Clinical and cortical decline in the aphasic variant of Alzheimer's disease

Abstract

Introduction: Primary progressive aphasia (PPA) displays variable progression trajectories that require further elucidation.

Methods: Longitudinal quantitation of atrophy and language over 12 months was completed for PPA patients with and without positive amyloid PET (PPA^Aβ+ and PPA^Aβ-), an imaging biomarker of underlying Alzheimer's disease.

Results: Over 12 months, both PPA groups showed significantly greater cortical atrophy rates in the left versus right hemisphere, with a more widespread pattern in PPA^Aβ+. The PPA^Aβ+ group also showed greater decline in performance on most language tasks. There was no obligatory relationship between the logopenic PPA variant and amyloid status. Effect sizes from quantitative MRI data were more robust than neuropsychological metrics.

Discussion: Preferential language network neurodegeneration is present in PPA irrespective of amyloid status. Clinical and anatomical progression appears to differ for PPA due to Alzheimer's disease versus non-Alzheimer's disease neuropathology, a distinction that may help to inform prognosis and the design of intervention trials.

Keywords: Amyloid PET; Biomarker; FreeSurfer; Frontotemporal dementia; Frontotemporal lobar degeneration; Neuropsychology; Primary progressive aphasia; Progression; Volumetric MRI.