level of understanding. A follow-up assessment will be conducted one year after the program completion to measure the longitudinal effects of mindfulness practice on persons with MCI over time.
Our hypotheses are:
- That mindfulness practice will improve the cognitive function, psychological health, mindfulness and ADL functioning of persons with MCI.
- The degree of these improvements in cognitive function, psychological health, mindfulness and ADL functioning will correlate positively with the amount of mindfulness practice.
To test these hypotheses, the following quantitative research questions were formulated:
- Does mindfulness practice improve the cognitive function, psychological health, mindfulness and ADL functioning of persons with MCI?
- Does the degree of improvement in cognitive function, psychological health, mindfulness and ADL functioning vary with the amount of mindfulness practice?
- How much of any observed improvement is due to formal mindfulness practice and how much is due to informal applications of mindfulness to ADL?
Further, this study aims to address the following qualitative research questions:
- How do the MCI participants and familiar support persons (FSPs) engage with the mindfulness training program?
- What is the nature of group interactions between the Mindfulness Trainer and the MCI participants/FSPs and amongst the MCI participants/FSPs during the program?
- What is the mindfulness training program experience for the MCI participants and FSPs (e.g. was it enjoyable, satisfactory, stimulating and useful)?
- What perceived effects do the mindfulness training program and mindfulness practice generally have on the health and life of MCI participants and FSPs?
- What are the challenges faced by MCI participants in implementing and maintaining mindfulness practice?
- Do the expectations of the MCI participant and his/her FSPs about mindfulness practice match with each other?
Study eligibility criteria
To participate in this study, the MCI participants must fulfil the following inclusion criteria:
- Clinical diagnosis of MCI;
- Must be able to give informed consent to participate by signing the Consent Form; and
- At least 60 years old.
The clinical diagnosis and minimum age requirement fit the target sample of participants that this study is investigating on the premise that they must possess the capacity to receive information about their involvement in this study, to consent to the research and to participate in it.
Participants will be excluded based on the following criteria:
- Current active or past significant experience with meditation or yoga;
- Current use of prescribed cognitive intervention or electromagnetic stimulation;
- Acquired/Traumatic brain injury;
- Started new neurological/psychoactive medication within 3 months prior to the first data collection session;
- Current intake of drugs that significantly alter cognition;
- Illicit drug or alcohol abuse or dependence (more than 2 standard units of alcohol at a time and/or more than 7 standard units of alcohol in 1 week) within the previous 5 years;
- Current intake of cholinesterase inhibitors;
- Current severe psychiatric condition (e.g., bipolar disorder or clinical depression); or neurological/cerebrovascular condition; or chronic medical condition (e.g., advanced stage of cancer, chemotherapy) that requires intensive medical treatment and monitoring; or advanced cognitive decline;
- Major impairments in eyesight, hearing or upper limb motor movements; or
- English language difficulties.
Exclusion criterion (a) of not having current active or past significant meditation or yoga experience is relevant so as to properly measure the effects of mindfulness on the outcome measures. Exclusion criteria (b) to (f) are necessary to exclude MCI participants currently using prescribed interventions; recently started taking new neurological/psychoactive medication or cognition-altering drugs; or who had suffered brain injury and drug or alcohol abuse due to their possible effects on cognition and behavior. Exclusion criterion (g) of current intake of cholinesterase inhibitors is relevant to screen out persons with severe cognitive impairment. Exclusion criterion (h) is important as this study is investigating the effects of mindfulness on persons with MCI, thus it should not be confounded by other current severe chronic conditions. Exclusion criteria (i) and (j) are relevant to ensure that the MCI participants are able to participate in this study as they will be asked to read, write, listen and speak in English during the program and data collection sessions that include completing cognitive assessments and questionnaires/scales, and communicating in interviews. Information about the potential MCI participants (contact details and relevant personal and health information) and their FSP (name and contact details) may be obtained from the MCI participants’ health records for the purpose of this research.
There are no lifestyle restrictions such as physical restrictions, sport participation or dietary restrictions imposed on the MCI participants who may continue to take their regular prescribed medications. However, if their medical condition, treatment or prescribed medications change during the entire duration of study participation, they or their FSP should inform researcher Wee Ping Wong (WW) as soon as possible. In addition, if the MCI participant or his/her FSP takes part in other research studies prior to involvement in this study or intends to participate in other research studies at any subsequent stages during this study duration, they are requested to inform the research team at the earliest opportunity.
Repeated measures analysis of variance will be used to test the relative effects of formal and informal mindfulness practices on changes in the following dependent variables, namely cognitive function, psychological health, mindfulness, and ADL functioning from pre- to post-intervention and from post-intervention to 1-year follow-up, with an experiment-wise error rate of 0.05. Normally, each ANOVA should be evaluated with an adjusted (for e.g., Bonferroni correction) decision-wise error rate for possible inflation of Type I error. However, Type I error rate will not be adjusted for these analyses, on the grounds that this is an exploratory study of which any possible effects should be examined by further research. Regression analysis will be used to determine the predictive values of measures of formal and informal mindfulness practices on the changes in the same dependent variables (cognitive function, psychological health, mindfulness, and ADL functioning). Age, gender, and education will be entered into the regression analysis to identify possible moderating effects. The MCI participants’ demographics, health and lifestyle information will be examined in relation to the outcome measures in order to interpret the results in context. However, possible trends instead of statistically significant results could be determined from the quantitative analysis. As such, the mixed-methods design of this study enables the qualitative findings to complement the quantitative results in greater depth so that their findings could inform each other and be integrated to better address the research questions. The IBM Statistical Package for the Social Sciences software package will be used for the statistical analysis of the quantitative data.
Qualitative data analyses by researchers (WW) and Jan Coles (JC) will entail the investigation of the participant observational field notes and the semi-structured interview transcripts. To safeguard privacy, any identifiable information such as the name of the MCI participant, FSP, CDAMS, health service, GP and treating health professional in the audio recording of the interviews will be coded (but re-identifiable by the researchers for qualitative data analyses) in the interview transcripts. The QSR International NVivo software will be used to perform thematic analyses for the identification of important patterns/themes. The iterative (repeating) and inductive (bottom up) process of thematic analysis in the qualitative data analysis phase breaks the data into “smaller chunks” and assigns names or “codes” that summarize the idea within the data chunk (Hansen, 2006; Liamputtong, 2013). The codes are then refined by comparing, sorting and reflecting on the meaning and subsequently developed into “themes”1. A coding framework will be developed to provide definitions of the codes and maximize coherence among the codes for coding the qualitative data and generating themes or categories (Creswell, 2014). For inter-coder reliability, codes developed by researchers (WW and JC) will be cross-checked for agreement in coding with the same or similar code in order to maintain consistency in coding (Creswell, 2014). The framework of the presentation of both qualitative and quantitative data is illustrated in Figure Figure22.
The MCI participants and FSPs have the option to receive an email containing a summary of the non-identifiable group results when this study is completed. The findings from this study will be disseminated through peer-reviewed academic journal publications and presented at national and international seminars and conferences. In any publication and presentation, the information will be presented in non-identifiable form to protect the privacy of the MCI participants and their FSP.
It is expected that the mindfulness training intervention will proactively engage the MCI participants early and yield the practical application of improving their cognitive function such as attention and memory if they maintain mindfulness practice over time. There may be a potential benefit of delaying the progression of MCI to AD but this will not be assessed in this study. In addition, other expected improvements in psychological health, mindfulness, and in functional abilities of ADL may also indicate better health outcomes of mindfulness for MCI. This study will contribute toward the clinical research of MCI and advance evidence-based knowledge about the effects of long-term mindfulness practice as a promising and feasible non-pharmacological therapeutic approach for persons with MCI. This could potentially translate to downstream significance of better quality of life and higher work productivity of persons with MCI and their FSP, and a reduced chronic disease burden on families of persons with MCI and the healthcare system. If effective, “partnerships could be eventually forged with the Alzheimer’s Australia and memory clinics/services such as the CDAMS to deliver the customized group mindfulness training program to the target population of persons with MCI and their FSP” (Wong et al., 2015).
The study findings could open a potential future research direction to explore the use of biomarkers such as beta-amyloid and tau proteins to monitor the longitudinal effects of mindfulness practice on the cognitive and functional progression of persons with MCI and the conversion rate from MCI to AD.
Wake Forest Baptist Medical Center
Joe McCloskey – Wake Forest Baptist Medical Center
The image is in the public domain.
Original Research: Closed access
“Can Adults with Mild Cognitive Impairment Build Cognitive Reserve and Learn Mindfulness Meditation? Qualitative Theme Analyses from a Small Pilot Study”. Rebecca Erwin Wells et al.
Journal of Azheimer’s Disease. doi:10.3233/JAD-190191