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Deep Sleep Linked to Early Alzheimer's Signs

— Non-REM slow wave activity tied to tau pathology

Ƶ MedicalToday

Deep sleep was associated with tau pathology, a study of older adults showed.

Non-rapid eye movement (non-REM) sleep slow wave activity was inversely related to Alzheimer's pathology, especially tauopathy, with the association most evident at the lowest 1- to 2-Hz frequencies, according to Brendan Lucey, MD, and David Holtzman, MD, both of Washington University in St. Louis, and colleagues.

This finding suggests that changes in non-REM slow wave activity might be able to discriminate tau pathology at or before the earliest stages of symptomatic Alzheimer's disease, the team wrote in .

"What's interesting is that we saw this inverse relationship between decreased slow wave sleep and more tau protein in people who were either cognitively normal or very mildly impaired, meaning that reduced slow wave activity may be a marker for the transition between normal and impaired," Lucey said in a statement.

"The key is that it wasn't the total amount of sleep that was linked to tau; it was the slow wave sleep, which reflects quality of sleep," he added. "The people with increased tau pathology were actually sleeping more at night and napping more in the day, but they weren't getting as good quality sleep."

Previous studies have found that increased napping was associated with increased amyloid beta (Aβ) accumulation over time, and that decreased non-REM slow waves in the medial prefrontal cortex.

"The hypothesis is that one function of sleep is to clear metabolites out of the brain, and amyloid may be one of those -- to the extent that, if you get disrupted sleep, you may get into a vicious cycle where amyloid builds up," said Ron Petersen, MD, PhD, director of the Mayo Clinic Alzheimer's Disease Research Center in Rochester, Minnesota, who was not involved with the study.

"The bigger question is a chicken-and-egg one: is it that your sleep is disrupted and the Alzheimer's proteins build up -- or are the Alzheimer's proteins being deposited in the brain disrupting sleep and that's where the cycle gets initiated? That still is uncertain," Petersen told Ƶ. "Nevertheless, the message is probably the same: disrupted sleep may enhance the buildup of the proteins and enhance the Alzheimer's process itself."

For the analysis, the researchers studied 119 people (mean age 74) recruited from the Knight Alzheimer's Disease Research Center at Washington University. About 80% of the patients were cognitively normal; the rest were very mildly impaired.

Participants had sleep assessments for up to six nights at home through three separate measures: a single-channel EEG device worn on the forehead, wrist-worn actigraphy, and sleep logs to record night sleep and day napping. In addition, participants were studied for sleep-disordered breathing and periodic leg movements. Each participant produced at least two nights of EEG data; some had six. A total of 38 people had PET scans for amyloid and tau tracers, 104 had cerebrospinal fluid (CSF) collected, and 27 had both.

After adjusting for multiple confounders -- including age, sex, race, Clinical Dementia Rating, APOE genotype, apnea-hypopnea index, periodic limb movement index, and sleep medications -- the researchers found that non-REM slow wave activity decreased with increased evidence of Aβ deposition and tau accumulation. This relationship was stronger with tau than with Aβ pathology on PET.

The team also observed that increased CSF tau/Aβ42 ratio -- another marker of Alzheimer's pathology -- was inversely tied to non-REM slow wave activity.

The findings have potential application in both clinical trials and patient screening, Lucey and colleagues observed: periodically measuring non-REM slow wave activity in conjunction with other biomarkers may help assess Alzheimer's risk or response to a treatment.

The study has several limitations, Lucey and co-authors said, including the fact that only 38 participants had imaging. Covariates such as sex, race, APOE, and sleep medications need additional study in larger cohorts, the researchers noted, adding that further longitudinal studies are needed to determine when non-REM slow wave activity decreases in relation to increased Aβ deposition and tauopathy.

Disclosures

The study was supported by the National Institutes of Health, the Ellison Medical Foundation, the Willman Scholar Fund, the Foundation for Barnes-Jewish Hospital, and the American Sleep Medicine Foundation. Avid Radiopharmaceuticals (Eli Lilly) provided support for PET scans.

The authors reported financial relationships with C2N Diagnostics, Genentech, AbbVie, Proclara, Denali, Eli Lilly, Biogen, Roche, Janssen, Fujirebio, Araclon/Grifols, and DiamiR.

Primary Source

Science Translational Medicine

Lucey B, Holtzman D, et al "Reduced non–rapid eye movement sleep is associated with tau pathology in early Alzheimer's disease" Science Translational Medicine 2019; 11 (474): eaau6550.