Pharmacological and Non-Pharmacological Interventions to Improve Sleep in People with Cognitive Impairment: A Systematic Review and Meta-Analysis

From Sleeplessness to Slumber: Person-Centered Approach to Insomnia

A subset of patients with schizophrenia do not respond sufficiently to conventional antipsychotic treatment and often have a more complex clinical course, including high rates of sleep disturbances, which can contribute to further worsening of symptoms. However, sleep disturbances are often overlooked in clinical psychiatric settings, and non-pharmacological treatment options are not initiated. Cognitive behavioral therapy for insomnia (CBT-I) has been shown to effectively ameliorate sleep disturbances in schizophrenia but is yet to be assessed in treatment-resistant schizophrenia. In the present study, we aim to investigate the efficacy of CBT-I versus standard cognitive behavioral therapy (CBT), an active control intervention. Sixty patients diagnosed with treatment-resistant schizophrenia and comorbid sleep disturbance will be included in this randomized intervention study. Included patients will be randomized to 8-10 sessions of psychotherapy with either CBT-I (active intervention) or regular CBT (active control) following baseline. At baseline and 12-week follow-up, patients will be assessed with clinical interviews (Positive and Negative Syndrome Scale), self-reported measures (e.g., Insomnia Severity Index), and polysomnography. The 24-week follow-up will include the same assessments apart from polysomnography. The active intervention group will receive an individual course of treatment with CBT-I focused on the patients' sleep patterns, while the active control group will receive an individual course of treatment with standard cognitive behavioral therapy (CBT) focused on patients' psychopathology. It is hypothesized that while both groups will show improvements on central outcome measures, CBT-I will show greater improvements in sleep disturbances. Further, it is hypothesized that the improvement in sleep disturbances will correlate with an improvement in positive symptoms. Lastly, it is anticipated that the CBT-I group will show objective improvements in sleep architecture, such as sleep latency, wake after sleep onset, sleep efficiency, and total sleep time, compared to the CBT group. Should CBT-I prove efficacious in improving sleep disturbances in treatment-resistant schizophrenia, it would provide an avenue for a cost-beneficial, short-term, and implementable non-pharmacological treatment of a severe comorbidity in complex schizophrenia patients. Potential issues pertaining to the completion of the study are discussed. ClinicalTrials.gov NCT06749444.Registered on December 27, 2024.

Mild cognitive impairment (MCI) impacts approximately 20% of older adults, with many also experiencing sleep disorders, such as insomnia. Given the relationship between sleep and dementia, addressing sleep issues may offer an opportunity to treat reversible causes. There are two primary treatments for insomnia: behavioral-based (cognitive behavioral therapy for insomnia, CBT-I) and pharmacological interventions. Although CBT-I is recommended as first-line treatment for insomnia in older adults, sedative-hypnotics are more likely to be recommended than non-pharmacological treatments given their convenience and accessibility. However, there are significant concerns in prescribing medications to patients with MCI. To explore this disconnect, we reviewed insomnia treatments in older adults with MCI studies and current guidelines of pharmacological therapy. First, we reviewed studies presenting non-pharmacological treatment of insomnia in older adults with MCI. Although the search yielded over 4,000 non-duplicate titles, only one article presented data on non-pharmacological treatment of insomnia in MCI. The literature covering comorbid insomnia, CBT-I, and MCI is sparse. In contrast to review of non-pharmacological studies, studies on the pharmacological treatment of insomnia in older adults were ample. Finally, we reviewed international guidelines for pharmacological treatment of insomnia in cognitive disorders. More widely used pharmacological interventions show short-term effectiveness with problems of recurrence, ineffectiveness in inadvertent or purposeful chronic use, and adverse side effects. Despite evidence regarding adverse consequences, pharmacological treatment of insomnia remains the most common treatment for insomnia. Reflecting on age-related changes in older adults, particularly those with MCI, inappropriate or mismanagement of medication can lead to unnecessary complications. Further research examining effective behavioral-based sleep management options in older adults with cognitive impairment is needed with exploration of improved sleep on cognitive function.

This study aims to examine the feasibility and effects of an empowerment-based cognitive behavioural therapy for insomnia on sleep, cognitive outcomes, and health-related quality of life in persons with mild cognitive impairment and insomnia. This mixed-methods study comprises a pilot randomized controlled trial and an exploratory qualitative study. A total of 60 community-dwelling patients aged≥50years with mild cognitive impairment and self-reported sleep complaints will be recruited from the community centres for older people operated by two non-governmental organizations in Hong Kong. The participants will be randomly allocated to intervention or control groups, which will receive the empowerment-based cognitive behavioural therapy for insomnia and usual care respectively. We hypothesize that the cognitive behavioural therapy for insomnia intervention featuring an empowerment-based approach can improve sleep and cognitive function among patients with mild cognitive impairment. A subsample of 10 participants from the intervention group will be invited to take part in a qualitative interview to obtain more in-depth comments about the feasibility and acceptability of the intervention. Ethical approval was obtained on 2 November 2020. This study is supported by the Seed Fund for Basic Research from the University of Hong Kong on 4 September 2020. This study will address a neglected risk factor for cognitive decline in persons with mild cognitive impairment. The theoretical integration of empowerment and cognitive model of behavioural changes may inform a wider and more successful application of cognitive behavioural therapy techniques for people with compromised cognitive ability and insomnia. This study will also advance our knowledge on the role of sleep on persons with mild cognitive impairment and generate relevant empirical evidence to inform the care of this vulnerable cohort to affect a worldwide reduction in social, economic and healthcare burdens associated with cognitive impairment. This study has been registered at ClinicalTrials.gov (NCT04635085).

Sleep disturbances are very common in patients suffering from post-traumatic stress disorder (PTSD) and can have various negative sequelae, including worsening of perceived levels of stress, depression, and suicidal ideation. Although PTSD treatment can lead to improved sleep in some patients, there are a number of patients whose sleep disturbances do not remit even after treatment and can persist long after the original trauma. There are various non-pharmacological and pharmacological treatment modalities that have been studied. Non-pharmacological therapies include image rehearsal therapy (IRT), cognitive behavioral therapy for insomnia (CBTI), prolonged exposure (PE), and eye-movement desensitization and reprocessing (EMDR). Pharmacological studies include alpha-1-adrenergic receptor antagonists, alpha-adrenergic agonists, selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs) monoamine oxidase inhibitors (MAOIs), other antidepressants, atypical antipsychotics, benzodiazepines, sedative hypnotics, and antiepileptics. The therapies with the most evidence to support their use are Image Rehearsal Therapy (IRT) and the alpha-1-adrenergic receptor antagonist, prazosin.

Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).

Effectiveness of cognitive behavioral therapy for pharmacotherapy-resistant chronic insomnia: a multi-center randomized controlled trial in Japan

TMS and CBT-I for comorbid depression and insomnia. Exploring feasibility and tolerability of transcranial magnetic stimulation (TMS) and cognitive behavioral therapy for insomnia (CBT-I) for comorbid major depressive disorder and insomnia during the COVID-19 pandemic

Mild cognitive impairment frequently represents a predementia stage of Alzheimer's disease. Although obstructive sleep apnea is increasingly recognized as a common comorbidity of mild cognitive impairment, most apnea research has focused on middle-aged adults with moderate-to-severe obstructive sleep apnea. Mild obstructive sleep apnea, defined as 5-14 apneas or hypopneas per hour slept, is common in older adults. Little is known about the effect on cognition of adherence to continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea in older adults with mild obstructive sleep apnea and mild cognitive impairment. The objective of this study was to explore the effect of CPAP adherence on cognition in older adults with mild obstructive sleep apnea and mild cognitive impairment. We conducted a secondary analysis of data from Memories 1, a 1-year quasiexperimental clinical trial on the effect of CPAP adherence in older adults with mild cognitive impairment and obstructive sleep apnea. Those with mild obstructive sleep apnea were divided into two groups based on their CPAP adherence over 1 year: (a) CPAP adherent group (mild cognitive impairment + CPAP) with an average CPAP use of ≥4 hours per night and (b) CPAP nonadherent group (mild cognitive impairment - CPAP) with an average CPAP use of <4 hours per night. Individuals currently using CPAP were not eligible. A CPAP adherence intervention was provided for all participants, and an attention control intervention was provided for participants who chose to discontinue CPAP use during the 1-year follow-up. Descriptive baseline analyses, paired t tests for within-group changes, and general linear and logistic regression models for between-group changes were conducted. Those in the mild cognitive impairment + CPAP group compared to the mild cognitive impairment - CPAP group demonstrated a significant improvement in psychomotor/cognitive processing speed, measured by the Digit Symbol Coding Test. Eight participants improved on the Clinical Dementia Rating Scale, whereas six worsened or were unchanged. Twelve participants rated themselves as improved on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale, whereas three reported their status as worsened or unchanged. The mild cognitive impairment + CPAP group had greater than an eightfold increased odds of improving on the Clinical Dementia Rating and greater than a ninefold increased odds of improving on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale, compared to the mild cognitive impairment - CPAP group. CPAP adherence may be a promising intervention for slowing cognitive decline in older adults with mild obstructive sleep apnea and mild cognitive impairment. A larger, adequately powered study is needed.

ABSTRACTObjectives: Improving the sleep of older adults with mild cognitive impairment (MCI) represents a first step in discovering whether interventions directed at modifying this risk factor also have the potential to alter the cognitive decline trajectory.Methods: A six-session, adapted version of a cognitive behavioral therapy for insomnia (CBT-I) was administered to older adults (N = 28; 14 per group) with MCI across two residential facilities. Participants were randomly assigned to either the sleep intervention or an active control group and completed a neuropsychological battery at three time points (e.g., baseline-T1, post-intervention-T2, 4 month follow-up-T3).Results: Results showed a significant improvement in sleep and a change (p < .05) on a key measure of executive functioning sub task of inhibition (Condition 3 of D-KEF Color-Word Interference Test), a positive trend on the inhibition-switching task (p < .10; Condition 4 of D-KEF Color-Word Interference Test), an no change in a measure of verbal memory (HVLT-R Delayed Recall) compared with the active control group.Conclusions: CBT-I is a nonpharmacological intervention that has the potential to cognitively benefit individuals with MCI suffering from comorbid insomnia.Clinical Implications: Results suggest that a non-pharmacological intervention to improve sleep in older adults with MCI also improve cognitive functioning. Further exploration of the mechanisms underlying these improvements is warranted.

Insomnia is a prevalent disorder that affects 4% to 22% of the population in the United States. While cognitive behavioral therapy for insomnia (CBT-I) remains the gold standard for non-pharmacological treatment, accessibility barriers exist owing to a shortage of trained professionals and high costs. This review examines the efficacy of the individual components of CBT-I as stand-alone interventions to improve treatment accessibility, digital CBT-I, and other non-pharmacological interventions. Guidelines from organizations such as the American Academy of Sleep Medicine and, European Sleep Research Society, along with recent meta-analyses, support the effectiveness of these components as stand-alone treatments. Sleep restriction therapy and stimulus control therapy show promise as effective interventions. Although recommended by certain guidelines, relaxation therapy has yielded mixed results. Sleep hygiene education, a common component of CBT-I, has not demonstrated significant efficacy as a stand-alone treatment. Cognitive strategies have shown promise in recent studies. Sufficient clinical evidence supports the efficacy of digital CBT-I in treating insomnia. Internationally, various platforms for digital CBT-I have already been developed and are in use, and in South Korea, some digital CBT-I software programs have received digital therapeutic device approval in 2023. This review highlights the potential of individual components of CBT-I as effective stand-alone interventions for insomnia, as well as digital CBT-I, emphasizing their importance for improving the accessibility of non-pharmacological insomnia treatments in clinical settings where full CBT-I may not be available.

Acute and chronic insomnia are common and difficult clinical problems that contribute to and are consequences of other mental and physical health problems. It is tempting to treat insomnia with medications for rapid relief; however, these medications have significant side effects that add health burden and may cause tolerance and dependency. First-line treatment for insomnia is cognitive-behavioral therapy for insomnia (CBT-I); however, this is less frequently prescribed than benzodiazepine and non-benzodiazepine sedative hypnotic agents. Prudent primary care and mental health clinicians should screen for insomnia using valid and reliable tools when clients report sleep difficulties. When screening is positive, further assessment with a sleep diary is warranted. The primary treatment for insomnia is CBT-I, and pharmacological treatment may provide temporary support for no more than 2 to 4 weeks. Non-benzodiazepine hypnotic agents, histamine blocking medications, dual orexin receptor antagonists, and over-the-counter herbal supplements may serve as adjuncts. [Journal of Psychosocial Nursing and Mental Health Services, 56(7), 9-14.].

Mild cognitive impairment (MCI) in older adults is often accompanied by poor sleep quality and mood disturbances, which can exacerbate cognitive decline.1 Regular physical activity and exercise have been identified as potential interventions to improve these conditions.2 With the ageing population rapidly increasing, the prevalence of MCI has become a significant public health concern. Mild cognitive impairment often leads to cognitive decline and is associated with symptoms such as sleep disturbances and mood disorders. These symptoms not only reduce the quality of life but also accelerate cognitive deterioration. Regular physical activity and exercise have been shown to mitigate these effects by improving physiological and psychological health outcomes. In particular, South Korea, with its rapidly growing population of older adults, needs to better understand and address the relationship between physical activity, sleep quality and mood in older adults with MCI. Sleep disturbances are common in individuals with MCI, often manifesting as difficulties in falling asleep, frequent awakenings and reduced sleep efficiency.3 Regular physical activity, particularly aerobic and resistance training, has been shown to regulate circadian rhythms and improve sleep architecture. Such activity promotes the release of melatonin and reduces sleep latency, leading to better restorative sleep.4 Improved sleep quality is essential for memory consolidation, emotional regulation and overall brain function, all of which are critical for managing MCI. Mood disorders, including depression and anxiety, are common among older adults with MCI. These conditions can significantly affect motivation, cognitive performance and social interactions.5 Regular physical activity, through its ability to induce endorphin release and reduce cortisol levels, has been associated with improved mood and reduced stress.6 It provides a non-pharmacological and accessible approach to enhancing emotional well-being and fostering greater autonomy in daily living. Public health interventions should prioritise the development and integration of exercise programs tailored to the needs of older adults with MCI. Engaging in at least 150 min of moderate-intensity activity or 75 min of vigorous-intensity activity per week has been shown to be effective in promoting physical and mental health.7 However, uncertainty remains regarding the specific types of physical activities or exercise that are most beneficial, leaving the question of optimal exercise regimens open. Community-based programs and caregiver involvement can play a crucial role in enhancing adherence and sustaining long-term benefits. Further research should focus on identifying optimal exercise protocols, including the appropriate intensity, frequency and duration, to maximise benefits for this population. Regular exercise holds significant promise in addressing the sleep and mood disturbances experienced by older adults with MCI. By improving sleep quality and emotional regulation, physical activity can enhance cognitive health, delay cognitive decline and improve the overall quality of life. Implementing exercise-based interventions should be a cornerstone of preventive health-care strategies for ageing populations. As a non-pharmacological treatment, exercise is very effective in improving sleep quality in older people. No conflicts of interest declared.

Cognitive-Behavioral Therapy for Insomnia (CBT-I) is the gold-standard treatment for insomnia, which is common among breast cancer survivors (BCS). This pilot randomized controlled trial tested the first CBT-I intervention for Spanish-speaking BCS delivered using eHealth. Participants (N = 30) were Spanish-speaking BCS with insomnia symptoms recruited in Puerto Rico and randomized to a 6-week eHealth CBT-I group intervention or a waitlist control. Primary outcomes were acceptability (recruitment, treatment satisfaction) and feasibility (retention, attendance). Secondary outcomes were group differences in sleep outcomes post-treatment (i.e., insomnia symptoms, sleep disturbance, sleep efficiency). Recruitment (95%) and retention (97%) were excellent. All CBT-I participants (100%) attended ≥ 3 of 6 sessions. Satisfaction with CBT-I was acceptable. Post-intervention, there were medium to large group differences for average insomnia symptoms (d = 1.02), sleep disturbance (d = 1.25), and sleep efficiency (d = 0.77) favoring CBT-I. There were small/medium to medium/large group differences for the proportion of participants with clinically significant insomnia symptoms (d = 0.52), sleep disturbance (d = 0.67), and low sleep efficiency (d = 0.33) favoring CBT-I. Spanish-language eHealth CBT-I for BCS was acceptable and feasible and showed preliminary efficacy.ClinicalTrials.gov TRN: NCT04101526 (Posted September 24, 2019).

This review explores the impact of cognitive behavioral therapy for insomnia (CBT-I) on menopausal women suffering from insomnia. The transition to menopause is often accompanies by sleep disturbances, which significantly affect women’s quality of life. This review applies a scoping approach to evaluate randomized controlled trials (RCTs) focused on CBT-I interventions for insomnia among menopausal women. The included studies examined variations in the number of CBT-I sessions, the duration of interventions, and their delivery methods (face-to-face, online, or telephone-based). The results consistently showed that CBT-I significantly improves sleep quality and reduces insomnia severity in menopausal women. CBT-I was particularly effective compared to other interventions such as sleep restriction therapy and sleep hygiene education. Sleep quality improvements were observed to persist for up to six months after treatment. These findings support the use of CBT-I as a first-line intervention for insomnia in menopausal women, offering a sustainable solution with fewer side effects compared to pharmacological treatments. However, the review also highlights the need for further research on CBT-I’s efficacy in diverse populations, as most studies focused on predominantly white and well-educated women.