Flortaucipir PET discriminates AD from other neurodegenerative disorders
medwireNews: The positron emission tomography (PET) tracer [18F]flortaucipir could be a useful test for distinguishing Alzheimer’s disease (AD) from other neurodegenerative disorders, say researchers.
When they traced [18F]flortaucipir uptake in the medial-basal and lateral temporal cortex of 719 patients with established diagnoses at a memory disorder clinic, the researchers were able to differentiate patients with AD dementia from those with non-AD neurodegenerative disorders with an estimated sensitivity of 89.9% and a specificity of 90.6%.
“[18F]flortaucipir outperformed established structural MRI [magnetic resonance imaging] markers for AD, and showed higher specificity for the diagnosis [of] AD dementia compared with [amyloid-beta] biomarkers,” notes the team, led by Rik Ossenkoppele (Lund University, Sweden).
The study participants, who were aged an average of 68.8 years, included 179 with AD dementia, 254 with non-AD neurodegenerative disorders, 126 with mild cognitive impairment (MCI) and 160 cognitively healthy individuals. Of these, 100%, 23.8%, 65.9% and 26.3% tested positive for amyloid beta.
The sensitivity and specificity of the test was based on the uptake of tau in five predefined regions of interest (ROI) that covered the full spectrum of tau aggregation, from early to late affected areas, to give a standardised uptake value ratio (SUVR).
In the temporal meta-ROI (medial-basal and lateral temporal cortex), which gave the best results, [18F]flortaucipir uptake at an SUVR cutoff point of 1.34 (mean in controls plus two standard deviations) was 90.3% accurate for distinguishing AD dementia from all patients with non-AD neurodegenerative disorders combined, at a sensitivity of 89.9% and a specificity of 90.6%.
The diagnostic performance of flortaucipir PET was also consistent when tested against the non-AD neurodegenerative disorders separately, with only a slight reduction in specificity when distinguishing AD dementia from dementia with Lewy bodies (66.7%) or semantic variant primary progressive aphasia (63.6%).
However, the discriminative accuracy of flortaucipir PET “dropped substantially” for the prodromal stage of AD, the team points out in JAMA. The test had an area under the receiver operating characteristic curve (AUC) for distinguishing patients with MCI from those with non-AD neurodegenerative disorders that ranged from 75% to 84%
Nevertheless, for detecting AD dementia the test significantly outperformed three established MRI markers – hippocampal volumes, a signature AD composite (bilateral entorhinal cortex, inferior and middle temporal cortices and fusiform cortex) and whole-brain cortical thickness at all ROI. The AUC for all five flortaucipir PET ROIs ranged from 92% to 95%, while the range was 63% to 75% for the MRI markers.
The researchers suggest that “[18F]flortaucipir PET may thus be most valuable for differential diagnosis rather than early disease detection”, and could be used before structural MRI.
In support of this, they found that flortaucipir PET had significantly greater specificity for detecting AD dementia from other non-AD neurodegenerative disorders than amyloid-beta status, which had an accuracy of 76.1%; and the difference was greater when distinguishing AD dementia patients from controls, at 95.6% versus 73.8%.
“[A]n intended clinical use of [18F]flortaucipir PET might be to improve the diagnostic workup as an add-on test to [amyloid-beta] biomarkers in patients with early-onset dementia and possibly as a triage or even replacement test in patients with late-onset dementia in whom incidental [amyloid-beta] pathology is common”, they propose.
But they acknowledge that“[t]he accuracy and potential utility of this test in patient care require further research in clinically more representative populations.”
By Lucy Piper
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