In the Journals

Less deep sleep tied to tau pathology in early Alzheimer’s disease

Image of Brendan Lucey
Brendan P. Lucey

Researchers observed an inverse relationship between decreased slow-wave sleep and more tau protein in older adults who were either cognitively normal or very mildly impaired.

These findings, published in Science Translational Medicine, indicate that poor-quality sleep may be a red flag before or in the earliest stages of symptomatic Alzheimer’s disease, according to researchers.

“Sleep and Alzheimer’s disease are currently thought to have a two-way or bidirectional relationship: There is evidence to suggest that sleep disturbances increase the risk of developing Alzheimer’s disease. Alternatively, changes in sleep-wake activity may be due to changes in the brain from Alzheimer’s disease,” Brendan P. Lucey, MD, assistant professor of neurology department and director of the sleep medicine section at Washington University School of Medicine, told Healio Psychiatry. “Our paper investigated this second question: sleep as a marker for Alzheimer’s disease changes in the brain.”

Lucey and colleagues examined the connection between sleep and Alzheimer's disease in 119 adults aged 60 years and older enrolled in longitudinal studies of aging.

They analyzed participants’ cognitive performance, brain imaging and Alzheimer’s disease biomarkers in cerebrospinal fluid (CSF). They assessed participants’ sleep-wake activity over 6 nights using portable EEG worn on the forehead, wrist-worn actigraphy and participant-reported sleep logs that recorded both nighttime sleep sessions and daytime napping.

The results showed that non-REM slow-wave activity was inversely related to Alzheimer’s disease pathology, measured by PET imaging and CSF biomarkers, after adjusting for covariates. Specifically, Lucey and colleagues found that decreased slow-wave sleep was linked to higher levels of tau in the brain as well as a higher tau-to-amyloid ratio in CSF, according to the press release.

“A major implication of our study is that measuring non-REM slow-wave activity may be a way to non-invasively and inexpensively screen for risk for cognitive decline due to Alzheimer’s disease,” Lucey said. “This would be very helpful in future clinical trials and possibly screening in the clinic. There are a number of experimental therapies targeting tau that are in clinical trials. If any of these agents prove to be successful, the early detection of non-REM slow-wave abnormalities may prove to be a useful way to monitor the success of such treatments.”

The investigators also found that higher CSF tau/amyloid-beta 42 ratio, another marker of Alzheimer’s disease pathology, was inversely linked to non-REM slow-wave activity. Furthermore, analyses showed that decreases in non-REM slow-wave activity were most distinct with amyloid-beta deposition in areas of the frontal, temporal and parietal lobes.

“Regarding recommendations for patients and clinicians today, I recommend that patients with a sleep concern or evidence of a sleep disorder should be referred to a sleep specialist for evaluation and treatment if needed,” Lucey told Healio Psychiatry. – by Savannah Demko

Disclosure: Lucey reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Image of Brendan Lucey
Brendan P. Lucey

Researchers observed an inverse relationship between decreased slow-wave sleep and more tau protein in older adults who were either cognitively normal or very mildly impaired.

These findings, published in Science Translational Medicine, indicate that poor-quality sleep may be a red flag before or in the earliest stages of symptomatic Alzheimer’s disease, according to researchers.

“Sleep and Alzheimer’s disease are currently thought to have a two-way or bidirectional relationship: There is evidence to suggest that sleep disturbances increase the risk of developing Alzheimer’s disease. Alternatively, changes in sleep-wake activity may be due to changes in the brain from Alzheimer’s disease,” Brendan P. Lucey, MD, assistant professor of neurology department and director of the sleep medicine section at Washington University School of Medicine, told Healio Psychiatry. “Our paper investigated this second question: sleep as a marker for Alzheimer’s disease changes in the brain.”

Lucey and colleagues examined the connection between sleep and Alzheimer's disease in 119 adults aged 60 years and older enrolled in longitudinal studies of aging.

They analyzed participants’ cognitive performance, brain imaging and Alzheimer’s disease biomarkers in cerebrospinal fluid (CSF). They assessed participants’ sleep-wake activity over 6 nights using portable EEG worn on the forehead, wrist-worn actigraphy and participant-reported sleep logs that recorded both nighttime sleep sessions and daytime napping.

The results showed that non-REM slow-wave activity was inversely related to Alzheimer’s disease pathology, measured by PET imaging and CSF biomarkers, after adjusting for covariates. Specifically, Lucey and colleagues found that decreased slow-wave sleep was linked to higher levels of tau in the brain as well as a higher tau-to-amyloid ratio in CSF, according to the press release.

“A major implication of our study is that measuring non-REM slow-wave activity may be a way to non-invasively and inexpensively screen for risk for cognitive decline due to Alzheimer’s disease,” Lucey said. “This would be very helpful in future clinical trials and possibly screening in the clinic. There are a number of experimental therapies targeting tau that are in clinical trials. If any of these agents prove to be successful, the early detection of non-REM slow-wave abnormalities may prove to be a useful way to monitor the success of such treatments.”

The investigators also found that higher CSF tau/amyloid-beta 42 ratio, another marker of Alzheimer’s disease pathology, was inversely linked to non-REM slow-wave activity. Furthermore, analyses showed that decreases in non-REM slow-wave activity were most distinct with amyloid-beta deposition in areas of the frontal, temporal and parietal lobes.

“Regarding recommendations for patients and clinicians today, I recommend that patients with a sleep concern or evidence of a sleep disorder should be referred to a sleep specialist for evaluation and treatment if needed,” Lucey told Healio Psychiatry. – by Savannah Demko

Disclosure: Lucey reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.