Treatment Reverses Brain Changes in Patients With Obstructive Sleep Apnea

Jim Kling

June 17, 2010

June 17, 2010 (San Antonio, Texas) — In patients with obstructive sleep apnea (OSA), changes in white matter and gray matter appear to be reversed after treatment with continuous positive airway pressure (CPAP).

"Adherence to treatment not only improves quality of life and decreases cardiovascular risk [but] also [reverses] changes in these areas of the brain," Vincenza Castranova, PhD, a clinical psychologist from the Sleep Disorders Center at the University Vita-Salute San Raffaele, in Milan, Italy, who presented the research, told Medscape Neurology. "This should motivate even more subjects to undergo therapy."

Their conclusions were presented in 2 studies here at SLEEP 2010: Associated Professional Sleep Societies 24th Annual Meeting.

The studies were supported by Respironics Foundation in Pittsburgh, Pennsylvania.

Neurocognitive Impairment

OSA causes sleep fragmentation and intermittent hypoxemia and has been linked to neurocognitive impairment, the authors write. These symptoms have not been strongly linked to specific brain structure abnormalities.

The first study used diffusion tensor imaging to investigate the integrity and organization of white matter, including diffusion anisotropy maps that reveal degeneration or vascular changes. Previous research has shown abnormal fractional anisotropy in patients with moderate to severe OSA.

The researchers enrolled 15 untreated male patients (mean age, 43.7 years) with severe OSA, defined as an apnea-hypopnea index of 30 or more. They were matched with 15 normal control patients for age, verbal IQ, education, sex, and hypertension.

Magnetic resonance imaging was performed before treatment and after 12 months of CPAP therapy. Diffusion tensor imaging data were collecting using a 3 Tesla scanner (Philips Achieva), and images were spatially normalized to a standard brain template. The researchers then performed voxel-by-voxel statistical analysis using SPM5 software, employing a threshold of significance of P < .001 and a minimum extension of 10 voxels for the significant clusters.

Baseline data revealed extensive alterations in white matter in patients with OSA compared with controls, as has been reported previously, they note.

"Patients after 12-months CPAP treatment showed a decrease in fractional anisotropy localized in the superior longitudinal fasciculus, bilaterally, in the fornix, in the fibers of corpus callosum close to the anterior frontal and prefrontal cingulated cortex," the researchers write in the abstract.

The extent of the lesions decreased with time. Mean diffusivity maps revealed a difference in the left uncinate between patients with OSA and control patients, which disappeared after 12 months of CPAP treatment.

Gray Matter Volume

In the second study, conducted by the same group, the researchers used voxel-based-morphometry to examine gray matter volume increases and other changes in brain morphology, again in patients with severe OSA.

The study included 17 patients who were analyzed before treatment (BL), when they were compared with 15 control patients at 3 months (compared with BL) and at 1 year (compared with BL). The researchers used SPM5 for statistical analysis.

Reductions of gray matter volume were seen at BL in the left hippocampus (enthorinal cortex), posterior parietal cortex, and right superior frontal gyrus. At 3 months, the researchers observed volume increase in hippocampal and frontal structures.

At 1 year, there was no significant increase in gray matter volume compared with the 3-month period using a statistical threshold corrected for multiple comparisons (at the voxel level or at the cluster level).

"Overall, our results show significant gray-matter volume expansions after 3 months CPAP treatment without further improvement after 1 year," the authors conclude. "This study offers hope to patients and physicians that adherence to CPAP therapy can lead not only to clinical, but also to brain-structural recovery."

Tracking Progress

The reasons for the brain changes seen in those with OSA, "are not clear at all, but it shows the plasticity of the brain and how much can perhaps be changed with treatment," said Sheldon Kapen, MD, associate professor of neurology and chief of neurology at the John D. Dingell VA Medical Center, Wayne State University, Detroit, Michigan, who moderated the session.

The study also suggests that brain imaging could track the progress of treatment. "The improvements in gray matter...correlate with some of the neuropsychological tests," Dr. Kapen told Medscape Neurology. "That could be an important tool."

The studies were supported by the Respironics Foundation. Dr. Castranova is a consultant for Respironics, which manufactures CPAP machines. Dr. Kapen has disclosed no relevant financial relationships.

SLEEP 2010: Associated Professional Sleep Societies 24th Annual Meeting: Abstract 0328, 0329. Presented June 7, 2010.

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