Weighty Matters

Obesity has been linked to neurologic problems such as migraine, dementia, and sleep apnea. Our experts review the evidence and offer advice for getting weight under control.

By Stacey Colino

Thirty-five percent of Americans tip the scales into the obese category, according to the US Centers for Disease Control and Prevention (CDC). This public health crisis affects rates of heart disease, type 2 diabetes, and some forms of cancer. Recently, that list of health problems has grown longer as scientists have discovered a connection between obesity and neurologic conditions such as obstructive sleep apnea, migraine, depression, Alzheimer’s disease, narcolepsy, and even carpal tunnel syndrome. What’s more, excessive weight has been identified as a risk factor for cognitive decline later in life.

In a 2009 study of 2,798 people published in the Archives of Neurology, researchers from the University of Washington in Seattle reported that people who were obese at midlife had a 39 percent higher risk of developing dementia later in life than people of a normal weight, based on their performance on various neuro-psychiatric tests and magnetic resonance imaging scans. A study published last April in Neurology found that obesity was associated with a higher rate of mild cognitive impairment, delayed logical memory (the ability to recall a narrative story after a time delay), and depression, among 397 older adults who were given a battery of neuropsychological tests.

“Obesity impacts your general health, and your overall health can affect your brain health and function,” says Jennifer Molano, MD, FAAN, an associate professor of neurology and rehabilitation medicine at the University of Cincinnati College of Medicine. “To make sure your brain is healthy, you need to make sure your body is healthy—and weight management is an essential part of that.”


These days, a healthy weight is defined as a body mass index (BMI) between 18.5 and 24.9, according to the CDC. An adult who has a BMI between 25 and 29.9 is considered overweight. Obesity is defined as having a BMI of 30 or higher, and extreme obesity (formerly called morbid obesity) is defined as having a BMI of 40 or higher.

The point at which excess weight increases the risk of developing neurologic disorders varies from one condition and individual to another and is based on genetic factors, underlying health conditions, lifestyle factors, and other considerations. But for many disorders, the risk begins to rise precipitously at a BMI of 30, Dr. Molano says. (Your doctor can chart your BMI based on your height and weight, or you can do it yourself at http://bit.ly/BMI-calc.)


After years of sleeping poorly and waking up feeling tired in the morning, Tim Powell, who is 6′1” and weighed 288 pounds in October 2013, went to his doctor at his wife’s urging; she suspected he had sleep apnea because of his loud snoring. “I had a general lack of energy and regularly had to catch myself from falling asleep behind the wheel,” recalls Powell, a software project manager and father of five in Salt Lake City. “I remember feeling foggy and not being able to focus.”

After an overnight sleep assessment, Powell was diagnosed with sleep apnea, a potentially serious disorder in which a person repeatedly stops breathing or breathes very shallowly for seconds to minutes at a time, then resumes breathing (often with a loud snort, gasp, or choking sound) throughout the night. Powell’s doctor thought his sleep apnea was caused or exacerbated by his excess weight. Because he didn’t want to rely on a machine or device to keep his airways open while he slept, Powell, now 50, says “that [diagnosis] was the tipping point for me to improve my health.”


What Powell didn’t know is that his sleep apnea could have been contributing to his excess weight, and vice versa. “People who don’t get enough sleep experience neurochemical changes, including an increase in stress hormones such as cortisol, which can lead to weight gain, elevated blood glucose, and insulin resistance [a precursor to diabetes],” explains Todd J. Swick, MD, FAAN, an assistant clinical professor of neurology at the University of Texas School of Medicine in Houston. In fact, the relationship between obesity and sleep apnea is a tricky two-way street. “The more obese you are, the worse your sleep apnea gets,” Dr. Swick says, “and the worse your sleep apnea gets, the more obese you become.”

With untreated sleep apnea or sleep deprivation of any kind, levels of ghrelin, an appetite-regulating hormone, increase. Elevated ghrelin levels increase appetite, which can lead to weight gain, notes Alon Avidan, MD, MPH, a professor of neurology at the University of California, Los Angeles (UCLA) and director of the UCLA Sleep Disorders Center. “From there, the cycle continues,” with a revved-up appetite causing weight gain, weight gain exacerbating sleep apnea, and so on.


The basic mechanism linking obesity with obstructive sleep apnea is largely anatomical. “The increased BMI and the effects of gravity make it more likely for the tissues in the back of the throat to collapse, causing the airways to close up while you’re sleeping,” Dr. Molano explains. But, she adds, the relationship between excess weight and other neurologic disorders isn’t so easily explained.

Depending on the condition, various obesity-related physiological factors may be at work. For example, obesity is also a risk factor for narcolepsy, a chronic neurologic disorder that causes severe daytime drowsiness and sudden attacks of sleep during waking hours, Dr. Avidan says. This may be related to levels of a neuropeptide called orexin or hypocretin, which regulates alertness, wakefulness, and appetite. Low levels of orexin are associated with both obesity and narcolepsy. In a 2011 study in the Journal of Sleep Research, for example, investigators measured orexin levels in 70 people with narcolepsy and found that the severity of excessive daytime sleepiness was associated with an orexin deficiency. As far back as 2000, in a study in The Lancet, researchers noted that people with narcolepsy have a higher BMI than the general population.


Scientists now know that excess body fat isn’t inert. It’s actually quite active, and depending on its location it can set off a hormonal cascade of detrimental effects. In particular, in people with central or abdominal obesity (the classic apple-shaped pattern), the fat surrounding organs can raise levels of stress hormones such as cortisol, promote systemic inflammation, increase oxidative stress (rust-like damage that’s caused by unstable molecules called free radicals), and create insulin resistance (a reduced response to the hormone insulin, which makes blood sugar rise). Each of these effects can harm the brain and neurologic function.

The underlying pathways connecting obesity with certain neurologic disorders are more complicated in some conditions than in others. The association between migraine and obesity, for instance, may stem partly from the fact that obesity is considered a pro-inflammatory state, explains Teshamae Monteith, MD, chief of the headache division at the University of Miami Miller School of Medicine. This state can increase the number of inflammatory substances in the brain such as calcitonin gene-related peptides, which are linked to an increase in the frequency, severity, and duration of migraine attacks. In addition, “obesity is associated with sympathetic activation of the autonomic nervous system—the fight-or-flight response—which is linked with migraine,” Dr. Monteith says. “It’s also linked to low levels of adiponectin, [a hormone] related to [increased inflammation] and pain.”

A meta-analysis published in the Journal of Headache and Pain in March 2015 found that women who are obese have a 44 percent higher risk of migraine than women whose weight is in the normal range. Additionally, overweight and obese women have, respectively, a 39 percent and 75 percent higher chance of developing chronic migraines than women who are not overweight.


Evidence suggests that those who develop metabolic syndrome have a higher risk of developing Alzheimer’s disease. The syndrome is characterized by a waist circumference of 40 inches or more for men and 35 inches or more for women plus two of the following: elevated blood pressure (130/85 or higher without taking medication for hypertension), high triglycerides (150 mg/dL or higher), low HDL or “good” cholesterol (below 40 mg/dL for men and below 50 mg/dL for women), and high fasting blood sugar (100 mg/dL or higher).

“Obesity quadruples the risk of developing Alzheimer’s,” says Gary Small, MD, director of the UCLA Longevity Center and coauthor of The Alzheimer’s Prevention Program (Workman Publishing Company, 2011). He cited a 2011 study of 8,534 twins published in Neurologythat found that obesity in midlife was associated with four times the risk of later developing dementia, including Alzheimer’s disease and vascular dementia, compared with a normal BMI. Excess belly fat, in particular, has been linked with an increased risk of late-onset Alzheimer’s disease.

Even without metabolic syndrome, people who have insulin resistance or type 2 diabetes—both of which can stem from being overweight or obese—may be at higher risk for Alzheimer’s disease. This may be due partly to increased inflammation, Dr. Small notes, but a 2015 study in Molecular Aspects of Medicine suggested that type 2 diabetes and Alzheimer’s may share genetic risk factors as well. Indeed, insulin resistance and diabetes have been shown to cause changes in brain structure and function that are seen with Alzheimer’s disease, injuring neurons and causing abnormal growth patterns such as the formation of tau tangles and amyloid plaques, says Dr. Small.


Some research suggests that obesity may be a risk factor for pediatric multiple sclerosis (MS), too. Scientists from Kaiser Permanente Southern California found that obesity was associated with a significantly increased risk of MS among girls between the ages of 11 and 18. The study, published in Neurology in 2013, showed that overweight girls had one and a half times the risk of developing MS compared with their normal-weight peers. Moderately obese girls had 1.8 times the risk, and those who were extremely obese (meaning their weight was off the charts for their age and sex) had nearly four times the risk. The researchers theorized that high estrogen exposure and the low-grade inflammatory state that occurs with obesity may accelerate the onset of MS.

“It has been more difficult to link obesity, independent of cardiovascular risk factors, to the risk of developing MS in adults,” says Dennis N. Bourdette, MD, FAAN, an endowed professor in the department of neurology at Oregon Health & Science University in Portland. “However, obesity appears to increase fatigue in people with MS and compounds other symptoms of MS. So an MS patient who is obese and develops mild leg weakness, for example, will have a lot more problems adapting to that weakness than someone who maintains a normal weight.”


Certain antiseizure drugs and corticosteroids, as well as antidepressants used to treat certain forms of pain, and beta blockers prescribed for migraines, can cause extra pounds to creep on, either because they decrease metabolic rate or stimulate appetite or both, notes Dr. Monteith. “Not all patients are going to get that effect, but some will,” she says.

Cynthia Fabian, who has epilepsy and sleep apnea related to nocturnal seizures, is one of them. “Depakote [divalproex sodium] has been nothing short of a miracle for me in terms of seizure control, but it hasn’t been without trade-offs. I follow a 1,200-calorie diet and take at least one class at the gym each day just to maintain my nearly 200-pound frame,” says Fabian, 57, a teacher and writer in Venice, FL.

At one point, Fabian switched to topiramate (Topamax), another antiseizure drug. While it helped her drop 60 pounds, it didn’t control her seizures sufficiently. So she went back on divalproex sodium and regained the weight. In her view, the added pounds have been a small price to pay for being able to drive and have a normal, active life. “I remain positive and meditate nearly every day,” she adds. “But it is difficult [for people] to understand how someone who does not eat much still has a larger frame.”


People who lose weight often see an improvement in their condition. Case in point: A 2011 study published in Cephalalgia found that when obese premenopausal women with migraine underwent bariatric surgery for weight reduction, the frequency of their episodic migraines dropped from four a month to one a month and their chronic migraine episodes decreased from 16.8 to 8.5 a month. What’s more, the attacks were shorter and the women needed less medication to manage them.

Even habits that facilitate weight loss can improve neurologic disorders linked with obesity. For example, some studies show that exercise can protect against migraine, says Dr. Monteith. A 2011 study of 91 patients with migraine published in Cephalalgia found that exercising for 40 minutes, three times a week, was more effective at reducing migraine attacks than taking topiramate. The forms of exercise that show the most benefit tend to be gentler, such as swimming or cycling, as opposed to jarring, pounding activities such as aerobics or jogging.


Just as sleep apnea can create an upward spiral of weight gain and worse apnea, weight loss can reverse that cycle and lead to better sleep and, in some cases, a remission of apnea. That was the experience of Tim Powell, the father of five from Salt Lake City. After revamping his diet and eating fewer refined carbohydrates, less sugar, fewer processed foods, and more vegetables, fruits, and healthy fats, and exercising for an hour a day (30 minutes of cardio, 30 minutes of resistance training) five or six days a week, he lost 77 pounds in seven months. His snoring disappeared, along with any signs of sleep apnea, and his blood pressure and cholesterol improved. “I have much more energy,” he reports. “It’s been a huge difference.”

For those who don’t have the energy to lose weight, a continuous positive airway pressure (CPAP) machine that keeps airways open during sleep can help, says Dr. Avidan. When the sleep disorder is well controlled, people may have more energy to make the dietary changes and perform the physical activities that will help them lose weight. Once they start to lose weight, “the pressure on the CPAP machine can be readjusted,” he says.


Even for people who are obese and have more than one neurologic disorder, losing weight can make a tremendous difference. Shelley Rafilson, a singer and writer in Scottsdale, AZ, has severe neuropathy, fibromyalgia, hypothyroidism, and arthritis. While caring for her elderly father, she gained 100 pounds and developed sleep apnea, which took a further toll on her energy, weight, and pain. When she found herself struggling to get off the floor after putting on her father’s shoes, she decided to take action.

A few years ago, Rafilson went on a 1,200-calorie diet, started walking for exercise, and began weighing herself once a week. “I decided it was time to turn my life around, and that’s exactly what I did,” says Rafilson, now 60. It was difficult, she says, but she persevered, and over the span of two years she lost more than 100 pounds, kicked her reliance on pain medications, and wrote and self-published 100 Pounds to Happiness!, a book about her transformation. “I want to help others learn from my experience,” she says.

Her take-home message? Losing weight is worth the effort for an improved quality of life and a future of good health. As Dr. Molano says, “What you do at midlife can have an impact on what happens later in terms of your brain health.”

BMI breakdown

These days, a healthy weight is defined less by the numbers on a scale than by body mass index (BMI). According to the US Centers for Disease Control, a BMI of between 18.5 and 24.9 is healthy for adults. A BMI higher than 24.9 breaks down as follows:

25–29: Overweight

30–40: Obese

OVER 40: Extremely obese (formerly called morbidly obese)

Lose Weight, Gain Health

Dropping pounds can help you reclaim and protect your health.

Many of the negative health effects of obesity can be reversed by losing weight. The challenge, of course, is getting started. We asked several weight-loss experts for advice.

START WITH CALORIES. “Limiting calories is much more effective for initial weight loss than exercising, so don’t worry if your [condition] limits what you can do in terms of physical activity,” says Lawrence Cheskin, MD, director of the Johns Hopkins Weight Management Center in Baltimore. Many weight-loss experts, including Dr. Cheskin, recommend reducing your calorie intake by 500 to 750 calories a day to lose one to one-and-half pounds a week.

AVOID REFINED CARBOHYDRATES. It’s not just the quantity of calories that count; quality matters, too. “Most people consume more carbohydrates than they need,” says Molly Kimball, RD, nutrition program manager of the Ochsner Health System’s Elmwood Fitness Center in New Orleans. She advises cutting down on refined carbohydrates and focusing on eating more fiber and whole grains like quinoa and brown rice, lean protein like skinless poultry and fish, vegetables, and spices and aromatic herbs.

CHOOSE BRAIN FOOD. Consuming antioxidant-rich berries, plums, cherries, apricots, grapes, broccoli, sweet potatoes, bell peppers, spinach, and tomatoes can help protect your brain from harmful free radicals that cause wear and tear on your cells, explains Gary Small, MD, director of the UCLA Longevity Center. The omega-3 fatty acids in fish such as salmon, mackerel, tuna, sardines, and anchovies can reduce harmful inflammation in your body.

EAT SMALLER PORTIONS. Be mindful of the size of your meals. If you don’t prepare your own food, make sure people involved in your care adhere to your nutritional goals, Kimball adds.

ENLIST A BUDDY. Get plenty of sleep and learn to manage stress without turning to food. “It helps if you have a friend for support,” Kimball says. “That buddy system helps keep up motivation.”

SET A CALORIE BUDGET. Pick your target weight, then determine how many calories you need to reach it. If, for example, you want to weigh 150 pounds and have no physical limitations, allow yourself 10 calories for each pound for a total of 1,500 calories per day, says Kimball. (If you exercise more than an hour a day, you may need more calories.) To track your calorie intake, Kimball recommends using a smartphone app like MyFitnessPal. If you have physical limitations or mobility problems, you may need to decrease your daily calorie allotment by 10 to 25 percent while trying to lose weight, depending on the extent of your limitations, Kimball says. If you don’t want to count calories, Kimball recommends limiting starchy carbohydrates of all types, including whole grains, and focusing on lean proteins, vegetables, and small amounts of healthy fats.

HONOR YOUR HUNGER SIGNALS. Get in the habit of listening to your body and paying attention to when you’re truly physically hungry and when you simply have the urge to eat, Kimball suggests. If you’re hungry, you should eat healthy foods but stop eating before you feel completely full. If you have an urge to eat, identify what’s causing it. If it’s loneliness, for example, call a friend. If you’re feeling sad, listen to upbeat music. If you’re tired, take a nap.

INCORPORATE AEROBIC ACTIVITY. Besides helping you burn extra calories during a workout, exercising helps shed body fat, add lean muscle (which will help you burn more calories all day), and increase your cardiovascular fitness, Dr. Cheskin says. If you’re new to exercise and have no physical limitations, start with 10 to 20 minutes a day and build up from there. Eventually, the goal is to do at least 45 minutes of aerobic exercise—such as walking, swimming, bicycling, or using the elliptical machine—most days of the week. “Cardio exercise is good for your heart and vascular health, your mood and stress levels,” Kimball says.

ADD STRENGTH TRAINING. Working out with resistance bands or weights twice a week builds lean muscle, increases your strength, and helps you with activities of daily living. “Increasing lean muscle can raise your resting metabolic rate: One pound of muscle can burn approximately seven calories [per day], so adding 3 to 4 pounds of lean muscle, which is very reasonable within 12 to 14 weeks in a proper strength training program, can increase your ability to burn calories when you aren’t exercising by up to 30 calories a day,” says Pete McCall, MS, a professor of exercise science at Mesa College in San Diego.

ACCOMMODATE PHYSICAL LIMITATIONS. If you have mobility problems, start by doing what you can three times a week and building from there. And consult your neurologist about any possible limitations. “Just getting up and moving for five minutes at a time with two to three 10- to 15-minute intervals throughout the day for activities such as walking, climbing stairs, or simply standing can improve your ability to burn calories,” says McCall. Find an activity you enjoy—whether it’s walking, riding a stationary bicycle, or doing exercises in a pool—and make it a habit. “Start slowly, then increase intensity and frequency,” McCall advises.

WORK WITH A THERAPIST. If you have limited use of your legs or difficulty gripping things, consider teaming up with a physical or occupational therapist who can show you how to use various exercise machines and pieces of equipment. For example, some people may benefit from using a hand cycle, which is powered by the arms instead of the legs, or resistance bands that are attached to a wall or door, or Velcro weights for the wrists or ankles for strength training. “Do anything to move your muscles and get your heart rate up so you can burn more calories,” Kimball says.

© 2016 American Academy of Neurology