Inside the Dementia Epidemic: A Daughter's Memoir

by Martha Stettinius

  As enzyme blockers, the first group—the cholinesterase inhibitors—work by restoring the balance of neurotransmitters in the brain. They include Aricept (donepezil HCl), approved by the FDA in 1993; Exelon (rivastigmine), approved in 1997; and Razadyne (galantamine), approved in 2001. Exelon and Razadyne are approved for mild to moderate dementia, and Aricept is approved for mild to severe dementia.

  The second type of medication is an N-methyl D-aspartate (NMDA) antagonist. Namenda (memantine), approved in 2003, can delay progression of some symptoms in moderate to severe cases of Alzheimer’s disease. It regulates glutamate, an important brain chemical.

  There is evidence that a combination of these two types of medications—Namenda plus a cholinesterase inhibitor—is more effective at relieving the symptoms of Alzheimer’s disease than treatment with only one type. A two-and-a-half-year study by the Memory Disorder Unit at Massachusetts General Hospital, published in 2008, showed that test subjects with mild dementia who took a combination of these drugs experienced a slower decline in memory and function than test subjects who took one type of medication or a placebo. A study published in the Journal of the American Medical Association in 2004 showed similar results with patients with moderate to severe dementia; when those already taking a cholinesterase inhibitor added Namenda, they experienced more of an increase in cognitive function and ability to perform activities of daily living than those solely on a cholinesterase inhibitor. Those on combination therapy also experienced a lower rate of side effects, especially gastrointestinal issues.

  Appendix C:

  Risk Factors and Antidotes for Dementia

  As a large French multi-center task force states in their report, Prevention of Progression to Dementia in the Elderly, “our present state of knowledge is inadequate.”

  None of us know if the health dictates we follow to avoid dementia will turn out in thirty years to have been bad advice. Mom taught me, for example, to avoid butter, to buy margarine because it didn’t have cholesterol (and because it was cheaper), but now the public knows about trans fat, and I wonder if that margarine and all the store-bought cookies she ate loaded her arteries with trans fat and contributed to her small strokes and dementia. (A 2011 study published by the journal Neurology shows a strong correlation between trans fat in the bloodstream and decreased brain function.)

  Most scientists agree, however, that there are certain risk factors for Alzheimer’s disease. They include old age; a family history; serious head trauma; poor cardiovascular health; high blood pressure; stroke; diabetes; high cholesterol; obesity in middle age; a low education level (which predisposes someone to less learning and brain development over their lifetime); and smoking.

  Exercise

  Some researchers say that exercise may be our most powerful antidote for Alzheimer’s disease. Because aerobic exercise increases blood flow to the brain, stimulates the growth of new brain cells, and decreases the risk of heart attack, stroke, and diabetes, the Alzheimer’s Association recommends thirty minutes of daily exercise.

  A recent study by neurologists at Rush University Medical Center shows that daily activity of all kinds—from formal exercise to activities such as washing dishes, cleaning, and cooking—may reduce the risk of developing Alzheimer’s disease, even in people over age 80. In another study, subjects who walked forty minutes a day for a year regained volume in their hippocampus, reversing brain shrinkage. In a third study, people with mild cognitive impairment who did resistance weight training two times a week over six months showed an increase in their memory and executive function (the ability to multi-task).

  Mental Stimulation

  Social activity and mental stimulation are also crucial. Combining social activity and mental stimulation with regular exercise is more effective than doing only one or the other. Sports, cultural activities, emotional support, and close personal relationships are all key. We should work as long as we can, volunteer, join social clubs, and travel. We should turn off the television, read, write, do crosswords and puzzles. Play games, do memory exercises, learn a new language, or learn to play an instrument. In fact, if we challenge ourselves regularly, our brains will continue to create new cells and connections.

  In the last ten years Mom lived at the cottage, she had little social interaction, scant mental stimulation beyond reading, and no exercise beyond climbing the hill to her car once or twice a week in winter.

  My life in an intentional community is quite different. I can hike with a friend through our fields, work with a team to cook a village meal, or play an instrument and perform skits in our village talent shows. There’s always something to do, and someone to do it with.

  The Role of Diet

  The Alzheimer’s Association recommends a low-fat, low-cholesterol diet, but acknowledges that all cholesterol is not the same: research suggests that HDL, or “good” cholesterol, may help protect brain cells. They recommend lots of dark vegetables and fruits that are high in antioxidants; mono- or polyunsaturated fats such as olive oil, cold water fish high in Omega 3’s (salmon, tuna, mackerel); and nuts such as almonds, pecans, and walnuts. Vitamin E, or vitamin E and C together, vitamin B12, and folate may also decrease the risk of Alzheimer’s.

  In 2005, when Mom lived with us, I barely had time to think of my own health. Not only was I seriously overweight, but I was insulin resistant and pre-diabetic and didn’t know it yet. (Insulin in the blood delivers glucose—blood sugar—to the body’s cells. With insulin resistance and pre-diabetes, cells grow resistant to the insulin, too much glucose remains in the blood and damages organs, and then the pancreas pumps out even more insulin to force the cells to absorb the glucose. If the pancreas grows exhausted and stops producing enough insulin, you get Type II diabetes.) I had also become quite allergic for the first time in my life to pollen, dust, and wheat, and was prone to frequent attacks of bronchitis.

  Gradually, over the past few years, while a variety of facilities have taken on the care of Mom’s daily physical needs, I have paid more attention to my own. I’ve lost weight and lowered my blood sugar level on a low-carbohydrate, wheat-free, sugar-free diet under the supervision of a nutritionist. I get shots every two weeks for my allergies, and garden, walk, and swim for exercise. I’m no longer felled by bronchitis, and rarely get sick.

  • • •

  The Importance of Vision Screening

  Research has found a connection between vision and Alzheimer’s disease. In a study of elderly people over the age of 71, all of whom had normal cognitive functioning at the beginning of the study, those who had undiagnosed or untreated vision problems showed a 9.5-fold increase in the risk of developing Alzheimer’s disease.

  Unfortunately, Medicare Parts A and B do not cover routine vision screenings, only a yearly exam for those at high risk for glaucoma. In France, a dementia task force recommends that vision screening be included in all evaluations to prevent Alzheimer’s.

  Sleep Apnea and Dementia

  I’m also getting treatment for sleep apnea, which I never knew I had. One day a few months ago, I was doing a relaxation meditation lying down, near the edge of sleep, and I felt the tissues of my throat close up and my breathing cut off. For several years, I’ve been exhausted all day despite nine or ten hours of sleep, but if it weren’t for my meditation practice I might never have discovered the sleep apnea. My husband is such a sound sleeper he never noticed if I snored a lot, or if I stopped breathing and startled awake. My only symptoms, aside from extreme fatigue, were frequent headaches first thing in the morning.

  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 ha
s 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?

  In 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?

  Vaccines 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.

  Appendix D:

  Is It “All in the Family” ?

  In 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.

  Appendix E:

  The Role of Infection

  New 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 brai
ns, which infect neurons. When Chlamydia pneumoniae, a common cause of pneumonia, is injected into mouse brains, they develop amyloid plaques.

  Appendix F:

  Sweet Poison: The Toxic Tide of Sugar

  As 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.