Researchers report, amyloid positivity, according to positron emission tomography (PET) findings, differs among the main clinical variants of primary progressive aphasia (PPA). The findings were published in the JAMA Neurology.

Dr. Miguel A said, "Primary progressive aphasia is a clinically and pathologically heterogeneous condition – generally frontotemporal lobar degeneration (FTLD), typically tau or tdp proteinopathies, or Alzheimer disease (AD) pathology – in which language impairment is the predominant cause of functional impairment during the initial phases of disease.”

He added,  “Classification of PPA cases into clinical-anatomical phenotypes is of great importance because they are linked to different prevalence of underlying pathology, and prediction of this pathology during life is critical due to the proximity of molecule-specific therapies.”

Of the three most common PPA variants, the semantic (svPPA) and nonfluent/agrammatic (nfvPPA) variants are generally caused by FTLD, while the logopenic variant (lvPPA) is mostly caused by Alzheimer disease. Few studies have reported amyloid imaging and pathologic results in PPA, and those have had inconsistent results.

Dr. Santos-Santos and colleagues studied amyloid brain imaging in 28 patients with svPPA, 31 with nfvPPA, 26 with lvPPA, 4 with mixed PPA (PPAm), and 10 healthy individuals (controls). Cognitive testing and MRI analysis revealed the expected differences among the PPA variants and between each PPA subgroup and controls.

Overall, the prevalence of amyloid positivity was 39.3% (35/89). Most patients with svPPA (85.7%) or nfvPPA (90.3%) had negative amyloid PET scans, and the rates of positivity in these patients were similar to those that have been reported in cognitively normal individuals at a similar age.

In contrast, the amyloid positivity rate in patients with lvPPA (96.1%) was much higher than expected for age. Three of the four patients with PPAm were amyloid positive; one was negative.

Among the 20 patients with autopsy diagnoses, all who had positive amyloid scans showed intermediate to high Alzheimer disease neuropathological changes. When the PPA phenotype was lvPPA, positive amyloid PET was associated with primary Alzheimer disease.

In contrast, when the PPA phenotype was nfvPPA or svPPA, the primary causative neuropathology was FTLD, with Alzheimer disease present as a contributing copathology.

All autopsy patients with negative amyloid imaging results had absent to low Alzheimer disease neuropathological changes, with FTLD as the primary causative neuropathology.

“These results suggest that typical clinical and MRI findings in svPPA and nfvPPA variants are highly predictive of the presence of FTLD pathology, even in the face of discordant molecular AD biomarker results,” Dr. Santos-Santos said.

“This work points towards several important unanswered questions that are interesting lines for future research,” he said. “The first is the identification of reliable biomarkers that could aid in the in-vivo prediction of atypical underlying pathologies in each of the PPA variants, in particular the differentiation of nfvPPA cases with underlying tau versus tdp proteinopathy is critical.”