Managing Alzheimer’s disease risk

Managing Alzheimer’s disease risk

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Mildly elevated sugar levels increase risk of disease

I recently wrote that mild cognitive impairment is one of the most feared disorders, especially as we age. One of the reasons for this is the fear of progressing to Alzheimer’s disease. The fear of developing Alzheimer’s with MCI is grounded in reality.

A recent study of patients with MCI and a protein biomarker called amyloid in the brain showed that the probability of developing Alzheimer’s disease was 50% after three years (ADI Conference 2012; Abstracts OC037 and OC035). However, those who had MCI without the amyloid proteins had a reduced one in ten chance of developing Alzheimer’s. Amyloid-beta plaques tend to accumulate in the brain and may be an early sign of Alzheimer’s. Researchers used a positron emissions tomography scan to make these assessments.

Modifiable risk factors for Alzheimer’s disease include chronic diseases, such as diabetes, high cholesterol and high blood pressure.

Where are we with medical therapies, and what can we do to possibly modify our risk for Alzheimer’s? Drug therapies in the research pipeline have had mixed results. However, one drug already on the market may be beneficial for those with diabetes: metformin.

What about diet? The answer depends on the type of diet. The standard American diet, with its high saturated fat and increased sugars, may increase the risk of Alzheimer’s, while a low-fat, nutrient-dense diet may reduce the risk of Alzheimer’s disease. Let’s review the evidence.

Future potential drug therapies

There is good news and bad news for potential Alzheimer’s drugs in development. Recently, the FDA stopped a drug trial because Phase III (the final stage) of development did not show better results than placebo in patients with Alzheimer’s (N Engl J Med. 2013;369:341-350). The drug that failed, semagacestat, was tested at two different doses and compared to a placebo. Its focus, like many Alzheimer’s drugs in development, was on reducing amyloid-beta plaques.

This was a well-designed, randomized controlled trial involving over 1,500 patients with a duration of about a year and a half. The patients on the drug actually did worse in terms of cognitive abilities and had more side effects than those on the placebo. This is disheartening.

However, don’t lose hope. There is another drug in the early stages of development, a microglial modulator. Microglia is to the brain as HDL or “good cholesterol” is to the cholesterol profile. They remove the “garbage.” Amyloid plaques interfere with microglia and ultimately cause inflammation. Microglial modulators are able to resist this process in mice, potentially reducing amyloid plaque deposits in the brain and improving memory. In a recent preliminary trial in humans, it showed promise for preventing patients with MCI from progressing to Alzheimer’s disease (AAI Conference 2013; oral presentation: O3-06-5). These were early results, and a much larger Phase III study is needed before conclusions can be drawn. But this is a potentially exciting new approach.

Dietary impact

Even mildly elevated blood glucose (sugar) levels may be a contributor to Alzheimer’s disease. In a recent study, even slightly elevated sugar levels led to increased risk (N Engl J Med. 2013;369:540-548). When a blood glucose level of 115 mg/dL, a prediabetes level, was compared to 100 mg/dL, risk increased by 18%. The risk of developing Alzheimer’s was even greater in those who were diabetic with higher sugars. Those with a blood glucose of 190 mg/dL, compared to those with a blood sugar of 160 mg/dL, had 40% greater risk for developing Alzheimer’s. This study followed over 2,000 patients for approximately seven years.

The scary aspect is that a slight rise in sugars from normal can lead to a significant rise in Alzheimer’s risk. The authors concluded that those who had slight glucose elevations should make lifestyle changes, including diet and exercise.


It is thought that diabetes may increase the risk of Alzheimer’s by at least twofold. In a recent observational trial, involving over 14,000 patients with a follow-up of five years, they found that metformin may reduce the risk of Alzheimer’s dementia substantially (AAIC 2013. Oral Presentation: O1-05-05). There was an approximate 20% reduced Alzheimer’s risk with metformin. Other medications, when compared to metformin, increased the risk of Alzheimer’s. For example, insulin increased risk 23%. However, this was not a randomized controlled trial. So, I might lean toward using metformin in diabetes patients, but not draw dramatic conclusions about other diabetic medications.

Integrative conference

In July, I attended an integrative conference, the International Conference on Nutrition and the Brain, hosted by Physicians Committee for Responsible Medicine in Washington, D.C. Presented evidence suggested that diet has an impact on Alzheimer’s disease ( A diet high in saturated fat may negatively affect cognition and increase the risk of Alzheimer’s. On the other hand, a high-nutrient, plant-based diet may have the opposite effect. The suggested diet consists of low saturated fat, a focus on fruits, vegetables, beans and legumes, and a small handful of nuts and seeds daily. They also stressed the importance of cardiovascular exercise, such as a walking with alacrity for 30 minutes, four times a week. You should also avoid aluminum from sources like cookware and antacids.

High saturated fat and high sugar effect

Interestingly there is a RCT that shows a high-saturated fat and high-sugar diet may increase the load of amyloid-beta protein plaques by preventing their clearance from the brain, whereas the diet with lower saturated fat and sugar had beneficial results (JAMA Neurol. 2013;70(8):972-980). According to the authors, diet may modify the risk profile for this disease, depending on the diet’s composition. Though the trial was small and short in duration, four weeks, it was still impressive.

I mentioned the word “fear” in the introduction several times. Hopefully, this article turned that fear into confidence that you can reduce the risk of developing Alzheimer’s disease. Decreasing saturated fat and sugar intake may be the first steps to reaching this goal. Whether metformin is needed by those with high blood sugar levels or not, lifestyle modifications, including a high-nutrient, plant-based diet, seems to have promise.

We hope for the best with drug therapies in the pipeline, though most have disappointed or are only in early stages of development, so it is even more imperative to utilize what may be our most powerful weapon, lifestyle changes.


Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website and/or consult your personal physician.