Summary: PET scans using a compound called FDDNP show promise for detecting Alzheimer’s and other neurodegenerative diseases before symptoms are apparent. If follow-up studies confirm the accuracy of this imaging technique, researchers will be a step closer to the vision of early detection and treatment to delay progression.
When my father complained about memory problems, his family doctor told him there was nothing wrong.
One year later, the doctor mailed my parents a letter saying he thought Dad had had a stroke. A neurologist at a major research center diagnosed probable Alzheimer’s; yet another at the same center said he thought the problem was iron overload and a vitamin B deficiency. If Dad would just take a vitamin B supplement and avoid foods enriched with iron, he thought, Dad’s memory would stabilize. My father’s last neurologist thought (correctly, it turns out), that the majority of Dad’s problems were due to the bleeding in his brain caused by cerebral amyloid angiopathy. It was very frustrating to not know what was causing his dementia, or whether any treatments would help.
Just how little this has changed in the two years since Dad’s death was demonstrated by the questions and comments I heard from attendees at the Early Memory Loss Forum held on October 27th in Los Angeles:
“How does one know whether a parent has age-related memory loss?”
“I had seven diagnoses over 18 months. I had a PET scan, SPECT scan, CT, and MRI, as well as genetic tests. It’s very difficult working with ‘it may be’ and ‘it has the potential of becoming.’ We need something that can more expediently diagnose so treatment can begin.”
“I’ve been told I have probable AD. Why don’t they know if I have AD?”
“My neurologist asked me ten questions – he said I’m fine. Does this mean I don’t have Alzheimer’s?”
“My doctor says I have ‘simple dementia.’ I need to know if it’s ‘simple dementia’ or Alzheimer’s.”
Despite recent progress in understanding neurodegeneration, doctors still can’t diagnose Alzheimer’s, vascular dementia and other disorders underlying memory loss with any certainty. This uncertainty, combined with some doctors’ reluctance to deliver bad news, means that even after months of testing, some memory loss patients come away with no diagnosis.
Besides the emotional toll on patients and families, uncertain diagnoses may delay treatment. In some cases, lack of a clear diagnosis can also cause disability or health insurance claims to be denied.
New imaging technique may allow early diagnosis of Alzheimer’s and related diseases
Diagnostic techniques are improving, and so are the chances of getting an accurate diagnosis. Dr. Gary Small, Director of the UCLA Center on Aging, and author of The Memory Bible: An Innovative Strategy for Keeping Your Brain Young and MEMORY PRESCRIPTION, THE: DR. GARY SMALL'S 14-DAY PLAN TO KEEP YOUR BRAIN AND BODY YOUNG, gave one of the keynote talks at the Early Memory Loss Forum. Along with other researchers, he envisions a future when doctors will know that a patient is developing Alzheimer’s disease or a related illness before the patient or his doctor have detected any symptoms. In this vision, the doctor will then be able to prescribe a treatment that will delay progression of the disease.
“If we can delay neurodegeneration long enough so the individual dies of other causes,” Dr. Small says, “we will have essentially ‘cured’ Alzheimer’s in that individual.”
Dr. Small co-invented an imaging compound that has the potential to help make this vision a reality. The compound, called FDDNP, is injected into the bloodstream, and travels through the blood to the brain. There it attaches to the abnormal protein deposits often found in Alzheimer’s brains, and allows those deposits to be seen during a PET (positron emission tomography) scan .
The potential use for FDDNP is similar to that for a compound called Pittsburgh Compound-B, or PIB, developed at the University of Pittsburgh. PIB binds to abnormal amyloid deposits that make up the plaques associated with Alzheimer’s. Unlike PIB, FDDNP shows both amyloid and tau. Since tau-based tangles are thought to build up in early stages of Alzheimer’s, the ability to detect tau may be important for early detection. In addition to amyloid and tau, FDDNP binds to multiple types of abnormal deposits, and could be used for diagnosing other types of neurodegeneration such as the cerebral amyloid angiopathy my father had.
Early studies of FDDNP show promise
Initial studies by Dr. Small and his colleagues seem to show PET scans using FDDNP to measure protein deposits correlate better with neuropsychological test results than some other imaging techniques. In one study, 83 people with memory complaints received FDDNP-PET scans, FDG-PET scans (to measure the brain’s metabolism) and MRI scans (to measure brain volume). The researchers concluded that FDDNP-PET scans were more useful for separating those with Alzheimer’s from those with Mild Cognitive Impairment and those whose neuropsychological evaluation showed no cognitive problems.
More testing with larger groups and different disorders is needed to confirm the accuracy of these scans.
What's next for FDDNP?
A PET scan using FDDNP is just one of many techniques being tested for early detection of Alzheimer’s and related diseases. Before researchers can make any recommendations on the use of these techniques, several questions must be answered:
*Which tests are best at detecting various types of pathology (plaques, tangles, deposits on blood vessels, etc.)?
*Which tests are best for measuring the effectiveness of medications?
*Will the most accurate diagnosis possible require a combination of imaging methods and other biomarkers such as protein levels in spinal fluid or blood?
*Which tests are most cost-effective?
While scientists are working to answer these questions, Siemens has licensed FDDNP from UCLA, and is working to develop the technology. PET scans using the compound may be commercially available in the U.S. as early as 2011.
Besides follow-up research and regulatory approval, widespread use of the technique will depend on reimbursement by insurance companies and government programs. Perhaps a case can be made that FDDNP-PET scans are cost-effective because they reduce the need for repeated testing, or because early diagnosis allows more effective treatment and reduces the need for long-term care.
Despite all the questions that remain, compounds like FDDNP represent significant progress towards the vision of early diagnosis and treatment. “None of the tests are one hundred percent,” says Dr. Small, “but you get a more definitive answer with some of these exams. I am optimistic with these kinds of new scans we’ll get to the next stage where we can be more definitive.”