Chronic brain inflammation that develops with age may disrupt fast sleep spindles, or brain waves that help promote long-term memory retention—which could ultimately lead to an increased risk of Alzheimer's, according to recent research published in Sleep.
Study details and key findings
For the study, researchers from Wake Forest University School of Medicine, the University of California, Irvine, and the University of Wisconsin-Madison (UW) examined whether inflammation impacted brain waves called fast sleep spindles, which have been found to promote long-term memory retention. Although brain inflammation, sleep disturbances, and disrupted brain waves have all been associated with Alzheimer's, an interaction among the three had not yet been investigated.
In total, 58 adults in their 50s and 60s underwent sleep examinations at UW Madison. All participants had either a parental history of Alzheimer's or a genetic risk factor for the disease, but none were currently cognitively impaired or had beta-amyloid plaques and neurofibrillary tau tangles.
Sleep was recorded with high-density electroencephalography, which allowed the researchers to map participants' brain wave expression, and the next day, overnight memory retention was assessed. In addition, participants underwent a lumbar puncture to assess cerebrospinal fluid biomarkers of inflammation in the central nervous system, beta-amyloid and tau proteins, and neuronal integrity.
Overall, the researchers found that the activation of two types of glial cells that trigger brain inflammation, microglia and astrocytes, were associated with disrupted fast sleep spindles. According to the researchers, the fact that these associations were present in people without beta-amyloid plaques and neurofibrillary tangles suggests that inflammation and sleep disruptions may be some of the earliest indicators of Alzheimer's disease.
"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 Bryce Mander, an assistant professor of psychiatry and human behavior at UC Irvine and the study's lead author. "This results in deficits in the brain's capacity to generate fast sleep spindles, which contribute to age-related memory impairment in older adults."
According to the researchers, the study's findings may help identify new treatment targets at Alzheimer's preclinical stages, which would ultimately improve efforts to detect and prevent the disease early in its course.
"Discovering these mechanisms is an important step in identifying at-risk individuals as early as possible and developing targeted interventions," Mander said.
Barbara Bendlin, a professor of medicine at UW Madison and one of the study's authors, said that the researchers "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."
Overall, the study's findings offer " a promising therapeutic target to stop cognitive decline associated with aging and Alzheimer's," said Ruth Benca, chair of psychiatry and behavioral medicine at Wake Forest's medical school and the study's senior author. (Atrium Health Wake Forest Baptist/Triad Business Journal, 8/14; Craver, Winston-Salem Journal, 7/17; Mander et al., Sleep, 6/7)