# Eligibility for Anti‐Amyloid‐β Monoclonal Antibodies in Patients With Primary Progressive Aphasia due to Alzheimer's Disease in Japan

## TL;DR

The study examines how well brain imaging and biomarkers can identify patients with a language-related Alzheimer's variant eligible for new antibody treatments.

## Contribution

The study provides insights into the use of SPECT imaging and biomarkers to identify patients with lvPPA due to Alzheimer's eligible for anti-amyloid therapy.

## Key findings

- Most lvPPA patients showed AD-like brain perfusion patterns and were eligible for anti-amyloid therapy.
- One patient was reclassified as having frontotemporal lobar degeneration after negative AD biomarkers.
- SPECT imaging may help differentiate Alzheimer's-related lvPPA from other PPA variants.

## Abstract

Primary progressive aphasia (PPA) is a clinical syndrome characterized by progressive language impairment. The logopenic variant (lvPPA) is frequently associated with Alzheimer's disease (AD) pathology. With the approval of anti‐amyloid‐β monoclonal antibodies, such as lecanemab and donanemab, for the treatment of AD, accurately differentiating lvPPA due to AD (lvAD) from the other PPA variants has become highly important.

Thirteen patients with PPA who underwent cognitive testing, including the Standard Language Test of Aphasia (SLTA), brain magnetic resonance imaging, single‐photon emission computed tomography (SPECT), cerebrospinal fluid (CSF) biomarker analysis, and amyloid positron emission tomography (PET) imaging were enrolled in this study. Patients were classified into the lvPPA, semantic variant PPA (svPPA), and nonfluent/agrammatic variant PPA (nfaPPA) groups based on the results of clinical and neuropsychological assessments. We determined the proportion of PPA patients in each group who met the optimal use guidelines for anti‐amyloid monoclonal antibody therapy.

Six (86%) of the 7 lvPPA patients were amyloid positive (A+), and 5 (71%) were eligible for lecanemab or donanemab. In most lvPPA patients, SPECT displayed an AD‐typical pattern of hypoperfusion in the bilateral temporoparietal regions, posterior cingulate gyrus, and precuneus. One lvPPA patient was negative for AD biomarkers and demonstrated an atypical perfusion pattern for AD, and was subsequently rediagnosed as having frontotemporal lobar degeneration.

These results suggest that SPECT may play a supportive role in differentiating lvAD from PPA. In the current clinical era of anti–amyloid‐β monoclonal antibody therapy, accurate identification of lvAD among patients with language‐predominant symptoms is increasingly important. Larger studies should be performed in the near future to validate these findings.