Short sleep may be early warning sign of Alzheimer’s disease

Sleep time, estimated by an actigraphy watch, correlates with cerebrospinal fluid (CSF) levels of t-tau and p-tau, suggesting its potential role as an early marker of Alzheimer’s disease (AD), according to a recent study.

“Our data suggest that a simple sleep parameter, such as total sleep time estimated by an actigraphy watch, is a valid predictor of tau pathology with potential clinical use,” the researchers said. “These devices allow complex and variable data to be monitored over long periods, enabling more ecological observation than laboratory assessments.”

A total of 127 cognitively unimpaired volunteers (mean age 65.47±6.33 years, 70.10 percent women) were enrolled in the study and were made to wear a commercial activity wristband to measure average total sleep time over seven nights. The Oviedo Sleep Questionnaire, a validated, self-reported sleep inventory, was also used. Aside from t-tau and p-tau, other CSF biomarkers assessed included amyloid-β (Aβ)-42 and Aβ40.

The mean total sleep time was 442.24±73 minutes (7.37 hours) per night. More than a third (37.8 percent) had at least one positive AD core CSF biomarker. According to the amyloid-tau-neurodegeneration (ATN) classification, 62.2 percent of participants tested negative in all three criteria, while 29.1 percent were deemed to be in the Alzheimer’s continuum. [Front Aging Neurosci 2021;13:663446]

Total sleep time shared an inverse and positive correlation with CSF levels of t-tau (r, –0.32; p=0.001) and p-tau (r, –0.26; p=0.005). These links remained significant even after adjusting for age, sex, and apolipoprotein E (APOE) mutation status (t-tau: β, –0.96; p=0.00036; p-tau: β, –0.14; p=0.0072). Sleep time was not associated with Aβ42/40.

General linear model (GLM) analysis also revealed that the interaction between sleep time and APOE status was statistically significant for the prediction of t-tau levels (β, 0.78; p=0.021). In particular, the correlation between sleep time and t-tau could be explained mainly by APOE ε4 carriers. These carriers also had significantly shorter sleep time than noncarriers (422.3±81.6 vs 451.57±67.13 min; p=0.044).

“Our analysis using objective estimation of total sleep and core AD CSF biomarkers as a proxy for dementia risk strongly supports that those cognitively healthy elderly individuals with lower sleep time are potentially at greater risk of future neurodegenerative diseases based on higher t-tau and p-tau levels in the CSF,” the researchers said.

Moreover, “the stratified analysis indicates that the relationship between sleep and tau was predominantly due to the APOE ε4 individuals,” they added.

“Our results are in line with previous studies suggesting the role of APOE as a modulator of the relationship between sleep and AD pathology,” they researchers said.

Notably, self-reported sleep was not correlated with any of the four core AD CSF biomarkers. Total sleep time likewise was unrelated to results in the Free and Cued Selective Reminding Test, the Face-Name Associative Memory Exam, and the Logical Memory Test of the Wechsler Memory Scale-III.

“Studies tracking sleep changes during more prolonged periods and the use of more accurate portable devices that provide information about the architecture of sleep could significantly improve the diagnostic performance of sleep assessment as an AD screening method,” the researchers said.

“Longitudinal studies may also help to understand better the direction of this association and the potential value of preventive measures,” they added.