Q&A: The Prevalence of Overdiagnosis in Alzheimer’s Disease

Overdiagnosis is commonly discussed in areas like breast imaging, where screening is widely conducted and media interest is high. While it’s under the radar for other diseases, it’s a big enough topic in the medical world to warrant a dedicated issue in Academic Radiology. Its August 2015 issue is devoted to overdiagnosis, a term used for disease that’s correctly diagnosed, but at the earliest stages when treatment may not be necessary and might even be harmful to the patient. This is in contrast to false positives, when the diagnostic test incorrectly indicates the possible presence of disease.

Overdiagnosis is more prevalent in modern times because the definition of disease has expanded, said Saurabh Jha, MBBS, assistant professor of radiology at the Hospital of the University of Pennsylvania, and guest editor of the Academic Radiology issue. “The rationale is the very intuitive concept that if we catch disease early on, we’ll avoid morbidity and mortality, that prevention is better than cure.”

Through screening, radiologists define the pathway to disease and are the gatekeepers of the technology often validating the diagnosis, since the gold standard of a diagnosis by pathology isn’t always an option.

With more advanced technology, radiologists can see deeper into structures in the body, discovering new (but often innocuous) abnormalities. Another reason for a growth in overdiagnosis is cultural. The division between “diseased” and “healthy” is arbitrarily set.

“There’s always going to be disputes about where the boundary takes place,” said Jha, with nothing magically happening at that threshold where disease is defined. However, in the United States, that threshold is often set at a place where doctors won’t miss any disease, erring on the side of overdiagnosing a person who doesn’t need treatment. “We live in an extremely risk averse environment.”

This Q&A series looks at a number of diseases that may be overdiagnosed in the United States, where we might be “treating health as opposed to solving sickness,” according to Jha.

The important question to ask with Alzheimer’s disease (AD), said Jha, is whether overdiagnosing it changes the management and course of the disease. “There’s little evidence, it’s tenuous,” he said.

Here’s our Q&A with author Jacob Dubroff, MD PhD, Assistant Professor of Radiology at the Hospital of the University of Pennsylvania.

Why do you think AD is being overdiagnosed?[[{"type":"media","view_mode":"media_crop","fid":"39873","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_8553460667287","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4015","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":"Jacob Dubroff, MD, PhD","typeof":"foaf:Image"}}]]

I don’t think AD is being overdiagnosed from a population perspective. On an individual basis, in patients seen by general practitioners and not experts at dementia evaluation, it probably is because of its insidious onset and similarity to other dementias in their early stages. With the development of this new technology, PET brain amyloid imaging, there is a potential for inappropriate use and, therefore, AD could be overdiagnosed if not properly coupled with clinical expertise. 

What is PET’s role in reducing or increase overdiagnosis of AD?

The goal is for amyloid PET to increase the accuracy of an AD diagnosis. AD is not the only dementia syndrome, but likely represents 50% of all dementia syndromes. For even the most skilled clinicians who diagnose dementia syndromes, such as cognitive neurologists and geriatric psychiatrists, studies have shown their accuracy to be 70%-80%. Right now, there are an estimated 3.2 million Americans with AD and, given our aging population, this number is expected to grow to 13.8 million by 2050. If used inappropriately or interpreted incorrectly, PET amyloid imaging could contribute to overdiagnosis.

How will you know that PET is appropriately diagnosing AD? What is your gold standard, the truth, for verification?

With what we know right now, in light of the relatively limited experience the medical community has with PET amyloid imaging, we know that a negative PET amyloid scan has very high negative predictive and, therefore, can essentially rule out a patient’s symptoms from being AD. We know about 10%-15% of 60 year olds have brain amyloid and this percentage continues to grow with age reaching around half of all those 80 years old. However, this is irrespective of symptoms-memory loss.  A positive study should not be equated with AD, it needs to fit properly with the clinical diagnosis.  Expert follow-up usually improves diagnosis as the disease progresses and symptoms are fully expressed. There is ongoing research focused on providing more accurate diagnosis while the patient is still alive.

PET imaging is expensive. Is it a worthwhile investment in diagnosis (or reducing overdiagnosis) of AD?

Indeed, by itself, a single amyloid PET scan may seem expensive. However, if an anti-amyloid is developed, and there are several ongoing promising trials, the cost of the PET would likely pale in comparison to the therapy. The upcoming IDEAS trial (Imaging Dementia-Evidence for Amyloid Scanning) is aimed at the here and now. It is a national multi-center study led by the Alzheimer’s Association and the American College of Radiology that strives to exam major medical outcomes (eg, hospital admissions and ED visits) 90 days after a PET amyloid scan is performed and also at 12 months.   If PET amyloid imaging can significantly influence outcomes, it seems like a reasonable investment, but only in the appropriate clinical context.