Brain Size and Alzheimer’s

"These twelve people — even though they were in their nineties — were able to function, live independently… do their day-to-day functions without any assistance," says Erten-Lyons. When she compared these twelve people to people who did have Alzheimer's Disease and the associated brain lesions, she found a surprise.

"The group that died with sharp minds had larger brains" compared to the Alzheimer's Disease group, she says.

Years of research have established the link between plaques, tangles, and Alzheimer's Disease. Plaques are proteins that build up around brain cells, while tangles are proteins that cluster inside of brain cells. Both cause stress to brain tissue, and lead to the destruction of brain cells. Erten-Lyons says her group is looking to see if the protected group has any differences in genes or proteins that might explain why their brains are bigger and why they don't show the characteristic dementia associated with Alzheimer's Disease.

Although the total brain volume of the special group was larger than normal, the hippocampus brain regions in particular had extra bulk. That's significant, says Erten-Lyons, because these regions are important for memory storage and memory formation. "We know that the changes in Alzheimer's Disease actually start in the hippocampi. The accumulation of these tangles usually starts in the hippocampi before they move to other parts of the brain," she says.

So, could big brain at birth protect you from dementia later on? Erten-Lyons says maybe, maybe not. "There may be two reasons why the brain volume and hippocampi volume may be larger in these individuals. One is that they were just born with bigger brains and that they actually need more plaques and tangles before they reach a threshold where they actually show symptoms," she says, adding that her group favors a different theory. Based on estimations of their subjects' maximum brain size, Erten-Lyons says that more likely, the sharp seniors are protected from brain shrinkage over their lifetime. The maximum brain size data, she explains, "may suggest that they really were not necessarily born with bigger brains, but they're more resistant to losing brain instead."

That protection from losing brain cells is where Erten-Lyons says the hope for treatments lies. "If we understand the mechanism that leads to this resistance — this brain damage resulting from plaques and tangles — that will eventually lead us to new prevention and therapeutic targets as well," she says.

The researchers hope finding the genes or behaviors that affect brain size during life will lead to new treatments for Alzheimer's Disease, and that participation in research is essential for progress. "It will be only through public participation in research activities like ours that I think we'll eventually come up with prevention and therapy strategies," she says.

Erten-Lyons collaborated on this research with Randal Woltjer, Hiroko Dodge, Randal Nixon, Remi Vorobik, James F. Calvert, Marjorie Leahy, Thomas Montine, and Jeffrey Kaye. She presented her findings at the annual meeting of the American Academy of Neurology on April 15, 2008.

The research was funded by the Department of Veterans Affairs, the National Institute on Aging, and the National Institutes of Health.