Human Unique Genes may Protect From Dementia

Many human gene variants have evolved specifically to protect older adults against neurodegenerative and cardiovascular diseases, thus preserving their contributions to society, report University of California, San Diego School of Medicine researchers in the November 30 issue of Proceedings of the National Academy of Sciences.

"We unexpectedly discovered that humans have evolved gene variants that can help protect the elderly from dementia," said Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine, adjunct professor at the Salk Institute for Biological Studies and co-director of the UC San Diego/Salk Center for Academic Research and Training in Anthropogeny (CARTA). "Such genes likely evolved to preserve valuable and wise grandmothers and other elders, as well as to delay or prevent the emergence of dependent individuals who could divert resources and effort away from the care of the young." Varki led the study, along with Pascal Gagneux, PhD, associate professor of pathology and associate director of CARTA.

The standard model of natural selection predicts that once the age of reproduction ends, individuals die. That's because selection early in life strongly favors variants that benefit reproductive success, even at the cost of negative consequences late in life -- one major reason we age. This is indeed the case in almost all vertebrates. Humans (and certain whales) are an exception to this rule, living decades beyond reproductive age. Such elders contribute to the fitness of younger individuals by caring for grandchildren and also by passing down important cultural knowledge. Age-related cognitive decline compromises these benefits, and eventually burdens the group with the need to care for dependent older members.

In this first-of-its kind discovery, Varki, Gagneux and their teams initially focused on the gene that encodes the CD33 protein. CD33 is a receptor that projects from the surface of immune cells, where it keeps immune reactions in check, preventing "self" attack and curtailing unwanted inflammation. Previous studies suggested that a certain form of CD33 suppresses amyloid beta peptide accumulation in the brain. Amyloid beta accumulation is thought to contribute to late-onset Alzheimer's disease, a post-reproductive condition that uniquely affects humans and is aggravated by inflammation and cerebral vascular disease.

The researchers compared CD33 regulation in humans and our closest living relatives, chimpanzees. They found that levels of the CD33 variant that protects against Alzheimer's are four-fold higher in humans than chimpanzees.

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Bad for Astronauts: Extended Exposure to Cosmic Rays may Cause Dementia

What happens to an astronaut's brain during a mission to Mars? Nothing good. It's besieged by destructive particles that can forever impair cognition, according to a UC Irvine radiation oncology study appearing in the May 1 edition of Science Advances.

Charles Limoli and colleagues found that exposure to highly energetic charged particles - much like those found in the galactic cosmic rays that bombard astronauts during extended spaceflights - cause significant damage to the central nervous system, resulting in cognitive impairments.

"This is not positive news for astronauts deployed on a two- to three-year round trip to Mars," said Limoli, a professor of radiation oncology in UCI's School of Medicine. "Performance decrements, memory deficits, and loss of awareness and focus during spaceflight may affect mission-critical activities, and exposure to these particles may have long-term adverse consequences to cognition throughout life."

For the study, rodents were subjected to charged particle irradiation (fully ionized oxygen and titanium) at the NASA Space Radiation Laboratory at the Brookhaven National Laboratory before being sent back to Limoli's Irvine lab.

The researchers found that exposure to these particles resulted in brain inflammation, which disrupted the transmission of signals among neurons. Imaging revealed how the brain's communication network was impaired through reductions in the structure of nerve cells called dendrites and spines. Additional synaptic alterations in combination with the structural changes interfered with the capability of nerve cells to efficiently transmit electrochemical signals. Furthermore, these differences were parallel to decreased performance on behavioral tasks designed to test learning and memory.

Similar types of more severe cognitive dysfunction are common in brain cancer patients who have received various photon-based radiation treatments at much higher doses. In other research, Limoli studies the impact of chemotherapy and cranial irradiation on cognition.

While cognitive deficits in astronauts would take months to manifest, Limoli said, the time required for a mission to Mars is sufficient for such deficits to develop. People working for extended periods on the International Space Station do not face the same level of bombardment with galactic cosmic rays, as they are still within the protective magnetosphere of the Earth.

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Now there is a nice natural control study: examine communities at high altitude.  Is 'cognitive impairment' at old age more prevalent than those who have lived their lives at sea level? Make sure you eliminate those who fly frequently from either study.  We know high altitude communities have a higher rate of brain cancer.  How about dementia and whatnot?  If not, perhaps this ought to be reconsidered.

Dementia, Other Geriatric Diseases to Present Health Care Crisis for China

In little more than half a century the average Chinese life span has almost doubled. Life expectancy in China is now 76 years, nearly on par with the U.S.’s 79 years. Yet this tremendous boon comes with a dark side: an aging population.

China’s one-child policy throttled population growth so successfully that the proportion of elderly Chinese is now soaring. A 2011 report from the Chinese Academy of Social Sciences predicts that the percentage of the population that is 65 or older will triple between 2000 and 2050. With an aging population comes a greater burden of diseases, chief among them neurodegeneration. Already China has more than nine million people with some form of dementia and more cases of Alzheimer’s disease than any other country, according to a 2013 paper in The Lancet. Its authors dubbed dementia “the single largest challenge to health and social care systems” in China.

The consequences of this trend are profound, and the country has only recently begun to prepare for them. In 2009 the government committed $124 billion to overhauling health care, with a goal of providing basic health insurance for 90 percent of its citizens. The plan also highlighted mental health services as a top priority for the first time. Last year China implemented its first mental health law, which expands psychiatric services throughout the country. Although the policy does not explicitly mention dementia, it underscores the urgent need for community mental health clinics, which could end up aiding families struggling to cope with a relative’s dementia.

To find out more about the implications of China’s demographic shift and the steps the country can take to buffer itself, Scientific American spoke with Michael Phillips, a psychiatrist who has lived in China for 30 years, during the annual meeting of the American Psychiatric Association last week. Phillips has dual appointments at Shanghai Jiao Tong University School of Medicine and the Collaborative Center for Global Mental Health at Emory University.

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