Expert Commentary: Steven Park, M.D. 3/9/2010

Posted by Admin on March 9, 2010
We know a lot about the molecular and biochemical processes that occur with Alzheimer's Disease. Autopsy studies show amyloid plaque deposition and neurofibrilary tangles. About 5% are hereditary, and the rest are spontaneous. There are different types of dementia, of which vascular dementia is the largest component. We also know that patients with atherosclerotic risk factors and history of stroke have the highest risk for AD.

We already know that patients with obstructive sleep apnea have increased markers of inflammation throughout the body. CRP, IL-2, and IL-6 are elevated, amongst others. Their blood is also thicker in general, and more prone to staisis and clotting. A recent study revealed that untreated sleep apnea patients have significantly diminished levels of brainstem reflexes, as measured by sound waves that are picked up using brain electrical signals. These patients were found to have thicker blood, which when diluted, their reflexes improved. Placing these patients on CPAP also improved their brainstem reflexes.

Various imaging studies show areas of brain injury and permanent damage. Lacunar infarcts are small areas of dead brain tissues scattered throughout the brain, typically seen on CT studies. Obstructive sleep apnea patients were found to have a significant higher number of these lesions as compared with normals. In another imaging study using a specialized MRI technique (DTI, or diffusion tensor imaging), untreated sleep apnea patients had multiple scattered areas of damaged brain tissue.

Mice that were subjected to repeated bouts of hypoxia (similar to that seen in obstructive sleep apnea) were sacrificed and their brain tissues examined. What they saw were very similar to what's seen in humans: neuritic plaques. They found that hypoxia increases an enzyme (beta-secretase) that cleaves the beta-amyloid precursor protein, which leads to deposition of the beta-amyloid plaques that is commonly seen with Alzheimer's patients. The authors conclude that impaired cerebral perfusion (such as what occurs with stroke) may be a major cause of sporadic Alzheimer's disease. Interestingly, other studies have shown that 65 to 80% of stroke patients have undiagnosed obstructive sleep apnea.

There are numerous studies that strongly link heart disease, heart attack and stroke to untreated obstructive sleep apnea. Your chances of suffering from a stroke or heart attack is 3-5 times higher if you have significant obstructive sleep apnea. A recent study showed that your risk of dying from any cause is 57%  greater than normals if you have untreated severe obstructive sleep apnea. Another way of looking at this number is that you'll die about 20 years prematurely. Alzheimer's is strongly linked to heart disease and cardiovascular disease. Not too surprisingly, 70-90% of Alzheimer's patients are found to have obstructive sleep apnea.

Recently, when researchers took patients with Alzheimer's and obstructive sleep apnea and treated their sleep apnea with CPAP, these patients had significantly less cognitive decline. Numerous other studies have found similar findings. It's common convention to believe that Alzheimer's causes a deterioration in brain functioning that leads to neurologic problems that eventually leads to sleep apnea, or it may be just coincidence. Since most neurologists believe that obstructive sleep apnea (and especially central sleep apnea) is a neurologic problem, this is an easy conclusion to make. In the above study, patients were enrolled to be treated for their sleep apnea with CPAP only if they already had Alzheimer's. It would make an interesting study if researchers screened patients with mild cognitive impairment (the earliest stage of dementia of which 12% progress to Alzheimer's every year), and treated patients with obstructive sleep apnea. Comparing treated patients vs. nontreated or noncompliant patients would potentially show a slower rate of progression to Alzheimer's in the treated group.

Obstructive sleep apnea is not something that occurs suddenly when you're middle aged.  This condition is due to narrowed anatomy and begins during early childhood years and progresses at various rates. Small areas of blood clots and brain injury can be dealt with when younger, but when these injuries in the brain accumulate, at a certain point, you'll begin to lose your memory, or suffer from various neurological problems. Something to remember when those you love can't remember.

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