SLEEP: Research has long connected sleep apnea and Alzheimer’s. A key study looking at Alzheimer’s and sleep-disordered breathing (SDB) is opening up new “chicken-or-egg” questions: Which comes first? Just who is causing what?
An important study looking at sleep-disordered breathing (SDB) and markers for
Alzheimer’s disease (AD) risk in cerebrospinal fluid (CSF) and neuroimaging adds to the growing body
of research linking the two.
Increased SDB in Elderly?
But this latest study also poses an interesting question: Could AD in its “preclinical stages” also lead to
SDB and explain the increased prevalence of SDB in the elderly?
“It’s really a chicken and egg story,” said Ricardo S. Osorio, MD, a research assistant professor at NYU
School of Medicine who led the study. “Our study did not determine the direction of the causality, and, in
fact, didn’t uncover a significant association between the two, until we broke out the data on lean and
When the researchers did consider body mass, they found that lean patients (defined as having a body
mass index <25) with SDB did possess several specific and non-specific biomarkers of AD risk
(increased P-Tau and T-Tau in CSF, hippocampal atrophy using structural MRI, and glucose
hypometabolism using FDG-PET in several AD-vulnerable regions). Among obese patients (BMI >25),
glucose hypometabolism was also found in the medial temporal lobe, but was not significant in other AD-vulnerable
10% to 20% Have SDB
“We know that about 10 to 20 percent of middle-aged adults in the United States have SDB [defined as an
apnea-hypopnea index greater than 5] and that the number jumps dramatically in those over the age of
65,” said Dr. Osorio, noting that studies put the percentage of people over the age of 65 with SDB
between 30 and 60 percent. “We don’t know why it becomes so prevalent, but one factor may be that
some of these patients are in the earliest preclinical stages of AD.”
According to Dr. Osorio, the biochemical harbingers of AD are present 15 to 20 years before any of its
currently recognized symptoms become apparent.
The NYU study enrolled 68 cognitively normal elderly patients (mean age 71.4±5.6, range 64-87) who
underwent two nights of home monitoring for SDB and were tested for at least one diagnostic indicator of
AD. The researchers looked at P-Tau, T-Tau and Aβ42 in CSF, FDG-PET (to measure glucose
metabolism), Pittsburgh compound B (PiB) PET to measure amyloid load, and/or structural MRI to
measure hippocampal volume. Reduced glucose metabolism in AD-vulnerable regions, decreased
hippocampal volume, changes in P-Tau, T-Tau and Aβ42, and increased binding of PiB-PET are
recognized as markers of risk for AD and have been reported to be abnormal in healthy subjects before
the disease onset.
Biomarkers for AD risk were found only among lean study participants with SDB. These patients
showed a linear association between the severity of SDB and CSF levels of the biomarker P-Tau (F =
5.83, t=2.41, β=0.47; p< 0.05) and between SDB and glucose hypometabolism using FDG-PET, in the
medial temporal lobe (F=6.34, t=-2.52, β=-0.57,p<0.05), the posterior cingulate cortex/precuneus
(F=11.62, t=-3.41, β=-0.69, p<0.01) and a composite score of all AD-vulnerable regions (F=4.48, t=-2.11,
β=-0.51, p<0.05). Lean SDB patients also showed smaller hippocampi when compared to lean controls
(F=4.2, p<0.05), but no differences were found in measures of amyloid burden such as decreased Aβ42 in
CSF or PiB positive scans.
Dr. Osorio and his colleagues are planning to test their hypothesis that very early stage preclinical AD
brain injury that associates with these biomarkers can lead to SDB. They have proposed a two-year
longitudinal study that would enroll 200 cognitively normal subjects, include AD biomarkers and treat
those patients with moderate to severe SDB with continuous positive airway pressure, or CPAP, over
“Sleep Apnea Skyrockets in the Elderly”
The purpose of the new study would be to determine the “direction” of causality between SDB and
preclinical AD in elderly patients. After an initial assessment, the patients would be given CPAP to treat
their sleep apnea. After six months, they would be evaluated again for biomarker evidence of AD.
“If the biomarkers change, it may indicate that SDB is causing AD,” explained Dr. Osorio. “If they don’t
change, the probable conclusion is that these patients are going to develop AD with or without CPAP, and
that AD may either be causing the apneas or may simply coexist with SDB as part of aging.”
Either way, Dr. Osorio believes the relationship between SDB and AD deserves further study.
“Sleep apnea skyrockets in the elderly, and this fact hasn’t been given the attention it deserves by the
sleep world or the Alzheimer’s world,” Dr. Osorio said. “Sleep particularly suffers from an outmoded
perception that it is an inactive physiological process, when, in reality, it is a very active part of the day
for the brain.”
American Thoracic Society