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ByLauranNeergaard TheAssociatedPress WASHINGTON Nearlytwo- thirds of Americans with Alzheimer's disease are women, and now some sci- entists are questioning the long-held assumption that it's just because they tend to live longer than men. What else may put woman at extra risk? Could it be genetics? Bio- logical differences in how women age? Maybe even lifestyle factors? Finding out might af- fect treatments or preven- tive care. One worrisome hint is that research shows a no- torious Alzheimer's-re- lated gene has a bigger im- pact on women than men. "There are enough bio- logical questions pointing to increased risk in women that we need to delve into that and find out why," said Maria Carrillo, chief science officer for the Al- zheimer's Association. Last month, the associ- ation brought 15 leading scientists together to ask what's known about wom- en's risk. Later this sum- mer, Carrillo said it plans to begin funding research to address some of the gaps. "There is a lot that is not understood and not known. It's time we did something about it," she added. A recent Alzheimer's As- sociation report estimates that at age 65, women have about a 1 in 6 chance of de- veloping Alzheimer's dur- ing the rest of their lives, compared with a 1 in 11 chance for men. The tricky part is deter- mining how much of the disparity is due to wom- en's longevity or other fac- tors. "It is true that age is the greatest risk factor for de- veloping Alzheimer's dis- ease," said University of Southern California pro- fessor Roberta Diaz Brin- ton, who presented data on gender differences at a meeting of the National Institutes of Health this year. But, she said, "on av- erage, women live four or five years longer than men, and we know that Alzheimer's is a disease that starts 20 years before the diagnosis." That's how early cellular damage can quietly begin. Brinton researches if menopause can be a tip- ping point that leaves cer- tain women vulnerable. However it starts brew- ing, there's some evidence that once Alzheimer's is diagnosed, women may worsen faster; scans show more rapid shrinkage of certain brain areas. But gene research of- fers the most startling ev- idence of a sex difference. Stanford University re- searchers analyzed records of more than 8,000 people for a form of a gene named ApoE-4, long known to in- crease Alzheimer's risk. Women who carry a copy of that gene variant were about twice as likely to eventually develop Al- zheimer's as women with- out the gene, while men's risk was only slightly in- creased, Stanford's Dr. Michael Greicius reported last year. It's not clear why. It may be in how the gene inter- acts with estrogen, Brin- ton said. Amy Shives, 57, of Spo- kane, Washington, recalls when her mother began showing symptoms of Al- zheimer's. But it wasn't un- til after her own diagno- sis a few years ago that Shives looked up the gen- der statistics. "That was alarming," said Shives, who is in the early stages of Alzheim- er's, which struck at a younger-than-usual age and forced her retire- ment as a college coun- selor. "The impact on our lives and that of our fami- lies is extraordinary." She points to another disproportionate burden: About 60 percent of care- givers for Alzheimer's pa- tients are women. "My daughters are in their 20s and I'm already ill," Shives worries. "It's very stressful for them to think about when their mother's going to need their help." What drives the differ- ence in Alzheimer's cases isn't clear, said Dr. Susan Resnick of the National Institutes of Health, pointing to conflicting research. "We really have had a tough time understanding whether or not women re- ally are more affected by the disease, or it's just that they live longer," Resnick said. Data from the long-run- ning Framingham, Massa- chusetts, health study sug- gests that because more men die from heart dis- ease in middle age, those who survive past 65 may have healthier hearts that in turn provide some brain protection. Many of the same factors — obesity, high cholesterol, diabetes — that damage arteries also are Alzheimer's risks. What about hormones? That's been hard to pin down. Years ago, a major study found that estrogen therapy after 65 might in- crease risk of dementia, although later research showed hormone replace- ment around the onset of menopause wasn't a prob- lem. Brinton studies how menopause changes the brain. Estrogen helps reg- ulate the brain's metabo- lism, how it produces the energy for proper cogni- tive function, and it must switch to a less efficient backup method as estro- gen plummets, she ex- plained. "It's like the brain is a little bit diabetic," said Brinton, who is studying whether that may relate to menopausal symptoms in women who later expe- rience cognitive problems. Carrillo notes that 40 years ago, heart disease was studied mainly in men, with little under- standing of how women's heart risks can differ. "How do we make sure we're not making that mis- take when it comes to Al- zheimer's?" she asked. DISEASE What'sknownaboutwomen'srisk? Scientists look into why most Alzheimer's patients are females ASSOCIATEDPRESSPHOTOS Amy Shives, right, and her husband George walk their cavalier King Charles spaniel Chester in their neighborhood in Spokane, Wash. Amy Shives was diagnosed with early onset Alzheimer's disease in 2011and has since been involved with the Alzheimer's Association. Nearly two-thirds of Americans with Alzheimer's disease are women, and now some scientists are questioning the long-held assumption that it's just because women tend to live longer than men. Amy Shives speaks about her experience with Alzheimer's disease, which she was diagnosed with in 2011. Amy Shives, who was diagnosed with Alzheimer's disease in 2011and subsequently epilepsy, holds her Medicalert bracelet at her house in Spokane, Wash. Since her diagnosis, Shives has since been involved with the Alzheimer's Association. She also says that in her case, the epilepsy is directly attributed to Alzheimer's disease. "There are enough biological questions pointing to increased risk in women that we need to delve into that and find out why." — Roberta Diaz Brinton, University of Southern California professor By Ricardo Alonso- Zaldivar The Associated Press WASHINGTON The coun- try finally has an opportu- nity to change the subject on health care, after the Su- preme Court again upheld President Barack Obama's law. There's no shortage of pressing issues, including prescription drug prices, high insurance deductibles and long-term care. But moving on will take time, partly because many Republicans want another chance to repeal the Af- fordable Care Act if they win the White House and both chambers of Congress next year. Also, it's difficult to start new conversations when po- litical divisions are so raw, and there's a big discon- nect between what people perceive as problems and the priorities of policymak- ers, business and the health care industry. Democrats say a change in focus is long overdue. "I do think the energy has already shifted," said Neera Tanden, president of the Center for American Progress, a think tank of- ten aligned with the White House. "It would be great if the health care conversa- tion moves to where people are, not relitigating these insurance issues." Wishful thinking, say Re- publicans. "The politics of this has gotten so unpleasant that we're locked into 'repeal- and-replace' for the next year and a half," said lob- byist Tom Scully, who ran Medicare in President George W. Bush's adminis- tration. "It may not be great for America, but that's the reality." Scully says Republicans may be able to make sub- stantial changes but not re- peal Obama's law entirely. 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