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Alzheimer's Treatments

Alzheimer’s disease affects one of nine Americans over age 65 and is the sixth leading cause of death in the United States. But many Alzheimer’s cases may be preventable, according to Alan J. Lerner, MD, and Stephen Rao, PhD.

Lerner, director of the Brain Health and Memory Center at University Hospitals Case Medical Center, and Rao, director of the Lou Ruvo Center for Brain Health at Cleveland Clinic, presented this optimistic perspective in April at the annual Association of Health Care Journalism conference in Cleveland. Here are some key takeaways from that discussion.

What You Should Know

There’s hope: Early detection means opportunities for intervention.

Modern imaging technology can measure levels of beta-amyloid and tau, two proteins that serve as biomarkers for Alzheimer’s. A definitive diagnosis of Alzheimer’s once could be made only through autopsy, but in vivo (Latin for “in the living”) imaging opens up new areas of understanding about the disease — and possibilities for intervention.

Identifiable brain changes begin to appear up to 15 years prior to a person’s first symptoms of mild cognitive impairment, or MCI. “By the time a person is diagnosed with MCI or Alzheimer’s disease, a lot of changes to the brain have already occurred, including loss of brain tissue,” said Rao. “This is hard or impossible to reverse.” The years between the first evidence of disease in the brain and actual symptoms of memory loss therefore represent a window of opportunity.

Early detection in at-risk individuals is driving the next generation of clinical drug trials and possible treatments. (No new Alzheimer’s drugs have been approved since 2003.) It’s also fueling research into lifestyle changes that at-risk people can make to stave off the most devastating symptoms of the disease.

Physicians and researchers now face the challenge of finding people who are in that critical preclinical window.

Rao identified several risk factors for Alzheimer’s:

  • advancing age
  • mild cognitive impairment (MCI)
  • metabolic disease
  • cerebrovascular disease (hypertension, etc.)
  • family history
  • the presence of ApoE4, an allele (alternative form of a gene), in the individual’s DNA

With regard to genetics, Rao explained that people with the ApoE4 genetic variation are as much as 13 times more likely to develop Alzheimer’s. Approximately 60 percent of Alzheimer’s disease patients have at least one ApoE4 allele, he said. “That means 40 percent do not.”

Gene testing can help identify risk in combination with family history. “The ApoE4 genotype is an imprecise predictor, but knowledge of this might be beneficial if you know about it in middle age,” he said. (For more on genetic variations called SNPs and how lifestyle choices may mitigate their impact, see “Making Sense of SNPs.”)

What You Can Do

More good news: Your lifestyle matters for prevention.

Researchers are investigating the degrees to which diet, social engagement, and exercise can delay symptoms in people who are at risk for Alzheimer’s disease.

“Physical activity attenuates age-related declines in brain-tissue volume and cognitive function, and increases the size of the hippocampus,” said Rao. “This is especially important for the high-risk group. If you’re at risk for Alzheimer’s disease and you’re sedentary, you’ll see a significant drop in hippocampal volume.”

Future research will focus on how physical activity works to reduce risk, he said. Researchers hypothesize it may work by reducing inflammation and increasing innate immunity, by improving vascular function, or perhaps by improving the clearance of beta-amyloid deposits.

Rao also discussed the importance of developing a “cognitive reserve,” explaining that people who are more intellectually engaged tend to fend off the disease longer than those who are less engaged. (For more on lifestyle strategies for fending off memory loss, see “Beyond Sudoku.”)

Extending the length of time between early evidence of the disease (via brain imaging) and cognitive symptoms would have a significant impact on the number of people who actually experience the worst effects of Alzheimer’s, Rao said.

“If we can delay onset of MCI by five years, we can reduce Alzheimer’s disease by 50 percent,” he explained. “If we delay MCI by 10 years, we can all but eliminate Alzheimer’s, because people will die of other things. Can we make sure the mind and the body go at the same time?”

For more on boosting brain health, read “Build a Better Brain” from our October 2007 issue.

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