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Signs of impaired memory, cognition, or mood often indicate deficient brain function and suggest loss of integrity of neural processes serving those behaviors. The diminished behavioral competence may derive from sleep deprivation or fatigue in OSA, but evidence is growing that loss of tissue or damage appears in brain areas that serve memory, planning, and emotional functions, as well as brain sites that regulate blood pressure and coordinate movement.³

Moreover, nerve fibers connecting brain areas serving affected brain sites are damaged.⁴ Some of the most dramatic injury appears in the mammillary bodies, small structures located on the underside of the brain that receive fibers from the hippocampus, a structure well known for roles in processing recent memory, as popularized in movies such as "50 First Dates."⁵ The hippocampus shows both tissue loss and damage in OSA, and the mammillary bodies are remarkably smaller.

Other injury appears in the insular and cingulate cortices, areas responsible for assisting blood pressure regulation, and mediating depressive signs, respectively, and in the cerebellum, which helps coordinate muscle activity and limit blood pressure changes.³

Other memory-deficient conditions

Mammillary body volume loss appears in other memory-deficient conditions, such as Wernicke-Korsakoff's syndrome, a syndrome found in chronic alcoholism, and beriberi, a disease resulting from B1 nutritional deficiency. Both conditions share a common nutritional deficiency, namely, reduced thiamine (vitamin B1). Gut absorption is impaired in alcoholics, and the alcohol diet provides inadequate nutrients. Beriberi initially was found with diets of polished rice, thus deficient in vitamin Bl.

Thiamine, assisted by magnesium, is essential to move glucose into cells. Brain cells, when excessively excited by low oxygen during apnea, can die from insufficient fuel, a process called "excitotoxicity." Thiamine supplementation can reverse memory deficiencies in Wernicke-Korsakoff's syndrome if intervention is sufficiently rapid.⁶

Patients with OSA typically do not present as being malnourished; thus, the obvious question is: How could they be thiamine or magnesium deficient? We do not know the answer to that question at this moment, but clues abound.

More than 75 percent of diabetics are both thiamine and magnesium deficient, and a very high proportion of obese diabetics (86 percent) show OSA. Thiamine is water soluble, and both diabetics and OSA patients have very high fluid turnover. Diabetics lose water through excessive urination, and OSA patients profusely sweat at night. Although the evidence is not complete to state that a thiamine deficiency occurs in OSA patients, the co-morbid conditions of diabetes and sweating characteristics provide a basis for such deficiencies, removing the neuroprotection provided by thiamine and magnesium.

Fortunately, the solutions for such nutrient deficiencies, vitamin B and magnesium supplements, are inexpensive and readily available. Physicians who manage OSA should consider the possibility that high fluid loss in the syndrome may be creating vital nutrient deficiencies.

References

1. Cross RL, Kumar R, Macey PM, Doering LV, Alger JR, Yan-Go FL, Harper RM. Neural alterations and depressive symptoms in obstructive sleep apnea patients. Sleep. 2008. 31:1103-9.

2. Kumar R, Macey PM, Cross RL, Woo MA, Yan-Go FL, Harper RM. Neural alterations associated with anxiety in obstructive sleep apnea syndrome. Depression and Anxiety. 2009. 26:480-91.

3. Macey PM, Henderson LA, Macey KE, Alger JR, Frysinger RC, Woo MA, Harper RK, Yan-Go FL, and Harper RM. Brain morphology associated with obstructive sleep apnea.  Am J Resp Crit Care Med. 2002. 166:1382-87.

4. Macey PM, Kumar R, Woo MA, Valladares EM, Yan-Go FL, and Harper RM. Brain structural changes in obstructive sleep apnea. 2008. Sleep. 31(7):967-77.

5. Kumar R, Birrer BVX, Macey PM, Woo MA, Gupta RK, Yan-Go FL, Harper RM. Reduced mammillary body volume in patients with obstructive sleep apnea. 2008. Neurosci Lett. 438:330-34.

6. Harper C. Thiamine (vitamin B1) deficiency and associated brain damage is still common throughout the world and prevention is simple and safe. Eur J Neurol. 2006. 13:1078-82.

Dr. Ronald M. Harper, PhD, is a distinguished professor in the department of neurobiology and the Brain Research Institute, David Geffen School of Medicine at the University of California at Los Angeles. He is a past president of the Sleep Research Society, and currently examines brain mechanisms controlling breathing and cardiovascular regulation in patients with sleep-disordered breathing, infants at risk for the Sudden Infant Death Syndrome, and Congenital Central Hypoventilation Syndrome. His research is supported by the NIH Heart and Lung Institute, (HL-60296), and by the National Institute of Child Health and Human Development (HD-22695).