Elderly people with obstructive sleep apnea may be at greater risk of developing Alzheimer’s disease, new research suggests.
In the study, researchers found that biomarkers for amyloid beta, the plaque-building peptides associated with Alzheimer’s disease, increase over time in elderly adults with obstructive sleep apnea (OSA) in proportion to OSA severity. Therefore, those with more apneas per hour had greater accumulation of brain amyloid over time.
“Several studies have suggested that sleep disturbances might contribute to amyloid deposits and accelerate cognitive decline in those at risk for AD. However, so far it has been challenging to verify causality for these associations because OSA and AD share risk factors and commonly coexist,"
said senior study author Ricardo S. Osorio, MD, assistant professor of psychiatry at New York University School of Medicine.
Obstructive Sleep Apnea Severity
The study investigated the associations between OSA severity and changes in Alzheimer’s disease (AD) biomarkers longitudinally, in particular whether amyloid deposits increase over time in healthy elderly participants with OSA.
The authors note that AD is a neurodegenerative disorder afflicting approximately five million older Americans. OSA is even more common, afflicting from 30 to 80 percent of the elderly, depending on how OSA is defined.
This study involved 208 participants, age 55 to 90, with normal cognition as measured by standardized tests and clinical evaluations. None of the participants was referred by a sleep center, used continuous positive airway pressure (CPAP) to treat sleep apnea, was depressed, or had a medical condition that might affect their brain function.
The researchers performed lumbar punctures (LPs) to obtain participants' cerebrospinal fluid (CSF) soluble amyloid beta levels, and then used positron emission tomography, or PET, to measure amyloid beta (Aβ) deposits directly in the brain in a subset of participants.
Amyloid Level Correlation
The results showed that over half the participants had obstructive sleep apnea, including 36.5 percent with mild OSA and 16.8 percent with moderate to severe OSA. From the total study sample, 104 participated in a two-year longitudinal study that found a correlation between OSA severity and a decrease in CSF Aβ levels over time.
The authors say this finding is compatible with an increase in amyloid deposits in the brain; the finding was confirmed in the subset of participants who underwent amyloid PET, which showed an increase in amyloid burden in those with OSA.
The study unexpectedly did not find that OSA severity predicted cognitive deterioration in these healthy elderly adults.
Andrew Varga, MD, PhD, study coauthor and a physician specializing in sleep medicine and neurology at the Icahn School of Medicine at Mount Sinai in New York, said this finding suggests that these changes were occurring in the preclinical stages of Alzheimer’s.
This study finding may also be attributable to the study’s relatively short duration, highly educated participants and use of tests that fail to discern changes in cognitive abilities that are subtle or sleep-dependent, the authors wrote.
The high prevalence of OSA the study found in these cognitively normal elderly participants and the link between OSA and amyloid burden in these very early stages of AD pathology, the researchers believe, suggest the CPAP, dental appliances, positional therapy and other treatments for sleep apnea could delay cognitive impairment and dementia in many older adults.
Ram A Sharma, Andrew W Varga, Omonigho M Bubu, Elizabeth Pirraglia, Korey Kam, Ankit Parekh, Margaret Wohlleber, Margo D Miller, Andreia Andrade, Clifton Lewis, Samuel Tweardy, Maja Buj, Po L Yau, Reem Sadda, Lisa Mosconi, Yi Li, Tracy Butler, Lidia Glodzik, Els Fieremans, James S Babb, Kaj Blennow, Henrik Zetterberg, Shou E Lu, Sandra G Badia, Sergio Romero, Ivana Rosenzweig, Nadia Gosselin, Girardin Jean-Louis, David M Rapoport, Mony J de Leon, Indu Ayappa, Ricardo S Osorio Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly: A Longitudinal Study American Journal of Respiratory and Critical Care Medicine, 2017; DOI: 10.1164/rccm.201704-0704OC