Sleep + Cognitive Training for Cognitive Impairment

(SLEEP-COG Trial)

Overseen By Maya N Elias, PhD, MA, RN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Washington

Must not be taking: Anti-dementia medications

Disqualifiers: Alzheimer's, Dementia, Bipolar, Schizophrenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 week

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assist ICU survivors at risk of memory and thinking problems, similar to early Alzheimer's. It tests whether combining sleep aids, such as earplugs and eye masks, with brain exercises (referred to as SLEEP + COG) can improve recovery. Participants will try different combinations of these treatments for up to a week. The trial seeks individuals over 60 who were recently in an ICU and are recovering in the hospital, excluding those with existing Alzheimer's, dementia, or certain other conditions. As an unphased trial, it provides a unique opportunity to contribute to innovative research that could enhance recovery for ICU survivors.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are currently prescribed anti-dementia medication, you would not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using earplugs and eye masks at night can help ICU patients sleep better. Several studies have found these tools reduce sleep disturbances and improve sleep quality. They are safe, easy to use, and affordable, making them a good option for better sleep.

Studies on computerized brain training programs, such as Lumosity, indicate they can improve memory and overall brain function, especially in people with mild memory problems. This type of training is generally safe and doesn't cause serious side effects.

Although specific safety data for using sleep aids and brain training together is lacking, the individual components—earplugs, eye masks, and brain exercises—are reported to be safe and well-tolerated in similar situations. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Sleep + Cognitive Training approach for cognitive impairment because it combines sleep enhancement techniques with cognitive exercises, which is a fresh angle compared to traditional methods like medications or standalone cognitive training. The SLEEP intervention uses simple tools like earplugs and eye masks to improve sleep quality, potentially boosting brain recovery more effectively than medication alone. The COG intervention employs personalized cognitive training sessions at optimal times based on individual sleep-wake patterns, which might enhance cognitive recovery in a more targeted way than the one-size-fits-all approach of existing cognitive training programs. By tailoring these interventions to each person's unique rhythms, this treatment could offer quicker and more effective improvements in cognitive function.

What evidence suggests that this trial's treatments could be effective for cognitive impairment?

Research has shown that improving sleep and engaging in brain exercises can reduce mental decline in people who have been in the ICU. In this trial, participants in the SLEEP arm will use earplugs and eye masks to enhance sleep quality, which studies suggest can aid brain function. Participants in the COG arm will engage in computer-based brain training programs, which have boosted memory and thinking skills in individuals with mild memory problems. The SLEEP + COG arm combines these sleep and brain exercises, potentially offering a stronger effect and better protection against memory issues. Additionally, aligning these activities with the body's natural clock could enhance their effectiveness. ^{2 3 4 5 6}

Who Is on the Research Team?

Maya N Elias, PhD, MA, RN

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

This trial is for older ICU survivors aged 60 and above who were functionally independent before hospitalization, stayed in the ICU for over 24 hours, are recovering or have been discharged from the ICU, and speak English or Spanish.

Inclusion Criteria

I am 60 years old or older.

I am currently admitted to the University of Washington Medical Center.

I have stayed in the ICU for more than 24 hours.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of SLEEP and COG interventions, or individual SLEEP or COG interventions, for up to 7 days/nights

1 week

Daily sessions (in-person or virtual)

Follow-up

Participants are monitored for cognitive function and risk of Alzheimer's disease and related dementias

12 months

Regular assessments at 1, 6, and 12 months post-hospital discharge

What Are the Treatments Tested in This Trial?

Interventions

• SLEEP + COG

Trial Overview The study tests a combination of sleep promotion (SLEEP) and cognitive training (COG), both separately and together (SLEEP + COG), against usual care (AC). It aims to see if these interventions can help prevent cognitive decline related to Alzheimer's disease in older adults after an ICU stay.

How Is the Trial Designed?

Group I: SLEEP + COG Experimental Treatment 1 Intervention

* Combination of SLEEP and COG interventions, for up to 7 days/nights + usual post-ICU inpatient care * Personalized timing of morning, afternoon, or evening COG sessions, based on CSM scale at baseline

Group II: SLEEP Experimental Treatment 1 Intervention

\- Nighttime use of earplugs and eye masks, for up to 7 nights + usual post-ICU inpatient care

Group III: COG Experimental Treatment 1 Intervention

* Daily 30-minute computerized cognitive training sessions (Lumosity), for up to 7 days + usual post-ICU inpatient care * Personalized timing of morning, afternoon, or evening COG intervention sessions, based on CSM scale at baseline

Group IV: AC Active Control 1 Intervention

\- Active comparator condition; delivery of educational modules on brain health + usual post-ICU inpatient care

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

A study on older adults showed that taking a nap or engaging in quiet wakefulness after working memory training significantly improved their working memory performance, while active wakefulness did not have the same effect.

The improvement in working memory was linked to increased slow oscillation power in the brain during naps and quiet wakefulness, suggesting that these offline periods are crucial for enhancing cognitive functions in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does working memory improvement benefit from sleep in older adults? Sattari, N., Whitehurst, LN., Ahmadi, M., et al.[2020]

Tg2576 mice, a model for Alzheimer's disease, show significant sleep abnormalities, including longer circadian periods and reduced delta power during non-rapid eye movement sleep, indicating disrupted sleep patterns similar to those seen in Alzheimer's patients.

The study found that the cholinergic deficit in Tg2576 mice contributes to these sleep issues, and interestingly, a brief passive immunization against amyloid beta improved rapid eye movement sleep in older female Tg2576 mice, suggesting potential therapeutic avenues for sleep deficits in Alzheimer's.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep and circadian abnormalities in a transgenic mouse model of Alzheimer's disease: a role for cholinergic transmission. Wisor, JP., Edgar, DM., Yesavage, J., et al.[2007]

In a study involving 11 healthy subjects, the effects of the Alzheimer's medications donepezil and memantine were analyzed using simultaneous EEG-fMRI, revealing significant alterations in brain connectivity linked to donepezil intake.

The research demonstrated that donepezil induced changes in brain networks that were distinct from those caused by sleep deprivation, suggesting that pharmacological effects can be assessed independently of the subjects' vigilance levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Networks are Independently Modulated by Donepezil, Sleep, and Sleep Deprivation. Wirsich, J., Rey, M., Guye, M., et al.[2019]

In a study of 3,957 participants aged 50 and older, initiating sleep treatment was associated with a slower decline in cognitive performance, particularly in those with higher baseline cognitive abilities.

The cognitive decline was significantly less after starting sleep treatment compared to before treatment, suggesting that addressing sleep disturbances may help protect cognitive health in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Performance Trajectories Before and After Sleep Treatment Initiation in Middle-Aged and Older Adults: Results From the Health and Retirement Study. Kaufmann, CN., Bondi, MW., Thompson, WK., et al.[2022]

In a study of 271 older adults, including those with mild cognitive impairment (MCI) and Alzheimer's disease (AD), longer total sleep time was linked to poorer cognitive performance, particularly in attention and processing speed tasks for MCI patients.

Elderly individuals with MCI had similar sleep durations to cognitively normal individuals, while those with AD slept longer, suggesting that longer sleep may indicate more severe cognitive impairment in MCI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations between sleep duration and cognitive impairment in mild cognitive impairment. Basta, M., Simos, P., Vgontzas, A., et al.[2020]

A 5-week non-pharmacological intervention involving bright light therapy, physical activity, and sleep education showed that it is feasible to improve sleep in individuals with mild cognitive impairment or dementia, with 6 out of 9 participants reporting minor improvements in sleep efficiency.

While the intervention primarily benefited the care recipients, some family carers also experienced improvements in their sleep and mental health, suggesting potential broader benefits of such interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-pharmacological interventions a feasible option for addressing dementia-related sleep problems in the context of family care. Gibson, R., Dowell, A., Jones, L., et al.[2021]

In a study of 15 older adults with mild cognitive impairment (MCI), greater wake after sleep onset (WASO) was linked to decreased attention and executive functioning, highlighting the impact of sleep disturbances on cognitive abilities.

Increased arousals during sleep were associated with poorer nonverbal learning and problem-solving skills, suggesting that sleep-wake disturbances in MCI may reflect underlying neurobiological issues related to cognitive decline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep well, think well: sleep-wake disturbance in mild cognitive impairment. Naismith, SL., Rogers, NL., Hickie, IB., et al.[2010]

Sleep deprivation increases cortical excitability by enhancing glutamate activity and reducing GABAergic inhibition, which can affect brain function and cognition.

The study found that sleep deprivation disrupts normal brain plasticity mechanisms, impairing learning and memory, as well as attention, highlighting the critical role of sleep in cognitive processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep-dependent upscaled excitability, saturated neuroplasticity, and modulated cognition in the human brain. Salehinejad, MA., Ghanavati, E., Reinders, J., et al.[2022]

Sleep is crucial for cognitive functioning, as even a small amount of sleep loss can negatively impact attention, memory, and decision-making processes.

Recent research suggests that sleep can enhance memory consolidation and learning through mechanisms like memory reactivation and specific brain oscillations, with potential methods to boost these effects including sensory cueing and pharmacological interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep for cognitive enhancement. Diekelmann, S.[2021]

In a study of 41 older adults with an average age of 83, it was found that sleep quality, specifically wake after sleep onset, influenced the relationship between amyloid-β (Aβ) levels and memory performance, indicating that poorer sleep may exacerbate memory issues associated with Aβ accumulation.

The findings suggest that improving sleep could potentially serve as a protective factor against cognitive decline in individuals at risk for Alzheimer's disease, highlighting the importance of modifiable health factors in managing neurodegeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep moderates the relationship between amyloid beta and memory recall. Wilckens, KA., Tudorascu, DL., Snitz, BE., et al.[2023]

In a study with 22 participants, improvements in the Corsi Block task were linked to increased REM sleep, while enhancements in the Tower of Hanoi task were associated with N2 sleep, suggesting different sleep stages contribute uniquely to memory consolidation.

The findings challenge existing models of sleep-dependent learning by indicating that not all memory tasks benefit equally from REM sleep, and that the effects of sleep on learning may be more complex than previously thought.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overnight improvements in two REM sleep-sensitive tasks are associated with both REM and NREM sleep changes, sleep spindle features, and awakenings for dream recall. Nielsen, T., O'Reilly, C., Carr, M., et al.[2015]

In a study involving 28 healthy young adults, 24 hours of sleep deprivation led to decreased brain activation in areas responsible for visual memory and attention, indicating that lack of sleep negatively impacts cognitive function.

The acetylcholinesterase inhibitor donepezil improved performance in tasks affected by sleep deprivation, particularly in individuals whose accuracy declined without treatment, suggesting that enhancing cholinergic activity can help mitigate cognitive deficits caused by lack of sleep.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cholinergic augmentation modulates visual task performance in sleep-deprived young adults. Chuah, LY., Chee, MW.[2020]

This scoping review analyzed 188 studies involving 17,139 participants with Mild Cognitive Impairment (MCI) and early dementia, highlighting that sleep abnormalities are prevalent in these populations and may contribute to cognitive decline.

Despite advances in technology, sleep was primarily measured using validated questionnaires rather than more objective methods like polysomnography, indicating a need for standardized sleep outcome measures to improve the assessment of sleep interventions in dementia research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The past, present, and future of sleep measurement in mild cognitive impairment and early dementia-towards a core outcome set: a scoping review. Blackman, J., Morrison, HD., Lloyd, K., et al.[2022]

Sleep deprivation significantly impairs cognitive performance, affecting areas such as attention, memory, and overall cognitive speed, which can lead to serious social and health-related consequences.

Chronic sleep restriction can cause cognitive deficits to accumulate over time, often without the individual realizing it, and genetic factors may influence how vulnerable a person is to these cognitive impairments from sleep loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurocognitive consequences of sleep deprivation. Goel, N., Rao, H., Durmer, JS., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10515553/

Effects of computer-based cognitive training combined with ... The purpose of this study was to determine whether SEQ and SIMUL motor-cognitive training can improve treatment outcomes compared with PHY or ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05467410?tab=table

Optimal Timing of Computerized Cognitive Training for ... A retention rate of 80% will determine feasibility: the percentage of participants who complete at least 60 minutes of COG-AM sessions and all cognitive ...

3. nature.com nature.com/articles/s41746-023-00987-5

Computerized cognitive training for memory functions in ... This meta-analysis evaluated the benefits of computerized cognitive training (CCT) on memory functions in individuals with MCI or dementia.

4. jmir.org jmir.org/2022/10/e38624/

Effectiveness of Computerized Cognitive Training in ... This systematic review suggests that CCT interventions could improve global cognitive function in patients with MCI.

5. ccjm.org ccjm.org/content/ccjom/79/10/705.full.pdf

Cognitive impairment in ICU survivors: Assessment and ... Interestingly, data suggest that cognition may improve somewhat in the first 6 to 12 months after ICU discharge.15 Therefore, if we can detect it early on and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05467410

Optimal Timing of Computerized Cognitive Training for ... More than 60% of intensive care unit (ICU) patients are adults ages 60 and older, who are at high risk for ICU-acquired cognitive impairment.