Improving Sleep Continuity Through Mindfulness Training for Better Cognitive Ageing. (MIST)

Poor sleep quality is a known risk factor for cognitive decline in the elderly. Hearteningly, sleep is also a prime target for behavioral modification. In this study, the investigators propose to test mindfulness-based training (MBT) as an intervention to improve sleep quality by reducing sleep fragmentation, and hypothesize that these improvements will mediate the beneficial effects of MBT on sustained and executive attention. MBT consists of a suite of techniques aimed at enhancing awareness and acceptance of one's internal (e.g., thoughts and feelings) and external experiences in the present moment. Learning these techniques has been shown to improve sleep quality in patients with primary insomnia, and in other conditions associated with sleep disturbance. There is also increasing evidence that mindfulness training enhances multiple facets of cognition, including components of attention. In this study, the investigators will recruit 120 participants in a randomized controlled design, with 60 participants receiving MBT, and 60 receiving a sleep hygiene education and exercise program (SHEEP). Each intervention will last 8 weeks. Before and after the intervention, the investigators will collect objective and subjective measures of sleep quality, resting-state and task-related functional magnetic resonance imaging scans, and performance on standard laboratory tests of attention. The investigators hypothesize that, relative to SHE, MBT will result in significantly greater improvements in sleep quality and attentional metrics. They also predict that the cognitive changes will be mediated by the changes in sleep quality. If a positive result is found, this would indicate the use of MBT as a cost-effective behavioral intervention to stabilize or even improve cognition in the elderly, thus reducing the risk of dementia in this vulnerable population.

Cognitive decline in the elderly is a rapidly growing concern in Singapore and other developed Asian nations. Among the major but understudied factors that may exacerbate this decline is poor sleep quality. Targeting sleep to decelerate or even reverse age-related cognitive decline may represent a low-cost, high-return solution to a widespread societal problem. To accomplish this goal, the investigators propose to test mindfulness-based training (MBT) as an intervention to improve sleep quality and cognition. In this pilot grant, the investigators will study a group of participants (N = 120) in a randomized controlled design pitting MBT (N =60) against sleep hygiene education (SHEEP, N = 60). Hypothesis 1: MBT will lead to significantly greater improvements in sustained and executive attention relative to SHEEP (measured both behaviorally and using functional magnetic resonance imaging). Hypothesis 2: Cognitive outcomes will be mediated by improvements in subjective and objective sleep quality. Good sleep is critical for cognition at all ages, and especially in the elderly Adequate sleep is important for optimal cognitive function across the lifespan. Although the association between sleep and cognitive function is bi-directional, alterations in sleep frequently occur prior to the appearance of cognitive symptoms in Alzheimer's Disease (AD). Almost 50% of older adults report at least one sleep problem, and there is growing evidence that sleep complaints and disturbances might have negative effects on cognition. Retired older adults have the freedom to sleep ad libitum but this benefit is offset by age-associated changes in sleep such as poorer subjective quality, increased fragmentation and/or altered macrostructure. Although sleep duration is the measure that has received the most attention, there is accumulating evidence that sleep quality (Blackwell et al., 2014) and sleep fragmentation in particular, can have deleterious effects on brain structure and cognition. A change in sleep pattern in late adulthood can foreshadow cognitive decline, perhaps as a result of accumulation of neurotoxic substances that are normally cleared during sleep.

Participants will be randomized to receive either a Mindfulness-based Therapy for Insomnia (MBTI) or a Sleep Hygiene Education Program (SHEP). The intervention is for 8 weeks. Measures will be administered prior to and on completion of the intervention.

The mindfulness-based intervention consists of eight 2-hour sessions covering various mindfulness techniques (e.g. mindfulness of breath, body and movement, senses and informal practice, and empathy and compassion) that pertain to people with sleep problems and insomnia. Participants will be provided handouts for the information covered during these talks and discussions.

The Sleep Hygiene Education and Exercise Program has known relationships with good sleep quality. It will comprise of eight weekly 2-hour sessions. Each session will introduce a concept related to sleep and sleep hygiene. The facilitator will provide the theory and rationale behind the concept, and encourage participants to share and discuss their experiences related to the concept. The session will end with the participants evaluating how to implement the specific concept in their daily lives, and its potential implications for their sleep. Participants will be provided with a manual that outlines the concept and how they intend to apply it to their daily lives.

The mindfulness-based intervention consists of eight 2-hour sessions covering various mindfulness techniques (e.g. mindfulness of breath, body and movement, senses and informal practice, and empathy and compassion) that pertain to people with sleep problems and insomnia. Participants will be provided handouts for the information covered during these talks and discussions.

The Sleep Hygiene Education and Exercise Program has known relationships with good sleep quality. It will comprise 8 weekly 2-hour sessions. Each session will introduce a concept related to sleep and sleep hygiene. The facilitator will provide the theory and rationale behind the concept, and encourage participants to share and discuss their experiences related to the concept. The session will end with the participants evaluating how to implement the specific concept in their daily lives, and its potential implications for their sleep. Participants will be provided with a manual that outlines the concept and how they intend to apply it to their daily lives.

Pittsburgh Sleep Quality Index Score (PSQI) is a 19-item self-rated questionnaire for evaluating subjective sleep quality over the previous month. The PSQI has a sensitivity of 89.6% and specificity of 86.5% for identifying cases with sleep disorder, using a cut-off score of 5. The first 4 items are open questions, whereas items 5 to 19 are rated on a 4-point Likert scale. Individual items scores yield 7 components. A total score, ranging from 0 to 21, is obtained by adding the 7 component scores. A score of 5 and above suggests poor sleep quality. A decrease in PSQI score following intervention would reflect and improvement of sleep quality.

Polysomnography is a multi-parametric test used in the study of sleep and as a diagnostic tool in sleep medicine. PSG is a comprehensive recording of bio-physiological changes that occur during sleep. It will be performed at night, at the convenience of the participants' home. PSG monitors many body functions including brain, eye movements, muscle activity or skeletal muscle activation and heart rhythm during sleep. The investigators will use a Somnimedics PSG kit. Sleep onset latency reflects the amount of time it takes to participants to fall asleep from the moment they go to bed in the evening, so higher SOL are indicative of poor sleep quality. This objective measure of participants sleep onset latency will judge sleep quality against the subjective measures obtained through the sleep questionnaires.

Wrist-worn actigraphy is a convenient and reliable way to monitor sleep. It will be performed using research-grade, wrist-worn accelerometers that are calibrated to detect sleep by inferring from movement patterns. The systems used in this proposal (Philips Respironics AW-2 or Spectrum) has been calibrated against PSG. Sleep onset latency reflects the amount of time it takes to participants to fall asleep from the moment they go to bed in the evening, on average over seven nights of recording. This objective measure of participants sleep onset latency will judge sleep quality against the subjective measures obtained through the sleep questionnaires.

In addition to Sleep Onset Latency (Primary outcome 2), a second objective measure of sleep quality is extracted from the polysomnography recording: periods of wakefulness occurring after defined sleep onset. WASO is calculated by taking into account the total time spent in bed, minus sleep latency and minus total sleep time. High WASO scores reflect low sleep continuity and poor sleep quality. This second measure of participants sleep will judge sleep quality against the subjective measures obtained through the sleep questionnaires.

As with measures from PSG, in addition to Sleep Onset Latency (Primary outcome 3), a second objective measure of sleep quality is extracted from the Actiwatch recording: periods of wakefulness occurring after defined sleep onset. WASO is calculated by taking into account the total time spent in bed, minus sleep latency and minus total sleep time, averaged over seven consecutive nights. This second measure of participants sleep will judge sleep quality against the subjective measures obtained through the sleep questionnaires.

Insomnia Severity Index (ISI) evaluates an individual's level of tendency for insomnia on a 7-item questionnaire, scoring in total from 0 to 28. Scores above 15 indicates moderate severity of clinical insomnia while scores above 22 are indicative of severe clinical insomnia. ISI internal consistency was excellent for population samples both in the community and clinical samples as well, (Cronbach α of 0.90 and 0.91 respectively).

Reaction time task (RTI) provides assays of motor and mental response speeds, as well as measures of movement time, reaction time and response accuracy. Primary outcome: reaction times. Lower reaction times are indicative of better performance.

Change in Cognitive and Attention tasks performance (CANTAB: Rapid Visual Information Processing primary outcome)

Rapid Visual Information Processing (RVP) is a sensitive tool for assessment of sustained attention. Primary outcomes: median response latency. Lower scores in this measure reflect better sustained attention.

Paired Associate Learning (PAL) assesses visual memory and new learning, and is a sensitive tool for accurate assessment of episodic memory. Primary outcome: accuracy on first trials memory score

Spatial Working Memory (SWM) requires retention and manipulation of visuospatial information. This test has notable executive function demands, and measures strategy use as well as errors. Primary outcome: number of errors.

Stocking of Cambridge (SOC) assesses spatial planning and requires individuals to use problem-solving strategies to match two sets of stimuli. Primary outcome: number of problems solved on first choice.

Structural and MRI brain scans will be used to assess the change in the volume of orbitofrontal cortex (OFC) - the key region that is both consistently altered by mindfulness meditation, leading to an increase in volume, and implicated in sleep pathology. Participants will have their baseline fMRI scan at least 1-week before the start of their participation in the intervention and after the end of the intervention.

During two rsfMRI scans, subjects are imaged over several minutes while their eyes are open, but without performing any explicit task. It has been recognized that a person's brain activity at rest contains a rich source of information about their brain function. One of the resting state scan will show only a fixation cross on the screen (resting state), and the second one (Inscape) will show a short video developed in order to minimize the cognitive processing involved while decreasing head movement and sleepiness in the scanner. These data are typically extracted by decomposing the time-varying signal during resting periods into independent, intrinsically connected networks. The investigators propose to use traditional connectivity analysis as well as a newer method: graph theory analysis Measure will be increase of task ready state in Dynamic Functional Connectivity, as previous literature suggested that this is positively linked with mindfulness predisposition.

Main measure is change in cortical activity during sustained attention task, before and after intervention. Similar analysis to the resting-state fMRI scans will be conducted to determine the change in Default Mode Network (DMN) and Executive Control Network (ECN) connectivity and anti-correlation between DMN and task-positive networks.

Change in cortical connectivity while performing a Letting go practice in the scanner. Analysis are similar to the resting state and breath counting task (outcomes 13 and 14).

Emotion Recognition Task: ERT assesses social cognition and measures the ability of the subject to identify emotions in facial expressions. Secondary outcomes: Accuracy and Reaction times.

Verbal Recognition Memory: RM measures the ability to encode and subsequently retrieve verbal information. Secondary outcomes: number of correct-incorrect responses. Higher scores are indicative of better verbal recognition memory.

Rapid Visual Information Processing: RVP is a sensitive tool for assessment of sustained attention. Secondary outcomes: A prime. Higher scores in this measure reflects better performance.

BCT is a behavioural measure of trait mindfulness found to be reliable and correlated with self-report mindfulness. Outcome measure: number of errors.

BCT is a behavioural measure of trait mindfulness found to be reliable and correlated with self-report mindfulness. Outcome measure: accuracy and number of miscounts and resets.

Widely used instrument in neuropsychological assessment to measure for speed of cognitive processing and executive functioning. The direct score of both parts A and B are represented by the time taken to complete each task.

This test is a nonverbal group test typically used in educational settings. It is a 60-item test used in measuring abstract reasoning and regarded as a non-verbal estimate of fluid intelligence.

This 39-item instrument is based on a factor analytic study of five independently developed mindfulness questionnaires. The analysis yielded five factors that appear to represent elements of mindfulness as it is currently conceptualized. The five facets are observing (8 items), describing (8 items), acting with awareness (8 items), non-judging of inner experience (8 items), and non-reactivity to inner experience (7 items). Scores for each subscales are calculated as the mean of the items, ranging from 1 to 5. Total FFMQ score is the mean of all the subscales, ranging 1-5.

Dysfunctional Beliefs and Attitudes about Sleep (DBAS) is a 30-item self reported questionnaire to measure people's beliefs and attitudes about their personal sleep situations. Items are ranked from 0, strongly disagree, to 10, strongly agree. Total score is mean of all questions, with a higher score representing more dysfunctional beliefs and attitude about sleep.

Pre-Sleep Arousal, PSA is a 16-item self report questionnaire having both cognitive and somatic dimensions of arousal. Scores on each subscale range from 8-40 (sum of individual answers); high scores on both subscale indicate more arousal. The Cronbach alpha of this scale was .88 and test-retest reliability is .72.

State Trait Anxiety Inventory (STAI) has 40 items, 20 items allocated to each of the State-Anxiety (questions 1-8) and Trait-Anxiety (questions 9-16) subscales, each ranging from 20 to 80. It is a self-report questionnaires to indicate the presence and severity of current symptoms of anxiety and a generalized propensity to be anxious. Higher scores are positively correlated with higher levels of anxiety.

Beck's Depression Inventory (BDI-II) is a 21- item questionnaire that evaluates the severity of depressive mood states. Each item is rated between 0 (no symptom impact) and 3 (maximum symptom impact) with a maximum score of 63. Two domains are evaluated: the cognitive-affective (questions 1-13, ranging from 0 to 39) and somatic domains (questions 14-21, ranging from 0 to 24). Higher scores in both subscales represent lower mood and more depressive symptoms.

Short-Form 36 (SF-36) is a 36-item self-report survey of health, including physical and mental health, with 8 scaled scores, each ranging from a minimum of 0 to max 100. Total score is the mean of all the subscales. Physical functioning : 10 items; Role functioning/physical : 4 items; Role emotional: 3 items; Energy/fatigue: 4 items; Mental Health: 5 items; Social functioning: 2 items; Body pain: 2 items; General health : 5 items; Reported health transition: 1 item.

Polysomnography is a multi-parametric test used in the study of sleep and as a diagnostic tool in sleep medicine. It will be performed at night, at the convenience of the participants' home. Total sleep time reflects the amount of time participants were effectively sleeping while in bed, without periods of wakefulness. This objective measure of participants total sleep time will judge sleep quality against the subjective measures obtained through the sleep questionnaires.

Wrist-worn actigraphy is a convenient and reliable way to monitor sleep. Total sleep time reflects the amount of time participants were effectively sleeping while in bed, without periods of wakefulness, on average over seven nights of recording. This objective measure of participants total sleep time will judge sleep quality against the subjective measures obtained through the sleep questionnaires.

A Pulse Oximetry (SPO device from Somnotouch RESP, SomnoMedics) will be clipped at the end of participants' finger overnight together with the PSG recording, pre and post intervention, to measure peripheral capillary oxygen saturation changes. When compared with PSG and Actiwatch measures, oxygen levels can provide additional information about sleep quality. A decrease in oxygen level is often linked to sleep disorders like obstructive sleep apnea.

The Pulse Oximetry used for measuring oxygen levels for outcome 31 can also provide information about heart rate during sleep. Heart rate will be recorded for a full night before and after the intervention, together with PSG. Heart rate for adults during sleep varies widely across individuals, usually between 40-100 beats per minute.

Inclusion Criteria: Adults aged 50 to 80 English-speaking Mini-Mental State Examination Score ≥ 26 Montreal Cognitive Assessment Score ≥ 23 At least one of the following sleep difficulties are expressed: (i) average reported sleep latency of more than 30 minutes (ii) average wakefulness after sleep onset of more than 30 minutes (iii) sleep efficiency or total sleep time of less than 6.5 hours and/or (iv) also a cut off in the PSQI>/=5 Exclusion Criteria: Presence of major neurological conditions such as epilepsy, stroke, Parkinson's Disease and/or brain injury Presence of major psychiatric conditions such as major depression or schizophrenia Unsuitability for fMRI scanning (e.g. pacemakers, metallic implants, claustrophobia) Unable to give independent consent or no consent available

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