Daniel M. Keller, PhD

June 25, 2013

BARCELONA, Spain — The use of continuous positive airway pressure (CPAP) correlates with improvement in white matter deficits seen in patients with obstructive sleep apnea (OSA), suggesting that the damage seen in these patients is reversible.

These changes correlate with improvements in neurocognitive functioning. The changes may take up to a year to become evident on white matter imaging, a study shows.

Using fractional anisotropy (FA) and mean diffusivity (MD) on magnetic resonance diffusion tensor imaging, 2 techniques that produce images of neural tracts and are especially good for localizing white matter lesions, researchers at the University Vita-Salute San Raffaele in Milan, Italy, studied 17 men with severe OSA (age 30 to 55 years) with a mean body mass index of 32.24 ± 4.35 kg/m2 before and after CPAP therapy.

"Our study showed significant FA and MD differences in the brain of OSA subjects before treatment," Luigi Ferini-Strambi, MD, associate professor in the Sleep Disorders Center at the University Vita-Salute San Raffaele reported here at the 23rd Meeting of the European Neurological Society (ENS). "After 12 months of treatment, increase in FA and MD demonstrating nonpermanent damage in OSA patients and improvement in the tests for short-term memory and executive functions" were seen.

Multiple Areas of Structural Damage

In previous studies, Dr. Ferini-Strambi showed that compared with controls, untreated patients with OSA had decreases in gray matter volume in the left posterior parietal cortex, the right superior frontal gyrus, and the left entorhinal cortex. There was significant negative correlation between gray matter volume and cognitive performance. The researchers found some small clusters of increase in gray matter volume after treatment compared with pretreatment values, but no region showed a significant gray matter volume increase after use of a statistical threshold corrected for multiple comparisons.

Bilateral white matter involvement has been seen in previous studies of patients with moderate to severe OSA, but no follow-up had been done after treatment. Thus, the present study was undertaken to assess white matter integrity in patients with OSA, comparing them with 15 age- and education-matched healthy male controls, and to assess any changes after CPAP therapy.

The researchers found that before CPAP therapy was initiated, patients with OSA had a significant reduction in FA in multiple brain areas and these changes correlated with performance on various neuropsychological tests. Significant FA and MD white matter abnormalities involved the corpus callosum (crucial for interhemispheric communication), the cingulum and fornix (components of the networks subserving episodic memory functions), and short and long distance association tracts (possibly responsible for the increased compensatory brain activations in working memory tasks).

After 3 months of CPAP, the structural neural injuries were unchanged. But at 1 year, increases in FA and MD showed that the structural damage was reversible. "At the same time we found a significant correlation of this FA [improvement] and neurocognitive function," Dr. Ferini-Strambi noted, including improvements in memory, attention, and executive function.

He explained that ischemic damage may occur, especially to small blood vessels, when cerebral perfusion is reduced during apneic episodes in OSA. Edema leading to cellular and axonal swelling reduces the extracellular space, thereby restricting water diffusion and reducing MD values.

Objective Assessment of Effect

Session chairman Pierre Maquet, MD, PhD, professor of neurology at the University of Liège, Belgium, who was not connected with the study, called the topic very interesting because up to now it was not known whether CPAP had any beneficial effect on brain structure and function. "It's nice to see that people are still trying to characterize these effects on an objective basis using MR [magnetic resonance] technology," he noted. And although it was good that the study included some controls, he said, having only 15 patients is still "a bit short in terms of statistical significance and power."

An important question is what the changes on diffusion tensor imaging really denote. Dr. Maquet commented to Medscape Medical News that in apneic patients "you can have differences in water diffusions just because they are submitted to hypoxia, or changes in venous return from the brain might change the water content of the brain parenchyma," so one cannot know whether the signal changes are related to changes in the conformation of fiber tracts or whether they are just related to the patients' apnea during the preceding night.

But he said that if the findings represent real white matter changes, these "connections are at least as important as the neurons, so if you have fiber tract lesions your brain isn't connected properly, and it doesn't function properly."

Because the study did not include enough patients to tell whether the changes are always reversible depending on how long the OSA existed, Dr. Maquet suggested that a multicenter study involving hundreds of patients would allow statisticians to stratify the results according to the time since OSA began; level of hypoxia; number of apneic/hypoxic episodes per night; and other variables, such as age, sex, and level of education.

Although the study suggests that changes induced by OSA may be reversible, Dr. Maquet says that from a public health standpoint, this is too late. He advises that to avoid apneas, the general population should eat healthier and get physical activity every day, which would also benefit the occurrence of diabetes and stroke.

There was no commercial funding for this study. Dr. Ferini-Strambi has received research funding from Respironics but not for any aspects of this study. Dr. Maquet has disclosed no relevant financial relationships.

23rd Meeting of the European Neurological Society (ENS). Abstract O311. Presented June 10, 2013.


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