Sleep-Disordered Breathing Linked to Alzheimer Disease Brain Changes


New data suggest that brain changes in the posterior cingulate cortex and precuneus as a result of SDB may increase the risk of Alzheimer disease, supporting prior findings which imply a link between the conditions.

Dr Gael Chetelat

Gael Chetelat, PhD, director of research, Institut National de la Sante et de la Recherche Medicale (Inserm)

Gaël Chételat, PhD

New study results on the brain changes associated with sleep-disordered breathing (SDB) in older adults without cognitive impairment suggest that screening for and treating SBD in older adults—particularly those who are asymptomatic—may be able to reduce the risk of Alzheimer disease.

Led by Gaël Chételat, PhD, director of research, Institut National de la Santé et de la Recherche Médicale (Inserm), the data suggest that SDB increases this risk due to its link with amyloid deposition and neuronal activity in Alzheimer-associated brain regions, most notably the posterior cingulate cortex and precuneus. These links, Chételat and colleagues wrote, “might explain why sleep-disordered breathing is associated with an increased risk for developing Alzheimer clinical syndrome at a younger age.”

“Importantly, to the best of our knowledge, our results show in vivo for the first time that greater amyloid burden colocalizes with greater gray matter volume, perfusion, and metabolism in older participants with SDB who are cognitively unimpaired,” they noted.

The assessment, dubbed the Age-Well clinical trial (NCT02977819), included 137 participants, of which 127 were included for analysis. The mean age was 69.1 (standard deviation [SD]. 3.9) years, and 63% (n = 80) were women. Using the apnea-hypopnea index (AHI) value, the participants were divided into a group with SDB (AHI <15 events per hour, n = 31) and those without SDB (AHI ≥15 events per hour, n = 96).

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Amyloid burden was notably greater in those with SDB than those without (t117 = 4.51; familywise error corrected P = .04; Cohen d = 0.83), as well as gray matter volume (t119 = 4.12; P = .001; Cohen d = 0.75). In addition to those, perfusion (t116&thinsp;=&thinsp;4.62; familywise error—corrected P&thinsp;=&thinsp;.001; Cohen d, 0.86) and metabolism (t79&thinsp;=&thinsp;4.63; familywise error—corrected P&thinsp;=&thinsp;.001; Cohen d, 1.04) were greater and overlapped primarily over the posterior cingulate cortex and precuneus.

“Interestingly, there was an overlap between brain changes observed in all 4 neuroimaging modalities over the posterior cingulate cortex, the precuneus, and the cuneus,” Chetelat and colleagues wrote.

The perfusion, metabolism, and gray mater volume signal values, extracted from significant clusters, showed strong intercorrelations (perfusion-metabolism: Pearson’s r = 0.70 [95% CI, 0.58—0.80]; P <.001; perfusion-gray matter: r = 0.59 [95% CI, 0.46—0.69]; P <.001; metabolism-gray matter: r = 0.40 [95% CI, 0.21—0.56]; P <.001). As well, amyloid deposition was significantly correlated with both gray matter volume (r = 0.21 [95% CI, 0.03—0.37]; P = .02) and perfusion (r = 0.34 [95% CI, 0.18—0.49]; P <.001).

There was no association observed with cognition, self-reported cognitive and sleep difficulties, or excessive daytime sleepiness symptoms.

“We believe that these overlapping patterns reinforce the likelihood of common underlying mechanisms. Indeed, it has been demonstrated that higher neuronal activity is associated with increased β-amyloid production,” Chetelat et al. detailed. “In addition, several studies have shown that neuroinflammatory processes play a central role in Alzheimer disease progression and are associated with higher levels of amyloid deposition. Thus, SDB-associated neuroinflammatory processes and associated neuronal hyperactivity are likely to promote amyloid deposition in the same area.”

To determine which aspect of SDB severity is most closely linked to these brain changes, the investigators performed forward stepwise regressions. The analysis reported that hypoxia composite score (unstandardized β, 0.06 [95% CI, 0.02—0.10]; P = .002), followed by APOE4 status (unstandardized β, 0.07 [95% CI, 0.001—0.14]; P = .05), which explained 8% and 4% of the variance, respectively, were most strongly associated with amyloid burden. The AHI value was the only variable associated with gray matter volume, explaining 4% of the variance (unstandardized β, 0.01; P = .04).

No variable was significantly associated with brain perfusion or metabolism, Chetelat and colleagues noted.

“Early neuroinflammatory and neuronal hyperactivity processes promoting amyloid deposition could represent the underlying mechanisms increasing the susceptibility to AD at an asymptomatic stage of SDB,” they concluded. “Our findings highlight the need to treat sleep disorders in the older population, even in the absence of cognitive or behavioral manifestations.”


Andre C, Rehel S, Kuhn E, et al. Association of Sleep-Disordered Breathing With Alzheimer Disease Biomarkers in Community-Dwelling Older Adults: A Secondary Analysis of a Randomized Clinical Trial. Jama Neurol. Published online March 23, 2020. doi: 10.1001/jamaneurol.2020.0311

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