Amyloid Burden in Obstructive Sleep Apnea

Abstract

Abstract. To test the hypothesis that excessive amyloid deposition is a biological link between obstructive sleep apnea (OSA) and Alzheimer's disease, we determined whether OSA increases cerebral amyloid burden, relative to controls, using Pittsburgh Compound B (PiB) PET imaging. The subjects were adult participants (age 50-65 years) from the Korean Genome and Epidemiology Study. Polysomnography, brain MRI including 3D images, and a detailed neuro-cognitive function test battery were done in 2011-2012. Nineteen OSA subjects (Apnea-Hypopnea Index [AHI] ≥15/h, 21.2 ± 5.1/h; age 58.5 ± 4.1 years; 9 male) and 19 controls (AHI 1.8 ± 1.3/h; age 58.5 ± 4.2 years; 9 male) underwent 60-min dynamic 11 C-PiB PET. All subjects were right-handed with normal cognitive function and brain MRI. Controls were matched by age, gender, education, and APOE genotype. A voxel-wise comparison of PiB-PET images between the two groups was performed after spatial and count normalization with cerebellar gray matter as a reference. Covariates included the status of sleep duration, hypertension, diabetes, body mass index, exercise, depressive mood, smoking, and alcohol drinking. Cortical thickness on 3D MRI was also measured and compared between the two groups. The OSA group showed a higher PiB deposition in the right posterior cingulate gyrus and right temporal cortex (corrected p < 0.05). There was no area of higher uptake in the control compared with OSA. Regional differences in cortical thickness were not significant. The study suggests that OSA accelerates amyloid deposition and may contribute to the development or progression of Alzheimer's disease.

Review: Impact of Helicobacter pylori on Alzheimer's disease: What do we know so far?

“…Hp may indirectly affect the brain and other target organs, for example, the heart, through the release of numerous cytokines such as TNF‐α acting at a distance. Our own data indicate that Hp‐I increases inflammatory mediators in the blood, including TNF‐α, and contributes to obstructive sleep apnea (OSA) pathophysiology; OSA accelerates amyloid deposition and could contribute to the development or progression of AD . Furthermore, increased TNF‐α secretion and elevated blood TNF‐α levels have been reported by others in patients with CagA‐positive Hp‐I .…”

Gray matter volume and estimated brain age gap are not associated with sleep-disordered breathing in subjects from the ADNI cohort

“…Historically, there has been an inability to replicate results among the brain imaging studies of SDB in non-demented populations. While several studies have reported gray matter atrophy in the insula, amygdala, middle and lateral temporal regions, and cerebellum in non-demented populations with SDB 13–16,46–48 , others have either shown no associations 17,49 or paradoxical enhancement in the gray matter volume of regions like the motor cortices, prefrontal cortex, thalamus, putamen, and the hippocampus 20–24,47 . In addition, there is a general lack of longitudinal studies, which would enable the study of non-linear associations between SDB and cortical atrophy as suggested by these cross-sectional findings.…”

“…Despite numerous studies and meta-analyses focused on the changes in gray matter in middle-aged patients with OSA, there are few studies on gray matter changes in older adults with SDB and neither have found any decreases in thickness or volume in cortical gray matter 52–54 . Second, it is possible that SDB-related brain damage impacts more selectively brain function 55 or amyloid burden 17 than gray matter volume alone, or that differential diagnosis between SDB-related and age-related brain atrophy is difficult in single-point observational studies, particulary in those cases in which groups are matched by age and cognitive status. Third, this could also be a sign of: a) survival bias, as most SDB+ may have transitioned to AD and only those with very low cortical atrophy or high in cognitive reserve at disease onset would remain as HC or MCI at cross-section; or, b) selection bias due to matching by the ApoE4 allele, as it has been reported that the ApoE4 allele interacts with brain aging scores measured by the BrainAGE method, revealing potential neuronal compensation in healthy ApoE4+ adults 73 , which could also result in null findings.…”

“…This is indicative that despite the frequent clinical co-occurrence of SDB and AD, there may be no synergy between them in accelerating gray matter atrophy. Recent investigations using cerebrospinal fluid and PET imaging suggest an interplay between amyloid production/clearance and SDB 17,42,56–58 . These include an impairment in the cerebrospinal fluid-interstitial fluid exchange 60 , cerebral edema secondary to an intermittent hypoxia 61 (similar to the increase in brain volume and pseudoatrophy observed in multiple sclerosis), and compensatory excessive neuronal synaptic activity 62 in SDB, all of which could potentially lead to an increase in beta-amyloid deposition and its clearance reduction.…”

“…Morphometric analysis of the structural magnetic resonance images (MRI) has shown to reliably reveal this effect 12 . While some studies have shown gray matter atrophy in brain regions like the hippocampus, a key region involved in AD, to be associated with SDB in non-demented subjects 13–16 , others have shown either null results 17 or paradoxical hypertrophy or thickening of gray matter in SDB 18–24 . Discrepancy between these findings is attributed to variations in cognitive status of participants, definitions of SDB severity, and method of gray matter volume assessment 14–16,18–24 .…”