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Cracking the Code of Longevity and Decreasing Dementia

For those lucky few who make it to the century mark, a crucial gene variation relating to HDL cholesterol levels may play an important part in their longevity. Researchers now believe that this gene variation could also protect against age-related memory loss and senility — keeping seniors sharp well into their 80s and 90s. The findings reported in this week’s issue of the journal Neurology say future drugs may eventually help to provide others with this protection.

"We looked for reasons of longevity among the study group," said study author Dr. Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine. "We realized that maybe it’s genetic because their habits varied widely."
The study looked at 158 people of Ashkenazi, or Eastern European Jewish descent, who were 95 years old or older.

Barzilai and his fellow researchers found that a quarter of those who lived to an average age of 100 had a certain genetic variation that increased the size of "good" HDL cholesterol particles in their blood. This variation was present in only about one out of 12 subjects who were 30 years younger, suggesting that having the gene was associated with a better chance of a longer life.

"The idea that treating the standard cardiovascular risk factors (high cholesterol, low HDL, high blood pressure, diabetes) could forestall cognitive decline is provocative," said Dr. Dan Rader, director of preventive cardiology at the University of Pennsylvania School of Medicine. "Specifically, if HDL is really protective against dementia, it strongly supports the idea of developing treatments targeted toward HDL."

Researchers also found those who had the gene variant were twice as likely to score well on a brain function test as those without it. Similar results were found in a group of 124 Ashkenazi Jews between the ages of 75 and 85.

HDL can work in a number of ways. It raises good cholesterol and increases lipoprotein particle size, which seems to prevent particle buildup in the arteries.

Usually, discussions of the interplay between "good" HDL cholesterol and "bad" LDL cholesterol are limited to heart health and the artery-hardening disease atherosclerosis. However, these new findings suggest a link between senility and high cholesterol problems.

"Many researchers in the cardiovascular field suspect that much cognitive decline and even dementia may be due to atherosclerosis of cerebral vessels, and high HDL is one of the strongest protective factors against atherosclerosis known," Rader said.

Potentially, these treatments could take the form of drugs designed to raise levels of HDL, such as one that pharmaceutical giant Pfizer was working on, known as torcetrapib.

It was developed to help those with high cholesterol, but the drug trial was halted when it was found that it resulted in a higher risk of death for those taking it. But future drugs to raise HDL without this side effects may eventually be developed to stave off senility.

"The big picture is that drugs being developed to raise HDL or improve its function in order to reduce cardiovascular disease might eventually be able to be shown to also protect against cognitive decline and dementia," Rader said.

Though therapies remain speculative, many researchers remain optimistic that the finding could lead to a greater overall understanding of the factors behind senility.

"The point is that you don’t have to get senile when you age, even if you are over 100," Messmer said. "If you don’t have atherosclerosis, you are much more likely to have your mental faculties preserved."

December 26, 2006, issue of Neurology

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