Fragmented sleep-wake rhythm precedes Alzheimer plaques in the brain

A fragmented sleep-wake rhythm, where people often transition from rest to active during the day and night, is already visible in the brain before the accumulation of the Alzheimer’s protein amyloid-beta. That has been shown by research from Erasmus MC involving over 300 residents of the Ommoord district in Rotterdam.

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Previous research has suggested a link between a disturbed sleep pattern and Alzheimer’s disease. New longitudinal research published in JAMA Neurology now confirms this association.

The researchers followed 319 participants without dementia as part of the Rotterdam Study in the Ommoord district, focusing on healthy aging. An accelerometer, a watch-like device measuring activity, was used to estimate their sleep-wake rhythm for a week. Study participants also kept a sleep diary. After an average of 7.8 years, the presence of amyloid-beta plaques in the brain was determined using a PET scan. Accumulation of amyloid-beta is one of the hallmarks of Alzheimer’s disease.

Genetic risk

The scientists found an association between fragmentation of the sleep-wake rhythm and amyloid-beta plaque burden. This association was particularly evident in people with an increased genetic risk of dementia. No participants had symptoms of Alzheimer’s disease dementia at the study’s beginning or end. This is not surprising, explains study leader Julia Neitzel. ‘There can be years between the buildup of amyloid-beta in the brain and the disease manifestation.’

To determine whether the rhythm fragmentation is a risk or a result of amyloid-beta accumulation, the researchers returned to the blood samples they had taken from participants while their sleep-wake rhythm was monitored. After excluding participants with abnormal levels of amyloid-beta protein in their blood from the analysis, the association between fragmentation of the sleep-wake rhythm and amyloid-beta plaques in the brain remained present. From this, the researchers conclude that a disruption in the sleep-wake rhythm likely precedes the buildup of the Alzheimer’s plaques in the brain.

Preventing Alzheimer’s

Neitzel hopes that this knowledge might help in preventing Alzheimer’s disease. ‘Getting good sleep and having a healthy sleep-wake rhythm is beneficial for health in general. Particularly in people who are genetically vulnerable for Alzheimer’s, we might be able to use this knowledge for prevention. However, intervention studies must determine whether improving the sleep-wake rhythm can prevent or delay Alzheimer’s.’

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