Brain amyloid burden, sleep, and 24-hour rest/activity rhythms: screening findings from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration Studies

Abstract

Study Objectives To examine in a subsample at the screening phase of a clinical trial of an β-amyloid (Aβ) antibody whether disturbed sleep and altered 24-hour rest/activity rhythms (RARs) may serve as markers of preclinical Alzheimer’s disease (AD). Methods Overall, 26 Aβ-positive (Aβ+) and 33 Aβ-negative (Aβ-) cognitively unimpaired participants (mean age = 71.3±4.6 years, 59% women) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies, respectively, wore actigraphs for 5.66±0.88 24-hour periods. We computed standard sleep parameters, standard RAR metrics (mesor, amplitude, acrophase, interdaily stability, intradaily variability, relative amplitude), and performed a novel RAR analysis (function-on-scalar regression (FOSR)). Results We were unable to detect any differences between Aβ+ or Aβ- participants in standard sleep parameters or RAR metrics with our sample size. When we used novel FOSR methods, however, Aβ+ participants had lower activity levels than Aβ- participants in the late night through early morning (11:30 PM to 3:00 AM), and higher levels in the early morning (4:30 AM to 8:30 AM) and from midday through late afternoon (12:30 PM to 5:30 PM; all p <0.05). Aβ+ participants also had higher variability in activity across days from 9:30 PM to 1:00 AM and 4:30 AM to 8:30 AM, and lower variability from 2:30 AM to 3:30 AM (all p <0.05). Conclusions Although we found no association of preclinical AD with standard actigraphic sleep or RAR metrics, a novel data-driven analytic method identified temporally “local” RAR alterations in preclinical AD.

Wrist accelerometry for monitoring dementia agitation behaviour in clinical settings: A scoping review

“…Those laboratory studies contributed more to the development of systems and classification models with more technical specifications than those studies that used secondary datasets or created data by instructing participants to perform agitated and non-agitated acts (64,65). There were other data analysis methods, such as the inter-daily stability and intradaily variability on actigraphic rest-and-activity rhythms (66). Some studies were also excluded because they were not focused on agitation, although they assessed the motor activity or rest patterns of the patients.…”

Circadian disruption and sleep disorders in neurodegeneration

“…The observed parameters also worsen as dementia deteriorates, indicating that the relationship between circadian disruption and AD progression is bidirectional. To specify the affected aspects of circadian rhythm, novel or refined analysis has been applied in some studies [ 171 , 172 ]. A 24-h time-limited difference of circadian rhythm was observed in individuals with preclinical PD in various periods in comparison to healthy controls [ 172 ].…”

“…To specify the affected aspects of circadian rhythm, novel or refined analysis has been applied in some studies [ 171 , 172 ]. A 24-h time-limited difference of circadian rhythm was observed in individuals with preclinical PD in various periods in comparison to healthy controls [ 172 ]. By using parametric and nonparametric analysis, reduced overall rhythmicity, lower amplitude and activity level, and later activity timing were revealed to be associated with development of MCI and dementia [ 175 ].…”

“…By using parametric and nonparametric analysis, reduced overall rhythmicity, lower amplitude and activity level, and later activity timing were revealed to be associated with development of MCI and dementia [ 175 ]. However, there are also some studies showing no association of 24-h activity rhythm fragmentation with dementia risk or preclinical AD [ 172 ]. Discrepancies in these findings could be due to different sample sizes, study populations or statistical methods.…”

“…The temporal association between circadian rhythm and AD or dementia has been explored in many epidemiological studies [166][167][168][169][170][171][172]. Habits of dysregulated circadian rhythm, such as long-time nightshift or delayed rising time, are associated with increased risk of dementia among healthy populations [166,167].…”