Sleep Movements and Respiratory Coupling as a Biobehavioral Marker for Early Alzheimer’s Disease in Independently Dwelling Adults

Abstract

INTRODUCTION: Sleep disorder is often the first symptom of age-related cognitive decline in Mild Cognitive Impairment (MCI), or early Alzheimer’s disease. Patient or family sleep complaints in primary care do not reliably lead to screening for sleep or cognitive loss. In this study, poor sleep and arousability were examined using movement arousals, a novel biobehavioral marker of cumulative sleep loss, identified by periodic (circa 4 min) sleep movements (SM). We report that SM events trigger respiratory upregulation (RR) in healthy, but not in MCI-related, sleep. Time latency (TL) between SM-RR events is proposed as a marker of sleep loss and potentially of neurodegeneration associated with cognitive loss in MCI.METHOD. Community-dwelling older adults (N=95; 62-90 years) were tested in the home bed for two days on an “under the sheets” mattress overlay with high sensitivity for respiration and all movement, including micro-movements of SM. Wrist actigraphy (7 days) and standard sleep self-reports were collected as well. A suite of neurocognitive testing identified three groups: Normal Cognition (NC; n=45); clinic diagnosed MCI (MCI-DX; n= 17); and MCI-Consensus determined by an expert panel (MCI-CON; n=33 consensus or pre-clinical MCI) groups.RESULTS: In adjusted cohort analyses, sleep fragmentation (SF) and WASO predicted poorer memory performance selectively. Actigraphy revealed greater sleep latency (SL; p<.008), sleep duration (p<.01) and SF (p=.008) in MCI-DX compared to NC groups. Longer SL and poor sleep were associated with depression which was more prevalent in both MCI groups than NC. Neural Networks AI methods were applied to discriminate MCI and NC cases using the TL metric between SM-RR coupling events. ROC diagnostics were applied which identified MCI vs. NC cases with 87% sensitivity; 89% specificity; and 88% positive predictive value. DISCUSSION: MCI cognitive phenotype was detected with a novel sleep biomarker TL, associated with the tight gap between SM-RR coupling, which is proposed as a corollary of sleep quality/loss that affects the autonomic regulation of respiration during sleep. Movement arousals are less effective in initiating respiratory upregulation in MCI which suggests a potential mechanism for neurodegenerative changes and cognitive loss in early MCI.

Friends and Foes in Alzheimer’s Disease

“…Changes in mood, disturbed sleep patterns, and memory loss are among the earliest symptoms of AD. Although AD primarily affects the brain, during the course of the disease, extracranial body systems can be affected, including the respiratory system [61], digestive system [62], and urinary system [63] as well as changes in the epidermal layer of the skin [64]. Considering these and other organ-related symptoms, AD is increasingly being recognized as a multi-organ disorder [65].…”