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 (PPAAß+ and PPAAß-), 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 PPAAß+. The PPAAß+ 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.
Subject(s)
Alzheimer Disease/pathology , Aphasia, Primary Progressive , Atrophy/pathology , Brain/pathology , Alzheimer Disease/diagnostic imaging , Amyloid beta-Peptides/genetics , Aphasia, Primary Progressive/diagnostic imaging , Aphasia, Primary Progressive/pathology , Biomarkers , Disease Progression , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Positron-Emission TomographyABSTRACT
The goal of this study was to determine if the apolipoprotein ε gene, which is a well-established susceptibility factor for Alzheimer disease (AD) pathology in typical amnestic dementias, may also represent a risk factor in the language-based dementia, primary progressive aphasia (PPA). Apolipoprotein E genotyping was obtained from 149 patients with a clinical diagnosis of PPA, 330 cognitively healthy individuals (NC), and 179 patients with a clinical diagnosis of probable Alzheimer's disease (PrAD). Allele frequencies were compared among the groups. Analyses were also completed by sex and in 2 subsets of PPA patients: 1 in which the patients were classified by subtype (logopenic, agrammatic, and semantic) and another in which pathologic data were available. The allele frequencies for the PPA group (ε2:5%, ε3:79.5%, and ε4:15.4%) showed a distribution similar to the NC group, but significantly different from the PrAD group. The presence of an ε4 allele did not influence the age of symptom onset or aid in the prediction of AD pathology in PPA. These data show that ε4 polymorphism, which is a well-known risk factor for AD pathology in typical amnestic dementias, has no similar relationship to the clinical syndrome of PPA or its association with AD pathology.