SIESTA: Sleep Intervention to Enhance Cognitive Status and Reduce Beta Amyloid

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to compare the efficacy of a sleep intervention on improving cognitive function in older adults with symptoms of insomnia, determine the association between change in sleep measures and change in cognitive function, and examine the efficacy of the sleep intervention on reducing the rate of Aβ deposition. Participants, ages 60-85, will be randomly assigned to a six-week sleep intervention program. A sub-group of fifty participants will undergo Florbetapir-Positron-emission tomography (PET) imaging during the one-year reassessment to examine the efficacy of the sleep intervention on reducing the rate of Aβ accumulation from baseline to one-year post-intervention.

Detailed Description
-----------------
Lifestyle interventions to increase exercise and improve diet have been the focus of recent clinical trials to potentially prevent Alzheimer's disease (AD). However, despite the strong links between sleep disruptions, cognitive decline, and AD, sleep enhancement has yet to be targeted as a lifestyle intervention to prevent AD. Approximately fifteen percent of AD may be prevented by an efficacious intervention aimed to reduce sleep disturbances and sleep disorders. Chronic insomnia is the most frequent sleep disorder occurring in at least forty percent of older adults. Individuals with insomnia are more likely to be diagnosed with AD and demonstrate a decline in cognitive function at long-term follow-up. AD is characterized by the accumulation of Aβ plaques and tau tangles in the brain, and growing evidence shows impaired sleep contributes to the accumulation of Aβ. An intervention aimed at improving insomnia may represent a critical opportunity for primary prevention to slow cognitive decline and potentially delay the onset of AD. Therefore, the long-term goal of this research agenda is to understand how addressing sleep disturbances, via sleep intervention, may delay the onset of AD.

Official Title
-----------------
SIESTA: Sleep Intervention to Enhance Cognitive Status and Reduce Beta Amyloid

Conditions
-----------------
Insomnia

Intervention / Treatment
-----------------
* Behavioral: Cognitive Behavioral Therapy for Insomnia (CBT-I)
* Behavioral: Sleep and Lifestyle Education


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Report of difficulty falling asleep, maintaining sleep, or waking up too early at least three nights a week for the past six months A score of greater than, or equal to, ten on the Insomnia Severity Index A score of greater than, or equal to, twenty-five on the Mini-Mental State Examination (MMSE) A score of less than, or equal to, two on the Dementia Screening Interview (AD8) Exclusion Criteria: A known untreated sleep disorder (i.e., sleep apnea or restless leg syndrome) Currently taking benzodiazepines, non-benzodiazepines, melatonin supplements, or agonists for insomnia A score of greater than, or equal to, fifteen on the Patient Health Questionnaire (PHQ-9) indicating severe depression or endorsement of any suicidal ideation (an answer of one, two, or three on item number nine of the PHQ-9) History of drug or alcohol abuse as defined by the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-4) criteria within the last two years History of a nervous system disorder (i.e., stroke, Parkinson's Disease) Severe mental illness (i.e., Schizophrenia, Bipolar Disorder) History of a learning disability or attention-deficit/hyperactivity disorder Current, or history of, shift work Currently receiving CBT-I treatment Unable to hear at a conversational level Failure of a near vision test utilizing the Logarithmic Near Visual Acuity Chart

Ages Eligible for Study
-----------------
Minimum Age: 60 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Six-Week CBT-I Program<br>CBT-I, six sessions, forty-five to sixty minutes in duration. Session 1: set up sleep restriction and stimulus control, discuss strategies for how to stay awake to a prescribed hour and what to do with wake after onset sleep time, provide sleep hygiene education. Session 2: determine if upward titration of total sleep time is warranted, review sleep hygiene. Session 3: continue upward titration of total sleep time, cognitive therapy for negative sleep beliefs if indicated. Session 4: continue upward titration of total sleep time, follow-up regarding negative sleep beliefs. Session 5: continue upward titration of total sleep time, discuss relapse prevention. Session 6: assess global treatment gains, discuss questions regarding relapse prevention. | Behavioral: Cognitive Behavioral Therapy for Insomnia (CBT-I)<br>* CBT-I is an in-person, one-on-one program with a graduate psychology research assistant who is trained in providing a standardized CBT-I. Participants will maintain a sleep diary during the course of the program to aid in tailoring the program. Each session will begin with a summary and graphing of sleep diary data and will include an assessment of treatment gains and adherence.<br>|
| Active Comparator: Six-Week Sleep and Lifestyle Education Program<br>Sleep and Lifestyle Education, six sessions, forty-five to sixty minutes in duration. Session 1: Sleep education, Instruction/demonstration on stretching exercises. Session 2: Education on environmental factors & sleeping positions that impact sleep. Session 3: Education on lifestyle factors that impact sleep. Session 4: Education on diet and sleep. Session 5: Education on exercises and sleep. Session 6: Discus maintaining achievements & preventing relapses. | Behavioral: Sleep and Lifestyle Education<br>* Participants in the sleep and lifestyle education group will attend six weekly, in-person, one-on-one, stretching, and thinking activity sessions with a graduate research assistant to control for socialization and contact with research personnel.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Continuous Performance Test (CPT) | Assessment of the participants attention. Participants will be given a set of rules for stimuli, and based on those rules they will determine if a presented stimuli fit within those rules. Scores will be determined by the number of correctly identified stimuli. | Baseline, 6-Week Reassessment, and One-Year Reassessment | 
| Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) | Twelve sub-tests assessing participants immediate memory, visuospatial/constructional, language, attention, and delayed memory skills.Participants will engage in list learning, story memory, figure copying, line orientation, picture naming, semantic fluency, digit span, coding, list recall, list recognition, story memory and figure recall. | Baseline, 6-Week Reassessment, and One-Year Reassessment | 
| Change in Stroop Test | Assessment of participants executive functioning. Participants will be required to inhibit their natural response and replace it with a different response (i.e., reading a word versus saying the color of the word). Scores are obtained by taking the difference between conditions and normalizing for the number of stimuli. | Baseline, 6-Week Reassessment, and One-Year Reassessment | 
| Change in Neuropsychological Assessment Battery-Digits Forward/Digits Backward Test | Assessment of the participants attention and working memory. Participants will be required to remember and recall strings of numbers ranging from three to nine. Primary scores are obtained by tallying the number of trials the participant accurately recalled in the forward direction and the backward direction. Secondary scores are obtained by determining the longest string of numbers the participant recalled in the forward and backward direction. | Baseline, 6-Week Reassessment, and One-Year Reassessment | 
| Change in Grooved Pegboard Test | Assessment of the participants speed at completing a task requiring fine motor skills. Outcome is the amount of time required for the participant to place twenty-five pegs into the pegboard first utilizing their dominant hand only, then using their non-dominant hand only. | Baseline, 6-Week Reassessment, and One-Year Reassessment | 
| Change in Coin in Hand | Assessment of the participants effort to ensure full effort is being given during testing. Participants will be required to recall the correct hand the examiner has placed a coin in after the examiner has shown them the coin and counting backward from ten. Effort is determined by the number of correct trials the participant obtains out of ten, with malingering participants performing at chance level. | Baseline, 6-Week Reassessment, and One-Year Reassessment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Polysomnography | Assessment to determine if the participants have a sleep disorder. This determination is made by a trained professional utilizing the patient's brain waves, blood oxygen level, heart rate, breathing, and eye and leg movements to determine. | Second Pre-Screening/Baseline, 6-Week Reassessment, and One-Year Assessment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cognitive Behavioral Therapy for Insomnia, CBT-I, Alzheimer's, Alzheimer's Disease