Bret S. Stetka, MD; Gary W. Small, MD


July 03, 2014

In This Article

Pass the Curcumin

Medscape: What other therapeutic approaches do you feel have real potential in Alzheimer disease?

Dr. Small: There is still much to be learned about how inflammation contributes to Alzheimer disease, but we are studying anti-inflammatory approaches.

We have a treatment trial right now using curcumin -- derived from turmeric, which is a spice that is anti-inflammatory -- and we are comparing it with placebo in people with normal aging and mild cognitive impairment. We are treating them for about 18 months and using a different kind of PET scan, one that we developed at UCLA, called FDDNP [2-(1-{6-[(2-[fluorine-18]fluoroethyl)(methyl)amino]-2-naphthyl}-ethylidene)malononitrile]; this scan which measures both plaques and tangles. We are seeing that the curcumin treatment delays the build-up of plaques and tangles in the brain and protects cognitive performance.

Medscape: A study in Science and Translational Medicine[5] showed that citalopram, the selective serotonin reuptake inhibitor (SSRI), reduced amyloid-beta production. Do you have any thoughts on that approach?

Dr. Small: It is interesting to explore these approaches. Certainly from epidemiologic data, we don't find any connection between taking antidepressants and lowering risk for Alzheimer disease. But some data show that untreated depression can accelerate cognitive decline.

It is a big jump from animal models to humans, but I'm excited about diversifying our research portfolio, because we don't know where the next breakthrough will be. It could be in amyloid, it could be in tau, it could be inflammation, or it could be in SSRIs. Who knows?

Medscape: Are you aware of any serotonin signaling effect on dementia or amyloid-beta production?

Dr. Small: I wasn't aware of that connection before this study, but it's certainly possible. I should mention that people are looking at deep-brain stimulation. They are testing it because we don't have a tremendously effective approach at this point.

Gallup Poll: How's Your Memory?

Medscape: Can you tell us about your collaboration with Gallup Poll Healthways?

Dr. Small: Our group has been collaborating with Gallup Poll Healthways to obtain data from a representative sample across the United States, aged 18-99 years. We published our first study last year.[6] We have another publication in press that should be coming out soon

In the earlier study, it was the first time that the Gallup Poll has asked questions about memory. We had data on more than 18,000 people, and we found that the more healthy behaviors people were engaged in, the less likely were they to complain about memory.

People with healthy diets had fewer memory complaints, and people who ate healthy foods, exercised, and didn't smoke did even better. There is almost, at least from that study, an additive effect of engaging in more than one healthy lifestyle behavior.

We also found that older people engaged in healthier lifestyles than middle-aged and younger people. Middle-aged people had healthier lifestyles than younger people. It may be that if you are reckless in your daily life, you are not going to live long. When you are young, you don't experience the immediate consequences of unhealthy behaviors. As you get older, your doctor will say you have to stop smoking, you have to watch your weight, and so forth.

We have another publication coming out in June in PLoS One, which is another analysis of this data set. It should be interesting.

Medscape: How about alcohol? There was a nice study in Neurology[7] earlier this year showing that heavy drinking drastically increases the progression of cognitive impairment. What about mild to moderate drinking?

Dr. Small: We didn't look alcohol in our study, but that is a consistent finding. On the other side, people who drink in moderation actually do better than people who abstain completely. There may be something about drinking in moderation that relaxes you, it may be associated with other healthy lifestyle behaviors, or there could be something in the alcohol that is protective. Some people have thought that maybe it's resveratrol. There was just a negative study about resveratrol and heart health. We don't know the answer with respect to brain health yet.

Medscape: People think fish oils might be protective against alcohol-induced progression of cognitive impairment. How do you counsel your patients about alcohol?

Dr. Small: I reassure them that if they are light drinkers, that is probably fine. If they are heavy drinkers, I try to help them manage that better.


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