Changes in altitude have many effects on the physiology of the human body and even metabolism. Some people exposed to high altitude develop acute or chronic mountain sickness due to hypoxia with a spectrum of symptoms including neurocognitive decline of performance and impacting brain function. Head truma at altitude is more likely to lead to brain injury or concussion than those at low altitude.

Imaging with PET/CT using FDG-18 has been used to measure brain metabolism in both human and mice subjects. This type of imaging scans the accumulation of a glucose analog in tissue, specifically the brain in this case. This allows determination of which regions have high or low uptake in metabolism in comparison to a brain at baseline at sea level.

In 2017, mice were studied by being placed in a hypobaric chamber to stimulate hypoxic conditions similar at 5000 meters. Conditions were placed to minimize brown adipose tissue uptake and imaging was performed 45 minutes after an estimated 0.5 mCi FDG injection. After appropriate processing, the results showed an increase in glucose metabolism in the cerebellum and medulla of the mice exposed to high altitude conditions compared to those at baseline. Additionally, certain cortical regions had lower metabolism than baseline mice, and lower cardiac uptake as well. It is thought that the brain’s acclimation response to high altitude.

Another study using mice as subjects compared brain metabolism at high altitude after a traumatic brain injury (TBI) to determine if hypoxia alters glucose uptake. A total of 32 mice were imaged at sea level (baseline) and again after 12 weeks exposure at 5000m (hypobaric stimulation), and again after a repetitive closed injury. An SUV (standard uptake value) was compared in each set of images to determine a change in glucose metabolism. 

This study showed a significant increase in FDG uptake in the medulla, cerebellum, and pons, and a decreased uptake in the corpus callosum, cortex, midbrain, and thalamus. A TBI affects glucose metabolism in the brain by decreasing cortical uptake in both high altitude and sea level. This study showed that high altitude affects the brain by making it more susceptible to repeated concussions than mice at sea level.

A third study employed PET/CT imaging to assess regional cerebral glucose metabolism rates in six US Marines before and after a rigorous training period from sea level to high altitude conditions ranging from 10,000-20,000 ft. It was thought that other conditions would be relatively stable as the military has similar regimens for their members. After comparing imaging performed at baseline sea level and after two months of high-altitude exposure, it was clear that brain metabolism changed. There was a decrease in glucose metabolism in three frontal regions, left occipital, and right thalamus. Right and left cerebellum showed an increase in glucose uptake and metabolism.

The data from these three studies clearly show high altitude exposure with hypoxia changes the way our brain tissue metabolism functions. Studies show Sherpas, native to the Himalayas are the most well adapted high-altitude humans.  Their brain metabolism is the same of that of “low-landers”. Conversely, the Quechuas who are native to the Andes of South America still show small amounts of hypometabolism in their brain. As mentioned previously, it is unknown how long it takes for humans to fully acclimate regarding brain metabolism.

These studies indicate the need for more research regarding brain metabolism and function.  Glucose metabolism is crucial for proper functioning of the brain, its neurons, and other regulatory functions. This brings into question what type of impact high altitude may have on the cognitive functions of the brain in people who move or even live at high altitude. Additionally, the fact that the human brain is more prone to injury or developing a concussion, safety should be a consideration for those involved in high impact sports at high altitude.

References

1.      Jaiswal S, Cramer N, Scott J, Meyer C, Xu X, Whiting K, Hoy A, Galdzicki Z, Dardzinski B.  [¹⁸F] FDG PET to study the effect of simulated high altitude on regional brain activity in mice. Journal of Nuclear Medicine May 2017, 58 (supplement 1) 1246.  https://jnm.snmjournals.org/content/58/supplement_1/1246

2.      Jaiswal S, Knutsen A, Pan H, Cramer N, Xu X, Dardzinski B, Galdzicki Z, Allison N, Haight T. FDG PET study showing the effect of high altitude and traumatic brain injury on regional glucose uptake in mice.  Journal of Nuclear Medicine May 2019, 60 (supplement 1) 180. https://jnm.snmjournals.org/content/60/supplement_1/180

3.      Hochachka PW, Clark CM, Matheson GO, et al. Effects on regional brain metabolism of high-altitude hypoxia: a study of six US marines. Am J Physiol. 1999;277(1):R314-R319. doi:10.1152/ajpregu.1999.277.1.R314.  https://pubmed.ncbi.nlm.nih.gov/10409288/

Roberta Grabocka is a second-year physician assistant student at Red Rocks Community College’s PA Program in Arvada, Colorado. Roberta attended Stony Brook University in Long Island, NY for her degree in Health Science and received a post-baccalaureate degree in Nuclear Medicine Technology. She practiced for 3 years as a Nuclear Medicine Technologist in multiple hospitals. This included working in oncological, cardiac, and general nuclear settings performing a variety of studies from PET/CTs, myocardial perfusion imaging, HIDAs, V/Qs, etc. Roberta decided to pursue a career as a Physician Assistant to expand her scope of practice and further her medical knowledge. In her free time, she likes to explore local culture and travel.