Can You Eat Your Way to Dementia?*
AN UNHEALTHY DIET NOT ONLY IS BAD FOR YOUR WAIST—IT MAY ALSO TRIGGER ALZHEIMER’S DISEASE
An unhealthy diet is bad for body and brain.
Suzanne de La Monte’s rats were disoriented and confused. Navigating their way around a circular water maze—a typical memory test—they forgot where they were and couldn’t remember how to locate the hidden, submerged safety platform. A closer look at their
brains uncovered devastating damage. Areas associated with memory were studded with bright pink plaques, like rocks in a climbing wall, while many neurons, full to bursting point with a toxic protein, were collapsing and crumbling, teetering on the brink of death.
Such changes are the hallmarks of Alzheimer’s disease, yet they arose in surprising circumstances. De la Monte, a neuropathologist at Brown University in Providence, Rhode Island, USA, had treated the rats with a diabetes drug that interfered with how their brains responded to insulin. The hormone is most famous for controlling blood sugar levels—poor sensitivity to insulin is typically associated with type 2 diabetes—but it also plays a key role in brain signalling. And results such as de la Monte’s have led some researchers to wonder whether Alzheimer’s may sometimes be a version of diabetes that hits the brain. De la Monte even renamed it “type 3 diabetes,” and others concur.
If they are right, the implications are deeply troubling. Since sugary, caloric foods are known to impair our body’s response to insulin, we may be poisoning our brains every time we chow down on burgers, fries, and soda.
This Is Your Brain on Insulin
For more than a century, scientists blamed beta-amyloid plaques that amass in the brains of people with Alzheimer’s as the cause of the disease. Beta-amyloid is a fragment of a larger protein that helps form brain cell membranes. It is also thought to carry out important functions, such as fighting microbes, transporting cholesterol, and regulating certain genes. What prompts the protein to release toxic fragments that clump into Alzheimer’s plaques is something of a mystery, but if the new research is right, a diabetes-like illness might be a trigger.
Until recently, insulin was typecast as a regulator of blood sugar, cueing muscle, liver, and fat cells to extract sugar from the blood and use it for energy or store it as fat. We now know that the hormone is a master multitasker: In the brain, it helps neurons take up glucose for energy and regulates neurotransmitters crucial for memory and learning. It also encourages plasticity—the process by which neurons make new connections. And it is important for the function of blood vessels, which supply the brain with oxygen and glucose.
As a result, reducing the level of insulin in the brain can immediately impair cognition. Spatial memory, in particular, seems to suffer when you block insulin uptake in the hippocampus. Conversely, a boost of insulin seems to improve its functioning.
How “Brain Diabetes” Develops
When people frequently gorge on fatty, sugary food, their insulin spikes repeatedly. Muscle, liver, and fat cells stop responding to the hormone and don’t mop up glucose and fat in the
blood. As a result, the pancreas desperately works overtime to make more insulin to control the glucose, and levels of the two molecules skyrocket. The theory: These constantly high insulin levels also overwhelm the brain, which then becomes less responsive to insulin, impairing the ability to think and form memories, before leading to permanent neural damage.
De la Monte’s study on the rats with dementia was one of the first experiments to confirm that a disrupted insulin system can lead to Alzheimer’s symptoms. There are other US studies: William Klein at Northwestern University in Evanston, Illinois, has found that triggering diabetes created Alzheimer’s-like brain changes in rabbits. Ewan McNay of the University at Albany in New York and Suzanne Craft at the University of Washington in Seattle fed rats a high-fat diet for 12 months, which destroyed their ability to regulate insulin and led to diabetes. They also had trouble navigating a maze and looked “much like an Alzheimer’s patient,” says McNay.
Animal studies can reveal only so much about human disease, but an almost Frankensteinian demonstra- tion confirms that the brains of people with Alzheimer’s are insulin- resistant. Using cadaver brains, Steven Arnold at the University of Pennsylvania bathed various samples in insulin; tissue from people who had not had Alzheimer’s seemed to spring back to life, triggering a cascade of reactions suggestive of synaptic activity. In contrast, the neurons of those who had had Alzheimer’s barely reacted at all. “The insulin signalling is paralyzed,” says Arnold.
Another line of research suggests how: Insulin and beta-amyloid are both broken down by the same enzyme. Under normal circumstances, that enzyme can deal with both, but if too much insulin is washing around, the enzyme gets overwhelmed. The beta-amyloid gets neglected and begins to accumulate, perhaps into the toxic plaques that kill brain cells.
By studying rat neurons, Klein has found that toxic clusters of betaamyloid attack and destroy brain tissue covered in insulin receptors, which would result in immediate cognitive impairment. Worse still, this
“The epidemic of type 2 diabetes is likely to be followed by an epidemic of dementia.”
Ewan McNay of the University at Albany in New York
insulin resistance encourages cells to make even more beta-amyloid, which then goes on to harm more brain cells, triggering a vicious cycle.
Insulin Innovations: Treating and Preventing Dementia
Researchers are keen to point out that this research is still in its early days. Klein, for example, thinks that lack of insulin in the brain may be just one of many triggers for beta-amyloid toxins, so he’s searching for other culprits. After all, most people with Alzheimer’s don’t have full-blown type 2 diabetes, though many do have some insulin resistance.
Even so, the research should ring warning bells for the future. In India alone, some 60 million people are diabetic, a figure that could reach 100 million by 2030. Many millions are also prediabetic, showing some of the early signs of insulin resistance. If Alzheimer’s and type 2 diabetes share a similar mechanism, levels of dementia may follow a similar trajectory.
But even if someone doesn’t develop diabetes, a bad diet might set the wheels in motion for brain degeneration, according to an ongoing study led by Craft. For one month, volunteers—none of whom had diabetes—ate foods high in saturated fat and sugar, while a control group ate a diet low in sugar and saturated fat. In just four weeks, the former had higher levels of insulin in their blood and significantly higher beta-amyloid levels in their spinal fluid. The control group showed decreases in both.
On the plus side, a new understanding of the disease might lead to new treatments. Craft, for instance, is investigating whether a boost
of insulin might improve symptoms in Alzheimer’s patients. She has tested a device that delivers insulin deep into the nose, where it then travels to the brain. The study lasted just four months and involved only 104 people, but those who received the treatment could recall more details of stories, had longer attention spans, regained more interest in their hobbies, and were better able to care for themselves. The glucose metabolism in their brains also improved.
Clinical trials are investigating whether certain diabetes drugs can improve Alzheimer’s symptoms by regulating insulin. Other groups plan to use advanced brain imag- ing to see if diabetes medications can shrink beta-amyloid plaques, which might reverse some brain damage.
In the meantime, this research indicates that maintaining a healthy weight and lifestyle may help stave off cognitive decline. Since insulin resistance emerges from a bad diet, laying off harmful fats and sweet foods might help reduce the risk of Alzheimer’s. Conversely, diets rich in omega-3 fatty acids might help the brain manage insulin efficiently. Exercise, too, can encourage the body to conquer insulin resistance, which may explain why regular physical activity reduces your risk of Alzheimer’s by 40 percent.