A new study suggests brain inflammation is the key factor linking sleep disturbances with Alzheimer’s disease. It's hypothesized the same overactive immune cells in the brain that ultimately contribute to cognitive decline can disrupt certain sleep cycles in the earliest stages of neurodegenerative disease.
By now, the relationship between poor sleep and dementia has been well established. We know disruptions in sleep cycles can be one of the earliest signs of Alzheimer’s disease, but what hasn’t been clear is whether poor sleep contributes to neurodegeneration or whether poor sleep is simply a consequence of the brain changes associated with dementia.
This new study indicates brain inflammation is the culprit, disturbing certain sleep cycles that, in turn, damage long-term memory retention mechanisms. The research focused on 58 volunteers in their 50s and 60s, all with a family history of Alzheimer’s but yet to report any cognitive or pathological symptoms of the disease.
The cohort had their brain activity monitored during an overnight stay in a sleep clinic and also had their spinal fluid analyzed for markers of brain inflammation.
The study found an association between increased activity of two kinds of brain immune cells – microglia and astrocytes – and disruptions to a type of brainwave activity called fast sleep spindles. During a pre-deep sleep stage, dubbed N2 sleep, certain spikes in brain activity can be detected. These spikes are called sleep spindles, and they have been associated with memory retention.
The new research found those subjects with higher levels of inflammatory cells in their spinal fluid samples were more likely to have disruptions to their fast sleep spindle activity. No one in the cohort displayed any other signs of Alzheimer’s, such as traces of amyloid or tau proteins, so the conclusion was that these sleep disturbances are likely the earliest sign of neurodegeneration.
“Our findings indicate that age-related increases in brain inflammation have a downstream effect on Alzheimer’s disease-related tau proteins and neuronal synaptic integrity,” said lead author Bryce Mander. “This results in deficits in the brain’s capacity to generate fast sleep spindles, which contribute to age-related memory impairment in older adults.”
Because no one in the study has actually developed Alzheimer’s disease yet the researchers are unable to definitively conclude this is an early signal of neurodegeneration. However, because everyone enrolled in the study was genetically susceptible to the disease it is likely some will go on the suffer from Alzheimer’s.
And so these findings, in tandem with a growing body of work linking sleep disturbance to dementia, suggest brain inflammation seems to trigger the cascade of events that move from disrupted slumber to cognitive decline. Ruth Benca, senior author on the new study, said these findings should help researchers understand the earliest stages of neurodegeneration and how this process of decline could be stopped.
“These findings show that the effects of brain inflammation on sleep spindles and memory occur through its effects on neuronal activity and Alzheimer’s disease-related proteins and are apparent even before pathological positivity,” said Benca. “This offers a promising therapeutic target to stop cognitive decline associated with aging and Alzheimer’s.”
The new study was published in the journal Sleep.
Source: UC Irvine
