Obstructive Sleep Apnea May Increase Amyloid Burden

Alzheimer's disease illustration
Alzheimer’s disease illustration
Obstructive sleep apenea may increase the amyloid burden in cognitively normal older patients.

Obstructive sleep apnea (OSA) and intermittent hypoxia may be mechanisms associated with markers of increased amyloid burden, according to a study published in the American Journal of Respiratory and Critical Care Medicine. 

Researchers identified and observed 208 individuals (without OSA n=97, mild OSA n=76, severe OSA n=35) from a 2-year prospective longitudinal study of healthy community-dwelling older individuals. Participants were between the ages of 55 and 90 years and had normal cognition by clinical assessment. Participants underwent medical, neurologic, and psychiatric evaluations, in addition to OSA home monitoring, magnetic resonance imaging, lumbar puncture and/or Pittsburgh compound B (PiB) positron emission tomography scan, and clinical laboratory studies.

The primary goal of the study was to determine whether there was an association between OSA severity and longitudinal increase in amyloid burden in elderly people with normal cognition.

The severity of OSA indices were defined as the sum of all apneas and all hypopneas (InAHIall; F1,88=4.26, P <.05) and apnea/hypopnea index with 4% desaturation (AHI4%; F1,87=4.36, P <.05) and was associated with an annual rate of change in cerebrospinal fluid amyloid beta 42 (Aβ42) using linear regression after adjustments for age, sex, body mass index, and apolipoprotein (Apo)E4 status.

In addition, the researchers observed a correlational longitudinal change in cerebrospinal fluid Aβ42 and AHIaII/AHI4 both before and after adjusting for age, sex, body mass index and ApoE4 status (rho= –0.24, P <.05, rho= –0.23, P <.05 and rho= –0.27, P <.05, rho= –0.24, P <.05, respectively). There was also a correlational longitudinal change in both ADPiB-mask (rho=0.374, P <.05) and AHIaII or AHI4 (rho=0.302, P =.09), also after adjusting for age, sex, body mass index, and ApoE4 status. However, OSA was not associated with a cognitive decline in participants.

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One potential limitation of the study was the strong correlation between AHIaII and AHI4% (r=0.91, P <.01) found in this cohort, which made it difficult for the researchers to differentiate between the individual effects of sleep fragmentation and intermittent hypoxia. 

Investigators concluded that 53% of cognitively normal community-dwelling elderly have OSA, with the severity of OSA found to be associated with a 2-year longitudinal decrease in cerebrospinal fluid Aβ42 and an increase in the update of cortical PiB-positron emission tomography. These results suggest that amyloid deposition later in life may be caused by OSA.

Further, the study suggests that sleep fragmentation is another mechanism by which OSA can increase risk for Alzheimer disease. The greater the severity of OSA, the greater amyloid deposition in the brain. Clinicians should assess patients for OSA and provide or recommend therapies to treat OSA, such as continuous positive airway pressure or dental appliances that can assist in preventing or delaying neuronal dysfunction and cognitive impairment associated with Alzheimer disease.


Sharma RA, Varga AW, Bubu OM, et al. Obstructive sleep apnea severity affects amyloid burden in cognitively normal elderly: a longitudinal study [published online November 10, 2017]. Am J Respir Crit Care Med. doi:10.1164/rccm.201704-0704OC