Cholesterol, Statins and Alzheimer’s, Part 2 of 3

Summary: In a small pilot trial, Lipitor (a statin), seemed to improve scores on neuropsychological tests, especially for patients with mild Alzheimer’s, high cholesterol and the APOE4 genetic variation. The results of two large trials of statins for treatment of Alzheimer’s should be published in 2008. Whether or not statins prove to be effective against Alzheimer’s, this research adds to the evidence of a connection between heart disease and some dementias.

In my last post, I wrote how recent research has dampened hopes that the cholesterol-lowering drugs called statins can reduce the risk of dementia. But what about people who’ve already been diagnosed with dementia?

Two large trials of statins to treat Alzheimer’s are underway. Dr. Larry Sparks, Head of the Ralph & Muriel Roberts Laboratory For Neurodegenerative Research at the Sun Health Research Institute in Arizona, is a lead investigator for one of these trials. He’s enthusiastic about exploring the connection between cholesterol and Alzheimer’s.

“Think about it,” Dr. Sparks says. “APOE4 [the genetic variation linked to increased risk of Alzheimer’s] leads to elevated cholesterol. I don’t think cholesterol causes Alzheimer’s, but I believe it negatively influences it, or causes it to progress faster. There’s definitely a vascular influence.”

Earlier in his career, Dr. Sparks was a Medical Examiner in Kentucky. While performing autopsies of non-demented people with coronary artery disease, he noticed they had amyloid plaques similar to those in people who had been diagnosed with Alzheimer’s. Later, working at the Sun Health Research Institute, he found that rabbits fed high cholesterol diets developed amyloid plaques in their brains. This plaque build-up was reversed when the cholesterol was removed from the rabbits’ diet.

Now, in a small pilot trial, Dr. Sparks and his colleagues have shown that a statin called Lipitor may actually improve scores on neuropsychological tests for some people with Alzheimer’s. In an article published last year, they wrote that Lipitor seemed to help the most in patients with mild Alzheimer’s, high cholesterol and the APOE4 genetic variation.

So reducing cholesterol to treat Alzheimer’s seems logical, right? Nothing is that simple with Alzheimer’s and dementia.

First, some scientists think statins might work by reducing inflammation in the brain, rather than by reducing cholesterol. Second, brain cells produce cholesterol because they need it to function. While bringing down cholesterol levels in the blood might prove helpful for Alzheimer’s, decreasing cholesterol in the brain may harm neurons. Three statins, Mevacor (Lovastatin), Zocor (Simvastatin) and Baycol (Cerivastatin – now off the market in the US) appear to work in the brain as well as in the blood. Two trials at the University of Pittsburgh testing the effects of Mevacor and Zocor on cognitive functioning in people with high cholesterol showed the drugs may have caused a small decrease in performance on some neuropsychological tests. While the effect of these statins on the brain is unknown, Dr. Sparks thinks a safer approach is to influence the brain indirectly by using statins that reduce cholesterol in the blood rather than in the brain.

Finally, a new study shows a late-life drop in cholesterol may actually be associated with an increased risk of Alzheimer’s. I’ll talk about that in my next post.

The results of the two large trials of statins for treatment of Alzheimer’s [CLASP (testing simvastatin or Zocor) and LEADe (testing atorvastatin or Lipitor)] should be published in 2008. Whether or not statins prove to be effective against Alzheimer’s, this research adds to the evidence of a connection between heart disease and some dementias. Dr. Sparks puts it this way: “if you’re sufficiently resilient that you don’t succumb to cardiovascular disease, then you’re looking down the barrel of dementia.”

Comments

[Gail Rae Hudson]

Funny, Mona, but high cholesterol is an issue that has touched off concern regarding my mother. A few year before I came to live with her, she was put on Pravocol by a previous physician. Within months after this, research surfaced that indicated that for people in her age group who have lived with fairly high cholesterol throughout their lives, the drugs not only didn't increase life span, those off the drugs lived longer than those on the drugs. So, she was taken off cholesterol medication. At that time, though, there wasn't any interest in the effect of heart disease on the development of dementia.
Now, there is. At my mother's last appointment her cholesterol registered rather high. Her physician, though, decided not to treat it and, in discussion with me, explained that, considering her CRF, the recorded effect of cholesterol medications on CRF, and her stability regarding her dementia and other ailments, he felt it best, at this point, not to add anything else to the soup. I agreed with him.
I think the hardest diagnostic, prognostic and treatment decisions to make are those involving stable cases of Dementia-Lite. Still, though, we're mucking around, aren't we, with all types of dementia? I sometimes consider that once we've figured out how to alleviate and/or cure those causes of dementia that we now suspect, others will crop up.
Weird, weird, weird.
This series is especially interesting to me, Mona. Can't wait for the next section!