A panel of medical experts from the National Institute on Aging and the Alzheimer’s Association last week proposed changes in the way doctors diagnose Alzheimer’s disease — including the use of so-called biomarkers, tests like PET brain scans and analyses of spinal fluids to promote early detection of the disease. Although these recommendations are well intentioned, evidence suggests that it would be a mistake to adopt them at this time. To understand why, it’s important to recognize what these tests mean, in what context the information will be used and what experience has shown us.
First, about the diagnostic tests: A PET scan detects clumps of a deformed protein called amyloid beta, commonly known as plaques. The presence of these plaques has been a gold standard of Alzheimer’s pathology since 1906, when Dr. Alois Alzheimer first identified them in a patient.
However, we now know that roughly one-third of all elderly adults have such plaques in their brains yet function normally. And eleven clinical trials, recently made public by a group of drug companies, that were aimed at reducing these plaques in Alzheimer’s patients all failed to show cognitive improvement, even when the brains were cleared of plaques.
Thus, the presence of plaques cannot predict with any accuracy or specificity that an individual is going to acquire the disease — and researchers are increasingly looking beyond the amyloid hypothesis for an adequate explanation for Alzheimer’s.
Another test being recommended by the panel is spinal fluid analysis — which measures the relative levels of two proteins, tau and amyloid beta. This method does seem quite promising, but its predictive potential remains uncertain.
There are also practical issues to be considered, not least of all the high cost of these procedures. What’s more, the spinal tap procedure is not easy to perform and is painful to undergo, and it is a long way from becoming a routine diagnostic tool. Dr. Janis Petzel, a geriatric psychiatrist in Maine, has noted how unfeasible this test is in “nonacademic, rural or non-Western settings”: “I pray that cerebrospinal fluid findings will never be part of diagnostic criteria for Alzheimer’s disease,” she wrote.
The diagnostic tests themselves can carry a risk of side effects. General imaging scans can expose patients to radiation, for instance; an invasive spinal tap could result in infection or damage to tissue. But there is also the psychological risk of false positives and misdiagnoses that greatly distress patients, at least until further tests show they do not have the disease.
This danger of overdiagnosis is very real, as the history of treatment for prostate cancer shows. A study last year about the prostate-specific antigen test found that in the two decades after the test was introduced, prostate cancer was detected in more than 1 million additional men, many of whom were likely overtreated.
Last, the most dreadful thing about Alzheimer’s disease, next to the slow deterioration of cognition, is that we do not yet have a cure and none seems to be on the horizon. So, even if the new recommendations rendered the diagnosis earlier and unassailable, there is no therapeutic avenue to use this information to effectively treat the patient. Many individuals would simply prefer to be spared the emotional trauma of a diagnosis if no treatment exists.
Taken together, these reasons suggest that the panel’s recommendations are likely to increase the emotional burden on individuals and the financial burden on society without providing proportional benefits. The doctor’s most basic tenet is that of primum non nocere — first, do no harm. Until we have a more definite idea about what causes Alzheimer’s, early-detection tests may do patients more harm than good.
Sanjay W. Pimplikar, an associate professor in the department of neurosciences at the Cleveland Clinic’s Lerner Research Institute.