Effects of Meditation versus Music Listening on Perceived Stress,Mood,Sleep,and Quality of Life in Adults with Early Memory Loss: A Pilot Randomized Controlled Trial

INTRODUCTION

Alzheimer’s disease (AD) is a devastating neurodegenerative condition affecting an estimated 44 million adults worldwide, with prevalence projected to reach over 75 million by 2030 and 135.5 million by 2050 [1]. Onset is usually slow and insidious, typically preceded years earlier by subjective deterioration in memory. There is growing evidence that subjective cognitive decline (SCD), characterized by the subjective perception that one’s memory is noticeably worse than a few years before, may represent a preclinical stage of AD, particularly when the decline is a cause for concern [2, 3]. SCD in older adults is a significant predictor of subsequent, accelerated cognitive decline and of incident mild cognitive impairment (MCI) and AD [3 –7]; this association is particularly strong in those with SCD who express worry regarding their memory problems, and is not explained by depression, demographics, APOE4 status, or other AD risk factors [8]. SCD is also accompanied by neuropathological changes linked to AD pathogenesis, including elevated amyloid-β deposition [9 –12], increased white matter lesions [13, 14], and reductions in hippocampal and grey matter volume [15 –17].

SCD is associated with elevated risk not only for cognitive decline and incident dementia, but also for other burdensome health outcomes, including increased neuropsychiatric impairment [18, 19] and diminished quality of life (QOL) [20, 21]. SCD has been strongly linked to chronic psychological distress [22 –24]; adults with SCD are also significantly more likely to report symptoms of sleep disturbance [18, 25], depression [19 , 25–27], and anxiety [21 , 27]. Chronic stress, along with mood and sleep disturbances, can lead, in turn, to accelerated cognitive decline, neurodegenerative changes, and deterioration of both physical and mental health [28 –37]. Like subjective memory complaints [3 , 38], these psychosocial factors are significant, independent predictors of subsequent cognitive decline and progression to AD [4 , 39–51], with reported risk estimates similar to or greater than those for hypertension, diabetes, obesity, and other established risk factors [42 , 53], highlighting the importance of timely and effective intervention.

After decades of disappointing trials, there are still no effective treatments for preventing, delaying, or reversing cognitive decline. While emphasis is increasingly shifting to early intervention [2, 54], approved treatments for those with early memory loss, including those with SCD [18 , 56], are lacking. Moreover, although memory complaints have been consistently associated with adverse psychosocial outcomes and poor perceived health, those with SCD rarely seek care for their symptoms [24]. Yet this prodromal or preclinical period may comprise a critical therapeutic window for altering the vicious cycle of increasing psychological distress, sleep deficits, poor quality of life, and associated cognitive decline and neuropathogenic change. As indicated above, neuropsychological impairment is common in those with early cognitive decline, and can lead to profound negative changes in both physical health and neurocognitive function [28–32 , 57]. Thus, interventions that address these psychosocial risk factors may hold promise for not only enhancing health and well-being, but for slowing and possibly preventing cognitive decline in those at risk for AD. Of particular interest in this regard are mind-body therapies, including music listening and meditation. There is growing evidence that both meditation and simple, passive music therapy can reduce stress and depression, enhance well-being, and improve sleep in a range of populations, including those with and at risk for cognitive impairment [36 , 58–67]. However, despite the promise of these simple practices, rigorous controlled studies remain few, and none has yet investigated the potential efficacy of these relaxation practices for improving psychological and related outcomes in those with preclinical memory loss. In this parallel arm randomized controlled trial (RCT), we assessed the effects of two simple 12-week relaxation programs, Kirtan Kriya Meditation (KK) and music listening (ML) on perceived stress, sleep, mood, and health-related QOL in older adults with SCD.

METHODS

RESULTS

Following consent and baseline screening, 60 eligible adults with SCD were enrolled in the study. Memory problems had been experienced for a mean of approximately 3 years (X = 35.42±4.2 months) prior to enrollment. Study participants were predominantly non-Hispanic white (93%) and female (85%), with an average age of 60.6±1.0 (range 50–84) years. The majority were employed at least part-time (73%), married or living with a partner (65%), and college-educated (58%). Prevalence of metabolic/vascular risk factors for AD was high in this sample, with 94% of participants reporting at least one, and 66% indicating a diagnosis of≥2 of these chronic conditions (Table 2). Commonly reported conditions included obesity (48%), dyslipidemia (58%), hypertension (32%), and diabetes (15%). In addition, almost 60% of participants indicated a history of diagnosed depression or anxiety disorder. Mean CAIDE (Cardiovascular Risk Factors, Aging, and Dementia) score [109] was 8.2±0.3, with only 13% scoring under 6, the cutoff used in selecting adults at risk for cognitive decline in the ongoing lifestyle intervention study in Finnish adults [110]. Clinically significant sleep impairment, defined as PSQI >5 [71, 111], was present in over 90% of participants at baseline.

Participants in the two groups did not differ significantly in demographic or lifestyle factors, BMI, or medical history (Table 2). Likewise, there were no significant between-group differences in baseline scores on mood, sleep, stress, well-being, or QOL measures (Table 3), in reported duration of memory problems, or in baseline measures of memory or cognitive functioning (p’s > 0.1).

Each participant received the intervention as allocated. Participant retention was high; 92% of participants (27/30 KK, 28/30 ML) completed the 12-week intervention, and 88% (26/30 KK, 27/30 ML) completed the full 6-month study period. Reasons for dropout included: Family emergency (n = 1), time constraints (n = 2), and unknown/lost to follow-up (n = 4). Those who dropped out were similar to completers in demographics, lifestyle factors, BMI, and health history and did not differ on baseline measures of cognition, mood, stress, sleep, or well-being (p’s≥0.3). Adherence was also high, with participants completing an average of 93% of the 84 possible sessions in the first 12 weeks and 71% of sessions during the practice-optional, 3-month follow-up period. There were no between group differences at any time point in either adherence or retention (p’s≥0.4). Similarly, there were no significant differences between the two groups in any domain of treatment expectancy (all p’s≥0.2), and treatment expectancy scores were not correlated, at any time point, with change over time in stress, well-being, or in any domain of mood, sleep, or quality of life (p’s≥0.1). No adverse events were observed or reported.

DISCUSSION

In this pilot randomized controlled trial of older adults with SCD, participants assigned to both the KK meditation and the ML groups demonstrated significant and sustained improvements in measures of mood, stress, sleep quality, well-being, and quality of life (mental health component), with improvements in most measures reflecting clinically significant differences [112, 113]. Overall gains were particularly marked in the KK group. Observed improvements were not explained by baseline treatment expectancies, suggesting that expectations of benefit did not significantly influence outcomes in this study. Likewise, we found no evidence of a modifying effect of depression or anxiety, age, gender, medication use, comorbidity, baseline scores on psychosocial or cognitive tests, or other factors, indicating that these simple mind-body practices may be suitable for a variety of populations experiencing early memory loss.

This study is the first to investigate the possible benefits of mind-body therapies for improving psychosocial outcomes in older adults with SCD, and helps to address the need for exploring effective interventions in this population. To date, the few completed trials assessing psychological and related endpoints in non-cognitively impaired adults at risk for AD have yielded mixed findings, and reported improvements have been modest. For example, in a recent 3 arm RCT in 44 older Israeli adults with memory complaints, participants showed only small, non-significant declines in loneliness, and no change in depressive symptoms following completion of a 10-week health promotion, cognitive training, or participation-centered course [114]. Similarly, in a 2008 RCT of an 18-month individualized home-based exercise program in adults with subjective memory impairment, participants showed no significant improvements, at any time point, in either depressive symptoms or QOL [115]. In a large ongoing RCT of Finnish adults at risk for cognitive decline, participants assigned to a 24-month intensive lifestyle intervention incorporating dietary counseling, exercise training, cognitive training, and vascular risk monitoring likewise showed no improvement in depressive symptoms [110], but appeared to demonstrate small gains in some QOL domains [116] (data published in abstract form).

Consistent with findings of previous observational studies [18 , 21–27], neuropsychiatric impairment was elevated in this population. Most participants indicated clinically significant sleep impairment at baseline, with mean PSQI scores similar to or exceeding those in adults with insomnia [117] or multiple chronic conditions [118]. In addition, mean baseline quality of life was comparable to or lower than that reported in adults with a range of serious chronic conditions, including prostate cancer, diabetes, multiple sclerosis (mental health component), and epilepsy and substantially lower than the general U.S. population means [112, 119]. Likewise, mean participant scores on all domains of the POMS, a well established and widely used measure of mood disturbance, were significantly worse than reported norms for older adults [120], and similar to or higher than those in adults with HIV, cancer, heart failure, and other serious chronic disorders [121 –126]. Similarly, participants indicated overall high levels of stress, with baseline PSS scores again comparable to or higher than those reported in patients with a variety of serious conditions, including advanced coronary artery disease [127], multiple sclerosis [128], and cancer [129].

The significant and sustained improvements in psychological status, sleep, and QOL following the practice of meditation and music listening may have important implications for addressing not only the neuropsychiatric impairment common in those with SCD, but also the decline in cognitive function. In this study, both groups showed marked and sustained gains in all measures of memory and cognitive performance (p’s < 0.05, data not shown) as well as in all psychosocial outcomes. Moreover, positive changes in perceived stress, affect, and well-being in this study were significantly and directly correlated with improvements in subjective memory function and, albeit more modestly, to certain gains in objective cognitive performance, suggesting a possible functional relationship between changes in psychosocial status and those in cognitive function. This relationship is likely bidirectional and synergistic. For example, growing evidence suggests that neuropsychiatric impairment in those with early memory loss can itself increase risk of accelerated cognitive decline, neuropathological change, and progression to AD. Like MCI and AD, SCD has been strongly linked to chronic psychological distress [22 –24], elevated depressive [19 , 25–27], and anxiety symptoms [21 , 27], and sleep disturbance [18, 25], factors shown to increase risk for accelerated cognitive decline and neurodegenerative changes [28 , 34–36], and ultimately, conversion to MCI and AD [4 , 131]. Conversely, perceived deterioration in one’s cognitive functioning can itself be a significant source of fear and distress [132, 133], potentially leading to increased symptoms of depression and anxiety, reduced quality of life, and impaired sleep, further contributing to a vicious cycle of increased psychological disturbance, worsening QOL, accelerated cognitive decline, and accompanying adverse neurological changes. Compounding these changes, adults with memory complaints are also significantly more likely to experience subsequent deterioration in physical health, dependency, and institutionalization [134].

However, despite the often substantial psychological and functional challenges associated with SCD, those with memory complaints rarely seek help for their concerns [24, 135]. This reluctance to seek care is likely due in part to the widespread fear and related stigma surrounding AD [136 –139], coupled with the recognized absence of effective treatments [56, 138]. Thus, identifying low cost, sustainable, non-stigmatizing therapies that can effectively address both neuropsychiatric and cognitive concerns early, when intervention is likely to be most effective, is of clear importance. Of particular promise are therapies such as meditation and ML that can promote multiple beneficial changes implicated in cognitive impairment and that likely operate via multiple pathways, including those detailed above.

For example, meditation and ML may reduce distress, improve well-being, and enhance cognitive function by selectively activating specific neurochemical systems and brain structures associated with positive mood, emotional regulation, attention, and memory, and promoting related beneficial neurostructural changes [63 , 140–143]. For instance, recent studies suggest that meditation can promote favorable changes in CNS dopaminergic and other neurochemical systems [144, 145], and increase blood flow, oxygen delivery, and glucose utilization in specific regions of the brain associated with mood elevation, memory, and attentional processing, including the hippocampus, prefrontal cortex, and anterior cingulate gyrus [94 , 146–148]. Long-term meditation practice has also been associated with cortical thickening and increased grey matter volume in brain regions involved in attentional performance, memory, sensory processing, and interoception [149 –151], apparently offsetting typical age-related cortical thinning and grey matter loss [149 , 152]. While data regarding CNS changes with music are more limited, neuroimaging studies likewise suggest that music therapy, including ML, activates pathways in brain areas involved in emotional reward and regulation, attention, memory, and other associated functions, including the prefrontal cortex, insular and cingulate cortex, hippocampus, and amygdala [63 , 143].

Recent studies in dementia caregivers [153] also suggest that meditation may buffer the effects of stress-induced cellular aging by directly or indirectly promoting telomere maintenance, and in this way, protecting immune function and decreasing neuronal loss and other degenerative changes associated with both mood impairment and cognitive decline. Decreases in telomerase activity and telomere length have been linked to both chronic distressful states and cognitive impairment [154 –166] and shown to predict cognitive decline in both clinical and non-clinical populations [167, 168]. Likewise, recent research in healthy adults [169 –171], lonely older adults [172], and depressed dementia caregivers [173, 174] suggest that meditation may also buffer or reverse multiple stress-related changes in specific gene expression pathways implicated in the development and progression of AD, including those regulating oxidative stress, inflammation, cellular aging, and other factors contributing to impaired brain structure and function, and ultimately, to cognitive decline [175 –181]. While gene expression studies of music therapy are sparse, recreational music has been shown to modulate genomic stress induction signatures [182], suggesting that ML may have beneficial effects on the transcriptome as well.

In addition, KK meditation may affect psychosocial status and cognition via other pathways as well. For example, KK is a multi-modal meditation practice involving multiple tasks and sensory modalities (chanting with progressive changes in volume, sequenced finger movements, visualization, and coordinated breathing). Participants in the KK program are thus learning new motor, sensory, and physical skills, a process that has been associated with improvements in cognitive function and associated positive neurostructural changes [183]. KK also involves training in maintenance of attention and focus, set shifting, and multi-tasking, which could, in turn, improve several domains of executive function, including working memory and cognitive flexibility. While reasons for the greater improvements in the KK versus ML group are unknown, observed differences may in part reflect the multi-modal nature of KK meditation, as well as the more active nature of this practice.

There is evidence that non-KK meditation practices, including other forms of mantra meditation, such as Transcendental Meditation (TM) and SOHAM meditation, and interventions involving mindfulness/open-monitoring meditation may also be beneficial for populations with or at risk for memory loss. For example, data from matched cross-sectional studies of experienced meditation practitioners versus non-meditators have suggested that the practice of mindfulness/open-monitoring meditation (including Vipassana, Zen, and Mindfulness) may increase cortical thickness and delay age-related cortical thinning and grey matter loss in brain regions associated with attention, memory, and other functional domains adversely affected in MCI and AD [149 –151]. Likewise, while prospective neuroimaging studies of meditation in older adults remain few, two small controlled trials in meditation naïve older adults with MCI [184] and healthy young and middle-aged adults [185] suggest that Mindfulness-based Stress Reduction (MBSR), an intensive, 8-week multi-component program, may increase functional connectivity and reduce grey matter atrophy in brain regions affected in AD. Similarly, recent small trials in young and middle-aged adults suggest that the practice of both mindfulness meditation [186] and other forms of meditation [146, 148] may activate and enhance cerebral blood flow to areas of the brain involved in memory, attention, learning, and emotional regulation. These findings are consistent with neuroimaging data from recent studies of KK in older memory impaired adults [94], depressed dementia caregivers [187] and experienced practitioners [188].

However, prospective clinical trials have yielded less consistent findings regarding the effects of non-KK meditation forms on cognitive indices in older adults. Of the few trials of non-KK mantra meditation [189, 190], mindfulness meditation [191 –195] and other meditation practices [196] in older adults that have assessed cognitive function, most have shown minimal or no improvement [190 –195], including two recent large RCTs of MBSR in generally healthy elders [191, 193]. To date, only two published trials of non-KK meditation have included adults with memory complaints, and only one specifically targeted this population. A four arm RCT of TM and mindfulness meditation in 73 senior home residents demonstrated significant and sustained improvements with TM and to a lesser extent mindfulness, in several cognitive indices [189], and an RCT of MBSR in 14 adults with MCI showed no improvement in any cognitive measure (and worsening on one measure) [194].

Likewise, observed effects on neuropsychiatric impairment and QOL in older adults, including those with memory loss, have tended to be modest, with several studies showing limited or no improvement with either insight meditation [191 –194] or TM [190]. In contrast, preliminary trials to date of KK meditation in dementia caregivers [153, 197] and adults with early memory loss [94] have shown improvements in both cognitive function and psychosocial status consistent with those observed in the current study. However, clinical intervention trials of older adults with memory loss remain sparse, and sample sizes for most published trials to date, including those of KK, have been small, limiting conclusions. While findings of the current study further support the promise of KK for adults with SCD, additional rigorous research in larger populations is warranted to further investigate the potential benefits of KK and other meditation practices for adults with and at risk for memory loss.

CONCLUSIONS

Findings of this preliminary RCT suggest that practice of KK meditation or a simple ML program can promote significant and sustained improvements in perceived stress, mood, well-being, sleep, and quality of life in adults with SCD. Observed gains in this study were particularly pronounced in the KK group. Clearly, additional high quality trials are warranted to further investigate the potential benefits of these simple mind-body programs for older adults with early memory loss; to determine the long term effects of KK and ML on psychosocial status, QOL, and cognitive function; and to investigate potential underlying mechanisms of action.