In older adults who are cognitively unimpaired, sleep-disordered breathing was found to alter Alzheimer disease–sensitive brain regions, causing greater amyloid deposition and neuronal activity, according to study findings.
In older adults who are cognitively unimpaired, sleep-disordered breathing (SDB) was found to alter Alzheimer disease (AD)—sensitive brain regions, causing greater amyloid deposition and neuronal activity, according to study findings published today in JAMA Neurology.
SDB is a respiratory disorder characterized by recurrent upper airway collapse during sleep, and it affects 30% to 80% of older adults who are cognitively unimpaired. When left untreated, SDB is associated with cognitive decline and conversion to Alzheimer clinical syndrome at a younger age. Additionally, patients with AD pose a higher risk of suffering from SDB.
While research has continued to suggest that SDB contributes to the development of clinically diagnosed AD, the study authors highlight that the brain mechanisms underlying the link remain unclear. They sought to examine which brain changes are associated with the presence of SDB by conducting a cross-sectional study on patients from the Age-Well randomized clinical trial of the Medit-Ageing European project, using data acquired between 2016 and 2018 at Cyceron Center in Caen, France.
The study analyzed a cognitively unimpaired patient cohort (n = 127; mean age, 69.1 years) for brain alterations, such as amyloid deposition, gray matter volume, perfusion, and glucose metabolism that may be affected by SDB. Diagnosis of SDB was classified as having an apnea-hypopnea index cutoff of 15 events per hour.
Participants with or without SDB were compared for each neuroimaging modality, with secondary analyses examining the SDB parameter (sleep fragmentation, hypoxia severity, frequency of respiratory disturbances) that best illustrated the observed brain alterations. Additionally, the researchers assessed whether SDB severity and/or SDB-associated brain changes are related to cognitive and behavioral changes.
The researchers found that participants with SDB exhibited a greater burden attributed to amyloid deposition (t114 = 4.51; familywise error—corrected P = .04; Cohen's d = 0.83), gray matter volume (t119= 4.12; familywise error—corrected P = .04; Cohen's d = 0.75), perfusion (t116 = 4.62; familywise error—corrected P = .001; Cohen's d, 0.86), and metabolism (t79 = 4.63; familywise error—corrected P = .001; Cohen's d, 1.04). These issues were found to most prominently overlap in the posterior cingulate cortex and precuneus, known AD-sensitive brain regions.
Although brain alterations were significantly transformed in patients with SDB, there was no association found in these patients in regard to cognition, self-reported cognitive and sleep difficulties, or excessive daytime sleepiness symptoms.
“Older adults with SDB may exhibit silent brain changes, including increased amyloid deposition, which may propagate with time and explain why they are more at risk of developing Alzheimer clinical syndrome,” said the study authors.
In addressing limitations, the researchers noted that the study’s cross-sectional design did not allow for the assessment of potential causal associations between SDB and brain changes. “Longitudinal studies are needed to investigate whether these early SDB-associated brain changes will progress to neurodegeneration and cognitive deficits,” they said.
André C, Rehel S, Kuhn E, et al. Association of Sleep-Disordered Breathing With Alzheimer Disease Biomarkers in Community-Dwelling Older Adults [published online March 23, 2020]. JAMA Neurol. doi: 10.1001/jamaneurol.2020.0311.