Inflammation may link Alzheimer’s risk and bad sleep

"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," says Bryce Mander. (Credit: Getty Images)

New research reveals how brain inflammation may link Alzheimer’s risk and sleep disturbance.

The findings may aid early detection and prevention efforts by identifying novel treatment targets at preclinical stages.

Brain inflammation, sleep disturbance, and disrupted brain waves have all been associated with Alzheimer’s disease, but the interactions among them have not been investigated until now.

The study in the journal Sleep examined whether inflammation had any effect on specific brain waves called fast sleep spindles, which have been shown to promote long-term memory retention.

“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,” says lead and co-corresponding author Bryce Mander, assistant professor of psychiatry and human behavior at the University of California, Irvine.

“This results in deficits in the brain’s capacity to generate fast sleep spindles, which contribute to age-related memory impairment in older adults. Discovering these mechanisms is an important step in identifying at-risk individuals as early as possible and developing targeted interventions.”

Chronic activation of the brain’s immune cells, called “glial cells,” increases with age, elevating production of beta-amyloid and tau proteins, the hallmarks of Alzheimer’s disease. Independently, sleep disturbance has been linked to Alzheimer’s disease pathology in the brain, and studies have also indicated an association between sleep disturbance and inflammation.

Selectively disrupted fast sleep spindles have been identified in normal aging as well as preclinical stages of Alzheimer’s disease, but it has not been clear what causes this and what it means for memory impairment in older at-risk adults.

For the study, 58 cognitively unimpaired adults in their 50s and 60s were examined at the University of Wisconsin-Madison. All had a parental history of Alzheimer’s or a genetic risk factor for it, but none of them had beta-amyloid plaques or neurofibrillary tau tangles. Sleep was recorded overnight using high-density electroencephalography to map brain wave expression during sleep, and overnight memory retention was assessed. Participants also underwent a lumbar puncture so that cerebrospinal fluid biomarkers of central nervous system inflammation, beta-amyloid and tau proteins, and neuronal integrity could be examined.

The researchers used statistical tests to evaluate whether the effect of age on fast sleep spindles was mediated by Alzheimer’s-related proteins. The researchers found that activation of two types of glial cells—microglia and astrocytes, which trigger brain inflammation—was associated with disrupted expression of fast sleep spindles.

The fact that these relationships were identified in people without any accumulation of beta-amyloid plaques or neurofibrillary tangles indicates that sleep deficits and inflammation might be among the earliest warning signs of Alzheimer’s disease.

“We don’t yet know whether anyone in this study will develop Alzheimer’s disease dementia, but one of the reasons that our studies enroll participants in midlife is so that we can potentially detect problems before people develop disease symptoms,” says coauthor Barbara Bendlin, professor of medicine at the University of Wisconsin-Madison.

“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,” says senior and co-corresponding author Ruth Benca, Wake Forest professor and chair of psychiatry and behavioral medicine. “This offers a promising therapeutic target to stop cognitive decline associated with aging and Alzheimer’s.”

The team included health professionals and academics from the US, England, Germany, Sweden, and Switzerland.

Support for the work came from the National Institute on Aging, the National Institutes of Health, the Swedish Research Council, the European Research Council, Swedish State Support for Clinical Research, the Swedish Alzheimer’s Foundation, and the UK Dementia Research Institute at University College London.

Source: UC Irvine