Alzheimer’s is a terrible disease. It robs people of their futures, of their minds, and ultimately of themselves. It’s a grim diagnosis at any age, but it is especially devastating when it strikes people in the prime of life. Though the early-onset form of Alzheimer’s is not common, it’s particularly burdensome since these patients are often still raising children and are career-climbers with plenty of ladder left. This early form of the disease has gotten greater attention thanks to Julianne Moore’s Oscar-winning performance in Still Alice, based on Lisa Genova’s novel about a 50-year-old Harvard professor’s decline from Alzheimer’s.
Lawrence Reiswig, 62, of Greeley, Colorado, has a family history of early-onset Alzheimer’s disease. His father was 1 of 14 children, only 1 of whom escaped the disease. His dad became ill when Lawrence was just 8 years old. His brother, 6 years older, died of Alzheimer’s at age 52.
“I started watching for signs of it,” says Bonnie Reiswig, Lawrence’s wife of 43 years. And when she and Lawrence were on vacation and had spent the day riding roller coasters, the first sign surfaced. At the end of the day, Lawrence, who was known for his terrific sense of direction, turned the wrong way out of the parking lot. “I knew then,” Bonnie says. “He was 50 years old.”
The vast majority of people who are diagnosed with Alzheimer’s disease — 93% — are over the age of 70, according to John Morris, MD, who directs the Alzheimer’s Disease Research Center at Washington University in St. Louis. Early onset is less common. “There’s no uniform definition, but most people consider it early onset if the patient is under 60 years old,” notes Dr. Morris.
Four years after he made that wrong turn, Reiswig went to see Thomas Bird, MD, chief of neurogenetics at the University of Washington. “Dr. Bird discovered the gene that causes Alzheimer’s disease in Lawrence’s family,” Bonnie says. Lawrence was tested and the results were positive.
Treating Early Onset Alzheimer’s
Lawrence started taking Aricept, 1 of 4 medications approved by the FDA for Alzheimer’s disease. Three of those — Aricept, Exelon, and Razadyne — are in a class of drugs called cholinesterase inhibitors. They work by boosting the levels of acetylcholine, a neurotransmitter in the brain that is important for thinking and memory. In Alzheimer’s disease, people suffer a progressive loss of acetylcholine in the brain.
Lawrence started on 10 mg of Aricept per day, then went to 23 mg/day. “He’s one of the few people who can tolerate that dose,” Bonnie says. “Most have stomach issues.”
Indeed, common side effects of all the anticholinesterase inhibitors are nausea, vomiting and diarrhea, affecting 5 to 10% of users to a moderate degree. Stomach ulcers, gastrointestinal bleeding and weight loss can also occur, as well as muscle cramps and a slower heart rate.
Some consumer advocacy groups, such as Public Citizen, believe that the side effects of Alzheimer’s meds are not worth the small benefit they confer, and that the drug companies are irresponsibly marketing to a desperate group of patients.
Aricept, Exelon and Razadyne help alleviate the symptoms of Alzheimer’s disease by countering the loss of the neurotransmitter acetylcholine. But the drugs have no impact on the progression of the disease. The problem is the more acetylcholine a person loses, the less there is to boost. “There is evidence of benefit, but the degree of benefit is very small,” says Dr. Morris.
A second Alzheimer’s drug, Namenda, was added to Lawrence’s regimen a couple years later. Namenda is a an NMDA antagonist, which blocks the action of an excitatory neurotransmitter in the brain. The medication is thought to work by dampening abnormal brain activity and improving thinking and memory.
It’s hard to know if confusion is a side-effect of medication or the result of the disease
Side effects of Namenda include dizziness, headache, constipation and confusion. (In any individual, it’s hard to know if confusion is the result of the disease or the medication, but in clinical trials it was reported slightly more often in patients on the drug than those on placebo, which presents an interesting irony.) As with the anticholinesterase inhibitors, Namenda diminishes symptoms of Alzheimer’s disease, but does not slow its progression.
“The problem is that we really don’t know how much they’re helping,” Bonnie says of the drugs in Lawrence’s regimen. “Certainly his disease is slower than it was for the rest of his family, but that could be for any number of reasons.”
“We need better drugs,” Dr. Morris says. “We don’t have them.”
Some Sufferers Carry an Alzheimer’s Gene
Early onset Alzheimer’s sufferers typically start to show symptoms at age 45, though the disease can occur in 20-somethings and it can wait until someone’s 70. Early signs include memory lapses, inability to recall words, and losing track of everyday items such as your keys and your glasses. About half of early-onset Alzheimer’s patients carry a known gene mutation that determines their fate. Very few people in the US population have an Alzheimer’s-causing gene. Even among Alzheimer’s patients, they are rare — less than 1% of cases, Dr. Morris says.
There are three known mutations that lead to early-onset Alzheimer’s disease. The mutations involve different genes, but they’re all involved in making amyloid-beta peptide, a brain protein. For reasons scientists don’t entirely understand, amyloid-beta peptide accumulates and clumps up in nerve cells, killing the cells, and creates the distinctive amyloid plaques that are a hallmark of Alzheimer’s disease.
These mutations are deterministic, Dr. Morris says, which means if you carry the gene, you will get the disease. Also, if you carry the gene and have children, they have a 50-50 chance of getting the gene.
Lawrence Reiswig has one of the known mutations. Bonnie and Lawrence have two adult sons. The oldest, Matt, 40, decided to get tested. He has 5 children and wanted to prepare. To everyone’s relief, he does not have the gene. His younger brother Marty, 36, has not been tested yet. “It’s a very personal decision,” says his mother.
For Bonnie, the knowledge of the course of disease, gained from direct experience with Lawrence’s relatives, is a double-edged sword. “I’m glad I know how the decline occurs,” she says. For instance, everyone in Lawrence’s family loses the ability to speak. (This isn’t true for all Alzheimer’s patients.) So she was as prepared as she could be for that to happen.
As helpful as it is to know what to expect, it’s also sad, Bonnie says. “I know, in a year from now, I’ll be facing a whole new level of challenges. The past 12 years have been easy compared to what’s ahead. This year has been the most difficult so far.”
Many early-onset Alzheimer’s patients, even with a strong family history, do not carry any of the three known mutations. It’s clear there’s more to learn about what causes Alzheimer’s disease in middle age. “Maybe there’s an undiscovered mutation,” Dr. Morris says. “Or other factors.”
Diagnosis is difficult, especially in early-onset cases. “Most physicians don’t expect people to have Alzheimer’s disease before age 60,” Dr. Morris says. “There’s a lot of poor recognition or misdiagnosis.”
Once diagnosed, early-onset disease is managed in the same way as late-onset: Medication to alleviate symptoms as much as possible, and planning for long-term care. “The Alzheimer’s Association has very good information,” Dr. Morris points out, including information about social security and disability insurance for people who face losing their earning potential. “We urge people to address legal issues,” including writing a will and assigning power-of-attorney, notes Dr. Morris.
The prognosis for early-onset disease is essentially the same as late-onset. Studies have shown both types have about the same survival — “on average, 10 years,” according to Dr. Morris. But there’s some evidence that the earlier the disease sets in, the more virulent it is. “It’s possible that the dementia phase is more severe,” Dr. Morris says of early-onset disease, “but the body is younger and survives better.”
The lack of good treatment options looms large over physicians and researchers who want to help people with Alzheimer’s disease. So far, new drug therapies, those that target the pathological features of the illness and were promising in animal models, have failed in human clinical trials.
That said, a potential new drug developed jointly by Biogen Idec and Japan’s Eisai (called BIIB037) is being pushed into Phase III clinical trails, thanks to promising early results in patients with early signs of Alzheimer’s. BIIB037 is designed reduce beta amyloid in the brain.
It remains to be seen what this or other new treatment efforts can do, but esearchers keep at it, in part because the unmet need is so great. An estimated 5.2 million Americans have the disease, including 200,000 under the age of 65. As they learn more about the causes and courses of the disease, researchers can make more informed hypotheses about how to intervene.
‘People with rheumatoid arthritis almost never have Alzheimer’s disease’
A relatively new strategy is looking for protective factors, studying why some people don’t get the disease. “People with rheumatoid arthritis almost never have Alzheimer’s disease,” says Huntington Potter, a researcher at the University of Colorado School of Medicine in Denver. His research group has identified a protein that is present in the blood of rheumatoid arthritis patients and “after a fair amount of work,” has shown it can reduce amyloid-beta peptide build-up in a mouse model of Alzheimer’s disease.
The protein is called GM-CSF (granulocyte-macrophage colony-stimulating factor) and it’s the active ingredient in an FDA-approved drug for bone marrow transplant patients, called Leukine. “We’re testing it in a phase II clinical trial now,” Potter says. (Phase II trials take place when a drug that’s already been tested in a small group of people is then tried out on a much larger group.)
Leukine is only one example of the protective or reversal strategy, Potter says. “A number of pharmaceutical companies are pursuing this strategy.”
So the research continues, on the causes of the disease and its progression, in the hopes of finding a manipulation that is protective or at least slows down the inexorable slide into dementia.
And Bonnie continues to care for her husband, expecting the worst and grateful for the moments she’s still able to share with him. “He’s a very joyful person and for that I am thankful,” she says. “I’ve lost a little piece of him every day for 12 years. But he is still a person who deserves respect.”
For More Information:
- Alzheimer’s Fast Facts (MedShadow)
- Preventing Alzheimer’s Disease: What Do We Know? (National Institute on Aging)
- Protein May Hold the Key to Who Gets Alzheimer’s (New York Times)
- Early Onset Familial AD (Alzforum)
- 2014 Alzheimer’s Disease Facts and Figures (PDF, Alzheimer’s Foundation)
- 10 Warning Signs of Alzheimer’s (Alzheimer’s Foundation)
- Medications Fact Sheet (National Institute on Aging)
- Caring for a loved one with Alzheimer’s disease (National Institute on Aging)