How accurate is PET scanning in the diagnosis of Alzheimer disease?

Updated: Apr 12, 2018
  • Author: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS; Chief Editor: L Gill Naul, MD  more...
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Despite the technical differences, results from PET and SPECT scanning are comparable, although data suggest that PET scanning is more sensitive than SPECT scanning. [73] On PET or SPECT scanning, mild Alzheimer disease may be more difficult to detect than moderate or severe disease. In Alzheimer disease, FDG-PET has a sensitivity of 94% and a specificity of 73%. It can also be used to correctly predict a progressive course of dementia with a 91% sensitivity and a nonprogressive course with a 75% specificity. [74] Efforts to develop a specific ligand for Aβ plaques may further enhance the sensitivity of PET scanning for early diagnosis of Alzheimer disease and may provide a biologic marker of disease progression. [72]

In their study, Boxer et al reported that different amyloid-binding PET scan agents—Pittsburgh Compound-B and FDDNP—may have differential sensitivity to prion-related brain pathology and that a combination of amyloid imaging agents may be useful in the diagnosis of early onset dementia. [75]

Florbetapir F-18 (AMYViD) was approved by the FDA in April 2012 as a diagnostic imaging agent. It is indicated for PET brain imaging of beta-amyloid neuritic plaques in adults being evaluated for Alzheimer disease or other cognitive decline.

Approval for florbetapir F-18 was based on 3 clinical studies that examined images from healthy adult patients as well as patients with a range of cognitive disorders, including some terminally ill patients who had agreed to participate in a postmortem brain donation program. Measurements from postmortem cortical amyloid burden correlated with median florbetapir F-18 scores (r=0.78; P<0.0001).<ref>57</ref>

In a study by Clark et al, the presence and density of beta amyloid correlated closely in individuals who had florbetapir-PET imaging within 99 days before death and then upon autopsy. [58] Patients with probable Alzheimer disease or mild cognitive impairment or older healthy control subjects showed significantly different mean cortical florbetapir uptake value ratios in a study by Fleisher et al. [59]

In October 2013, the FDA approved the a second 18F-labeled Pittsburgh compound B (PIB) derivative, flutemetamol F-18 injection (Vizamyl), for use with PET brain imaging in adults undergoing evaluation for Alzheimer disease and dementia. Like florbetapir F-18, flutemetamol F-18 attaches to beta amyloid in the brain and produces a PET image that can be used to assess its presence. A positive scan indicates there is likely a moderate or greater amount of amyloid in the brain, but it does not establish a diagnosis of Alzheimer disease or other dementia. The effectiveness of flutemetamol F-18 was established in 2 clinical studies with 384 participants who had a range of cognitive function. [60]

A third agent, florbetaben F-18 (Neuraceq), was approved by the FDA in March 2014. Images may be obtained between 45 and 130 minutes after the injected dose. FDA approval was based on safety data from 872 patients who participated in global clinical trials, as well as 3 studies that examined images from adults with a range of cognitive function, including 205 end-of-life patients who had agreed to participate in a postmortem brain donation program. Images were analyzed from 82 subjects with postmortem confirmation of the presence or absence of beta amyloid neuritic plaques. [61]

Fluorine-18 AV1451 study results have shown that pathologic aggregation of tau is closely linked to patterns of neurodegeneration and clinical manifestations of Alzheimer disease, in contrast to the more diffuse distribution of amyloid-β pathology. [76]

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