More than 300 million people worldwide are considered obese (BMI >30) and more than a billion people are classified as overweight (BMI 25-30). This is a global epidemic that puts to shame such well-known epidemics as the black plague of the 14th century, which wiped out about a third of the European population. So what does this epidemic wipe out? Among other things, your memory. Quite surprising, considering that our attention is riveted by the cardiovascular and renal effects of type 2 diabetes.

Research suggests that consuming between 2,100 and 6,000 calories per day may double the risk of memory loss, or mild cognitive impairment (MCI), among people age 70 and older. The study will be presented at the American Academy of Neurology’s 64th Annual Meeting in New Orleans April 21 to April 28, 2012. MCI is the stage between normal memory loss that comes with aging and early Alzheimer’s disease.

elderly husband caregiver
Mild Cognitive Impairment (MCI)

The study involved 1,233 people between the ages of 70 and 89 and free of dementia residing in Olmsted County, Minn. Of those, 163 had MCI. Participants reported the amount of calories they ate or drank in a food questionnaire and were divided into three equal groups based on their daily caloric consumption. One-third of the participants consumed between 600 and 1,526 calories per day. The other one-third between 1,526 and 2,143. And lastly, the other between 2,143 and 6,000 calories per day.

The odds of having MCI more than doubled for those in the highest calorie-consuming group compared to those in the lowest calorie-consuming group. The results were the same after adjusting for history of stroke, diabetes, amount of education, and other factors that can affect risk of memory loss. There was no significant difference in risk for the middle group.

Self-reporting studies are not ideal; in fact, they are not very reliable unless there is independent supporting evidence. So let’s see what kind of objective evidence is available.


The neuroimaging evidence

obesity and memory loss
Representation of Normal, Overweight, and Obese

In the journal Human Brain Mapping, Paul Thompson, senior author and a UCLA professor of neurology, and lead author Cyrus A. Raji, a medical student at the University of Pittsburgh School of Medicine, and colleagues compared the brains of people who were obese, overweight, and of normal weight, to see if they had differences in brain structure.

They found that obese people had 8% less brain tissue than normal-weight people, while overweight people had 4% less tissue. Now, 8% may not sound very much, but when you consider that it means loss of 8 billion neurons (we have about 100 billion neurons), it is a very significant loss.

The researchers used brain images from an earlier study called the Cardiovascular Health Study Cognition Study. Scans were selected of 94 elderly people in their 70s who were healthy—not cognitively impaired—five years after the scan was taken.

The researchers then converted the scans into detailed three-dimensional images using tensor-based morphometry, a neuroimaging method that offers high-resolution mapping of anatomical differences in the brain.

And here is why loss of “only” 8% neural tissue is so important. The loss is highly targeted. In looking at both gray matter and white matter of the brain, they found that the people defined as obese had lost brain tissue in the frontal and temporal lobes, areas of the brain critical for planning and memory, and in the anterior cingulate gyrus (attention and executive functions), hippocampus (long-term memory), and basal ganglia (movement).


The biochemical evidence

obesity and memory loss

To find out why the hippocampus underperforms in its memory functions, we’d have to get a tissue biopsy which would be essentially impossible to do in humans (any volunteers?). But we do have a strain of rats, Zucker rats, that have all the hallmarks of human obesity and type 2 diabetes. When biopsies of the rat hippocampus were examined, it was found that the insulin-sensitive glucose transporter GLUT4 showed a significant reduction in binding and transporting glucose into the cell. When you have no supply of glucose to the cell, it cannot perform energy-requiring tasks, in this case, memory processing and storage.

This explains why existing hippocampal neurons fail to perform their function in memory storage. But how does that relate to a reduction in the number of neurons?


The all-important BDNF

One of the most important hormones in the formation of brain neural tissue is called brain-derived neurotrophic factor or BDNF; it regulates the development, survival, and differentiation of neurons. Recently, BDNF has been implicated in the regulation of body weight, as its expression is reduced by fasting, and BDNF administration causes weight loss in wild-type mice through a reduction in food intake.

BDNF has also been implicated in memory and a range of behaviors using a number of conditional knockout models. But all these observations were made in mice. Would it be nice if there was a mutation in the human BDNF gene from which we could infer what its normal function is and what abnormalities would result from a mutation?

Such a mutation was reported in 2006 in a girl presenting with hyperphagia (uncontrolled excessive eating), extreme obesity, cognitive impairment, and hyperactivity.

Is BDNF the be-all and end-all of the genetic causes of the obesity/memory loss story? Not at all. There is a syndrome called Prader-Willi, in which the affected individuals suffer from the hyperphagia and obesity. In addition, they also suffer from reduced muscle tone and no production of sex hormones. Their mutation is on a different chromosome (chromosome 11) than BDNF (chromosome 15).

And it is quite likely that more genes involved in the effect of obesity on brain function will be discovered.

So now we have evidence ranging from neurological studies, neuroimaging studies, biochemical studies, and genetics. All pointing to the fact that people with obesity, may it be genetically based or behaviorally caused, ends up with memory impairment.

So, if you remember, please eat well and less. Your brain will be grateful for that.

Featured photo credit:

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.



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