A sweep of more than 550 articles from the medical literature on Alzheimer’s disease diagnosis left reviewers questioning the utility of a positive beta-amyloid scan, according to a meta-analysis published in the January issue of JAMA Internal Medicine.

The only protocol considered an absolute confirmation of Alzheimer’s disease remains a duo of clinical diagnosis and evidence of beta-amyloid plaques as well as neurofibrillary tangles of tau proteins upon autopsy. Diagnostic amyloid imaging has suffered a series of setbacks that have little to do with the high sensitivity of PET imaging for amyloid. 

Steven D. Pearson, MD, from the Institute for Clinical and Economic Review in Boston, pored over a total of 558 peer-reviewed articles focused on Alzheimer’s diagnoses and narrowed them down to 15 reports centered on amyloid PET imaging.

There were 14 studies included that evaluated the diagnostic accuracy of amyloid PET imaging, while 13 compared results of imaging to biopsy. A major study, which was used by the U.S. Food and Drug Administration to determine the efficacy of amyloid imaging as a diagnostic tool for Alzheimer’s disease, compared the sensitivity and specificity of amyloid PET with results from biopsy. Amyloid PET was found to be 92 percent sensitive and 95 percent specific, but the full range was 69 percent to 95 percent sensitivity and 90 to 100 percent specificity.

“At present, the medical literature provides extremely limited data with which to evaluate the clinical utility of beta-amyloid PET,” wrote Pearson et al. “There are reasonable data showing that, when read by well-trained interpreters, beta-amyoid PET is highly accurate in determining whether there is amyloid in the brain. However, the clinical utility of a positive scan result remains uncertain. If tested, approximately one-third of cognitively normal older adults would have a ‘positive’ test result for brain amyloid. Thus a positive beta-amyloid PET result is not diagnostic of [Alzheimer’s disease], nor can the test be used to accurately predict the risk or the timing of progression of mild cognitive impairment.”

The researchers included one study that focused on the prognostic value of amyloid PET imaging for progression from mild cognitive impairment to Alzheimer’s disease. Results of the study showed that 29 percent of subjects who tested positive for amyloid had full-blown dementia inside of 18 months instead of the 10 percent who tested negative, but it was still unclear to the study authors how cognitive decline would follow. Still, a negative amyloid PET scan may be a better bet for clinical use than a positive scan.

“The clinical utility of a negative beta-amyloid PET result seems greater than the clinical utility of a positive result because the high sensitivity of a negative test result allows [Alzheimer’s disease] to be effectively ruled out as the cause of a patient’s cognitive impairment,” concluded the authors.