Mark Karasow and his wife, Connie Bastek-Karasow, are part of a giant national experiment to determine whether more precise diagnoses can help patients with hard-to-diagnose dementia symptoms even though there still is little medical help for them.
Karasow has joined a $100 million clinical trial backed by the Alzheimer's Association and funded largely by Medicare. The unusual effort, which began this year, is measuring the impact of expensive PET scans that reveal clumps of amyloid, a protein found in the brains of people with Alzheimer's disease.
Trial leaders hope that the study, known as Imaging Dementia - Evidence for Amyloid Scanning (IDEAS), will prove that doctors and families make different decisions when they know what they're dealing with.
This trial could also lay the groundwork for how insurers will cover imaging that is being developed for the other misformed protein found in Alzheimer's patients, tau, and for proteins found in other forms of dementia.
Setting aside the impact on clinical care, the Alzheimer's Association argues that diagnoses help caregivers cope and plan.
"This is not a single person's disease," said Maria Carrillo, the association's chief scientific officer. "This is a whole family's disease."
In the past, amyloid plaques could be seen only during autopsies, making it impossible to give living patients a definitive diagnosis.
That was hugely frustrating for Karasow, who desperately wanted an explanation for his declining memory.
The first tracer that made it possible to see amyloid in living brains was approved by the Food and Drug Administration in 2012. But it and two competitors are rarely used except in clinical trials because insurers won't pay for the $5,000 tests.
Medicare, which typically leads the pack in insurance decisions, ruled against covering most amyloid imaging in 2013, saying there was insufficient evidence of benefit. None of the drugs available to dementia patients change the underlying pathology, although some can improve symptoms for a while.
The IDEAS trial is part of Medicare's Coverage with Evidence Development (CED) program, an effort begun in 2005 to test whether new services and treatments provide enough clinical value to warrant reimbursement.
The study, which will recruit more than 18,000 patients, will use three amyloid PET imaging compounds that have been approved by the FDA for clinical use: Amyvid, made by Avid Radiopharmaceuticals, a Philadelphia subsidiary of Eli Lilly & Co.; Vizamyl, a GE Healthcare compound that grew from the University of Pittsburgh's Pittsburgh Compound-B; and NeuraCeq, made by Piramal Pharma Inc. in Boston.
Dementia is an umbrella term for diseases that cause memory and thinking problems, most often in old age. Alzheimer's is the most common and best known, but the landscape of dementia is more complex than once thought. Some abilities decline in most people with "normal" aging. Strokes contribute to vascular dementia. Then there are Lewy body and frontotemporal dementias. Patients can have more than one source of dementia.
Many other things, including depression, a vitamin deficiency, and medications, can cause cognitive problems that sometimes look like dementia.
In the absence of good diagnostic tests, doctors can have trouble sorting things out, especially in the early stages.
For example, about a fifth of study subjects in some trials of drugs meant to combat amyloid did not have Alzheimer's. Now trials of such drugs require PET imaging.
"People end up with no diagnosis and a lot of uncertainty and anxiety," said Mark Mintun, Avid's president and chief medical officer.
Interpreting amyloid brain scans is complex. A negative scan almost certainly means a patient does not have Alzheimer's, but a positive scan - one that shows amyloid deposits - is less clear-cut. Studies show that people without thinking problems can have abnormal amyloid. That doesn't mean they wouldn't eventually get dementia, but they may die before they do. Amyloid can also be present in Lewy body dementia. Combined with symptoms, though, amyloid may strengthen a diagnosis.
The argument for testing is that some things that cause dementia are fixable. "You may not think about some very rare things unless you've ruled out Alzheimer's," said Gil Rabinovici, a neurologist at the University of California-San Francisco, who is the principal investigator of the IDEAS trial. In addition, some of the drugs that can help Alzheimer's patients make symptoms worse in people with frontotemporal dementia.
David Weisman, a neurologist at Abington Neurological Associates, told Mark Karasow seven years ago that he probably had Alzheimer's.
Karasow, a retired Levittown salesman who is now 75, was devastated. He went to a geriatric psychiatrist who thought his superior language skills, combined with slow-moving changes in memory and problems with walking, were not "typical" for Alzheimer's.
He went to another neurologist, who agreed and suspected Parkinson's.
After his symptoms worsened this year, Karasow went back to Weisman. The doctor still thought it was Alzheimer's but told Karasow there was a 10 percent chance he was wrong.
Karasow joined the IDEAS trial and had his brain scanned at Adler Institute for Advanced Imaging in Jenkintown.
He now knows he has amyloid building up in his brain.
He is glad, though, that he had a chance to help science through the trial. Feeling more sure of his diagnosis has also helped him switch from denial to dealing with reality.
"When I first heard it, I was a little perturbed," Karasow said. "Obviously, I was hoping it would go the opposite way. But I'm the kind of person who likes to know things that will affect him and his family."
Connie Bastek-Karasow, 67, who retired last year because of her husband's illness, said the scan had made her more aware of their shortened time together. "If nothing else, I can drop into his space and be with him," she said. "If he gets tired, I can lay down with him and hold hands."
For now, Medicare patients can get the PET scans only after being evaluated by specialists participating in the trial and only if their case is difficult.
Howard Natter, a neurologist with Meadowbrook Neurology Group in Montgomery County, has sent three patients for scans through IDEAS and has found the results "very helpful." One was negative, allowing him to reassure an anxious patient. The two positive ones helped him and the patients make decisions.
"It gives us a piece to the diagnostic puzzle," he said. "It can't be the only piece that's relied on."
David Wolk, codirector of the Penn Memory Center, said he sees a patient a week he would like to see join IDEAS.
He has little doubt the results will change physician management and help families. "Having the label and knowing where things are going, I find that opens up families," Wolk said. "There's a lot of denial with these conditions."
Trial organizers are hoping the scans will lead to fewer hospitalizations as the new diagnoses make families more vigilant. Dementia patients often wind up sick because they get confused about medications for heart problems or diabetes.
Still, Wolk understands concerns that testing could get out of hand in a country where five million people have Alzheimer's. Doctors need to be "judicious" in ordering the tests, he said.
Raj Agarwal, a radiologist with Montgomery County Advanced Imaging, thinks the PET scans could eventually lead to less testing. Now, he said, patients keep going to doctors as symptoms progress because they want answers. Each time, there may be a new round of tests. Knowing whether they have amyloid might lead to fewer CT and MRI scans.
Researchers say the IDEAS study is likely to boost enrollment in other trials testing potential dementia drugs. Rabinovici said 90 percent of IDEAS participants so far were willing to hear about other trials.
Mark Karasow is now being evaluated to join a clinical trial of a new medication.
His wife is finally thinking about financial planning and long-term care.
Having a diagnosis, she said, has given her a chance to rethink her expectations.
"It does matter, naming things," she said. "At least you don't feel like you're shadowboxing."
To find out more about the trial and which doctors are participating locally, go to http://www.ideas-study.org.