A third of the brain's volume is composed of blood vessels. Maintaining a healthy blood flow to those blood vessels is critical to keeping the brain young. Here are six ways you can keep your mind sharp: 
Research has shown exercise improves brain health, and it's never too early or too late to begin. Even moderate exercise has been shown to increase memory, mental processing speed and the size of the hippocampus, the part of the brain responsible for forming new memories, even in previously sedentary adults. Simply walking three times a week has been shown to produce significant gains in memory and mental processing speed. 
Neurologists agree a diet rich in vegetables, fruits, whole grains and legumes will help keep the brain healthy. They also advocate eating fish, walnuts, flax seed or other sources of omega-3 fatty acids. Curcumin, found in the spice curry, may also be protective against Alzheimer's. Conversely, a high-fat diet and obesity raise the risk for dementia. So do high cholesterol, diabetes and high blood pressure if left untreated. 
Research has shown high levels of the amino acid homocysteine is associated with a poor memory and doubles the risk of Alzheimer's. Vitamin B12 and folic acid lowers the level of homocysteine, which is also associated with heart disease and strokes. Green, leafy vegetables and fruits contain folic acid; meat, fish, yogurt and fortified cereals contain vitamin B12. 
Lowering the amount of stress in your life lowers the risk for dementia. A glass of wine (or other moderate alcohol consumption), laughter and meditation are all considered beneficial. A Harvard Medical School study showed 30 minutes of meditation a day for eight weeks even increased the size of the hippocampus. Studies at Loma Linda University have shown laughter reduces the stress hormone cortisol, which is toxic to the hippocampus. 
Maintaining an active social life provides mental stimulation and lowers stress. It also lowers the risk for dementia and Alzheimer's disease. The more social activities, the better, and people who choose mentally challenging leisure pursuits such as playing cards with friends or joining a community organization do better in general than those whose activities are primarily physical or social. Living alone or avoiding social ties raises the risk of dementia. 
More formal education is associated with lower rates of dementia and Alzheimer's, but "use it or lose it" applies at any age -- and more with the brain than the muscles, neurologists say. To keep the brain sharp, experts recommend learning new and fun mental activities. Crossword puzzles or sudoku, once mastered after a month or so, may not stimulate the brain the way learning a new language, picking up a musical instrument or joining a book club might. - APOE-4 is a genetic variant linked to up to 25% of Alzheimer's cases
- Signs of Alzheimer's can be seen in brain imaging and cerebrospinal fluid tests
- Ethical questions surround informing people of their biomarker status
- There is no cure for Alzheimer's disease
(CNN) -- Anne Kolesar thought she had packed well for her biking trip last month in Pennsylvania's "Grand Canyon," with clothes for cold weather and snacks. But after driving about a hundred miles, she looked through her rearview mirror and realized: Oops, no bike!
Kolesar, 61, laughs heartily as she tells this story. But hovering over the incident is her knowledge that she has an elevated genetic risk of Alzheimer's disease.
"I do feel like there's this sword, sort of hanging over my head, that might drop, and I don't know when," said Kolesar, who splits her time between Pittsburgh and Indiana, Pennsylvania. " And I'm not sure how you know."
It's not just that she watched her father's mental faculties deteriorate over the past 20 years or that her aunt and grandmother also succumbed to the disease. Kolesar participated in a clinical trial that revealed to her that she has one copy of the APOE-4 genetic variant. This gene has been linked to up to 25% of Alzheimer's cases, according to the Alzheimer's Association.
Screening for forms of APOE isn't part of routine medical practice. But Kolesar was curious about her risk, so she volunteered to participate in a research study that tested participants for APOE variants.
Alzheimer's disease has no cure or effective long-term treatment. Many drug trials have failed to show lasting delays or reversals of symptoms in people who already have dementia.
That's why scientists are exploring what signatures Alzheimer's disease might create in the body before symptoms ever begin. Besides genes such as APOE-4, they are looking at proteins associated with plaques and tangles in the brain.
The hope is that understanding both risk factors and the timing of the development of disease pathologies will lead to successful treatments in people who haven't begun to show any impairments in memory or thinking.
The 10 warning signs of Alzheimer's
But to set up human experiments aimed at prevention, researchers need to identify a whole new category of patient: Those in the "preclinical" stage of Alzheimer's. By performing brain scans and testing cerebrospinal fluid, scientists can single out individuals likely to show symptoms of Alzheimer's within up to 15 years. That's not about genetics per se; it's about the appearance of biomarkers before symptoms begin.
An important ethical question is emerging: Should people without symptoms be told that they are, indeed, "preclinical"? Is it useful or meaningful to know that you could be 15 years away from the inevitable?
"Medically and socially, we have to get ready for this era of using biomarkers and imaging for early detection," said Rudy Tanzi, a professor of neurology at Harvard Medical School and leading Alzheimer's researcher.
Gene hunter by day, organist by night
Better not to know?
An ongoing study at Washington University School of Medicine in St. Louis does not inform participants of the genetic or biomarker risk profile for Alzheimer's disease. The Washington University Adult Children Study aims to study these risks, but researchers don't think participants' individual results are appropriate to give them because even the researchers entirely aren't sure what they mean.
"This is a hot topic of discussion amongst the participants and the investigators" at an annual breakfast meeting with participants, said Dr. David Holtzman, a neurologist at the medical school. "We've been doing a study the last year to try to determine the best way to proceed. Should we make (the biomarker results) available to them or not?"
Currently, the answer is no.
All of the study volunteers begin the study cognitively normal, between 45 and 74. Participants are enrolled according to two criteria: Those who have at least one biological parent with an Alzheimer's diagnosis before 80, and those who had two parents who lived to at least 70 without developing Alzheimer's.
Researchers are presenting the latest findings from this study at the Society for Neuroscience conference in San Diego this weekend.
In this study, participants' cerebrospinal fluid is tested for decreases in beta-amyloid -- suggestive of plaque buildup in the brain -- and tau proteins, which are associated with neurofibrillary tangles and neuronal degeneration. They also get a genetic test for APOE status, the strongest genetic risk factor for Alzheimer's.
The idea is to follow participants over many years to monitor changes in these key biomarkers and see how they vary in relation to APOE status and future cognitive symptoms.
Consistent with their hypothesis, lead researcher Courtney Sutphen and colleagues found that people with at least one copy of APOE-4 are likely to develop biological signatures of Alzheimer's pathologies earlier in life than those who don't have any APOE-4 copies.
It's possible that some changes in the APOE-4-positive group begin even before 45, researchers said, but that would have to be tested with younger participants.
That doesn't mean that APOE-4 positivity guarantees the early formation of Alzheimer's-linked biomarkers -- beta-amyloid and tau proteins -- or that these biomarkers guarantee symptoms of Alzheimer's.
That's partly why the Adult Children Study does not disclose biomarker results to the participants, said Anne Fagan, a research professor in the department of neurology at Washington University School of Medicine.
"Perhaps even more importantly, there's also the possibility that if you tell someone they're APOE-4-negative, they think they're out of the woods," she said. "And that's not true either. Many, many people who are APOE-4-negative get the disease. So knowing one's genotype is not really clinically meaningful at this point."
In perhaps five or 10 years, though, if a drug exists to prevent the disease before the onset symptoms, that's when the biomarker information will become clinically relevant, she said. Additionally, knowing one's APOE genotype may provide information regarding the timing of the development of such pathologies.
Or should some be told now?
On the other hand, other researchers say telling study participants their results would yield some benefit. They've not advocating for widespread testing of the general population, but in the context of a study, some researchers say knowledge can be power.
Dr. Reisa Sperling, professor of neurology at Harvard Medical School, agrees that there's not enough evidence to support widespread testing of Alzheimer's biomarkers. But she's leading a drug trial that tells participants upfront about whether their PET scans show accumulation of beta-amyloid in the brain, indicative of plaques.
"To me, it makes sense to learn whether you have amyloid or not, because you have the opportunity to come into a trial to try to do something about it," she said.
The trial, sponsored by Eli Lilly,, is called the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease prevention clinical trial -- or A4 for short. This will be the first trial to test a drug designed to clear amyloid from the brain in older people who do not show symptoms of Alzheimer's, Sperling said.
The drug showed a "modest signal that it was slowing cognitive decline" in people with mild dementia in phase 3 trials, Sperling said. Recruitment for this next phase in people without symptoms starts in December; Sperling is looking for 1,000 people ages 65 to 85 to participate in a 39-month trial.
Each A4 clinical trial location has to identify and train someone to discuss amyloid results with participants before and after they receive them. If volunteers are positive for amyloid accumulation, they can move forward with trying the drug.
How will people cope?
Ultimately, what's needed for preventing Alzheimer's is the equivalent of a statin, which lowers cholesterol to prevent heart problems before they occur, says Harvard's Tanzi, who's also working on a drug trial. But in the absence of a proven prevention method, it's debatable whether anyone without symptoms should seek out biomarker testing.
"I'm not sure that we're socially ready for the power of biomarkers," he said. "But if someone wants to know, it's done right, and they can deal with the fact that there's no therapy, but they're willing to make lifestyle changes even though there are no guarantees, it could be a good thing."
Besides empowering people to sign up to take an experimental drug, knowing biomarker status might also encourage people to make healthy lifestyle choices, Tanzi said. Exercise, intellectual stimulation and a Mediterranean diet -- which emphasizes fish, fruits and vegetables -- have all been linked to improving dementia risk.
But there's no guarantee that anything will slow the progression of Alzheimer's down.
As people become aware of their Alzheimer's biomarkers, Tanzi also envisions the need for policy changes to protect the privacy of that information. There could be a "Biomarker Information Nondiscrimination Act," similar to the GINA legislation that prohibits genetic information in insurance and employment.
He also sees a need for "biomarker counselors" to advise people of what their results mean -- and how much uncertainty there is about their significance -- in addition to psychological counselors who will help people working through these issues.
"It's not going to work if we don't have enough people to counsel scientifically and psychologically," he said.
Great Grams inspires teen to hunt for Alzheimer's cure
A sword over her head
More than anything, Anne Kolesar's APOE-4 result confirmed what she already suspected, given her family history. She has also signed up for the Alzheimer's Prevention Registry, an online community of people who want to learn about, and potentially join, prevention trials.
While participating in a study, she was asked how her outlook on the future been affected by the knowledge that she's positive for APOE-4. She answered that if she felt herself deteriorating from Alzheimer's, she would seriously contemplate suicide.
"I think that the burden is more, obviously, it's with the living. It's with those who are still capable, because they have the emotional and financial and potentially the physical burden," she said. "I just don't see any point in making a burden when there's not a lot a great deal left for me."
But right now, mentally, Kolesar says she feels clearer than at many points in time over the past 20 years. She gave birth to her son at 37, and went "straight from mush mind of motherhood to the mush mind of menopause." She's retired, but not sitting idly -- she is planning to travel to Vietnam alone in January and is learning Vietnamese.
Language learning is her "hedge against Alzheimer's," she says, referencing research suggesting that keeping the mind active might delay the onset of Alzheimer's.
But her optimism on this point is sobered because her father did crossword puzzles, too.
"More than anything else, the part I find terrifying, is that period when you start forgetting things but you still know who you are," she said. "How did that feel to him? How is that going to feel to me, if it happens?"
It's a foggy area of Kolesar's possible future, which science can't yet say is certain.
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