Obstructive sleep apnea increases amyloid beta burden
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Individuals with obstructive sleep apnea — especially severe obstructive sleep apnea — experienced an increased amyloid burden compared with controls, according to findings from a small study published in Journal of Alzheimer’s Disease.
“It has been recently discovered that sleep is an important process for clearing neurotoxic proteins that accumulate during wake, including beta-amyloid, a protein implicated in Alzheimer's disease. Disruption to sleep can impede the clearance of these proteins and increase the formation of amyloid plaques in the brain,” Melinda Jackson, PhD, a senior lecturer in psychology at Monash University, told Healio Neurology. “In conjunction with this, we know that people with Alzheimer's disease are five times more likely to have the sleep disorder obstructive sleep apnea (OSA) than their counterparts and that individuals with OSA are at a greater risk for developing Alzheimer’s disease.”
As a result, Jackson and colleagues “were interested in exploring if there were more amyloid plaques in individuals with sleep apnea, who experience severe and chronic sleep disruption.”
The researchers enrolled 34 individuals with recently diagnosed, untreated obstructive sleep apnea, as well as 12 age- and sex-matched healthy controls, in a cross-sectional comparison study. They included age range (35-75 years) as part of the eligibility criteria “in order to examine whether significant amyloid burden is unexpectedly present in a group of relatively young [patients with obstructive sleep apnea] who would not be anticipated to have significant amyloid burden,” according to the study results.
The trial comprised patients with obstructive sleep apnea who had completed a diagnostic sleep study at the Austin Health Sleep Laboratory. Control patients underwent polysomnography to determine that they did not have a sleep or circadian disorder. All participants then attended two separate testing sessions; the first examined cognition, sleep and mood and the second included a PET scan to determine amyloid burden and a blood test.
Mean age of individuals with obstructive sleep apnea was 57.5 years. That group included more men (n = 19) than women. The mean age of control participants was 58.5 years; that group had as many men (n = 6) as women.
Jackson and colleagues found no significant pathology on PET imaging for any participants. They observed amyloid beta burdens between 15.1 and 24.9 Centiloid (CL) — “a single common quantitative output value” developed for amyloid beta imaging that was meant to improve clinical and research use of different amyloid beta tracers, which all have unique pharmacokinetics properties — in three participants with obstructive sleep apnea, who were therefore determined to be amyloid beta-negative. Researchers also confirmed this by visual inspection, according to Jackson and colleagues.
In general, the researchers found “some evidence” for a greater amyloid beta burden in participants with obstructive sleep apnea compared with controls (0.79 [± 9.17] vs. –3.89 [± 10.65]; P = .05; Cohen’s d = 0.49). They observed, “as expected,” strong evidence for the link between global amyloid beta burden and age across the entire sample (r = 0.53; P < .001). Jackson and colleagues found a link between the apnea-hypoxia index and amyloid beta burden when controlling for age (r43 = 0.33; P = .025) and both age and apolipoprotein E allele status (r34 = 0.37; P = .027). In particular, the nonrapid eye movement apnea-hypoxia index correlated with amyloid beta burden (r43 = 0.33; P = .027).
Jackson and colleagues observed a significant relationship between higher CL and decreased sleep efficiency (r43 = –0.31; P = .037) and fewer minutes spent in stage N3 sleep (r43 = –0.31; P = .04). The researchers also demonstrated a significant relationship between BMI and higher CL (r = 0.39; P = .008). An increased vascular risk factor score correlated with a higher apnea-hypoxia index (Spearman's rank correlation coefficient = 0.51; P < .001) and a trend for global amyloid beta load (Spearman's rank correlation coefficient = 0.28; P = .06).
When the researchers grouped participants according to type of obstructive sleep apnea (none/moderate, n = 22 [mean apnea-hypoxia index = 12.6]; severe, n = 24 [mean apnea-hypoxia index = 47.7]), they observed a significant difference in global amyloid beta burden between groups, with a higher amyloid beta burden in the severe apnea-hypoxia index group after controlling for age (F1,43 = 10.8; P = .002; Cohen’s d = 0.12).
“One of the interesting findings was that participants with less slow-wave sleep had higher levels of amyloid burden, but this is not surprising, as slow wave sleep seems to be the critical stage for clearance of neurotoxins,” Jackson said.
She also noted that study results have implications for clinical practice.
“It is important to screen for and treat obstructive sleep apnea in individuals who are at-risk for dementia, especially those who are attending memory clinics for possible cognitive impairment, as treatment of the sleep problem may help to slow accumulation of these proteins,” Jackson said. “The next steps for this research are to explore whether treatment of obstructive sleep apnea can slow the accumulation of amyloid plaques in the brain and possibly slow the progression of cognitive decline and dementia. Large longitudinal studies are required to examine this intriguing hypothesis.”