Trial Outcomes & Findings for SIESTA: Sleep Intervention to Enhance Cognitive Status and Reduce Beta Amyloid (NCT NCT03954210)

All study assessments took place at the University of Kansas Medical Center (KUMC) from August 2019 to April 2025.

Everyone who was enrolled in study was randomized into CBT-I or active control.

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

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. Hit Reaction Time (HRT) is reported as a T-score (M = 50, SD = 10), where higher scores indicate slower reaction time and worse performance.

Cognitive function will be assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The RBANS consists of 12 subtests assessing immediate memory, visuospatial/constructional abilities, language, attention, and delayed memory. The RBANS Total Scale Score is reported as a Standard Score with a normative mean of 100 and standard deviation of 15. Possible scores range from 40 to 160. Higher scores indicate better overall cognitive performance.

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. Stroop Interference outcomes were reported as T-scores (M = 50, SD = 10), with higher scores reflecting greater interference and worse executive function.

Participants are asked to recall strings of numbers in order (Forward) and in reverse order (Backward). The outcome is the longest string of numbers correctly recalled in each direction. Scores are reported as Standard Scores (M = 10, SD = 3), with possible scores ranging from 1 to 19. Higher scores indicate better auditory attention, immediate memory (Forward), and working memory/executive function (Backward).

Sleep measures were evaluated using one overnight polysomnography (PSG). Standardized protocols were used to prepare the participants and place six electroencephalogram sensors to detect brain wave activity. Total sleep time (TST), time in bed (TIB), wake after sleep onset (WASO), sleep onset latency (SOL), sleep stages 1 (N1), 2 (N2), and 3 (N3), and rapid eye movement sleep (REM) were determined using standardized scoring procedures.

Assessment of patients depression over the past two weeks. There are nine items that yield a maximum score of twenty-seven. Each item is anchored on a four-point scale with 0 being "Not at all" and 3 being "Nearly Everyday." Participants can demonstrate a minimum score of zero (no depression) or twenty-seven (severe depression). The tenth item that assesses how depressive symptoms affect functional level will not be utilized.

Assessment of patients anxiety over the past two weeks. There are eight items anchored on a scale of zero ("Not at all") to three ("Nearly Everyday"), that yield a minimum score of zero (no anxiety) and a maximum score of twenty-one (daily anxiety). An additional item was added to assess if anxiety impacts daily activities and sociability. GAD-7 outcomes were reported as total scores ranging from 0 to 21, calculated by summing the seven individual item scores. Higher scores reflect greater anxiety severity and worse outcomes.

Assessment of patients level of confidence in being able to implement behaviors that are helpful in promoting sleep. There are nine items that are scored on a four-point scale ranging from one (not confident) to five (very confident), with a minimum score of nine, indicating lower self-efficacy, and a maximum score of forty-five indicating higher self-efficacy.

Change in global cortical beta amyloid deposition over time will be assessed using Florbetapir PET imaging. Cortical regions of interest, including the frontal lobes, anterior cingulate, posterior cingulate, parietal lobes, and temporal lobes, were combined to compute a single global cortical Centiloid score. Scores are reported on the Centiloid scale, with values ranging from 0 to 100. Higher scores indicate greater beta amyloid deposition.

Cortical beta amyloid deposition was assessed using MRI spatially aligned with Florbetapir PET imaging. Cortical regions of interest were analyzed to derive the Beta Amyloid Centiloid Score. Scores range from 0 to 100, with higher scores indicating greater beta amyloid deposition. This outcome mirrors the Centiloid score obtained from the Florbetapir PET outcome.

Participants self-reported their motivation to change sleep behaviors using a single item rated on a five-point Likert scale from 0 (not at all motivated) to 4 (very motivated). Higher scores reflect greater motivation to change sleep behaviors, with a minimum possible score of 0 and a maximum of 4.

Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Participants completed 11 items assessing orientation, registration, attention and calculation, recall, language, and visuospatial skills. Scores range from 0 to 30, with higher scores indicating better cognitive performance. Participants with scores ≥25 were excluded from the study. The outcome was assessed at baseline.

Participants completed a brief vision screening to assess basic visual acuity and function. Higher scores indicate better visual performance. The outcome was assessed at baseline.

Participants' APOE genotype was determined via blood draw using standard genotyping methods. Participants were classified as E4-negative (no e4 allele) or E4-positive (at least one e4 allele). E4-positive participants are considered to have a higher genetic risk for Alzheimer's disease. Counts of participants are reported for each category, with the sum of both categories equal to the total number of participants analyzed in each study arm.

The Coin in Hand Assessment is a brief test of participant effort and motivation. On each trial, the examiner shows a coin in one of two hands for \~2 seconds. The participant then closes their eyes, counts backward from 10, and indicates which hand held the coin. Ten trials are administered, with the coin equally distributed between hands in random order. The outcome measure is the total number of correct responses, with higher scores indicating better attention and effort.

Fine motor coordination and manual dexterity will be assessed using the Grooved Pegboard Test. Participants are asked to place pegs into the pegboard as quickly as possible. The primary outcome is the time required to complete the task. Scores are reported as mean ± standard deviation. Higher values indicate slower performance.