Inside the Dementia Epidemic: A Daughter's Memoir (36 page)

The hospital’s sleep clinic discovered that I stop breathing up to twenty times an hour. With sleep apnea, you wake up partially over and over, but you don’t remember waking up. Now I use a Continuous Positive Airway Pressure (CPAP) machine each night, a mask over my nose and mouth that pumps a stream of air into my throat to keep the tissues from collapsing. I wake refreshed, and throughout the day my energy stays constant.

I suspect that my mother also has sleep apnea. Years ago, before I married, I’d visit her and sleep in the extra twin bed in her
bedroom. She sounded like a chainsaw revved and turned off, revved and turned off. Every few minutes her loud, rumbling snores would stop, and after a moment she would snort, as if catching her breath, and continue snoring. She snored at our house, too. She had never been tested for sleep apnea, and at this point she wouldn’t be able to wear a CPAP mask without tugging it off.

After a few months of feeling better on the CPAP, I researched the condition online. A study led by the University of California, San Francisco, shows that elderly women who have sleep apnea are about twice as likely to develop dementia as those without the condition. Other researchers find that people whose nightly sleep is short or disturbed have higher levels of beta amyloid, the protein that causes plaques between brain cells. According to a study at the Washington University School of Medicine in St. Louis, in younger people, or older people who sleep well, excess beta amyloid drains out of their brains during sleep into their spinal fluid. Dr. Stephen Duntley, professor of neurology and director of Washington University’s Sleep Medicine Center, says, “It’s still speculation, but there are tantalizing hints that better sleep may be helpful in reducing Alzheimer’s disease risk.”

Is Damage Reversible?

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n 2010, researchers in Milan, Italy, found that CPAP therapy can restore brain tissue in people with sleep apnea. Before treatment, the subjects had less gray matter volume than normal, but after three months on a CPAP machine their gray matter had increased significantly. Restored gray matter in specific hippocampal and frontal brain regions can improve executive functioning (cognitive abilities such as planning, verbal reasoning, problem-solving, and multi-tasking) and short-term memory. The lead researcher, Vincenza Castronovo, Ph.D., a clinical psychologist and
psychotherapist, states in an article in Science Daily that not only does gray matter increase with CPAP treatment, but “neuropsy-chological deficits are reversed.”

My mother’s neuropsychological exam in 1997 showed mildly slowed executive functioning, diminished sustained attention, and mild word finding difficulties. I wish that the doctors had asked her about her snoring and her day-time fatigue. There’s no mention in their report of her odd sleeping patterns—the difficulty sleeping at night, the napping half the day. Not only could sleep apnea have explained these patterns, and killed off some of her gray matter, it would have exacerbated all of the other health problems that put her at risk for Alzheimer’s—her high blood pressure, depression, and small strokes.

We know that the obese have a higher rate of sleep apnea than people of normal weight, but research shows that slim people who sit for many hours a day—office workers and truck drivers, for example—are also at risk. My mother carried extra weight in her fifties and sixties, and sat for many hours a day at her desk the last ten years she lived at the cottage. (As a writer, I also sit a lot, of course, but I try to take a break every hour to move around.) The Sleep Research Laboratory of the Toronto Rehabilitation Institute has found that, in men of normal weight who sit for hours, fluid builds up in their legs during the day, and then, at night in bed, shifts to their necks. The fluid reduces the size of their airways and increases the likelihood of tissue collapse.

The National Sleep Foundation estimates that more than 18 million American adults have sleep apnea. According to the American Sleep Apnea Association, sleep apnea is as common as Type II diabetes, but “because of the lack of awareness by the public and health care professionals, the vast majority of sleep apnea patients remain undiagnosed and therefore untreated.”

CPAP machines have been widely available since the late 1980s. Perhaps if doctors had suggested to my mother years ago that she be evaluated at a sleep clinic, perhaps if she had started to wear a CPAP machine in the early stages of her dementia, its progression could have been slowed.

Hope in Vaccines?

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accines to reduce the build-up of these amyloid molecules are now being tested in more than 40 clinical trials with approximately 20,000 people. Similar trials in 2000 resulted in the death of two people from inflammation of the brain, and even though autopsies showed that the plaques had been reduced, their dementia had continued unabated. Diamond says, “if we stop the amyloid from accumulating, it doesn’t mean we’ve found the cure we need.”

Other studies are being conducted to create a vaccine for the tau protein tangles that form inside nerve cells. Some say that cognitive decline really starts when tau protein, not amyloid, builds up, damaging nerve cells.

Startling new research in February, 2012, shows that tau plays a major role in the spread of Alzheimer’s disease in the brain, proving in studies with genetically-engineered mice that Alzheimer’s disease originates in one particular area behind the ears, the entorhinal cortex (where memories are created and stored), and that it spreads like an infection to neighboring parts of the brain. This research, conducted separately in independent studies at Columbia and Harvard Universities, shows that broken, tangled tau protein in one neuron somehow causes tau in adjacent neurons to break down and develop tangles. The mice were genetically engineered to make human tau protein only in their entorhinal cortex, and in no other areas of their brain. When that human tau protein began to break and tangle, and then appeared in adjacent areas of their brain, it was clear for the first time that broken tau does not
develop sporadically in more susceptible parts of the brain (what has been called the “bad neighborhood” hypothesis), but is passed from neuron to neuron.

These findings offer the tantalizing possibility that there may be a way to stop Alzheimer’s disease by preventing broken tau protein from “infecting” its neighbors. However, it remains unclear how tau and amyloid beta work together, and scientists warn that any treatment or antibody based on this tau research would require many more years of study, and significant funding.

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n Familial (early-onset) Alzheimer’s, gene mutations cause a cascade of effects in the brain leading to increased amyloid. If one parent carries the mutated gene, the child has a fifty percent chance of developing the disease; if both parents carry the gene, the risk increases to seventy-five percent.

In Alzheimer’s disease over age sixty, there is something called a “risk factor” gene—APOE ε4 allele. This gene increases your risk somewhat if you inherit it from your parents. According to the National Institute on Aging, “Some people with one or two APOEε4 alleles never get the disease, and others who develop Alzheimer’s do not have any APOEε4 alleles.” For that reason a blood test for the allele is not recommended for people at risk for Alzheimer’s disease.

Because of my mother’s breast cancer in her forties, I did have the blood test done for the gene that would place me at higher risk for breast cancer (I don’t have it), but for this Alzheimer’s risk factor gene I’m unlikely, for the reasons above, to get a blood test. I consider myself fortunate that I’ve learned as much as I have in my forties about Alzheimer’s disease, and that through prevention and self-education, I may be able to avoid many of the risk factors.

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ew and on-going Alzheimer’s research ranges widely over many branches of inquiry: stem cell treatments, “growth factors” to repair damage to nerve cells, the damage caused by free radicals, the role of stress in cell damage (glucocorticoids such as cortisol may cause insulin resistance), and infection.

To look at just one of these subjects—infection—researchers know that parasites, bacteria, and viruses in the central nervous system can excrete toxins and cause inflammation, which in turn damage neurons. People with cold sores, from the herpes virus HSVI, are more likely to develop Alzheimer’s. (Mom and I both get cold sores.) Other viruses connected with Alzheimer’s risk are the herpes virus that produces the roseola rash, HIV, hepatitis C, and cytomegalovirus. Research into bacteria shows that people with Alzheimer’s have more spirochetes in their brains, which infect neurons. When Chlamydia pneumoniae, a common cause of pneumonia, is injected into mouse brains, they develop amyloid plaques.

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s I watch my mother’s deterioration I have become more determined to prevent my own.

After I discovered that I have sleep apnea—a risk factor for dementia—I found more evidence in my research that sleep apnea may be tied to insulin resistance and pre-diabetes, and to Alzheimer’s disease. During sleep, insulin levels in the body normally decline, but if the sleep is disrupted, insulin levels remain high. High insulin has been connected to inflammation in many parts of the body, including the brain, and inflammation puts a person at risk for stroke and heart disease, among other things. Our brains produce insulin independent of that produced in the pancreas, but if there is too much insulin it seems to increase the amount of amyloid beta. Also, a study at the University of Pittsburgh Medical Center determined that the brains of mice subjected to intermittent periods of low oxygen, as with sleep apnea, showed less sensitivity to insulin. (However, if the mice were consistently subject to a low oxygen level, as when people hike at high elevations, there was no change in their insulin sensitivity.) We need more research on the relationship of sleep apnea to metabolic disorders such as insulin resistance, pre-diabetes, and diabetes.

Many researchers now describe Alzheimer’s disease as “Type III diabetes,” diabetes of the brain. Researchers have known for some time that people with Type II diabetes are twice as likely as those without diabetes to develop Alzheimer’s. Diabetics on
insulin therapy are four times as likely as non-diabetics to develop Alzheimer’s. The worldwide epidemic of Alzheimer’s disease has grown alongside the worldwide epidemic of Type II diabetes. Someone like me who is insulin resistant and pre-diabetic is 70% more likely than someone with normal blood sugar and insulin levels to develop Alzheimer’s disease. We do not need to be fully diabetic to raise our risk considerably. Being overweight or obese, or having a lot of belly fat in middle age (as I do, and my mother did), are often related to insulin resistance and increase the risk of dementia.

I think of all the years my mother ate large amounts of sugar—when she stopped drinking, the pound bags of M&M’s; over the last years at the cottage, tons of cookies and ice cream. Although she was never diagnosed with diabetes, it’s likely that, like me, Mom has been pre-diabetic and insulin-resistant for years.

While twenty million people in the United States have Type II diabetes, twice that number are insulin resistant and pre-diabetic. Unfortunately, this condition often goes undiagnosed until it progresses into full-blown diabetes. With so many of us pre-diabetic, we need more awareness of this condition, and more research into its connection to Alzheimer’s.

In 2010, researchers at Kyushu University in Japan reported that people with diabetes or pre-diabetes are more likely to develop beta amyloid brain plaques. Another study has determined that a nasal spray of insulin improves the brain’s use of glucose, as well as memory and cognitive functioning. Some anti-diabetic drugs, such as rosiglitazone, seem to help brain functioning in people with Alzheimer’s.

A team at Northwestern University has determined that a toxic protein, called an ADDL (amyloid beta-derived diffusible ligand), strips brain nerve cells of insulin receptors, leaving them insulin resistant. Both brain insulin and its receptors are lower in
people with Alzheimer’s disease. ADDL’s start to build up at the beginning of Alzheimer’s disease, but may prove to be reversible.

Low-Carb Diets for the Brain

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or the past year I’ve slowly eaten less and less sugar and starch—down, now, to less than 30 mg a day, mostly from vegetables; I eat primarily animal fat and protein (organic whenever I can), raw cheese, eggs, olive oil, and low-carb vegetables. When I started this diet I didn’t know about the connection between insulin sensitivity and neuron damage. I wanted simply to lose weight and to lower my high blood sugar level so I wouldn’t develop diabetes; in the past, a less drastic reduction in carbohydrates had not worked for me. For my whole adult life I’d followed the general medical advice since the 1980s to eat low fat—which essentially means high-carbohydrate—and by my mid-thirties I carried the extra eighty pounds I mentioned earlier.

With this low-carb diet I hope to move my metabolism from glucose-based and insulin resistant to something called “ketonic” or “ketogenic.” When our bodies, including our brains, run on fat, not glucose, we’re using ketones for energy, which is perfectly healthy and efficient. In fact, a product called Axona
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has been shown in a recent study to improve the cognitive functioning of some people with Alzheimer’s disease by overcoming their brains’ resistance to glucose by fueling them with ketones. A prescription, FDA-designated “medical food,” Axona is a powder mixed with water or food and consumed once a day. According to Accera, the maker of Axona, “Ketone bodies are naturally occurring compounds that are produced mainly by the liver from fatty acids during periods of extended fasting. Ketone bodies have been demonstrated to protect neurons.”